[Elenco soci]


Gloria Antonio

Professore Associato


Università degli Studi di Napoli Federico II
antonio.gloria@unina.it

Sito istituzionale
SCOPUS ID: 16039011500
Orcid: 0000-0001-5233-5687



Pubblicazioni scientifiche

[1] Ausiello P., Martorelli M., Papallo I., Gloria A., Montanari R., Richetta M., Lanzotti A., Optimal Design of Surface Functionally Graded Dental Implants with Improved Properties, Lecture Notes in Mechanical Engineering, 294-305, (2023). Abstract
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Abstract: Over the past years, a wide range of dental implants has been proposed. In general, the dentists may find the best solutions according to the specific needs of the patients. A variety of factors influences the level of osseointegration and, consequently, the anchorage of the implant to the bone. The stress transfer mechanism along the bone-implant interface depends upon the surface area of the bone-implant contact. Great efforts have been devoted to the design of 3D porous lattice structures with tailored architectural features in order to reduce the implant stiffness as well as to favour bone ingrowth, thus stabilizing the device. Accordingly, the aim of the current study was to provide further insight into the design criteria for dental implants. In particular, starting from a screw implant (Implant A), different concepts of dental implants were developed: i) Implants B1–B5, with lattice shell surrounding a solid core, without thread; ii) Implant C, with lattice structure; iii) Implant D as topography optimized implant. Finite element analysis on the several models of bone-implant provided interesting information in terms of stress distributions in cortical and trabecular bone. Some differences among the implants may be ascribed to the different design criteria.

Keywords: Dental implants | Design criteria | Finite element analysis | Lattice structure | Topography optimization | Topology optimization

[2] Speranza D., Di Bernardo R., Martorelli M., Gloria A., Pensa C., Papa S., Basic Design and Virtual Prototyping of a Hydrofoil Hybrid Daysailer, Lecture Notes in Mechanical Engineering, 122-134, (2023). Abstract
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Abstract: The paper presents a preliminary design activity and virtual prototyping of an innovative boat equipped with hydrofoils and hybrid propulsion, with the aim of extending the foil technology from the field of competition boats to recreational day-cruiser yachts and creating a craft with minimal environmental impact. Hydrofoils allow boats to rise from the water, greatly reducing resistance and increasing performance. The current work dealt with the preliminary design of a daysailer with foil technology and hybrid propulsion that allow to combine green and comfortable navigation both under sail and motor and that, when required, can sail in a more performing way by exploiting the foil technology and the thrust of the wind. After having deepened the theory and physics of sailing on foils, a MATLAB code was created to integrate the stability equations that characterize hydrofoil sailboats: connecting the acting forces and allowing to define the dimensions of the geometries, the code was fundamental in speeding up the iterative preliminary design process. The next step was to model the geometry of the hull and the appendages in the CAD environment and, subsequently, the wing movement mechanism so that it could both manage the incidence of the wings and retract the foils when the boat is moored. The hull, profiles, and wings were subsequently placed in a CFD and VPP virtual environment for testing their resistance. Future developments will include a detailed design and the physical prototyping of a first boat for water testing.

Keywords: Green | Hybrid | Hydrofoil | Virtual prototyping

[3] Santoro A., Grimaldi M., Buonocore M., Stillitano I., Gloria A., Santin M., Bobba F., Sublimi Saponetti M., Ciaglia E., D'Ursi A.M., New Aβ(1–42) ligands from anti-amyloid antibodies: Design, synthesis, and structural interaction, European Journal of Medicinal Chemistry, 237, (2022). Abstract
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Abstract: Alzheimer's disease (AD), is the most common neurodegenerative disorder of the aging population resulting in progressive cognitive and functional decline. Accumulation of amyloid plaques around neuronal cells is considered a critical pathogenetic event and, in most cases, a hallmark of the pathology. In the attempt to identify anti-AD drug candidates, hundreds of molecules targeting Aβ peptides have been screened. Peptide molecules have been widely explored, appreciating chemical stability, biocompatibility, and low production cost. More recently, many anti-Aβ(1–42) monoclonal antibodies have been developed, given the excellent potential of immunotherapy for treating or preventing AD. Antibodies are versatile ligands that bind a large variety of molecules with high affinity and specificity; however, their extensive therapeutic application is complex and requires huge economic investments. Novel approaches to identify alternative antibody formats are considered with great interest. In this context, taking advantage of the favorable peptide properties and the availability of Aβ-antibodies structural data, we followed an innovative research approach to identify short peptide sequences on the model of the binding sites of Aβ(1–42)/antibodies. WAibH and SYSTPGK were designed as mimics of solanezumab and aducanumab, respectively. Circular dichroism and nuclear magnetic resonance analysis reveal that the antibody-derived peptides interact with Aβ(1–42) in the soluble monomeric form. Moreover, AFM microscopy imaging shows that WAibH and SYSTPGK are capable of controlling the Aβ(1–42) aggregation. The strategy to identify WAibH and SYSTPGK is innovative and can be widely applied for new anti-Aβ antibody mimicking peptides.

Keywords: Alzheimer | Amyloid plaques | Antibody | Aptamers | Biomarkers | Immunotherapy | Peptide design

[4] Schiano Lo Moriello R., Liccardo A., Bonavolonta F., Caputo E., Gloria A., De Alteriis G., On the Suitability of Augmented Reality for Safe Experiments on Radioactive Materials in Physics Educational Applications, IEEE Access, 10, 54185-54196, (2022). Abstract
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Abstract: Laboratory experiences have proved to be a key moment of the educational path in most of the so-called Sciences, Technology, Engineering and Mathematics (STEM) subjects. Having the opportunity of practicing on actual experiments about the theoretical knowledge achieved during the classroom lectures is a fundamental step from a didactic point of view. However, lab activities could be forbidden in the presence of tests characterized by safety issues, thus limiting students' cultural growth; this is particularly true for physics experiments involving radioactive materials, sources of dangerous radiations. To face the considered problems, the authors propose hereinafter a mixed-reality solution involving augmented reality (AR) at students-side and actual instrumentation at laboratory-side. It is worth noting that the proposed solution can be applied for any type of experiment involving the remote control of measurement instruments and generic risk conditions (physical, chemical or biological). As for the considered case study on gamma radiation measurements, an ad-hoc AR application along with a microcontroller-based prototype allows students, located in a safe classroom, to (i) control distance and orientation of a remote actual detector with respect to different radioactive sources and (ii) retrieve and display on their smartphones the corresponding energy spectrum. The communication between classroom equipment and remote laboratory is carried out by means of enabling technologies typical of Internet of Things paradigm, thus making it possible a straightforward integration of the measurement results in cloud environment as dashboard, storage or processing.

Keywords: Augmented reality | Mixed-reality education | MQTT protocol | Physics experiments | Radiation measurements | Remote laboratory | Reverse engineering

[5] Martorelli M., Gallicchio V., Gloria A., Lanzotti A., A Preliminary Analysis of the Effects of Process Parameters on the Impact Resistance of 3D Printed PETG and HIPS, Lecture Notes in Mechanical Engineering, 524-534, (2022). Abstract
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Abstract: Additive manufacturing (AM) allows the development of novel and customized products with tailored properties. However, the application of extrusion-based AM techniques (i.e., fused deposition modeling – FDM) in the design of functional parts is often limited because of the poor mechanical performance as a consequence of the nature of the process to build the object in a layer-by-layer fashion. In the current study, the impact resistance of the 3D printed polyethylene terephthalate glycol-modified (PETG) and high impact polystyrene (HIPS) was evaluated as a function of three printing parameters (i.e., printing temperature, layer height and line width). Izod-type test specimens were fabricated and analyzed according to the ASTM D256. The contribution of each factor was properly analyzed. The results also indicated that the printing temperature was the most significant parameter for the impact resistance of 3D printed PETG and HIPS. The obtained findings may be considered as valid only within the limit of parameters and ranges investigated in the current study.

Keywords: Design of experiments | Fused deposition modeling | Impact resistance

[6] de Crescenzo C., Richetta M., Martorelli M., Gloria A., Lanzotti A., A Further Investigation Toward the Design of Topology Optimized Solid-Lattice Hybrid Structures for Biomedical Applications, Lecture Notes in Mechanical Engineering, 514-523, (2022). Abstract
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Abstract: Titanium alloys (e.g., Ti6Al4V) have been widely considered for the design of biomedical implants. To avoid stress shielding effects, bone atrophy and implant loosening bone, 3D porous devices with controlled geometry and architecture should represent a promising solution. Several cellular structures were already investigated to obtain a wide range of mechanical properties. Many studies focused on the mechanical performance of diamond and body-centered-cubic. Different kinds of porous and semi-porous femoral stems were also proposed and analyzed. Accordingly, the aim of the current research was to provide further insight into the design of solid-lattice hybrid structures through a two-step process involving the classical and lattice topology optimization. A cementless femoral stem was considered as a case study. The solid isotropic material with penalization (SIMP) was used at varying values of the penalty factor and the effect of the geometrical features of each beam forming the lattice structure was also determined. Differences were found in terms of functional and structural performances according to the selected strategy for the design of the solid-lattice hybrid structures, as a consequence of the material distribution/layout and geometrical features.

Keywords: Biomedical applications | Solid-lattice hybrid structures | Topology optimization

[7] Russo T., Peluso V., Fucile P., De Santis R., Gloria A., Magnetism in dentistry: Review and future perspectives, Applied Sciences (Switzerland), 12(1), (2022). Abstract
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Abstract: Tissue engineering or tissue reconstruction/repair/regeneration may be considered as a guiding strategy in oral and maxillofacial surgery, as well as in endodontics, orthodontics, peri-odontics, and daily clinical practice. A wide range of techniques has been developed over the past years, from tissue grafts to the more recent and innovative regenerative procedures. Continuous research in the field of natural and artificial materials and biomaterials, as well as in advanced scaffold design strategies has been carried out. The focus has also been on various growth factors involved in dental tissue repair or reconstruction. Benefiting from the recent literature, this review paper illustrates current innovative strategies and technological approaches in oral and maxillofacial tissue engineering, trying to offer some information regarding the available scientific data and practical applications. After introducing tissue engineering aspects, an overview on additive manufacturing technologies will be provided, with a focus on the applications of superparamagnetic iron oxide nanoparticles in the biomedical field. The potential applications of magnetic fields and magnetic devices on the acceleration of orthodontic tooth movement will be analysed.

Keywords: 3D/4D printing | Dentistry | Design for additive manufacturing | Magnetism | SPIONs | Tissue engineering

[8] Peluso V., Rinaldi L., Russo T., Oliviero O., Di Vito A., Garbi C., Giudice A., De Santis R., Gloria A., D’antò V., Impact of magnetic stimulation on periodontal ligament stem cells, International Journal of Molecular Sciences, 23(1), (2022). Abstract
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Abstract: The aim of this study was to evaluate the effect of a time‐dependent magnetic field on the biological performance of periodontal ligament stem cells (PDLSCs). A Western blot analysis and Alamar Blue assay were performed to investigate the proliferative capacity of magnetically stimulated PDLSCs (PDLSCs MAG) through the study of the MAPK cascade (p‐ERK1/2). The observation of ALP levels allowed the evaluation of the effect of the magnetic field on osteogenic differentiation. Metabolomics data, such as oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and ATP production provided an overview of the PDLSCs MAG metabolic state. Moreover, the mitochondrial state was investigated through confocal laser scanning microscopy. Results showed a good viability for PDLSCs MAG. Magnetic stimulation can activate the ERK phosphorylation more than the FGF factor alone by promoting a better cell proliferation. Osteogenic differentiation was more effectively induced by magnetic stimulation. The metabolic panel indicated significant changes in the mitochondrial cellular respiration of PDLSCs MAG. The results suggested that periodontal ligament stem cells (PDLSCs) can respond to biophysical stimuli such as a time‐dependent magnetic field, which is able to induce changes in cell proliferation and differentiation. Moreover, the magnetic stimulation also produced an effect on the cell metabolic profile. Therefore, the current study demonstrated that a time‐dependent magnetic stimulation may improve the regenerative properties of PDLSCs.

Keywords: Cellular respiration | Magnetic stimulation design | Metabolomics | Osteogenesis | Stem cells | Tissue engineering

[9] Dal Sasso E., Zamuner A., Filippi A., Romanato F., Palmosi T., Vedovelli L., Gregori D., Gómez Ribelles J.L., Russo T., Gloria A., Iop L., Gerosa G., Dettin M., Covalent functionalization of decellularized tissues accelerates endothelialization, Bioactive Materials, 6(11), 3851-3864, (2021). Abstract
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Abstract: In the field of tissue regeneration, the lack of a stable endothelial lining may affect the hemocompatibility of both synthetic and biological replacements. These drawbacks might be prevented by specific biomaterial functionalization to induce selective endothelial cell (EC) adhesion. Decellularized bovine pericardia and porcine aortas were selectively functionalized with a REDV tetrapeptide at 10−5 M and 10−6 M working concentrations. The scaffold-bound peptide was quantified and REDV potential EC adhesion enhancement was evaluated in vitro by static seeding of human umbilical vein ECs. The viable cells and MTS production were statistically higher in functionalized tissues than in control. Scaffold histoarchitecture, geometrical features, and mechanical properties were unaffected by peptide anchoring. The selective immobilization of REDV was effective in accelerating ECs adhesion while promoting proliferation in functionalized decellularized tissues intended for blood-contacting applications.

Keywords: Covalent functionalization | Decellularized aorta | Decellularized pericardium | Endothelialization | Mechanical analysis | REDV

[10] Higuera G.A., Ramos T., Gloria A., Ambrosio L., Di Luca A., Pechkov N., de Wijn J.R., van Blitterswijk C.A., Moroni L., PEOT/PBT Polymeric Pastes to Fabricate Additive Manufactured Scaffolds for Tissue Engineering, Frontiers in Bioengineering and Biotechnology, 9, (2021). Abstract
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Abstract: The advantages of additive manufactured scaffolds, as custom-shaped structures with a completely interconnected and accessible pore network from the micro- to the macroscale, are nowadays well established in tissue engineering. Pore volume and architecture can be designed in a controlled fashion, resulting in a modulation of scaffold’s mechanical properties and in an optimal nutrient perfusion determinant for cell survival. However, the success of an engineered tissue architecture is often linked to its surface properties as well. The aim of this study was to create a family of polymeric pastes comprised of poly(ethylene oxide therephthalate)/poly(butylene terephthalate) (PEOT/PBT) microspheres and of a second biocompatible polymeric phase acting as a binder. By combining microspheres with additive manufacturing technologies, we produced 3D scaffolds possessing a tailorable surface roughness, which resulted in improved cell adhesion and increased metabolic activity. Furthermore, these scaffolds may offer the potential to act as drug delivery systems to steer tissue regeneration.

Keywords: additive manufacturing | mechanical analysis | mesenchymal stem cells | microparticles | polymers | tissue engineering

[11] De Santis R., Papallo I., Onofrio I., Peluso V., Gallicchio V., Rega A., D'Antò V., Improta G., Catauro M., Gloria A., Russo T., Analyzing the Role of Magnetic Features in Additive Manufactured Scaffolds for Enhanced Bone Tissue Regeneration, Macromolecular Symposia, 396(1), (2021). Abstract
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Abstract: The concept of magnetic guidance has opened a wide range of perspectives in the field of tissue regeneration. Accordingly, the aim of the current research is to design magnetic responsive scaffolds for enhanced bone tissue regeneration. Specifically, magnetic nanocomposite scaffolds are additively manufactured using 3D fibre deposition technique. The mechanical and magnetic properties of the fabricated scaffolds are first assessed. The role of magnetic features on the biological performances is properly analyzed.

Keywords: bone tissue engineering | design for additive manufacturing | magnetic nanocomposite scaffolds | mechanical and functional properties

[12] Rocco N., Montagna G., Criscitiello C., Nava M.B., Privitera F., Taher W., Gloria A., Catanuto G., Nipple sparing mastectomy as a risk‐reducing procedure for brca‐mutated patients, Genes, 12(2), 1-7, (2021). Abstract
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Abstract: Growing numbers of asymptomatic women who become aware of carrying a breast cancer gene mutation (BRCA) mutation are choosing to undergo risk‐reducing bilateral mastectomies with immediate breast reconstruction. We reviewed the literature with the aim of assessing the oncological safety of nipple‐sparing mastectomy (NSM) as a risk‐reduction procedure in BRCA-mutated patients. Nine studies reporting on the incidence of primary breast cancer post NSM in asymptomatic BRCA mutated patients undergoing risk‐reducing bilateral procedures met the inclusion criteria. NSM appears to be a safe option for BRCA mutation carriers from an oncological point of view, with low reported rates of new breast cancers, low rates of postoperative complications, and high levels of satisfaction and postoperative quality of life. However, larger multi‐institutional studies with longer follow‐up are needed to establish this procedure as the best surgical option in this setting.

Keywords: BRCA mutations | Breast cancer | Nipple‐sparing mastectomies | Risk reduction

[13] Fucile P., Russo T., De Santis R., Martorelli M., Catauro M., Gloria A., Integrated Design Strategy for Additively Manufactured Scaffolds in Tissue Engineering, Macromolecular Symposia, 395(1), (2021). Abstract
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Abstract: Additive manufacturing technologies allow for the direct fabrication of 3D scaffolds with improved properties for tissue regeneration. In this scenario, design strategies and 3D fiber deposition technique are considered to develop advanced scaffolds with different lay-down patterns, tailored mechanical and biological properties. 3D poly(ε-caprolactone) scaffolds are manufactured and surface-modified (i.e., aminolysis). The effect of surface modification on the mechanical and biological performances of the designed 3D scaffolds is assessed.

Keywords: computer-aided design | design for additive manufacturing | mechanical analysis | scaffold design

[14] De Santis R., Russo T., Fucile P., Martorelli M., Catauro M., Gloria A., Photo-Curing 3D Printing and Innovative Design of Porous Composite Structures for Biomedical Applications, Macromolecular Symposia, 395(1), (2021). Abstract
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Abstract: Light-activated resins and composites are used in conjunction with a light curing unit and allow an on-demand process of polymerization. These kinds of materials usually represent the most popular choice in the restorative dental practice. Some works have already highlighted contemporary tendencies in the use of nondegradable scaffolds and mesenchymal stem cells in regenerative medicine. Accordingly, the aim of the current research is to develop 3D porous and light-activated composite structures with optimized functional properties. Preliminary mechanical and biological tests are carried out.

Keywords: composite structure design | computer-aided design | design for photo-curing 3D printing | mechanical and functional properties

[15] Liccardo A., Arpaia P., Bonavolonta F., De Pandi F., Caputo E., Lo Moriello R.S., Gloria A., Augmented Reality Laboratory for Instrumentationand Measurements Online Course, 6th International Forum on Research and Technology for Society and Industry, RTSI 2021 - Proceedings, 86-90, (2021). Abstract
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Abstract: The limitations due to the SARS-Cov-2 pandemic affected both interactions between people and work activities; particularly in the educational field. In fact, the students were forced to face the lessons from home, which did not bring problems in the understanding of theoretical aspects, but turned out to be a problem regarding the laboratory activities, since they did not have the possibility to test on real instruments what they learned in theory. In this sense, this article describes the development of a remote laboratory in augmented reality, which allows instruments to be faithfully replicated on any portable device available to the students. Furthermore, by exploiting the protocols typical of the Internet of Things, it is possible to guarantee proper control of the real workstation by interacting with the one in augmented reality.

Keywords: Augmented Reality | Internet of Things | Remote Laboratory | Remote Measurements

[16] Liccardo A., Arpaia P., Bonavolonta F., Caputo E., De Pandi F., Gallicchio V., Gloria A., Moriello R.S.L., An Augmented Reality Approach to Remote Controlling Measurement Instruments for Educational Purposes during Pandemic Restrictions, IEEE Transactions on Instrumentation and Measurement, 70, (2021). Abstract
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Abstract: The restrictions associated with the current SARS-Cov-2 pandemic are having a major impact on nearly all human activities and interactions; among these, the didactic and education field certainly has a prominent place. In the case of either complete lockdown or reduced accessibility to facilities and classrooms, the participation of students was severely limited for safety reasons. In particular, laboratory activities, already compromised by a large number of students of some classes, suffered from the restrictions, thus making it difficult to guarantee the possibility of live operating on instruments for the execution of measurements of different quantities of interest. To overcome the considered problem, this article proposes the use of enabling technologies of the Internet of Things and the fourth industrial revolution to allow students to achieve correct and complete training in laboratory activities. To this aim, remotely controlled instruments are used and displayed in augmented reality on consumer devices, such as mobile phones, tablets, or personal computers. The continuous availability of access to the instruments along with the realism in their representation and use ensures a positive and effective involvement of the students.

Keywords: Augmented reality (AR) | enabling technologies | Industry 40 | Internet of Things | remote laboratories | remote measurements | reverse engineering

[17] Martorelli M., Gloria A., Bignardi C., Calì M., Maietta S., Erratum: Design of Additively Manufactured Lattice Structures for Biomedical Applications (Journal of Healthcare Engineering (2020) 2020 (2707560) DOI: 10.1155/2020/2707560), Journal of Healthcare Engineering, 2021, (2021). Abstract
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Abstract: In the article titled “Design of Additively Manufactured Lattice Structures for Biomedical Applications” [1], there was an error in the author’s name, where “Sverio Maietta” should be corrected to “Saverio Maietta.” e corrected author name is shown in the author group above.

[18] Bazzolo B., Sieni E., Zamuner A., Roso M., Russo T., Gloria A., Dettin M., Conconi M.T., Breast cancer cell cultures on electrospun poly(ε-caprolactone) as a potential tool for preclinical studies on anticancer treatments, Bioengineering, 8(1), 1-16, (2021). Abstract
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Abstract: During anticancer drug development, most compounds selected by in vitro screening are ineffective in in vivo studies and clinical trials due to the unreliability of two-dimensional (2D) in vitro cultures that are unable to mimic the cancer microenvironment. Herein, HCC1954 cell cultures on electrospun polycaprolactone (PCL) were characterized by morphological analysis, cell viability assays, histochemical staining, immunouorescence, and RT-PCR. Our data showed that electrospun PCL allows the in vitro formation of cultures characterized by mucopolysaccharide production and increased cancer stem cell population. Moreover, PCL-based cultures were less sensitive to doxorubicin and electroporation/bleomycin than those grown on polystyrene plates. Collectively, our data indicate that PCL-based cultures may be promising tools for preclinical studies.

Keywords: breast cancer | Electroporation | In vitro models | Mechanical analysis | Polycaprolactone

[19] Cometa S., Bonifacio M.A., Tranquillo E., Gloria A., Domingos M., De Giglio E., A 3d printed composite scaffold loaded with clodronate to regenerate osteoporotic bone: In vitro characterization, Polymers, 13(1), 1-17, (2021). Abstract
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Abstract: Additive manufacturing (AM) is changing our current approach to the clinical treatment of bone diseases, providing new opportunities to fabricate customized, complex 3D structures with bioactive materials. Among several AM techniques, the BioCell Printing is an advanced, integrated system for material manufacture, sterilization, direct cell seeding and growth, which allows for the production of high-resolution micro-architectures. This work proposes the use of the BioCell Printing to fabricate polymer-based scaffolds reinforced with ceramics and loaded with bisphosphonates for the treatment of osteoporotic bone fractures. In particular, biodegradable poly(ε-caprolactone) was blended with hydroxyapatite particles and clodronate, a bisphosphonate with known efficacy against several bone diseases. The scaffolds’ morphology was investigated by means of Scanning Electron Microscopy (SEM) and micro-Computed Tomography (micro-CT) while Energy Dispersive X-ray Spectroscopy (EDX) and X-ray Photoelectron Spectroscopy (XPS) revealed the scaffolds’ elemental composition. A thermal characterization of the composites was accomplished by Thermogravimetric analyses (TGA). The mechanical performance of printed scaffolds was investigated under static compression and compared against that of native human bone. The designed 3D scaffolds promoted the attachment and proliferation of human MSCs. In addition, the presence of clodronate supported cell differentiation, as demonstrated by the normalized alkaline phosphatase activity. The obtained results show that the BioCell Printing can easily be employed to generate 3D constructs with predefined internal/external shapes capable of acting as a temporary physical template for regeneration of cancellous bone tissues.

Keywords: Additive manufacturing | Biocompatibility | Bone substitute | Clodronate | Composite scaffold design | Hydroxyapatite | Mechanical analysis | Poly(ε-caprolactone) | Thermal analysis | X-ray Photoelectron Spectroscopy

[20] De Santis R., Russo T., Rau J.V., Papallo I., Martorelli M., Gloria A., Design of 3d additively manufactured hybrid structures for cranioplasty, Materials, 14(1), 1-15, (2021). Abstract
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Abstract: A wide range of materials has been considered to repair cranial defects. In the field of cranioplasty, poly(methyl methacrylate) (PMMA)-based bone cements and modifications through the inclusion of copper doped tricalcium phosphate (Cu-TCP) particles have been already investigated. On the other hand, aliphatic polyesters such as poly (e-caprolactone) (PCL) and polylactic acid (PLA) have been frequently investigated to make scaffolds for cranial bone regeneration. Accordingly, the aim of the current research was to design and fabricate customized hybrid devices for the repair of large cranial defects integrating the reverse engineering approach with additive manufacturing, The hybrid device consisted of a 3D additive manufactured polyester porous structures infiltrated with PMMA/Cu-TCP (97.5/2.5 w/w) bone cement. Temperature profiles were first evaluated for 3D hybrid devices (PCL/PMMA, PLA/PMMA, PCL/PMMA/Cu-TCP and PLA/PMMA/Cu-TCP). Peak temperatures recorded for hybrid PCL/PMMA and PCL/PMMA/Cu-TCP were significantly lower than those found for the PLA-based ones. Virtual and physical models of customized devices for large cranial defect were developed to assess the feasibility of the proposed technical solutions. A theoretical analysis was preliminarily performed on the entire head model trying to simulate severe impact conditions for people with the customized hybrid device (PCL/PMMA/Cu-TCP) (i.e., a rigid sphere impacting the implant region of the head). Results from finite element analysis (FEA) provided information on the different components of the model.

Keywords: Composite bone cement for cranioplasty | Design for additive manufacturing | Finite element analysis | Reverse engineering | Temperature profile analysis

[21] Solari D., Papallo I., Ugga L., Cavallo L.M., Onofrio I., Cuocolo R., Improta G., Brunetti A., Martorelli M., Gloria A., Cappabianca P., Russo T., Novel concepts and strategies in skull base reconstruction after endoscopic endonasal surgery, Acta IMEKO, 9(4), 67-73, (2020). Abstract
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Abstract: Recently, a variety of craniofacial approaches has been adopted to enter the skull base, including the endonasal endoscopic technique. An effective watertight technique, the reconstruction can be performed using different materials, both autologous and non-autologous, individually or combined in a multilayer fashion. The current study focuses on the development of new advanced devices and techniques that help to reduce the postoperative cerebrospinal fluid leak rate. Additive manufacturing allows the design of devices with tailored structural and functional features, as well as injectable semi-interpenetrating polymer networks and composites; therefore, specific mechanical/rheological and injectability studies are valuable. Accordingly, we propose new additive manufactured and injectable devices.

Keywords: Additive manufacturing | CSF leakage | Design of injectable systems | Endoscopic endonasal surgery | Reverse engineering | Skull base reconstruction

[22] Fucile P., Onofrio I., Papallo I., Gallicchio V., Rega A., D'Antò V., Improta G., de Santis R., Gloria A., Russo T., Strategies for the design of additively manufactured nanocomposite scaffolds for hard tissue regeneration, Acta IMEKO, 9(4), 53-59, (2020). Abstract
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Abstract: Additive manufacturing represents a powerful tool for the direct fabrication of lightweight and porous structures with tuneable properties. In this study, a fused deposition modelling/3D fibre deposition technique was considered for designing 3D nanocomposite scaffolds with specific architectures and tailored biological, mechanical, and mass transport properties. 3D poly(ε-caprolactone) (PCL)/hydroxyapatite (HA) nanocomposite scaffolds were designed for bone tissue engineering. An optimisation design strategy for the additive manufacturing processes based on extrusion/injection methods was at first extended to the development of the PCL/HA scaffolds. Further insight into the effect of the process parameters on the mechanical properties and morphological features of the nanocomposite scaffolds was provided. The nanocomposite structures were analysed at different levels, and the possibility of designing 3D customised scaffolds for mandibular defect regeneration (i.e., symphysis and ramus) was also reported.

Keywords: Additive manufacturing | Design of Experiments | Nanocomposites | Reverse Engineering | Scaffold Design and Analysis

[23] Rocco N., Papallo I., Nava M.B., Catanuto G., Accurso A., Onofrio I., Oliviero O., Improta G., Speranza D., Domingos M., Russo T., de Santis R., Martorelli M., Gloria A., Additive manufacturing and technical strategies for improving outcomes in breast reconstructive surgery, Acta IMEKO, 9(4), 74-79, (2020). Abstract
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Abstract: It has been widely reported that breast reconstruction improves the quality of life of women who undergo mastectomy for breast cancer. This approach provides many psychological advantages. Today, different techniques are available for the breast oncoplastic surgeon that involve the use of breast implants and autologous tissues, also offering interesting results in terms of aesthetic and patient-reported outcomes. On the other hand, advanced technologies and design strategies (i.e. design for additive manufacturing, reverse engineering) may allow the development of customised porous structures with tailored morphological, mechanical, biological, and mass transport properties. For this reason, the current study deals with the challenges, principles, and methods of developing 3D additive manufactured structures in breast reconstructive surgery. Specifically, the aim was to design 3D additive manufactured poly(ε-caprolactone) scaffolds with different architectures (i.e. lay-down patterns). Preliminary mechanical and biological analyses have shown the effect of the lay-down pattern on the performances of the manufactured structures.

Keywords: Additive manufacturing | Breast reconstructive surgery | Fat grafting | Functional properties | Mechanical | Pore geometry and lay-down pattern | Reverse engineering | Scaffold design

[24] Goranov V., Shelyakova T., De Santis R., Haranava Y., Makhaniok A., Gloria A., Tampieri A., Russo A., Kon E., Marcacci M., Ambrosio L., Dediu V.A., 3D Patterning of cells in Magnetic Scaffolds for Tissue Engineering, Scientific Reports, 10(1), (2020). Abstract
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Abstract: A three dimensional magnetic patterning of two cell types was realised in vitro inside an additive manufactured magnetic scaffold, as a conceptual precursor for the vascularised tissue. The realisation of separate arrangements of vascular and osteoprogenitor cells, labelled with biocompatible magnetic nanoparticles, was established on the opposite sides of the scaffold fibres under the effect of non-homogeneous magnetic gradients and loading magnetic configuration. The magnetisation of the scaffold amplified the guiding effects by an additional trapping of cells due to short range magnetic forces. The mathematical modelling confirmed the strong enhancement of the magnetic gradients and their particular geometrical distribution near the fibres, defining the preferential cell positioning on the micro-scale. The manipulation of cells inside suitably designed magnetic scaffolds represents a unique solution for the assembling of cellular constructs organised in biologically adequate arrangements.

[25] Moxon S.R., Ferreira M.J.S., dos Santos P., Popa B., Gloria A., Katsarava R., Tugushi D., Serra A.C., Hooper N.M., Kimber S.J., Fonseca A.C., Domingos M.A.N., A preliminary evaluation of the pro-chondrogenic potential of 3D-bioprinted poly(ester urea) scaffolds, Polymers, 12(7), 1-15, (2020). Abstract
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Abstract: Degeneration of articular cartilage (AC) is a common healthcare issue that can result in significantly impaired function and mobility for affected patients. The avascular nature of the tissue strongly burdens its regenerative capacity contributing to the development of more serious conditions such as osteoarthritis. Recent advances in bioprinting have prompted the development of alternative tissue engineering therapies for the generation of AC. Particular interest has been dedicated to scaffold-based strategies where 3D substrates are used to guide cellular function and tissue ingrowth. Despite its extensive use in bioprinting, the application of polycaprolactone (PCL) in AC is, however, restricted by properties that inhibit pro-chondrogenic cell phenotypes. This study proposes the use of a new bioprintable poly(ester urea) (PEU) material as an alternative to PCL for the generation of an in vitro model of early chondrogenesis. The polymer was successfully printed into 3D constructs displaying adequate substrate stiffness and increased hydrophilicity compared to PCL. Human chondrocytes cultured on the scaffolds exhibited higher cell viability and improved chondrogenic phenotype with upregulation of genes associated with type II collagen and aggrecan synthesis. Bioprinted PEU scaffolds could, therefore, provide a potential platform for the fabrication of bespoke, pro-chondrogenic tissue engineering constructs.

Keywords: 3D bioprinting | Cartilage repair | Poly(ester urea) | Scaffold design | Tissue engineering

[26] Martorelli M., Speranza D., Ferraro P., Genovese A., Gloria A., Pagliarulo V., Optical characterizations of airless radial tire, 2020 IEEE International Workshop on Metrology for AeroSpace, MetroAeroSpace 2020 - Proceedings, 561-565, (2020). Abstract
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Abstract: In this work is analyzed the possibility to use optical techniques for the characterization of airless radial tire. Electronic Speckle Pattern Interferometry (ESPI), laser scanner based on principle of triangulation and Digital Image Correlation (DIC) have been used to acquire and study this kind of tire. A MICHELIN® X® TWEEL® UTV has been considered as case study. The acquisitions have been used for the measurement of the shape for testing junction areas and to evaluate the structure behavior under a vertical load.

Keywords: Composite laminates | Laser scanner | NDI | Tire

[27] Gloria A., Russo T., D’Amora U., Santin M., De Santis R., Ambrosio L., Customised multiphasic nucleus/annulus scaffold for intervertebral disc repair/regeneration, Connective Tissue Research, 61(2), 152-162, (2020). Abstract
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Abstract: Background: In the case of a degenerated intervertebral disc (IVD), even though spinal fusion has provided good short-term clinical results, an alteration of the spine stability has been demonstrated by long-term studies. In this context, different designs of IVD prostheses have been proposed as alternative to spinal fusion. However, over the past few years, much of the recent research has been devoted to IVD tissue engineering, even if several limitations related to the complex structure of IVD are still presented.Purpose/Aim: Accordingly, the aim of the current paper was to develop a strategy in designing customised multiphasic nucleus/annulus scaffolds for IVD tissue engineering, benefiting from the great potential of reverse engineering, additive manufacturing and gels technology.Materials and Methods: The device consisted of a customised additive-manufactured poly(ε-caprolactone) scaffold with tailored architectural features as annulus and a cell-laden collagen-low molecular weight hyaluronic acid-based material as nucleus with specific rheological and functional properties. To this aim, injectability and viscoelastic properties of the hydrogel were analyzed. Furthermore, a mechanical and biological characterization of cell-laden multiphasic nucleus/annulus scaffold was performed.Results and Conclusions: Analyses on the developed devices demonstrated appropriate viscoelastic and mechanical properties. As evidenced by rheological tests, the hydrogel showed a shear-thinning behaviour, supporting the possibility to inject the material. The mechanical characterization highlighted a compressive modulus which falls in the range of lumbar discs, with the typical initial J-shaped stress–strain curve of natural IVDs. Furthermore, preliminary biological tests showed that human mesenchymal stem cells were viable over the culture period.

Keywords: additive manufacturing | gels | intervertebral disc | Polymers | reverse engineering | tissue engineering

[28] Grimaldi M., Buonocore M., Scrima M., Stillitano I., D’Errico G., Santoro A., Amodio G., Eletto D., Gloria A., Russo T., Ornella M., Remondelli P., Tosco A., Wienk H.L.J., D’Ursi A.M., NMR structure of the FIV gp36 C-terminal heptad repeat and membrane-proximal external region, International Journal of Molecular Sciences, 21(6), (2020). Abstract
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Abstract: Feline immunodeficiency virus (FIV), a lentivirus causing an immunodeficiency syndrome in cats, represents a relevant model of pre-screening therapies for human immunodeficiency virus (HIV). The envelope glycoproteins gp36 in FIV and gp41 in HIV mediate the fusion of the virus with the host cell membrane. They have a common structural framework in the C-terminal region that includes a Trp-rich membrane-proximal external region (MPER) and a C-terminal heptad repeat (CHR). MPER is essential for the correct positioning of gp36 on the lipid membrane, whereas CHR is essential for the stabilization of the low-energy six-helical bundle (6HB) that is necessary for the fusion of the virus envelope with the cell membrane. Conformational data for gp36 are missing, and several aspects of the MPER structure of different lentiviruses are still debated. In the present work, we report the structural investigation of a gp36 construct that includes the MPER and part of the CHR domain (737-786gp36 CHR–MPER). Using 2D and 3D homo and heteronuclear NMR spectra on15N and13C double-labelled samples, we solved the NMR structure in micelles composed of dodecyl phosphocholine (DPC) and sodium dodecyl sulfate (SDS) 90/10 M: M. The structure of737-786gp36 CHR–MPER is characterized by a helix–turn–helix motif, with a regular α-helix and a moderately flexible 310 helix, characterizing the CHR and the MPER domains, respectively. The two helices are linked by a flexible loop regulating their orientation at a ~43° angle. We investigated the positioning of737-786gp36 CHR–MPER on the lipid membrane using spin label-enhanced NMR and ESR spectroscopies. On a different scale, using confocal microscopy imaging, we studied the effect of737-786gp36 CHR–MPER on 1,2-dioleoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DOPC/DOPG) multilamellar vesicles (MLVs). This effect results in membrane budding and tubulation that is reminiscent of a membrane-plasticizing role that is typical of MPER domains during the event in which the virus envelope merges with the host cell membrane.

Keywords: Envelope glicoproteins | FIV | HIV | MPER | NMR

[29] Russo T., Peluso V., Gloria A., Oliviero O., Rinaldi L., Improta G., De Santis R., D’antò V., Combination design of time-dependent magnetic field and magnetic nanocomposites to guide cell behavior, Nanomaterials, 10(3), (2020). Abstract
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Abstract: The concept of magnetic guidance is still challenging and has opened a wide range of perspectives in the field of tissue engineering. In this context, magnetic nanocomposites consisting of a poly(ε-caprolactone) (PCL) matrix and iron oxide (Fe3 O4) nanoparticles were designed and manufactured for bone tissue engineering. The mechanical properties of PCL/Fe3 O4 (80/20 w/w) nanocomposites were first assessed through small punch tests. The inclusion of Fe3 O4 nanoparticles improved the punching properties as the values of peak load were higher than those obtained for the neat PCL without significantly affecting the work to failure. The effect of a time-dependent magnetic field on the adhesion, proliferation, and differentiation of human mesenchymal stem cells (hMSCs) was analyzed. The Alamar Blue assay, confocal laser scanning microscopy, and image analysis (i.e., shape factor) provided information on cell adhesion and viability over time, whereas the normalized alkaline phosphatase activity (ALP/DNA) demonstrated that the combination of a time-dependent field with magnetic nanocomposites (PCL/Fe3 O4 Mag) influenced cell differentiation. Furthermore, in terms of extracellular signal-regulated kinase (ERK)1/2 phosphorylation, an insight into the role of the magnetic stimulation was reported, also demonstrating a strong effect due the combination of the magnetic field with PCL/Fe3 O4 nanocomposites (PCL/Fe3 O4 Mag).

Keywords: Bone tissue engineering | Design of magnetic nanocomposite substrates | Magnetic stimulation | Material interaction | Mechanical properties and cell | Reverse engineering/image analysis

[30] Zhang Y., Ullah I., Zhang W., Ou H., Domingos M., Gloria A., Zhou J., Li W., Zhang X., Preparation of electrospun nanofibrous polycaprolactone scaffolds using nontoxic ethylene carbonate and glacial acetic acid solvent system, Journal of Applied Polymer Science, 137(8), (2020). Abstract
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Abstract: In recent years, solution electrospinning has attracted the interest of researchers due to the possibility to design nanofibrous scaffolds with large surface area to volume ratios. Polycaprolactone (PCL), because of its biocompatibility and easy processability, has been widely used to develop electrospun structures for tissue engineering. However, the use of organic solvents and the poor PCL solution stability still hinder the development of the solution electrospinning process. The relatively benign glacial acetic acid (GAC) as a solvent of PCL was used to fabricate microfibrous fibers or beaded fibers. Thus, ethylene carbonate (EC) as a nontoxic assistant solvent was added to the PCL/GAC solution to successfully fabricate electrospun nanofibrous PCL scaffolds. The stability of the PCL/GAC/EC solution system was demonstrated as the viscosity, which showed no significant change during 48 h. The ultrafine PCL fiber diameter decreased as EC concentration was increased from 0 to 9 vol% and started to slightly increase when EC concentration increased beyond 9 vol%. MTT assay evidenced that MC3T3-E1 cells on the nanofibrous PCL scaffolds exhibited a better enhancement on cell proliferation. In summary, EC was added in PCL/GAC to establish a stable and low toxic solution electrospinning system, which provides promising strategy in tissue engineering field. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48387.

Keywords: biomaterials | electrospinning | fibers | polyesters

[31] Calvanese L., Brun P., Messina G.M.L., Russo T., Zamuner A., Falcigno L., D'Auria G., Gloria A., Vitagliano L., Marletta G., Dettin M., EAK Hydrogels Cross-Linked by Disulfide Bonds: Cys Number and Position Are Matched to Performances, ACS Biomaterials Science and Engineering, 6(2), 1154-1164, (2020). Abstract
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Abstract: Hydrogels produced by self-assembling peptides are intrinsically biocompatible and thus appropriate for many biomedical purposes. Their application field may be even made wider by reducing the softness and improving the hydrogel mechanical properties through cross-linking treatments. To this aim, modifications of EAK16-II sequence by including Cys residues in its sequence were here investigated in order to obtain hydrogels cross-linkable through a disulfide bridge. Two sequences, namely, C-EAK and C-EAK-C, that contain Cys residues at the N-terminus or at both ends were characterized. Fiber-forming abilities and biological and dynamic mechanical properties were explored before and after the oxidative treatment. In particular, the oxidized version of C-EAK presents a good cell viability and sustains osteoblast proliferation. Furthermore, molecular dynamics (MD) simulations on monomeric and assembled forms of the peptides were performed. MD simulations explained how a specific Cys functionalization was better than the other one. In particular, the results suggested that EAK16-II functionalization with a single Cys residue, instead of two, together with biocompatible cross-linking may be considered an intriguing strategy to obtain a support with better dynamic mechanical properties and biological performances.

Keywords: atomic force microscopy | biomaterials | cross-linking | dynamic mechanical analysis | h-osteoblast | molecular dynamics | self-assembling peptides

[32] Ullah I., Gloria A., Zhang W., Ullah M.W., Wu B., Li W., Domingos M., Zhang X., Synthesis and Characterization of Sintered Sr/Fe-Modified Hydroxyapatite Bioceramics for Bone Tissue Engineering Applications, ACS Biomaterials Science and Engineering, 6(1), 375-388, (2020). Abstract
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Abstract: In the current study, Sr/Fe co-substituted hydroxyapatite (HAp) bioceramics were prepared by the sonication-assisted aqueous chemical precipitation method followed by sintering at 1100 °C for bone tissue regeneration applications. The sintered bioceramics were analyzed for various structural and chemical properties through X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy, which confirmed the phase purity of HAp and Sr/Fe co-substitution into its lattice. The Vickers hardness measurement, high blood compatibility (less than 5% hemolysis), and ability to support the adhesion, proliferation, and osteogenic differentiation of human mesenchymal stem cells suggest the suitability of Sr/Fe:HAp bioceramics for bone implant applications. The physicochemical analysis revealed that the developed Sr/Fe:HAp bioceramics exhibited a polyphasic nature (HAp and βTCP) with almost identical structural morphology having a particle size less than 0.8 μm. The dielectric constant (ϵ′) and dielectric loss (ϵ″) were potentially affected by the incorporated foreign ions together with the polyphasic nature of the material. The Sr/Fe co-substituted samples demonstrated extended drug (5-fluorouracil and amoxicillin) release profiles at the pH of physiological medium. The multifunctional properties of the developed HAp bioceramics enabled them to be an auspicious candidate for potential biomedical applications, including targeted drug-delivery applications, heating mediator in hyperthermia, and bone tissue repair implants.

Keywords: biocompatibility | biomechanical properties | drug release | osteogenic differentiation | polyphasic nature | Sr/Fe co-substitution

[33] Ausiello P., Gloria A., Maietta S., Watts D.C., Martorelli M., Stress distributions for hybrid composite endodontic post designs with and without a ferrule: FEA study, Polymers, 12(8), (2020). Abstract
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Abstract: The aim of the current work was to analyze the influence of the ferrule effect for hybrid composite endodontic post designs consisting of carbon (C) and glass (G) fiber-reinforced polyetherimide (PEI), in upper canine teeth. Starting from theoretical designs of C-G/PEI hybrid composite posts with different Young's moduli (Post A-57.7 GPa, Post B-31.6 GPa, Post C-graduated from 57.7 to 9.0 GPa in the coronal-apical direction) in endodontically treated anterior teeth, the influence of the ferrule effect was determined through finite element analysis (FEA). On the surface of the crown, a load of 50 N was applied at 45° to the longitudinal axis of the tooth. Maximum principal stresses were evaluated along the C-G/PEI post as well as at the interface between the surrounding tooth structure and the post. Maximum stress values were lower than those obtained for the corresponding models without a ferrule. The presence of a ferrule led to a marked decrease of stress and gradients especially for posts A and B. A less marked effect was globally found for Post C, except in a cervical margin section along a specific direction, where a significant decrease of the stress was probably due to local geometric features, compared to the model without a ferrule. The presence of a ferrule did not generally provide a marked benefit in the case of the graduated Post C, in comparison to other C-G/PEI posts. The outcomes suggest how such a hybrid composite post alone should be sufficient to optimize the stress distribution, dissipating stress from the coronal to the apical end.

Keywords: Computer-Aided Design | Endodontic post design | Finite element analysis | Polyetherimide composites | Reverse engineering

[34] Gloria A., Domingos M., Maietta S., Martorelli M., Lanzotti A., Optimization Design Strategy for Additive Manufacturing Process to Develop 3D Magnetic Nanocomposite Scaffolds, Lecture Notes in Mechanical Engineering, 948-958, (2020). Abstract
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Abstract: In the current research, an optimization design strategy for additive manufacturing processes based on extrusion/injection methods was extended to the fabrication of poly(ε-caprolactone) (PCL)/iron oxide (Fe3O4) scaffolds for tissue engineering. The attention was focused on four parameters: process temperature (PT), deposition velocity (DV), screw rotation velocity (SRV), slice thickness (ST). Specifically, PCL/Fe3O4 scaffolds were manufactured varying iteratively one parameter, while maintaining constant the other three parameters. A further insight into the influence of process parameters on the morphological features and mechanical properties of PCL/Fe3O4 scaffolds was provided.

Keywords: Design for additive manufacturing | Magnetic nanocomposite scaffolds | Mechanical and morphological properties | Tissue engineering

[35] Martorelli M., Gloria A., Bignardi C., Calì M., Maietta S., Design of Additively Manufactured Lattice Structures for Biomedical Applications, Journal of Healthcare Engineering, 2020, (2020). Abstract
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Abstract: The special issue focuses on different features related to the design of additively manufactured lattice structures for biomedical applications. In many cases, the process-structure- property relationship and technical features are discussed from a morphological, mechanical, and functional point of view. In particular, an overview of the Additive Manufacturing processes, software methods, and design criteria, which allow the direct fabrication of 3D porous structures and lattices with tailored properties, are reported. Accordingly, the current special issue aims at providing new insights into the development of advanced devices and illustrates theoretical/experimental approaches used by researchers working in the field.

[36] Russo T., de Santis R., Gloria A., Barbaro K., Altigeri A., Fadeeva I.V., Rau J.V., Modification of PMMA cements for cranioplasty with bioactive glass and copper doped tricalcium phosphate particles, Polymers, 12(1), (2020). Abstract
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Abstract: Cranioplasty represents the surgical repair of bone defects or deformities in the cranium arising from traumatic skull bone fracture, cranial bone deformities, bone cancer, and infections. The actual gold standard in surgery procedures for cranioplasty involves the use of biocompatible materials, and repair or regeneration of large cranial defects is particularly challenging from both a functional and aesthetic point of view. PMMA-based bone cement are the most widely biomaterials adopted in the field, with at least four different surgical approaches. Modifications for improving biological and mechanical functions of PMMA-based bone cement have been suggested. To this aim, the inclusion of antibiotics to prevent infection has been shown to provide a reduction of mechanical properties in bending. Therefore, the development of novel antibacterial active agents to overcome issues related to mechanical properties and bacterial resistance to antibiotics is still encouraged. In this context, mechanical, biological, and antibacterial feature against P. aeruginosa and S. aureus bacterial strains of surgical PMMA cement modified with BG and recently developed Cu-TCP bioactive particles have been highlighted.

Keywords: Bacterial strains | Bending properties | Bioactive particles | Biocomposites | Compressive properties | Cranioplasty | MTT assay | PMMA

[37] Tunesi M., Raimondi I., Russo T., Colombo L., Micotti E., Brandi E., Cappelletti P., Cigada A., Negro A., Ambrosio L., Forloni G., Pollegioni L., Gloria A., Giordano C., Albani D., Hydrogel-based delivery of Tat-fused protein Hsp70 protects dopaminergic cells in vitro and in a mouse model of Parkinson’s disease, NPG Asia Materials, 11(1), (2019). Abstract
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Abstract: Neurodegenerative disorders such as Parkinson’s disease (PD) have no effective therapies. However, many promising drugs are precluded from clinical trials because of their poor brain availability. The chaperone protein Hsp70 has been reported to be effective in PD models, but its brain targeting is challenging. We developed a novel brain Hsp70 delivery system using injectable, biocompatible, and biodegradable semi-interpenetrating polymer networks of collagen (COLL) and low-molecular-weight hyaluronic acid (LMW HA) structured with gelatin particles. We produced human recombinant Hsp70-1A fused with the cell-penetrating peptide Tat (Tat-Hsp70) that was neuroprotective in vitro against the dopaminergic toxin 6-hydroxydopamine (6-OHDA). We assessed Tat-Hsp70 release from the selected COLL-LMW HA composites in vitro, observing a 95% release of loaded protein after 96 h. The release kinetics FITTED the Korsmeyer-Peppas model (regression coefficient 0.98) and the released Tat-Hsp70 remained neuroprotective for SH-SY5Y cells. Magnetic resonance imaging revealed that COLL-LMW HA composites lasted at least 96 h at the brain level, and in vivo Tat-Hsp70 release studies indicated that hydrogel presence is pivotal for a spatially focused neuroprotective effect. In an in vivo model of dopaminergic degeneration, Tat-Hsp70-loaded composites conveyed neuroprotection at both the behavioral and dopaminergic neuronal levels against the striatal injection of 6-OHDA. After the injection of Tat-Hsp70-loaded composites, mice showed a transient inflammatory response, with a decrease in GFAP and CD11b immunostaining after 7 days. Our delivery system enabled the effective brain release of Tat-Hsp70 and is ready for further improvements.

[38] Solari D., Cavallo L.M., Cappabianca P., Onofrio I., Papallo I., Brunetti A., Ugga L., Cuocolo R., Gloria A., Improta G., Martorelli M., Russo T., Skull base reconstruction after endoscopic endonasal surgery: New strategies for raising the dam, 2019 IEEE International Workshop on Metrology for Industry 4.0 and IoT, MetroInd 4.0 and IoT 2019 - Proceedings, 28-32, (2019). Abstract
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Abstract: In the last decades a variety of innovative craniofacial approaches has been adopted to entire skull base. The endonasal endoscopic route has emerged as a suitable methodology for several skull base lesions. An effective watertight closure is essential to isolate the intracranial cavity in order to restore the natural intra and extradural compartment division, necessary to prevent postoperative cerebrospinal fluid (CSF) leakage and complications such as meningitis, brain herniation, and tension pneumocephalus. The reconstruction can be performed using different materials, both autologous (autologous grafts) and non-autologous, individually or combined in a multilayer fashion. The harvesting a nasoseptal flap is one of the most effective techniques: it reinforces the skull base closure granting isolation of the surgical field. The current study was focused on the development of new advanced devices and techniques, aiding in reducing postoperative CSF leak, which is one of the most feared complication of this surgical procedure. Additive manufacturing allows to design devices with tailored structural and functional features, in order to satisfy all the requirements. On the other hand, the development of injectable semi-IPNs and composites clearly benefits from specific mechanical/rheological and injectability studies. Accordingly, starting from some basic concepts, innovative principles and strategies were also proposed towards the design of additively manufactured and injectable devices.

Keywords: additive manufacturing | CSF leakage | design of injectable systems | endoscopic endonasal surgery | reverse engineering | skull base reconstruction

[39] Cascone F.D., Martorelli M., Gloria A., Nathan-Roberts D., Lanzotti A., Towards Adaptive Switches through implementation of visual feedback in assistive devices, 2019 IEEE International Workshop on Metrology for Industry 4.0 and IoT, MetroInd 4.0 and IoT 2019 - Proceedings, 43-48, (2019). Abstract
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Abstract: Products aimed at individuals with disabiliy could not match user requirements under conditions imposed by the user. Also, frequent modifications and adaptation are required to increase the match between user requirements and prototypes. The importance to test different solutions and gain a knowledge base is an important aspect as the time in trials and experimentation is still a limit of personalized devices. An experimentation is conducted to test a solution of hardware interface for an Augmentative and Alternative Communication System which implements visual feedbacks and visual tutorial in training phase. In this study, visual feedbacks demonstrate an improvement of performances due to three main effects: reducing training time through an interactive tutorial, improving automatic behaviour and limiting cognitive load. The prototypes are realized using open-source electronic boards and Additive Manufacturing to realize the housing. A usability test is performed to calculate metrics and benchmark solutions with and without visual aids. Measures of Lostness and Keystroke Level Model estimates the effectiveness of software interface and interaction of users with hardware and software interfaces.Also, this study can lead to the definition of an adaptive switch that modify its status in order to eliminate redundant operations and ineffective actions.Visual feedback has proven some advantages in training user and Additive Manufacturing enabled the study and lead the way for devices that are adaptive on software interface and control and personalized in the hardware interface.

Keywords: augmentative and alternative communication | biomedical devices | usability

[40] Fucile P., Papallo I., Improta G., De Santis R., Gloria A., Onofrio I., D'Anto V., Maietta S., Russo T., Reverse Engineering and Additive Manufacturing towards the design of 3D advanced scaffolds for hard tissue regeneration, 2019 IEEE International Workshop on Metrology for Industry 4.0 and IoT, MetroInd 4.0 and IoT 2019 - Proceedings, 33-37, (2019). Abstract
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Abstract: 3D Printing and Additive Manufacturing technologies represent powerful tools for the direct fabrication of lightweight structures with improved and tunable properties. In current research, Fused Deposition Modeling (FDM)/3D fiber deposition technique was considered to design 3D multifunctional scaffolds with complex morphology, tailored biological, mechanical and mass transport properties. Polymeric and nanocomposite materials were used for scaffold design and optimization, with a particular focus on bone tissue engineering. As an example, poly(ϵ-caprolactone) (PCL), and PCL-based nanocomposite scaffolds were fabricated and analyzed. The effects of structural and morphological features (i.e., sequence of stacking, fiber spacing, pore size and geometry) as well as of nanoparticle inclusion on the mechanical performances were reported. Furthermore, the possibility to design 3D customized scaffolds for mandibular defect regeneration (i.e., symphysis and ramus) was also considered.

Keywords: Additive manufacturing | nanocomposites | reverse engineering | scaffold design

[41] Rocco N., Nava M.B., Catanuto G., Accurso A., Martorelli M., Oliviero O., Improta G., Papallo I., De Santis R., Gloria A., Speranza D., Additive manufacturing and tissue engineering to improve outcomes in breast reconstructive surgery, 2019 IEEE International Workshop on Metrology for Industry 4.0 and IoT, MetroInd 4.0 and IoT 2019 - Proceedings, 38-42, (2019). Abstract
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Abstract: Many women with early breast cancer undergo mastectomy as a consequence of an unfavorable tumor/breast ratio or because they prefer this option to breast conservation. As reported, breast reconstruction offers significant psychological advantages. Several techniques are currently available for the breast oncoplastic surgeon and offer interesting results in terms of aesthetic and patient-reported outcomes, using both breast implants and autologous tissues. On the other hand, advanced methodologies and technologies, such as reverse engineering and additive manufacturing, allow the development of customized porous scaffolds with tailored architectures, biological, mechanical and mass transport properties. Accordingly, the current research dealt with challenges, design methods and principles to develop 3D additively manufactured structures in breast reconstructive surgery.

Keywords: additive manufacturing | breast reconstructive surgery | design | fat grafting | reverse engineering | scaffold design

[42] Gloria A., Montanari R., Richetta M., Varone A., Alloys for aeronautic applications: State of the art and perspectives, Metals, 9(6), (2019). Abstract
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Abstract: In recent years, a great effort has been devoted to developing a new generation of materials for aeronautic applications. The driving force behind this effort is the reduction of costs, by extending the service life of aircraft parts (structural and engine components) and increasing fuel efficiency, load capacity and flight range. The present paper examines the most important classes of metallic materials including Al alloys, Ti alloys, Mg alloys, steels, Ni superalloys and metal matrix composites (MMC), with the scope to provide an overview of recent advancements and to highlight current problems and perspectives related to metals for aeronautics.

Keywords: Aeronautic applications | Alloys | Corrosion resistance | Mechanical properties

[43] Scialla S., Barca A., Palazzo B., D'Amora U., Russo T., Gloria A., De Santis R., Verri T., Sannino A., Ambrosio L., Gervaso F., Bioactive chitosan-based scaffolds with improved properties induced by dextran-grafted nano-maghemite and l-arginine amino acid, Journal of Biomedical Materials Research - Part A, 107(6), 1244-1252, (2019). Abstract
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Abstract: Over the past years, fundamentals of magnetism opened a wide research area of interest, in the field of tissue engineering and regenerative medicine. The integration of magnetic nanoarchitectures into synthetic/natural scaffold formulations allowed obtaining “on demand” responsive structures able to guide the regeneration process. The aim of this work was the design and characterization of three-dimensional (3D) chitosan-based scaffolds containing dextran-grafted maghemite nanoarchitectures (DM) and functionalized with l-arginine (l-Arg) amino acid as bioactive agent. A homogeneous pore distribution and a high degree of interconnection were obtained for all the structures with DMs, which resulted well distributed inside the polymer matrix. All the results suggest that the simultaneous presence of DMs and l-Arg conferred interesting mechano-structural and bioactive properties toward osteoblast-like and human mesenchymal stem cells, differentially stimulating their proliferation both in the absence and in the presence of a time-dependent magnetic field. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1244–1252, 2019.

Keywords: chitosan | L-arginine | magnetic nanoarchitecture | magnetic scaffold

[44] Gloria A., Frydman B., Lamas M.L., Serra A.C., Martorelli M., Coelho J.F.J., Fonseca A.C., Domingos M., The influence of poly(ester amide) on the structural and functional features of 3D additive manufactured poly(ε-caprolactone) scaffolds, Materials Science and Engineering C, 98, 994-1004, (2019). Abstract
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Abstract: The current research reports for the first time the use of blends of poly(ε-caprolactone) (PCL) and poly(ester amide) (PEA) for the fabrication of 3D additive manufactured scaffolds. Tailor made PEA was synthesized to afford fully miscible blends of PCL and PEA using different percentages (5, 10, 15 and 20% w/w). Stability, characteristic temperatures and material's compatibility were studied through thermal analyses (i.e., TGA, DSC). Even though DMTA and static compression tests demonstrated the possibility to improve the storage modulus, Young's modulus and maximum stress by increasing the amount of PEA, a decrease of hardness was found beyond a threshold concentration of PEA as the lowest values were achieved for PCL/PEA (20% w/w) scaffolds (from 0.39 ± 0.03 GPa to 0.21 ± 0.02 GPa in the analysed load range). The scaffolds presented a controlled morphology and a fully interconnected network of internal channels. The water contact angle measurements showed a clear increase of hydrophilicity resulting from the addition of PEA. This result was further corroborated with the improved adhesion and proliferation of human mesenchymal stem cells (hMSCs). The presence of PEA also influenced the cell morphology. Better cell spreading and a much higher and homogenous number of cells were observed for PCL/PEA scaffolds when compared to PCL ones.

Keywords: Additive manufacturing | Biological properties | Image analysis | Poly(ester amide) | Scaffold design | Thermal and mechanical properties

[45] Gloria A., Martorelli M., Gerbino S., Tagliaferri F., Kräusel V., Lanzotti A., Functional analyses to assess the effect of the curing process on the properties of light activated composites, Production Engineering, 13(2), 239-246, (2019). Abstract
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Abstract: Light activated composites are the most popular choice in the field of dental restoration. They generally show internal stress even after a prolonged time period. The knowledge of mechanical properties and residual stress should provide interesting information on the clinical performance of such materials. Accordingly, in the current research experimental analyses were carried out to assess the effect of the curing process on the properties of one of the most commonly employed light activated dental composites (Gradia Direct—GC Corporation, Japan). At 10 min, 1 h and 24 h after light curing, the bending modulus (4.7–6.2 GPa) as well as the punching performance (peak load of 12.1–17.5 N) were evaluated for the micro-hybrid composite. Scanning electron microscopy also allowed to analyze the fracture surface. Residual stresses ranging from 0.67 ± 0.15 MPa to 1.12 ± 0.17 MPa were measured by means of the thin-ring-slitting approach reported in the literature, according to measurement time and cutting time.

Keywords: CAD/CAM system | Dental materials | Mechanical and morphological properties | Residual stress

[46] Gloria A., Maietta S., Richetta M., Ausiello P., Martorelli M., Metal posts and the effect of material–shape combination on the mechanical behavior of endodontically treated anterior teeth, Metals, 9(2), (2019). Abstract
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Abstract: The control of the process–structure–property relationship of a material plays an important role in the design of biomedical metal devices featuring desired properties. In the field of endodontics, several post-core systems have been considered, which include a wide range of industrially developed posts. Endodontists generally use posts characterized by different materials, sizes, and shapes. Computer-aided design (CAD) and finite element (FE) analysis were taken into account to provide further insight into the effect of the material–shape combination of metal posts on the mechanical behavior of endodontically treated anterior teeth. In particular, theoretical designs of metal posts with two different shapes (conical-tapered and conical-cylindrical) and consisting of materials with Young’s moduli of 110 GPa and 200 GPa were proposed. A load of 100 N was applied on the palatal surface of the crown at 45◦ to the longitudinal axis of the tooth. Linear static analyses were performed with a non-failure condition. The results suggested the possibility to tailor the stress distribution along the metal posts and at the interface between the post and the surrounding structures, benefiting from an appropriate combination of a CAD-based approach and material selection. The obtained results could help to design metal posts that minimize stress concentrations.

Keywords: Computer-aided design (CAD) | Dental materials | Finite element analysis | Image analysis | Mechanical properties | Metal posts

[47] Cascone F.D., Gironimo G.D., Gloria A., Martorelli M., Lanzotti A., An intuitive hardware layout for personalized augmentative and alternative communication systems, CEUR Workshop Proceedings, 2524, (2019). Abstract
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Abstract: The complexity of the interaction between user and computer can limit usability in products. When products are aimed at individuals with disability, the complexity increases the cognitive load and can reduce performances. The identification of interaction models and usability issues plays a role in product development as it enables designers to reduce this complexity. Methodology to identify lacking areas in products are required and permits to correct issues leading to an improvement of performances. A custom Augmentative and Alternative Communication system was developed for a student of the University of Naples Federico II. The user has complex communication needs and motor impairments and requires a personalized device to communicate. To promote an efficient interaction, hardware and software interfaces were personalized. Several studies were conducted: a usability evaluation, determination of the learning rate and Hardware/Software layout optimization were used to reduce the cognitive demands required by the system in its functioning. In this paper the HW layout optimization is investigated and strategies to reduce the cognitive load modifying order and position of the sensors of the input peripherals are provided.

Keywords: Augmentative and Alternative Communication | Human-Computer Interaction | Usability Testing

[48] Cascone F.D., Martorelli M., Gloria A., Papa S., Lanzotti A., Towards the development of interfaces for students with speech disorder and motor impairments, Procedia Manufacturing, 38, 455-463, (2019). Abstract
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Abstract: In a complex case of speech disorder, the communication is entrusted to systems equipped with a speech synthesizer. When the user has a motor disability, in addition, hardware and software interfaces are personalized to make technology more accessible. Interaction design methods can be applied to develop improved assistive systems and, particularly, for Augmentative and Alternative Communication (AAC). Interaction design methods and usability evaluation could have a positive impact in reducing product barriers and improving performances as the effort state associated to its use can be reduced. Minimizing cognitive and physical efforts through the development of new solutions and interface optimization can be challenging. A usability test and an interface optimization of a personalized AAC system developed for a student of the University of Naples Federico II with complex communication needs due to a traumatic injury and motor impairment are discussed to fix usability issues, highlight critical areas and design new prototypes.

Keywords: Augmentative and alternative communication | Biomedical devices | Disability | Interaction design | Learnability | Usability

[49] Maietta S., Gloria A., Improta G., Richetta M., De Santis R., Martorelli M., A further analysis on Ti6Al4V lattice structures manufactured by selective laser melting, Journal of Healthcare Engineering, 2019, (2019). Abstract
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Abstract: Mechanical and architectural features play an important role in designing biomedical devices. The use of materials (i.e., Ti6Al4V) with Young's modulus higher than those of natural tissues generally cause stress shielding effects, bone atrophy, and implant loosening. However, porous devices may be designed to reduce the implant stiffness and, consequently, to improve its stability by promoting tissue ingrowth. If porosity increases, mass transport properties, which are crucial for cell behavior and tissue ingrowth, increase, whereas mechanical properties decrease. As reported in the literature, it is always possible to tailor mass transport and mechanical properties of additively manufactured structures by varying the architectural features, as well as pore shape and size. Even though many studies have already been made on different porous structures with controlled morphology, the aim of current study was to provide only a further analysis on Ti6Al4V lattice structures manufactured by selective laser melting. Experimental and theoretical analyses also demonstrated the possibility to vary the architectural features, pore size, and geometry, without dramatically altering the mechanical performance of the structure.

[50] Lanzotti A., Martorelli M., Maietta S., Gerbino S., Penta F., Gloria A., A comparison between mechanical properties of specimens 3D printed with virgin and recycled PLA, Procedia CIRP, 79, 143-146, (2019). Abstract
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Abstract: The current research was focused on a further insight into the mechanical properties of 3D parts printed with virgin and recycled polylactic acid (PLA). A first set of specimens was printed with virgin PLA lament and mechanically tested. Such specimens were then ground up and re-extruded into filament using a homemade extruder. The re-extruded filament was employed to manufacture a new set of specimens which were also analysed. Three recycling processes were performed to assess the effect on the mechanical properties. The obtained results suggested that 3D printing with recycled PLA may be a viable option.

Keywords: Additive Manufacturing | Mechanical properties | Recycled polymers

[51] Bordoni D., Cadenelli P., Ornelli M., Falco G., Accurso A., Gloria A., Maietta S., Rocco N., Magalotti C., The axillary flap in oncoplastic resection of breast cancers located in the upper-outer quadrants: A new surgical technique, BMC Surgery, 18, (2019). Abstract
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Abstract: Background: The combination of breast conserving surgery (BCS) with plastic surgery techniques has provided a useful surgical tool matching the radicality of the oncological excision with the preservation of breast cosmesis. Even though BCS represents a good option for surgical treatment of tumors located in these quadrants, wide excisions often necessitate breast reshaping in order to avoid nipple areola complex (NAC) displacement and skin retraction. We present a new surgical technique to repair upper-outer quadrants' defects following breast cancer excision using dermo-glandular flaps and an axillary adipo-fascial flap. Methods: During the period from January 2014 to December 2015, 168 patients with an upper-outer quadrant's breast cancer have been treated in our Department. 83 women have been treated with the described oncoplastic technique and immediate contra-lateral symmetrisation and 85 women underwent standard BCS. We present surgical, oncological and cosmetic outcomes comparing our results with standard BCS. Results: At a mean follow-up of 27 months loco-regional recurrences in the two groups were comparable. Short-term complication rates were comparable between the two groups. Re-intervention rates for positive margins were significantly higher in the standard BCS group. The overall satisfaction with cosmetic outcome both assessed by the patient and the surgeon was significantly higher in the oncoplastic group. Conclusions: The proposed oncoplastic technique represents a safe and effective solution for reshaping that follows upper-outer breast cancer wide excision, achieving comparable complication rates, lower re-intervention rates for positive margins and better cosmetic results when compared with standard BCS.

Keywords: Breast Cancer | Oncoplastic breast surgery | Surgical technique

[52] De Santis R., Gloria A., Viglione S., Maietta S., Nappi F., Ambrosio L., Ronca D., 3D laser scanning in conjunction with surface texturing to evaluate shift and reduction of the tibiofemoral contact area after meniscectomy, Journal of the Mechanical Behavior of Biomedical Materials, 88, 41-47, (2018). Abstract
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Abstract: Meniscectomy significantly change the kinematics of the knee joint by reducing the contact area between femoral condyles and the tibial plateau, but the shift in the contact area has been poorly described. The aim of our investigation was to measure the shift of the tibiofemoral contact area occurring after meniscectomy. We used laser scans combined to surface texturing for measuring the 3D position and area of the femoral and tibial surfaces involved in the joint. In particular, natural condyles (porcine model) were analysed and the reverse engineering approach was used for the interpretation of the results from compression tests and local force measurements in conjunction with staining techniques. The results suggested that laser scans combined to surface texturing may be considered as a powerful tool to investigate the stained contours of the contact area. Beside the largely documented reduction of contact area and local pressure increase, a shift of the centroid of the contact area toward the intercondylar notch was measured after meniscectomy. As a consequence of the contact area shift and pressure increase, cartilage degeneration close to the intercondylar notch may occur.

Keywords: Biomechanics | Centroid | Image analysis | Laser scanning | Surface texturing | Tibiofemoral contact area

[53] De Santis R., Russo T., Gloria A., An analysis on the potential of diode-pumped solid-state lasers for dental materials, Materials Science and Engineering C, 92, 862-867, (2018). Abstract
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Abstract: Material structure-property relationship is strongly related to the employed process technology. Over the past years, laser processing of engineering materials has been proposed in many fields and different uses for diode lasers have been found in dentistry. In this contest, the potential of GaN- and InGaN-based laser diodes to cure dental materials was analysed. Two wavelengths of 405 nm and 445 nm were used as heat or light sources for warm condensation of gutta-percha, light transmission in dental posts and brackets or light curing of dental composites. Additive manufacturing approach was considered to fabricate 3D root analogues, suitable supports, positioning systems and moulds for optical measurements. A three-axis CAD/CAM system was implemented for positioning and aligning the laser beam. The ability of diode-pumped solid-state lasers to cure dental materials or to transmit light was compared to that of a traditional instrument. Temperature profile at the apex of an additive manufactured root canal sealed with gutta-percha, light transmission through translucent quartz fiber post or through aesthetic ceramic bracket, bending properties and morphological features of light cured dental composites (Gradia Direct - GC Corporation and Venus Diamond - Heraeus Kulzer) were measured. Results showed a very high potential of diode-pumped solid-state lasers to be used in endodontics, orthodontics and restorative dentistry.

Keywords: CAD/CAM system | Ceramic bracket | Dental materials | Laser diode | Mechanical analysis

[54] Calì M., Oliveri S.M., Cella U., Martorelli M., Gloria A., Speranza D., Mechanical characterization and modeling of downwind sailcloth in fluid-structure interaction analysis, Ocean Engineering, 165, 488-504, (2018). Abstract
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Abstract: Computational Fluid Dynamics (CFD), as early used in the design stage, helps engineers to come up with the optimum design of a sail in a reasonable timeframe. However, traditional CFD tools are approximate and need to be validated when it comes to predicting the dynamic behaviour of non-developable shape with high camber and massively detached flow around thin and flexible membranes. Some of these approximations are related to the implementation of the constitutive material characteristics and assumption of their isotropic properties, while the sail aerodynamic performance is strongly influenced by the arrangement of sail panels as well as the orientation of the fibres in the composite structure. The present paper offers a methodology that enhances the understanding of the influence of panel arrangement and fibre orientation on sail performance. Fluid-structure-interaction (FSI) in a symmetric spinnaker was studied through an integrated CFD-CSM (Computational Structural Mechanics) analysis. A suitable triangular membrane element formulation of sail was adopted and the constitutive characteristics (elasticity and damping) of the Nylon superkote 75 were implemented in CSM model after being experimentally measured. The aerodynamic performance of sail in terms of drive force and side force was evaluated using both Reynolds Averaged Navier Stokes Simulations (RANS) and Shear Stress Transport (SST) turbulence model with a finite volume approach. A comparison between different panel arrangements was carried out under altered downwind flow conditions of wind speed and wind angle. Digital photogrammetry was employed to create the 3D reconstruction of the sail's flying shape and validate the results obtained by aeroelastic analysis.

Keywords: CFD-CSM analysis | Flying shape photogrammetry acquisition | Sail panel arrangement | SST model | Triangular membrane elements

[55] Penta F., Amodeo G., Gloria A., Martorelli M., Odenwald S., Lanzotti A., Low-velocity impacts on a polymeric foam for the passive safety improvement of sports fields: Meshless approach and experimental validation, Applied Sciences (Switzerland), 8(7), (2018). Abstract
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Abstract: Over the past few years, foam materials have been increasingly used in the passive safety of sport fields, to mitigate the risk of crash injury. Currently, the passive safety certification process of these materials represents an expensive and time-consuming task, since a considerable number of impact tests on material samples have to be carried out by an ad hoc testing apparatus. To overcome this difficulty and speed up the design process of new protective devices, a virtual model for the low-velocity impact behaviour of foam protective mats is needed. In this study a modelling approach based on the mesh-free Element Galerkin method was developed to investigate the impact behaviour of ethylene-vinyl acetate (EVA) foam protective mats. The main advantage of this novel technique is that the difficulties related to the computational mesh distortion and caused by the large deformation of the foam material are avoided and a good accuracy is achieved at a relatively low computational cost. The numerical model was validated statistically by comparing numerical and experimental acceleration data acquired during a series of impact events on EVA foam mats of various thicknesses. The findings of this study are useful for the design and improvement of foam protective devices and allow for optimizing sports fields' facilities by reducing head injury risk by a reliable computational method.

Keywords: EFG method | Foam protective mats | Impact testing | Sports safety

[56] Gloria A., Maietta S., Martorelli M., Lanzotti A., Watts D.C., Ausiello P., FE analysis of conceptual hybrid composite endodontic post designs in anterior teeth, Dental Materials, 34(7), 1063-1071, (2018). Abstract
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Abstract: Objectives: To assess conceptual designs of dental posts consisting of polyetherimide (PEI) reinforced with carbon (C) and glass (G) glass fibers in endodontically treated anterior teeth. Methods: 3D tessellated CAD and geometric models of endodontically treated anterior teeth were generated from Micro-CT scan images. Model C-G/PEI composite posts with different Young's moduli were analyzed by Finite Element (FE) methods post A (57.7 GPa), post B (31.6 GPa), post C (from 57.7 to 9.0 GPa in the coronal–apical direction). A load of 50 N was applied at 45° to the longitudinal axis of the tooth, acting on the palatal surface of the crown. The maximum principal stress distribution was determined along the post and at the interface between the post and the surrounding structure. Results: Post C, with Young's modulus decreasing from 57.7 to 9.0 GPa in the coronal–apical direction, reduced the maximum principal stress distribution in the restored tooth. Post C gave reduced stress and the most uniform stress distribution with no stress concentration, compared to the other C-G/PEI composite posts. Significance: The FE analysis confirmed the ability of the functionally graded post to dissipate stress from the coronal to the apical end. Hence actual (physical) C-G/PEI posts could permit optimization of stress distributions in endodontically treated anterior teeth.

Keywords: CAD | Dental materials | Design | Endodontic treatment | Finite Element analysis | Image analysis

[57] De Santis R., Gloria A., Maietta S., Martorelli M., De Luca A., Spagnuolo G., Riccitiello F., Rengo S., Mechanical and thermal properties of dental composites cured with CAD/CAM assisted solid-state laser, Materials, 11(4), (2018). Abstract
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Abstract: Over the last three decades, it has been frequently reported that the properties of dental restorative composites cured with argon laser are similar or superior to those achieved with conventional halogen and light emitting diode (LED) curing units. Whereas laser curing is not dependent on the distance between the curing unit and the material, such distance represents a drawback for conventional curing units. However, a widespread clinical application of this kind of laser remains difficult due to cost, heavy weight, and bulky size. Recently, with regard to the radiation in the blue region of the spectrum, powerful solid-state lasers have been commercialized. In the current research, CAD (computer-aided design)/CAM (computer-aided manufacturing) assisted solid-state lasers were employed for curing of different dental restorative composites consisting of micro- and nanoparticle-reinforced materials based on acrylic resins. Commercial LED curing units were used as a control. Temperature rise during the photopolymerisation process and bending properties were measured. By providing similar light energy dose, no significant difference in temperature rise was observed when the two light sources provided similar intensity. In addition, after 7 days since curing, bending properties of composites cured with laser and LED were similar. The results suggested that this kind of laser would be suitable for curing dental composites, and the curing process does not suffer from the tip-to-tooth distance.

Keywords: Composites | Computer-aided design/computer-aided systems | Dental materials | Laser | Mechanical properties | Thermal properties

[58] Maietta S., Russo T., De Santis R., Ronca D., Riccardi F., Catauro M., Martorelli M., Gloria A., Further theoretical insight into the mechanical properties of polycaprolactone loaded with organic-inorganic hybrid fillers, Materials, 11(2), (2018). Abstract
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Abstract: Experimental/theoretical analyses have already been performed on poly(ε-caprolactone) (PCL) loaded with organic-inorganic fillers (PCL/TiO2 and PCL/ZrO2) to find a correlation between the results from the small punch test and Young's modulus of the materials. PCL loaded with Ti2 (PCL = 12, TiO2 = 88 wt %) and Zr2 (PCL = 12, ZrO2 = 88 wt %) hybrid fillers showed better performances than those obtained for the other particle composition. In this context, the aim of current research is to provide further insight into the mechanical properties of PCL loaded with sol-gel-synthesized organic-inorganic hybrid fillers for bone tissue engineering. For this reason, theoretical analyses were performed by the finite element method. The results from the small punch test and Young's modulus of the materials were newly correlated. The obtained values of Young's modulus (193 MPa for PCL, 378 MPa for PCL/Ti2 and 415 MPa for PCL/Zr2) were higher than those obtained from a previous theoretical modelling (144 MPa for PCL, 282 MPa for PCL/Ti2 and 310 MPa for PCL/Zr2). This correlation will be an important step for the evaluation of Young's modulus, starting from the small punch test data.

Keywords: Biomedical applications | Composites | Computer-aided design (CAD) | Finite element analysis (FEA) | Mechanical analysis | Organic-inorganic hybrid materials

[59] D'Amora U., D'Este M., Eglin D., Safari F., Sprecher C.M., Gloria A., De Santis R., Alini M., Ambrosio L., Collagen density gradient on three-dimensional printed poly(ε-caprolactone) scaffolds for interface tissue engineering, Journal of Tissue Engineering and Regenerative Medicine, 12(2), 321-329, (2018). Abstract
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Abstract: The ability to engineer scaffolds that resemble the transition between tissues would be beneficial to improve repair of complex organs, but has yet to be achieved. In order to mimic tissue organization, such constructs should present continuous gradients of geometry, stiffness and biochemical composition. Although the introduction of rapid prototyping or additive manufacturing techniques allows deposition of heterogeneous layers and shape control, the creation of surface chemical gradients has not been explored on three-dimensional (3D) scaffolds obtained through fused deposition modelling technique. Thus, the goal of this study was to introduce a gradient functionalization method in which a poly(ε-caprolactone) surface was first aminolysed and subsequently covered with collagen via carbodiimide reaction. The 2D constructs were characterized for their amine and collagen contents, wettability, surface topography and biofunctionality. Finally, chemical gradients were created in 3D printed scaffolds with controlled geometry and porosity. The combination of additive manufacturing and surface modification is a viable tool for the fabrication of 3D constructs with controlled structural and chemical gradients. These constructs can be employed for mimicking continuous tissue gradients for interface tissue engineering.

Keywords: collagen | functionalization | interface tissue engineering | poly(ε-caprolactone) | scaffold

[60] Staiano G., Gloria A., Ausanio G., Lanzotti A., Pensa C., Martorelli M., Experimental study on hydrodynamic performances of naval propellers to adopt new additive manufacturing processes, International Journal on Interactive Design and Manufacturing, 12(1), 1-14, (2018). Abstract
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Abstract: In the past few years, a new generation of additive manufacturing (AM) techniques has rapidly become available due to the expiration of some AM patents which allowed significant cost reductions. This article explores some available techniques fostering products innovation in experimental laboratories for the development of naval propulsion, where high costs represent an important limitation for both basic research and industrial testing, by identifying significant knowledge and variables and by providing reliable and accurate data to support designers and researchers. The propeller INSEAN E779a case study was taken into account and fabricated by direct metal laser sintering in AlSi10Mg aluminium alloy and by fused deposition modeling in acrylonitrile–butadiene–styrene, and UltraT polymeric materials. The study of printing parameters, flexural tests, differential scanning calorimetry and thermogravimetric analysis, allowed to optimize the printing process conditions. A reverse engineering system, Faro-CAM2, and the iterative closest point algorithm of the geomagic control software were used to analyse deviations from the printed propeller and the CAD nominal model. The atomic force microscopy test allowed to assess the morphological features and surface roughness of printed propellers. Towing Tank tests were carried out and the hydrodynamic performance comparison was analysed in terms of torque and drag. The results of this study show differences between the benchmark and AM propellers, as a function of the advance coefficient J, the morphological characteristics and the materials. However this study also shows a substantial adequacy of AM propellers in most studies carried out in Towing Tank.

Keywords: Additive manufacturing (AM) | Marine propeller | Reverse engineering (RE)

[61] Lanzotti A., Martorelli M., Russo T., Gloria A., Design of additively manufactured lattice structures for tissue regeneration, Materials Science Forum, 941 MSF, 2154-2159, (2018). Abstract
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Abstract: Additive Manufacturing technologies allow for the direct fabrication of lightweight structures with improved properties. In this context, Fused Deposition Modelling (FDM) has also been considered to design 3D multifunctional scaffolds with complex morphology, tailored biological, mechanical and mass transport properties. As an example, poly(ε-caprolactone) (PCL), surface-modified PCL and PCL-based nanocomposite scaffolds were fabricated and analysed. The effects of structural and morphological features (i.e., sequence of stacking, fiber spacing distance, pore size and geometry), surface modification and nanoparticles on the in vitro biological and mechanical performances were investigated.

Keywords: Additive Manufacturing | Design | Mechanical and Functional Analyses | Scaffolds

[62] Lanzotti A., Martorelli M., Papa S., Sicignano G., Pepino A., Orrei S., Ciaramella S., Del Giudice D.M., Gloria A., Gerbino S., Participatory design of a personalized device for a student with spastic quadriplegia at federico ii, Advances in Transdisciplinary Engineering, 7, 339-349, (2018). Abstract
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Abstract: In the field of movement disorders, each disabled person is different for both motor performance for functional requirements and expectations. This paper describes the development of a personalized device for a student with spastic quadriplegia at Federico II. This device is an Alternative Augmentative Communication system and it consists of hardware and software, which have been adapted to the individual characteristics of the student. According to participatory design and using the task analysis, we proceed to the hardware prototyping and to the software interface improving. An approach based on Analytic Hierarchy Process and Multiple-Criteria Decision Analysis is used. Tests under laboratory conditions are performed for evaluating the usability index of the device. Considering the data analysis, some critical issues are identified. The knowledge acquired in the case study is a point of strength of the proposed paper because it can be re-used for other persons with severe motor disabilities to improve their inclusion, integration and participation and to carry out tasks in different areas of application with minimum stress and maximum efficiency and effectiveness.

Keywords: Alternative augmentative communication | Participatory design | Spastic quadriplegia | Usability assessment

[63] Maietta S., De Santis R., Catauro M., Martorelli M., Gloria A., Theoretical design of multilayer dental posts using CAD-based approach and sol-gel chemistry, Materials, 11(5), (2018). Abstract
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Abstract: A computer-aided design (CAD)-based approach and sol-gel chemistry were used to design a multilayer dental post with a compositional gradient and a Young's modulus varying from 12.4 to 2.3 GPa in the coronal-apical direction. Specifically, we propose a theoretical multilayer post design, consisting of titanium dioxide (TiO2) and TiO2/poly("-caprolactone) (PCL) hybrid materials containing PCL up to 24% by weight obtained using the sol-gel method. The current study aimed to analyze the effect of the designed multilayer dental post in endodontically treated anterior teeth. Stress distribution was investigated along and between the post and the surrounding structures. In comparison to a metal post, the most uniform distributions with lower stress values and no significant stress concentration were found when using the multilayer post.

Keywords: Biomedical applications | Composites | Computer-aided design (CAD) | Finite element analysis (FEA) | Hybrid materials | Mechanical analysis

[64] Ronca A., Ronca S., Forte G., Zeppetelli S., Gloria A., De Santis R., Ambrosio L., Synthesis and characterization of divinyl-fumarate poly-ε-caprolactone for scaffolds with controlled architectures, Journal of Tissue Engineering and Regenerative Medicine, 12(1), e523-e531, (2018). Abstract
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Abstract: A vinyl-terminated polycaprolactone has been developed for tissue engineering applications using a one-step synthesis and functionalization method based on ring opening polymerization (ROP) of ε-Caprolactone, with hydroxyl ethyl vinyl ether (HEVE) acting both as the initiator of ROP and as photo-curable functional group. The proposed method employs a catalyst based on aluminium, instead of the most popular Tin(II) 2-ethylhexanoate, to reduce the cytotoxicity. Following the synthesis of the vinyl-terminated polycaprolactone, its reaction with fumaryl chloride (FuCl) results in a divinyl-fumarate polycaprolactone (VPCLF). The polymers obtained were thoroughly characterized using Fourier transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC) techniques. The polymer has been successfully employed, in combination with N-vinyl pyrrolidone (NVP), to fabricate films and computer-designed porous scaffolds by micro-stereolithography (μ-SL) with gyroid and diamond architectures. Characterization of the networks indicated the influence of NVP content on the network properties. Human mesenchymal stem cells adhered and spread onto VPCLF/NVP networks showing good biological properties and no cytotoxic effect. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: biocompatibility | cell–material interactions | mathematically defined scaffold | photocrosslinkable polymer | polycaprolactone fumarate | stereolithography

[65] Ausiello P., Ciaramella S., Martorelli M., Lanzotti A., Gloria A., Watts D.C., CAD-FE modeling and analysis of class II restorations incorporating resin-composite, glass ionomer and glass ceramic materials, Dental Materials, 33(12), 1456-1465, (2017). Abstract
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Abstract: Objectives To investigate the influence of specific resin-composite, glass ceramic and glass ionomer cement (GIC) material combinations in a “multi-layer” technique to replace enamel and dentin in class II mesio-occlusal-distal (MOD) dental restorations using 3D-Finite Element Analysis (FEA). Methods Four 3D-FE models (A–D) of teeth, adhesively restored with different filling materials, were created and analyzed in comparison with a 3D model (E) of a sound lower molar. Models A, B & C had “multilayer” constructions, consisting of three layers: adhesive, dentin replacement and enamel replacement. Model A: had a low modulus (8 GPa) composite replacing dentin and a higher modulus (12 GPa) composite replacing enamel. Model B: had a GI cement replacing dentin and a higher modulus (12 GPa) composite replacing enamel. Model C: had a low modulus (8 GPa) composite replacing dentin and a very high modulus (70 GPa) inlay replacing enamel. Model D: had a lithium disilicate inlay replacing both dentin and enamel with a luting cement base-layer. Polymerization shrinkage effects were simulated and a load of 600 N was applied. All the materials were assumed to behave elastically throughout the entire deformation. Results Model A showed the highest stress distribution along all the adhesive interfaces of the shrinking resin-based materials with a critical condition and failure risk marginally and internally. Model D, by contrast, showed a more favorable performance than either of the multilayer groups (A–C). Stress and displacement plots showed an elastic response similar to that obtained for the sound tooth model. Model B and Model C performed according to their bilayer material properties. The use of a non-shrink dentin component simulating a GIC clearly affected the shrinkage stress at the basis of the Model B; while the bulk resin composite having a 12 GPa Young's modulus and linear polymerization shrinkage of 1% strongly influenced the biomechanical response in the bucco-lingual direction. Significance Direct resin-based composite materials applied in multilayer techniques to large class II cavities, with or without shrinking dentin layers, produced adverse FEA stress distributions and displacements. An indirect lithium disilicate inlay used to replace lost dentin and enamel in posterior restored teeth generated lower stress levels, within the limits of the elastic FEA model.

Keywords: CAD | Class II restorations | Finite element analysis | Image analysis | Materials properties

[66] Ausiello P., Ciaramella S., Martorelli M., Lanzotti A., Zarone F., Watts D.C., Gloria A., Mechanical behavior of endodontically restored canine teeth: Effects of ferrule, post material and shape, Dental Materials, 33(12), 1466-1472, (2017). Abstract
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Abstract: Objective To assess the effect of a ferrule design with specific post material-shape combinations on the mechanical behavior of post-restored canine teeth. Methods Micro-CT scan images of an intact canine were used to create a 3-D tessellated CAD model, from which the shapes of dentin, pulp and enamel were obtained and geometric models of post-endodontically restored teeth were created. Two types of 15 mm post were evaluated: a quartz fiber post with conical–tapered shape, and a carbon (C) fiber post with conical–cylindrical shape. The abutment was created around the coronal portion of the posts and 0.1 mm cement was added between prepared crown and abutment. Cement was also added between the post and root canal and a 0.25 mm periodontal ligament was modeled around the root. Four models were analysed by Finite Element (FE) Analysis: with/without a ferrule for both types of post material and shape. A load of 50 N was applied at 45° to the longitudinal axis of the tooth, acting on the palatal surface of the crown. The maximum normal stress criterion was adopted as a measure of potential damage. Results Models without a ferrule showed greater stresses (16.3 MPa) than those for models with a ferrule (9.2 MPa). With a ferrule, stress was uniformly distributed along the abutment and the root, with no critical stress concentration. In all models, the highest stresses were in the palatal wall of the root. Models with the C-fiber post had higher stress than models with the quartz fiber posts. The most uniform stress distribution was with the combination of ferrule and quartz fiber post. Significance The FE analysis confirmed a beneficial ferrule effect with the combination of ferrule and quartz fiber post, with tapered shape, affording no critical stress concentrations within the restored system.

Keywords: CAD | Dental materials | Endodontic treatment | Finite element analysis | Image analysis | Materials properties

[67] D'Amora U., Russo T., Gloria A., Rivieccio V., D'Antò V., Negri G., Ambrosio L., De Santis R., 3D additive-manufactured nanocomposite magnetic scaffolds: Effect of the application mode of a time-dependent magnetic field on hMSCs behavior, Bioactive Materials, 2(3), 138-145, (2017). Abstract
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Abstract: Over the past few years, the influence of static or dynamic magnetic fields on biological systems has become a topic of considerable interest. Magnetism has recently been implicated to play significant roles in the regulation of cell responses and, for this reason, it is revolutionizing many aspects of healthcare, also suggesting new opportunities in tissue engineering. The aim of the present study was to analyze the effect of the application mode of a time-dependent magnetic field on the behavior of human mesenchymal stem cells (hMSCs) seeded on 3D additive-manufactured poly(ɛ-caprolactone)/iron-doped hydroxyapatite (PCL/FeHA) nanocomposite scaffolds.

Keywords: Additive manufacturing | Cell-material interaction | Magnetic field | Scaffold

[68] Russo T., Gloria A., De Santis R., D'Amora U., Balato G., Vollaro A., Oliviero O., Improta G., Triassi M., Ambrosio L., Preliminary focus on the mechanical and antibacterial activity of a PMMA-based bone cement loaded with gold nanoparticles, Bioactive Materials, 2(3), 156-161, (2017). Abstract
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Abstract: In total knee arthroplasty (TKA) and total hip replacement (THR) the restoration of the normal joint function represents a fundamental feature. A prosthetic joint must be able to provide motions and to transmit functional loads. As reported in the literature, the stress distribution may be altered in bones after the implantation of a total joint prosthesis. Some scientific works have also correlated uncemented TKA to a progressive decrease of bone density below the tibial component. Antibiotic-loaded bone cements are commonly employed in conjunction with systemic antibiotics to treat infections. Furthermore, nanoparticles with antimicrobial activity have been widely analysed. Accordingly, the current research was focused on a preliminary analysis of the mechanical and antibacterial activity of a PMMA-based bone cement loaded with gold nanoparticles. The obtained results demonstrated that nanocomposite cements with a specific concentration of gold nanoparticles improved the punching performance and antibacterial activity. However, critical aspects were found in the optimization of the nanocomposite bone cement.

Keywords: Antibacterial activity | Bone cement | Gold nanoparticles | Mechanical properties | Nanocomposite

[69] Ronca A., Maiullari F., Milan M., Pace V., Gloria A., Rizzi R., De Santis R., Ambrosio L., Surface functionalization of acrylic based photocrosslinkable resin for 3D printing applications, Bioactive Materials, 2(3), 131-137, (2017). Abstract
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Abstract: The limited number of resins, available for stereolithography applications, is one of the key drivers in research applied to rapid prototyping. In this work an acrylic photocrosslinkable resin based on methyl methacrylate (MMA), butyl methacrylate (BMA) and poly(ethylene glycol) dimethacrylate (PEGDA) was developed with different composition and characterized in terms of mechanical, thermal and biological behaviour. Two different systems have been developed using different amount of reagent. The influence of every components have been evaluated on the final characteristic of the resin in order to optimize the final composition for applications in bone tissue engineering. The crosslinked materials showed good mechanical properties and thermal stabilities and moreover cytotoxicity test confirms good biocompatibility with no cytotoxic effect on cells metabolism. Moreover two different treatments have been proposed, using fetal bovine serum (FBS) and methanol (MeOH), in order to improve cell recognition of the surfaces. Samples threatened with MeOH allow cell adhesion and survival, promoting spreading, elongation and fusion of C2C12 muscle myoblast cells.

[70] Ausiello P., Ciaramella S., Garcia-Godoy F., Martorelli M., Sorrentino R., Gloria A., Stress distribution of bulk-fill resin composite in class II restorations, American Journal of Dentistry, 30(4), 227-232, (2017). Abstract
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Abstract: Purpose: To study the influence of the resin bonding layer thickness and the bulk filling material stiffness in adhesive class II mesio-occlusal-distal (MOD) restorations using numerical finite element analysis (FEA). Methods: Four 3D-FE models of teeth restored with different filling material stiffness and resin bonding layer thickness were built-up and analyzed. The 3D model of a sound lower molar was also analyzed and compared with restored ones. The tooth tissues . (enamel, dentin), dental restoration and bolus on the occlusal surface, was divided into 3D solid CTETRA elements with four grid points. The adhesive bonding around the dental restoration was modeled with shell elements. Polymerization shrinkage was simulated with a thermal expansion approach. Mechanical behavior of restored models in terms of stress and displacement distributions, under the combination effects of polymerization shrinkage and occlusal load (600 N), was analyzed. All the materials were assumed to behave as elastic materials throughout the entire deformation. Results: Numerical results show that the mechanical response of the restored models was very different compared to the sound tooth ones, where the stress was uniformly distributed from enamel to dentin with no critical stress concentration. In the | restored models, the highest stress values were detected in the enamel, near the enamel-dentin interface and in the bulk ' restorative material. Tooth preparations A and B showed lower gradient stresses than corresponding C and D. The value of the vertical displacement components in models A and B were higher than corresponding C and D. The maximum displacement values were mainly located around the groove and were higher by an order of magnitude than the sound models. The results showed better mechanical response with models A and B compared to C and D. It is also evident that resin bonding thickness slightly affected the stress level of the restored teeth.

[71] Bonifacio M.A., Cometa S., Dicarlo M., Baruzzi F., de Candia S., Gloria A., Giangregorio M.M., Mattioli-Belmonte M., De Giglio E., Gallium-modified chitosan/poly(acrylic acid) bilayer coatings for improved titanium implant performances, Carbohydrate Polymers, 166, 348-357, (2017). Abstract
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Abstract: A gallium-modified chitosan/poly(acrylic acid) bilayer was obtained by electrochemical techniques on titanium to reduce orthopaedic and/or dental implants failure. The bilayer in vitro antibacterial properties and biocompatibility were evaluated against Escherichia coli and Pseudomonas aeruginosa and on MG63 osteoblast-like cells, respectively. Gallium loading into the bilayer was carefully tuned by the electrochemical deposition time to ensure the best balance between antibacterial activity and cytocompatibility. The 30 min deposition time was able to reduce in vitro the viable cell counts of E. coli and P. aeruginosa of 2 and 3 log cfu/sheet, respectively. Our results evidenced that the developed antibacterial coating did not considerably alter the mechanical flexural properties of titanium substrates and, in addition, influenced positively MG63 adhesion and proliferation. Therefore, the gallium-modified chitosan/poly(acrylic acid) bilayer can be exploited as a promising titanium coating to limit bacterial adhesion and proliferation, while maintaining osseointegrative potential.

Keywords: Antibacterial agents | Biocompatibility | Chitosan-based bilayer | Electrochemical deposition | Gallium | Titanium

[72] Domingos M., Gloria A., Coelho J., Bartolo P., Ciurana J., Three-dimensional printed bone scaffolds: The role of nano/micro-hydroxyapatite particles on the adhesion and differentiation of human mesenchymal stem cells, Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 231(6), 555-564, (2017). Abstract
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Abstract: Bone tissue engineering is strongly dependent on the use of three-dimensional scaffolds that can act as templates to accommodate cells and support tissue ingrowth. Despite its wide application in tissue engineering research, polycaprolactone presents a very limited ability to induce adhesion, proliferation and osteogenic cell differentiation. To overcome some of these limitations, different calcium phosphates, such as hydroxyapatite and tricalcium phosphate, have been employed with relative success. This work investigates the influence of nano-hydroxyapatite and micro-hydroxyapatite (nHA and mHA, respectively) particles on the in vitro biomechanical performance of polycaprolactone/hydroxyapatite scaffolds. Morphological analysis performed with scanning electron microscopy allowed us to confirm the production of polycaprolactone/hydroxyapatite constructs with square interconnected pores of approximately 350 μm and to assess the distribution of hydroxyapatite particles within the polymer matrix. Compression mechanical tests showed an increase in polycaprolactone compressive modulus (E) from 105.5 ± 11.2 to 138.8 ± 12.9 MPa (PCL-nHA) and 217.2 ± 21.8 MPa (PCL-mHA). In comparison to PCL-mHA scaffolds, the addition of nano-hydroxyapatite enhanced the adhesion and viability of human mesenchymal stem cells as confirmed by Alamar Blue assay. In addition, after 14 days of incubation, PCL-nHA scaffolds showed higher levels of alkaline phosphatase activity compared to polycaprolactone or PCL-mHA structures.

Keywords: bioactive materials | Biomanufacturing | bone tissue engineering | hydroxyapatite | mesenchymal stem cells | scaffold development

[73] Ausiello P., Ciaramella S., Fabianelli A., Gloria A., Martorelli M., Lanzotti A., Watts D.C., Mechanical behavior of bulk direct composite versus block composite and lithium disilicate indirect Class II restorations by CAD-FEM modeling, Dental Materials, 33(6), 690-701, (2017). Abstract
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Abstract: Objectives To study the influence of resin based and lithium disilicate materials on the stress and strain distributions in adhesive class II mesio-occlusal-distal (MOD) restorations using numerical finite element analysis (FEA). To investigate the materials combinations in the restored teeth during mastication and their ability to relieve stresses. Methods One 3D model of a sound lower molar and three 3D class II MOD cavity models with 95° cavity-margin-angle shapes were modelled. Different material combinations were simulated: model A, with a 10 μm thick resin bonding layer and a resin composite bulk filling material; model B, with a 70 μm resin cement with an indirect CAD-CAM resin composite inlay; model C, with a 70 μm thick resin cement with an indirect lithium disilicate machinable inlay. To simulate polymerization shrinkage effects in the adhesive layers and bulk fill composite, the thermal expansion approach was used. Shell elements were employed for representing the adhesive layers. 3D solid CTETRA elements with four grid points were employed for modelling the food bolus and tooth. Slide-type contact elements were used between the tooth surface and food. A vertical occlusal load of 600 N was applied, and nodal displacements on the bottom cutting surfaces were constrained in all directions. All the materials were assumed to be isotropic and elastic and a static linear analysis was performed. Results Displacements were different in models A, B and C. Polymerization shrinkage hardly affected model A and mastication only partially affected mechanical behavior. Shrinkage stress peaks were mainly located marginally along the enamel-restoration interface at occlusal and mesio-distal sites. However, at the internal dentinal walls, stress distributions were critical with the highest maximum stresses concentrated in the proximal boxes. In models B and C, shrinkage stress was only produced by the 70 μm thick resin layer, but the magnitudes depended on the Young's modulus (E) of the inlay materials. Model B mastication behavior (with E = 20 GPa) was similar to the sound tooth stress relief pattern. Model B internally showed differences from the sound tooth model but reduced maximum stresses than model A and partially than model C. Model C (with E = 70 GPa) behaved similarly to model B with well redistributed stresses at the occlusal margins and the lateral sides with higher stress concentrations in the proximal boxes. Models B and C showed a more favorable performance than model A with elastic biomechanics similar to the sound tooth model. Significance Bulk filling resin composite with 1% linear polymerization shrinkage negatively affected the mechanical behavior of class II MOD restored teeth. Class II MOD direct resin composite showed greater potential for damage because of higher internal and marginal stress evolution during resin polymerization shrinkage. With a large class II MOD cavity an indirect composite or a lithium disilicate inlay restoration may provide a mechanical response close to that of a sound tooth.

Keywords: CAD | Composite | FEA | Inlay | Lithium Disilicate | Micro-CT | Stress analysis

[74] Gonçalves F.A.M.M., Fonseca A.C., Domingos M., Gloria A., Serra A.C., Coelho J.F.J., The potential of unsaturated polyesters in biomedicine and tissue engineering: Synthesis, structure-properties relationships and additive manufacturing, Progress in Polymer Science, 68, 1-34, (2017). Abstract
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Abstract: The success of Tissue Engineering (TE) based approaches is strongly dependent on the development of novel biomaterials for the design of 3D matrices with tailored biomechanical properties to promote the regeneration of human tissues and organs. This review covers the critical aspects related with the preparation of new unsaturated polyester (UP) resin formulations with suitable biological, chemical, thermal and morphological properties for the additive manufacturing (AM) of TE constructs. In this context, the basic principles of available AM technologies, with a special focus on novel stereolithography processes such as microstereolithography (micro-SLA), stereo-thermal-lithography (STLA), two-photon polymerization (TPP) and nanostereolithography (nano-SLA), are also presented and discussed. Ultimately, the present review will provide a better insight into the limitations and potential of combining UP and AM towards the rationale design/fabrication of complex artificial tissue substitutes.

Keywords: Additive manufacturing | Stereolithography processes | Structure/properties relationships | Tissue engineering | Unsaturated polyesters

[75] Lepore D., De Santis R., Pagliara M.M., Gloria A., Oliviero O., Nucci C., Improta G., Triassi M., Ambrosio L., Effect of topical antiinflammatory drugs on mechanical behavior of rabbit cornea, Journal of Applied Biomaterials and Functional Materials, 15(2), e142-e148, (2017). Abstract
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Abstract: Background: A variety of antiinflammatory therapies are employed to promote corneal wound healing. The effects of steroidal and nonsteroidal antiinflammatory drugs on the biomechanical properties of rabbit cornea were investigated over time using tensile tests. Methods: Full-thickness incisions were made and used to analyze the effects of dexamethasone sodium phosphate 0.1% and diclofenac sodium 0.1% on corneal biomechanical properties during wound healing at 7, 14 and 21 days after surgery. Results: The full-thickness incision deeply modified all of the mechanical properties. At 3 weeks after incision, regardless of the drug therapy, the tensile modulus was about 70% of the value for the intact cornea. Conclusions: Topical treatment with dexamethasone was particularly effective during the first week after surgery; the second week after surgery, a similar result was observed in the corneas treated with diclofenac. Low doses of steroidal and nonsteroidal antiinflammatory drugs would seem to have the potential to improve biomechanical properties only during the early stage of the healing process of the cornea.

Keywords: Biomechanics | Corneal wound healing | Nonsteroidal drugs | Steroidal drugs | Stress-strain

[76] Calì M., Oliveri S.M., Gloria A., Martorelli M., Speranza D., Comparison of Commonly Used Sail Cloths through Photogrammetric Acquisitions, Experimental Tests and Numerical Aerodynamic Simulations, Procedia Manufacturing, 11, 1651-1658, (2017). Abstract
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Abstract: The use of polymer composites has been increasing over the years and nowadays the requirements for designing high performance and lightweight fabrics and laminates for sail manufacturing have become more stringent than ever. The present paper offers an effective methodology that enhances the understanding of the influence of fibres orientation and arrangement of panels on sail performance. Constitutive characteristics of the ten commonly used sail cloths are experimentally measured and their influence on sail dynamic performance is compared using an aerodynamic approach. As expected also in industry 4.0 the method allows to control the production process and final product optimization.

Keywords: Aerodynamic coefficient | Apparent wind angle (AWA) | Apparent Wind Speed (AWS) | CFD analysis | Digital photogrammetry | RE | Turbulence model

[77] Gargiulo N., De Santis R., Gloria A., Caputo D., Composites for bone tissue engineering based on antibacterial mesoporous bioactive glassy oxides, Advanced Science Letters, 23(6), 6023-6025, (2017). Abstract
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Abstract: In the field of tissue engineering, the development of biomaterials with enhanced properties results a great challenge. In designing multifunctional substrates for tissue engineering, many strategies been reported to improve the performances of polymer-based composite materials. As reported in the literature, silver-containing mesoporous bioactive glasses (Ag-MBGs) were properly synthesized and analysed. The aim of the present study was to develop composite substrates consisting of a poly(ε-caprolactone) (PCL) matrix and Ag-MBGs with improved antibacterial properties. Preliminary structural/functional and biological analyses allowed to evaluate the effect of Ag-MBGs embedded in the polymer matrix.

Keywords: Biological analysis | Composites | Mesoporous bioactive glasses | Polycaprolactone | Small punch test

[78] Ferreira J., Gloria A., Cometa S., Coelho J.F.J., Domingos M., Effect of in vitro enzymatic degradation on 3D printed poly(ε-caprolactone) scaffolds: Morphological, chemical and mechanical properties, Journal of Applied Biomaterials and Functional Materials, 15(3), e185-e195, (2017). Abstract
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Abstract: Background: In recent years, the tissue engineering (TE) field has significantly benefited from advanced techniques such as additive manufacturing (AM), for the design of customized 3D scaffolds with the aim of guided tissue repair. Among the wide range of materials available to biomanufacture 3D scaffolds, poly(ε-caprolactone) (PCL) clearly arises as the synthetic polymer with the greatest potential, due to its unique properties – namely, biocompatibility, biodegradability, thermal and chemical stability and processability. This study aimed for the first time to investigate the effect of pore geometry on the in vitro enzymatic chain cleavage mechanism of PCL scaffolds manufactured by the AM extrusion process. Methods: Methods: Morphological properties of 3D printed PCL scaffolds before and after degradation were evaluated using Scanning Electron Microscopy (SEM) and micro-computed tomography (μ-CT). Differential Scanning Calorimetry (DSC) was employed to determine possible variations in the crystallinity of the scaffolds during the degradation period. The molecular weight was assessed using Size Exclusion Chromatography (SEC) while the mechanical properties were investigated under static compression conditions. Results: Morphological results suggested a uniform reduction of filament diameter, while increasing the scaffolds’ porosity. DSC analysis revealed and increment in the crystallinity degree while the molecular weight, evaluated through SEC, remained almost constant during the incubation period (25 days). Mechanical analysis highlighted a decrease in the compressive modulus and maximum stress over time, probably related to the significant weight loss of the scaffolds. Conclusions: All of these results suggest that PCL scaffolds undergo enzymatic degradation through a surface erosion mechanism, which leads to significant variations in mechanical, physical and chemical properties, but which has little influence on pore geometry.

Keywords: Biomanufacturing | Enzymatic degradation | Polycaprolactone | Scaffolds | Tissue engineering

[79] Ausiello P., Ciaramella S., Garcia-Godoy F., Gloria A., Lanzotti A., Maietta S., Martorelli M., The effects of cavity-margin-angles and bolus stiffness on the mechanical behavior of indirect resin composite class II restorations, Dental Materials, 33(1), e39-e47, (2017). Abstract
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Abstract: Objective To study the influence of the different class II mesio-occlusal-distal (MOD) cavity shape on the stress and strain distributions in adhesive indirect restorations, using numerical finite element analysis (FEA). To investigate the relationship between restored teeth failure and stiffness of food, three values of Young's modulus were used for the food. Methods A 3D model of a sound lower molar and three class II MOD cavities with different shape were created. Slide-type contact elements were used between tooth surface and food. An adhesive resin-based cement, modeled with fixed-type contact elements, and a single restorative filling materials were considered. To simulate polymerization shrinkage effect, which is basically restricted to the thin composite cement layer, shell elements were employed and the thermal expansion approach was used. A vertical occlusal load of 600 N was applied, while assigning fixed zero-displacements on the cutting surfaces below the crevices. All the materials were assumed to be isotropic and elastic. A static linear analysis was carried out. Results In the lingual cusp, the displacements increased as the values of the stiffness food increased. In the restored teeth, the stress near the restoration-tooth interface was strongly dependent on the MOD cavity shape. The stress peaks were mainly located along the enamel–dentin interface at the lingual side; wedge-shaped MOD cavity with a low angle, in combination with the lowest food stiffness provided the best results. Significance A more complex load application on the occlusal surfaces was introduced. Food stiffness slightly affected the stress distribution of the restored and sound teeth. Teeth with adhesive class II MOD indirect resin composite restorations were potentially more susceptible to damage if the class II MOD cavity-margin-angle was higher than 95°. Restored teeth with a higher cavity-margin-angle led to considerable stress concentration in the lingual cusp along the enamel–dentin interface. These models were more susceptible to fracture in the lingual cusps when compared to the buccal ones.

Keywords: CAD | Endodontics | Finite element analysis | Micro-computed tomography | Stress analysis

[80] Zamuner A., Cavo M., Scaglione S., Messina G.M.L., Russo T., Gloria A., Marletta G., Dettin M., Design of decorated self-assembling peptide hydrogels as architecture for mesenchymal stem cells, Materials, 9(9), (2016). Abstract
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Abstract: Hydrogels from self-assembling ionic complementary peptides have been receiving a lot of interest from the scientific community as mimetic of the extracellular matrix that can offer three-dimensional supports for cell growth or can become vehicles for the delivery of stem cells, drugs or bioactive proteins. In order to develop a 3D "architecture" for mesenchymal stem cells, we propose the introduction in the hydrogel of conjugates obtained by chemoselective ligation between a ionic-complementary self-assembling peptide (called EAK) and three different bioactive molecules: an adhesive sequence with 4 Glycine-Arginine-Glycine-Aspartic Acid-Serine-Proline (GRGDSP) motifs per chain, an adhesive peptide mapped on h-Vitronectin and the growth factor Insulin-like Growth Factor-1 (IGF-1). The mesenchymal stem cell adhesion assays showed a significant increase in adhesion and proliferation for the hydrogels decorated with each of the synthesized conjugates; moreover, such functionalized 3D hydrogels support cell spreading and elongation, validating the use of this class of self-assembly peptides-based material as very promising 3D model scaffolds for cell cultures, at variance of the less realistic 2D ones. Furthermore, small amplitude oscillatory shear tests showed that the presence of IGF-1-conjugate did not alter significantly the viscoelastic properties of the hydrogels even though differences were observed in the nanoscale structure of the scaffolds obtained by changing their composition, ranging from long, well-defined fibers for conjugates with adhesion sequences to the compact and dense film for the IGF-1-conjugate.

Keywords: Bio-transamination | Chemoselectiveligation | IGF-1 | Mesenchymal stem cells | RGD | Self-assembling peptides | Vitronectin

[81] Catauro M., Bollino F., Gloria A., Sol-gel silica-based nanocomposites containing a high PEG amount: Chemical characterization and study of biological properties, AIP Conference Proceedings, 1736, (2016). Abstract
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Abstract: The objective of the present study was to synthesize and to characterize Silica/polyethylene glycol (SiO2/PEG) organic-inorganic hybrid materials containing a high polymer amount (60 and 70 wt%) for biomedical applications. Scanning electron microscopy (SEM) showed that the samples are homogeneous on the nanometer scale, confirming that they are nanocomposites. Fourier transform infrared spectroscopy (FT-IR) proved that the materials are class I hybrids because the two phases (SiO2 and PEG) interact by hydrogen bonds. To evaluate the possibility of using them in the biomedical field, the bioactivity and biocompatibility of the synthesized hybrids have been ascertained. The formation of a hydroxyapatite layer was observed on the hybrid surface by SEM/EDX and FTIR after soaking in simulated body fluid (SBF). Moreover, their biocompatibility was assessed by performing WST-8 cytotoxicity assay in vitro.

Keywords: Bioactivity | Biocompatibility | Organic/Inorganic Hybrid Nanocomposites | Sol-Gel

[82] Catauro M., Bollino F., Gloria A., Sol-gel synthesis and characterization of SiO<inf>2</inf>/PEG hybrid materials containing quercetin as implants with antioxidant properties, AIP Conference Proceedings, 1736, (2016). Abstract
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Abstract: In the present work, Silica/Polyethylene glycol (PEG) hybrid nanocomposites containing an antioxidant agent, the quercetin, were synthesized via sol-gel to be used as implants with antioxidant properties. Fourier transform infrared (FT-IR) analysis proved that a modification of both polymer and quercetin occurs due to synthesis process. Scanning electron microscope (SEM) showed that the proposed materials were hybrid nanocomposites. The bioactivity was ascertained by soaking the samples in a simulated body fluid (SBF).

Keywords: bioactivity | quercetin | sol-gel hybrid materials

[83] D'Amora U., Russo T., De Santis R., Gloria A., Ambrosioa L., Hybrid nanocomposites with magnetic activation for advanced bone tissue engineering, Bio-Inspired Regenerative Medicine: Materials, Processes and Clinical Applications, 179-209, (2016).
[84] Rocco N., Gloria A., De Santis R., Catanuto G., Nava M.B., Accurso A., Improving Outcomes in Breast Reconstruction: From Implant - based Techniques towards Tissue Regeneration, Procedia CIRP, 49, 23-27, (2016). Abstract
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Abstract: Patients undergoing mastectomy for breast cancer have nowadays many options for breast reconstruction, that will help in re-establishing patient's self confidence in her own body image. Implant-based reconstruction remains the most common form of post-mastectomy reconstruction, but it could also present some complications, the most common being capsular contracture. Accordingly, a novel breast mound may be perfectly designed using the reverse engineering approach and additive manufacturing methods combined with autologous fat grafting. A 3D hierarchical structure with autologous adipose-derived stem cells may be used as a construct for tissue regeneration. The 3D morphologically controlled scaffold may be placed in the subcutaneous position at the level of the conservative mastectomy side. The scaffold will be colonized with autologous fat tissue in some sessions. The biodegradable customized structure will help to maintain the breast shape and the natural consistency may be obtained with the fat grafting, also considering adequate enhancement techniques (Stromal Vascular Fraction derived growth factors). The principles of regenerative medicine may be combined and integrated with those of reverse engineering (3D image capture, 3D modelling and rapid prototyping) to design custom-made and high functional hierarchical structures with tailored properties and 3D complex geometry. The current study will focus on the basic principles and strategies in designing 3D advanced and complex structures for breast repair and regeneration.

Keywords: Additive Manufacturing | Breast reconstruction | Fat Grafting | Reverse Engineering | Tissue Regeneration

[85] Martorelli M., Maietta S., Gloria A., De Santis R., Pei E., Lanzotti A., Design and Analysis of 3D Customized Models of a Human Mandible, Procedia CIRP, 49, 199-202, (2016). Abstract
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Abstract: Polymer-based composites are ideal for applications where high strength-to-weight and stiffness-to-weight ratios are required. In the biomedical field, fiber-reinforced polymers have replaced metals, emerging as suitable alternative. Reverse engineering and additive manufacturing methods are required to achieve the design of customized devices with specific shape and size. At the same time, micro-mechanics and macro-mechanics play an important role in the development of highly functional composite materials. The aim of this research is to develop customized 3D models of a human mandible using reverse engineering, additive manufacturing and composite material technology. Experiments were carried out by loading the models through the condyles and the results show the potential to reproduce the mechanical behavior of a human mandible. Taking into account the curves of the load-arch width decrease, the stiffness of the 3D composite model was 14.1± 1.9 N/mm, which is close to the tested human mandible (17.5 ± 1.8 N/mm).

Keywords: Experimental Testing | Fiber-reinforced composites | Mandible | Reverse Engineering | Stereolithography

[86] Gloria A., Russo T., Rodrigues D.F.L., D'Amora U., Colella F., Improta G., Triassi M., De Santis R., Ambrosio L., From 3D Hierarchical Scaffolds for Tissue Engineering to Advanced Hydrogel-Based and Complex Devices for in situ Cell or Drug Release, Procedia CIRP, 49, 72-75, (2016). Abstract
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Abstract: In the past few years, researchers have focused on the development of three-dimensional (3D) advanced scaffolds and multifunctional hydrogel-based materials. As reported in literature, 3D polymer-based composite scaffolds for tissue engineering have been manufactured through conventional and advanced manufacturing techniques, and different injectable materials and hydrogel-based systems have been proposed and studied. The aim of the current research was to define an approach in the development of multifunctional tools spanning from 3D hierarchical scaffolds for soft tissue engineering to advanced hydrogel-based devices for in situ cell or drug release. The mechanical/rheological behaviour as well as the structural/functional features of the designed devices were discussed and analyzed.

Keywords: Additive Manufacturing | Hierarchical Scaffolds | Injectable Materials | Mechanical/Rheological Properties | Multilayer Hydrogels

[87] De Santis R., Gloria A., Russo T., Ronca A., D'Amora U., Negri G., Ronca D., Ambrosio L., Viscoelastic Properties of Rapid Prototyped Magnetic Nanocomposite Scaffolds for Osteochondral Tissue Regeneration, Procedia CIRP, 49, 76-82, (2016). Abstract
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Abstract: Poly(ϵ-caprolactone) and poly(ethylene glycol) based magnetic nanocomposite scaffolds were fabricated using fused deposition modeling and stereolithography approaches, and a hybrid scaffold was obtained by combining these additive manufacturing technologies. Viscoelastic properties in compression were investigated at 37 °C, spanning a range frequency of four decades. Results suggest that poly(ϵ-caprolactone) and poly(ethylene glycol) based scaffolds adequately reproduce viscoelastic properties of subchondral bone and articular cartilage tissues, respectively. By combining fused deposition modeling and stereolithography it is possible to manufacture a hybrid scaffold suitable for osteochondral tissue regeneration.

Keywords: Fused deposition modeling | Magnetic nanoparticles | Magnetic scaffolds | Nanocomposite | Poly(ethylene glycol) | Poly(ϵ-caprolactone) | Stereolithography | Viscoelastic properties

[88] Rocco N., Gloria A., De Santis R., Catanuto G., Nava M.B., Accurso A., Improving Outcomes in Breast Reconstruction: From Implant-Based Techniques Towards Tissue Regeneration, Procedia CIRP, 49, 183-187, (2016). Abstract
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Abstract: Patients undergoing mastectomy for breast cancer have nowadays many options for breast reconstruction, that will help in re-establishing patient's self confidence in her own body image. Implant-based reconstruction remains the most common form of post-mastectomy reconstruction, but it could also present some complications, the most common being capsular contracture. Accordingly, a novel breast mound may be perfectly designed using the reverse engineering approach and additive manufacturing methods combined with autologous fat grafting. A 3D hierarchical structure with autologous adipose-derived stem cells may be used as a construct for tissue regeneration. The 3D morphologically controlled scaffold may be placed in the subcutaneous position at the level of the conservative mastectomy side. The scaffold will be colonized with autologous fat tissue in some sessions. The biodegradable customized structure will help to maintain the breast shape and the natural consistency may be obtained with the fat grafting, also considering adequate enhancement techniques (Stromal Vascular Fraction derived growth factors). The principles of regenerative medicine may be combined and integrated with those of reverse engineering (3D image capture, 3D modelling and rapid prototyping) to design custom-made and high functional hierarchical structures with tailored properties and 3D complex geometry. The current study will focus on the basic principles and strategies in designing 3D advanced and complex structures for breast repair and regeneration.

Keywords: Additive Manufacturing | Breast reconstruction | Fat Grafting | Reverse Engineering | Tissue Regeneration

[89] Ronca D., Langella F., Chierchia M., D'Amora U., Russo T., Domingos M., Gloria A., Bartolo P., Ambrosio L., Bone Tissue Engineering: 3D PCL-based Nanocomposite Scaffolds with Tailored Properties, Procedia CIRP, 49, 51-54, (2016). Abstract
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Abstract: In the field of reconstructive surgery, a great challenge is represented by bone injuries beyond the self-repair threshold. Autologous bone grafts may be considered the gold standard. Anyway, such approach is limited by the amount of tissue required for grafting and by donor site morbidity. To overcome these drawbacks, bone tissue engineering represents a promising solution. 3D fully biodegradable and nanocomposite scaffolds for bone tissue regeneration, consisting of poly(ϵ-caprolactone) (PCL) reinforced with hydroxyapatite (HA) nanoparticles, were developed using an additive manufacturing process. The effect of nanoparticles and architecture (i.e., lay-down pattern) on the mechanical/functional and biological properties was discussed.

Keywords: Additive Manufacturing | Bone | Nanocomposite Scaffolds | Tissue Regeneration

[90] Russo T., Tunesi M., Giordano C., Gloria A., Ambrosio L., Hydrogels for central nervous system therapeutic strategies, Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 229(12), 905-916, (2015). Abstract
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Abstract: The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described.

Keywords: central nervous system | Hydrogels | injectable materials | therapeutic strategies | viscoelastic properties

[91] De Santis R., D’Amora U., Russo T., Ronca A., Gloria A., Ambrosio L., 3D fibre deposition and stereolithography techniques for the design of multifunctional nanocomposite magnetic scaffolds, Journal of Materials Science: Materials in Medicine, 26(10), (2015). Abstract
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Abstract: Magnetic nanocomposite scaffolds based on poly(ε-caprolactone) and poly(ethylene glycol) were fabricated by 3D fibre deposition modelling (FDM) and stereolithography techniques. In addition, hybrid coaxial and bilayer magnetic scaffolds were produced by combining such techniques. The aim of the current research was to analyse some structural and functional features of 3D magnetic scaffolds obtained by the 3D fibre deposition technique and by stereolithography as well as features of multimaterial scaffolds in the form of coaxial and bilayer structures obtained by the proper integration of such methods. The compressive mechanical behaviour of these scaffolds was investigated in a wet environment at 37 °C, and the morphological features were analysed through scanning electron microscopy (SEM) and X-ray micro-computed tomography. The capability of a magnetic scaffold to absorb magnetic nanoparticles (MNPs) in water solution was also assessed. confocal laser scanning microscopy was used to assess the in vitro biological behaviour of human mesenchymal stem cells (hMSCs) seeded on 3D structures. Results showed that a wide range of mechanical properties, covering those spanning hard and soft tissues, can be obtained by 3D FDM and stereolithography techniques. 3D virtual reconstruction and SEM showed the precision with which the scaffolds were fabricated, and a good-quality interface between poly(ε-caprolactone) and poly(ethylene glycol) based scaffolds was observed for bilayer and coaxial scaffolds. Magnetised scaffolds are capable of absorbing water solution of MNPs, and a preliminary information on cell adhesion and spreading of hMSCs was obtained without the application of an external magnetic field.

[92] Dettin M., Zamuner A., Roso M., Gloria A., Iucci G., Messina G.M.L., D'Amora U., Marletta G., Modesti M., Castagliuolo I., Brun P., Electrospun scaffolds for osteoblast cells: Peptide-induced concentration-dependent improvements of polycaprolactone, PLoS ONE, 10(9), (2015). Abstract
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Abstract: The design of hybrid poly-e-caprolactone (PCL)-self-assembling peptides (SAPs) matrices represents a simple method for the surface functionalization of synthetic scaffolds, which is essential for cell compatibility. This study investigates the influence of increasing concentrations (2.5%, 5%, 10% and 15% w/w SAP compared to PCL) of three different SAPs on the physico-chemical/mechanical and biological properties of PCL fibers. We demonstrated that physico-chemical surface characteristics were slightly improved at increasing SAP concentrations: the fiber diameter increased; surface wettability increased with the first SAP addition (2.5%) and slightly less for the following ones; SAP-surface density increased but no change in the conformation was registered. These results could allow engineering matrices with structural characteristics and desired wettability according to the needs and the cell system used. The biological and mechanical characteristics of these scaffolds showed a particular trend at increasing SAP concentrations suggesting a prevailing correlation between cell behavior and mechanical features of the matrices. As compared with bare PCL, SAP enrichment increased the number of metabolic active h-osteoblast cells, fostered the expression of specific osteoblast-related mRNA transcripts, and guided calcium deposition, revealing the potential application of PCL-SAP scaffolds for the maintenance of osteoblast phenotype.

[93] Tsaryk R., Gloria A., Russo T., Anspach L., De Santis R., Ghanaati S., Unger R.E., Ambrosio L., Kirkpatrick C.J., Collagen-low molecular weight hyaluronic acid semi-interpenetrating network loaded with gelatin microspheres for cell and growth factor delivery for nucleus pulposus regeneration, Acta Biomaterialia, 20, 10-21, (2015). Abstract
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Abstract: Intervertebral disc (IVD) degeneration is one of the main causes of low back pain. Current surgical treatments are complex and generally do not fully restore spine mobility. Development of injectable extracellular matrix-based hydrogels offers an opportunity for minimally invasive treatment of IVD degeneration. Here we analyze a specific formulation of collagen-low molecular weight hyaluronic acid (LMW HA) semi-interpenetrating network (semi-IPN) loaded with gelatin microspheres as a potential material for tissue engineering of the inner part of the IVD, the nucleus pulposus (NP). The material displayed a gel-like behavior, it was easily injectable as demonstrated by suitable tests and did not induce cytotoxicity or inflammation. Importantly, it supported the growth and chondrogenic differentiation potential of mesenchymal stem cells (MSC) and nasal chondrocytes (NC) in vitro and in vivo. These properties of the hydrogel were successfully combined with TGF-β3 delivery by gelatin microspheres, which promoted the chondrogenic phenotype. Altogether, collagen-LMW HA loaded with gelatin microspheres represents a good candidate material for NP tissue engineering as it combines important rheological, functional and biological features.

Keywords: Chondrocyte | Collagen | Hydrogel | Intervertebral disc | Mesenchymal stem cell

[94] Russo L., Russo T., Battocchio C., Taraballi F., Gloria A., D'Amora U., De Santis R., Polzonetti G., Nicotra F., Ambrosio L., Cipolla L., Galactose grafting on poly(ε-caprolactone) substrates for tissue engineering: A preliminary study, Carbohydrate Research, 405, 39-46, (2015). Abstract
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Abstract: The grafting of galactose units onto poly(ε-caprolactone) (PCL) substrates by a wet chemistry two-step procedure is proposed. Even though a reduction of hardness from 0.58-0.31 GPa to 0.12-0.05 GPa is achieved, the chemical functionalization does not negatively affect the tensile modulus (332.2 ± 31.3 MPa and 328.5 ± 34.7 MPa for unmodified and surface-modified PCL, respectively) and strength (15.1 ± 1.3 MPa and 14.8 ± 1.5 MPa as assessed before and after the surface modification, respectively), as well as the mechanical behaviour evaluated through small punch test. XPS and enzyme-linked lectin assay (ELLA) demonstrate the presence, and also the correct exposition of the saccharidic epitope on PCL substrates. The introduction of carbohydrate moieties on the PCL surfaces clearly enhances the hydrophilicity of the substrate, as the water contact angle decreases from 82.1 ± 5.8° to 62.1 ± 4.2°. Furthermore, preliminary biological analysis shows human mesenchymal stem cell viability over time and an improvement of cell adhesion and spreading.

Keywords: Biological evaluation | Carbohydrates | Nanoindentation | Poly(ε-caprolactone) | Small punch test | Tensile properties

[95] De Santis R., Russo A., Gloria A., D'Amora U., Russo T., Panseri S., Sandri M., Tampieri A., Marcacci M., Dediu V.A., Wilde C.J., Ambrosio L., Towards the design of 3D fiber-deposited poly(ε-caprolactone)/iron-doped hydroxyapatite nanocomposite magnetic scaffolds for bone regeneration, Journal of Biomedical Nanotechnology, 11(7), 1236-1246, (2015). Abstract
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Abstract: In the past few years, researchers have focused on the design and development of three-dimensional (3D) advanced scaffolds, which offer significant advantages in terms of cell performance. The introduction of magnetic features into scaffold technology could offer innovative opportunities to control cell populations within 3D microenvironments, with the potential to enhance their use in tissue regeneration or in cell-based analysis. In the present study, 3D fully biodegradable and magnetic nanocomposite scaffolds for bone tissue engineering, consisting of a poly(ε-caprolactone) (PCL) matrix reinforced with iron-doped hydroxyapatite (FeHA) nanoparticles, were designed and manufactured using a rapid prototyping technique. The performances of these novel 3D PCL/FeHA scaffolds were assessed through a combination of theoretical evaluation, experimental in vitro analyses and in vivo testing in a rabbit animal model. The results from mechanical compression tests were consistent with FEM simulations. The in vitro results showed that the cell growth in the magnetized scaffolds was 2.2-fold greater than that in non-magnetized ones. In vivo experiments further suggested that, after only 4 weeks, the PCL/FeHA scaffolds were completely filled with newly formed bone, proving a good level of histocompatibility. All of the results suggest that the introduction of magnetic features into biocompatible materials may confer significant advantages in terms of 3D cell assembly.

Keywords: Bone tissue engineering | Experimental/theoretical analysis | Nanocomposite | Rapid prototyping | Scaffold

[96] De Santis R., Gloria A., Russo T., D'Amora U., Varriale A., Veltri M., Balleri P., Mollica F., Riccitiello F., Ambrosio L., Reverse engineering of mandible and prosthetic framework: Effect of titanium implants in conjunction with titanium milled full arch bridge prostheses on the biomechanics of the mandible, Journal of Biomechanics, 47(16), 3825-3829, (2014). Abstract
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Abstract: This study aimed at investigating the effects of titanium implants and different configurations of full-arch prostheses on the biomechanics of edentulous mandibles. Reverse engineered, composite, anisotropic, edentulous mandibles made of a poly(methylmethacrylate) core and a glass fibre reinforced outer shell were rapid prototyped and instrumented with strain gauges. Brånemark implants RP platforms in conjunction with titanium Procera one-piece or two-piece bridges were used to simulate oral rehabilitations. A lateral load through the gonion regions was used to test the biomechanical effects of the rehabilitations. In addition, strains due to misfit of the one-piece titanium bridge were compared to those produced by one-piece cast gold bridges. Milled titanium bridges had a better fit than cast gold bridges. The stress distribution in mandibular bone rehabilitated with a one-piece bridge was more perturbed than that observed with a two-piece bridge. In particular the former induced a stress concentration and stress shielding in the molar and symphysis regions, while for the latter design these stresses were strongly reduced. In conclusion, prosthetic frameworks changed the biomechanics of the mandible as a result of both their design and manufacturing technology.

Keywords: Composite | Dental implants | Mandible | Stress concentration | Stress shielding

[97] Ruan G.L., Velasco J.I., Vallés C., Li Z.M., Gloria A., Lin W.Z., Liu F., Review: Frontiers of materials science and engineering, Materials Research Innovations, 18, S21-S24, (2014). Abstract
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Abstract: Materials science and engineering is one of the hot research topics in the world, which is changing the way we live daily. As a result of this, the 2nd Global Conference on Materials Science and Engineering was held on November 20-22, 2013. During this event, more than 200 attendees discussed the frontiers of materials science and engineering. This editorial highlights some of these papers that present the new frontiers of materials science research in 2013.

[98] Patrício T., Domingos M., Gloria A., D'Amora U., Coelho J.F., Bártolo P.J., Fabrication and characterisation of PCL and PCL/PLA scaffolds for tissue engineering, Rapid Prototyping Journal, 20(2), 145-156, (2014). Abstract
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Abstract: Purpose: The main purpose of this research work is to study the effect of poly lactic acid (PLA) addition into poly (e-caprolactone) (PCL) matrices, as well the influence of the mixing process on the morphological, thermal, chemical, mechanical and biological performance of the 3D constructs produced with a novel biomanufacturing device (BioCell Printing). Design/methodology/ approach: Two mixing processes are used to prepare PCL/PLA blends, namely melt blending and solvent casting. PCL and PCL/PLA scaffolds are produced via BioCell Printing using a 300-mm nozzle, 0/908 lay down pattern and 350-μm pore size. Several techniques such as scanning electron microscopy (SEM), simultaneous thermal analyzer (STA), nuclear magnetic resonance (NMR), static compression analysis and Alamar BlueTM are used to evaluate scaffold's morphological, thermal, chemical, mechanical and biological properties. Findings: Results show that the addition of PLA to PCL scaffolds strongly improves the biomechanical performance of the constructs. Additionally, polymer blends obtained by solvent casting present better mechanical and biological properties, compared to blends prepared by melt blending. Originality/value: This paper undertakes a detailed study on the effect of the mixing process on the biomechanical properties of PCL/PLA scaffolds. Results will enable to prepare customized PCL/PLA scaffolds for tissue engineering applications with improved biological and mechanical properties, compared to PCL scaffolds alone. Additionally, the accuracy and reproducibility of by the BioCell Printing enables to modulate the micro/macro architecture of the scaffolds enhancing tissue regeneration. © Emerald Group Publishing Limited.

Keywords: Biological analysis and testing | Fused deposition modelling | Polymers | Scaffolds

[99] Rongo R., Ametrano G., Gloria A., Spagnuolo G., Galeotti A., Paduano S., Valletta R., D'Antò V., Effects of intraoral aging on surface properties of coated nickel-titanium archwires, Angle Orthodontist, 84(4), 665-672, (2014). Abstract
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Abstract: Objective: To evaluate the effects of intraoral aging on surface properties of esthetic and conventional nickel-titanium (NiTi) archwires. Materials and Methods: Five NiTi wires were considered for this study (Sentalloy, Sentalloy High Aesthetic, Superelastic Titanium Memory Wire, Esthetic Superelastic Titanium Memory Wire, and EverWhite). For each type of wire, four samples were analyzed as received and after 1month of clinical use by an atomic force microscope (AFM) and a scanning electronic microscope (SEM). To evaluate sliding resistance, two stainless steel plates with three metallic or three monocrystalline brackets, bonded in passive configuration, were manufactured; four as-received and retrieved samples for every wire were pulled five times at 5 mm/min for 1 minute by means of an Instron 5566, recording the greatest friction value (N). Data were analyzed by one-way analysis of variance and by Student's t-test. Results: After clinical use, surface roughness increased considerably. The SEM images showed homogeneity for the as-received control wires; however, after clinical use esthetic wires exhibited a heterogeneous surface with craters and bumps. The lowest levels of friction were observed with the as-received Superelastic Titanium Memory Wire on metallic brackets. When tested on ceramic brackets, all the wires exhibited an increase in friction (t-test; P , .05). Furthermore, all the wires, except Sentalloy, showed a statistically significant increase in friction between the as-received and retrieved groups (t-test; P , .05). Conclusion: Clinical use of the orthodontic wires increases their surface roughness and the level of friction. (Angle Orthod. 2014;84:665-672.) © 2014 by The EH Angle Education and Research Foundation, Inc.

Keywords: Atomic force microscopy | Orthodontic archwire | Retrieved analysis | Surface roughness | Surface treatment

[100] Tu M.Y., Velasco J.I., Valles C., Gloria A., Lin W.Z., Li Z.M., Ruan G.L., Liu F., Review: Progress in the studies on mechanical properties of materials, Strength of Materials, 46(2), 160-163, (2014). Abstract
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Abstract: Materials science and engineering is one of the hot research topics in the world, among which mechanical properties of materials play a critical role in application of the new materials. Based on this, a special session Mechanical Properties of Materials was held within the 2nd Global Conference on Materials Science and Engineering, Nov. 20-22, 2013. This special issue contains a selection of twenty scientific papers, which are focused on the structure, mechanical properties, and strength of materials. In this review, the selected papers from the special session are summarized. © 2014 Springer Science+Business Media New York.

[101] Domingos M., Intranuovo F., Russo T., Santis R.D., Gloria A., Ambrosio L., Ciurana J., Bartolo P., The first systematic analysis of 3D rapid prototyped poly(ε- caprolactone) scaffolds manufactured through BioCell printing: The effect of pore size and geometry on compressive mechanical behaviour and in vitro hMSC viability, Biofabrication, 5(4), (2013). Abstract
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Abstract: Novel additive manufacturing processes are increasingly recognized as ideal techniques to produce 3D biodegradable structures with optimal pore size and spatial distribution, providing an adequate mechanical support for tissue regeneration while shaping in-growing tissues. With regard to the mechanical and biological performances of 3D scaffolds, pore size and geometry play a crucial role. In this study, a novel integrated automated system for the production and in vitro culture of 3D constructs, known as BioCell Printing, was used only to manufacture poly(ε-caprolactone) scaffolds for tissue engineering; the influence of pore size and shape on their mechanical and biological performances was investigated. Imposing a single lay-down pattern of 0°/90° and varying the filament distance, it was possible to produce scaffolds with square interconnected pores with channel sizes falling in the range of 245-433 μm, porosity 49-57% and a constant road width. Three different lay-down patterns were also adopted (0°/90°, 0°/60/120° and 0°/45°/ 90°/135°), thus resulting in scaffolds with quadrangular, triangular and complex internal geometries, respectively. Mechanical compression tests revealed a decrease of scaffold stiffness with the increasing porosity and number of deposition angles (from 0°/90° to 0°/45°/90°/ 135°). Results from biological analysis, carried out using human mesenchymal stem cells, suggest a strong influence of pore size and geometry on cell viability. On the other hand, after 21 days of in vitro static culture, it was not possible to detect any significant variation in terms of cell morphology promoted by scaffold topology. As a first systematic analysis, the obtained results clearly demonstrate the potential of the BioCell Printing process to produce 3D scaffolds with reproducible well organized architectures and tailored mechanical properties. © 2013 IOP Publishing Ltd.

[102] Silva-Correia J., Gloria A., Oliveira M.B., Mano J.F., Oliveira J.M., Ambrosio L., Reis R.L., Rheological and mechanical properties of acellular and cell-laden methacrylated gellan gum hydrogels, Journal of Biomedical Materials Research - Part A, 101(12), 3438-3446, (2013). Abstract
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Abstract: Tissue engineered hydrogels hold great potential as nucleus pulposus substitutes (NP), as they promote intervertebral disc (IVD) regeneration and re-establish its original function. But, the key to their success in future clinical applications greatly depends on its ability to replicate the native 3D micro-environment and circumvent their limitation in terms of mechanical performance. In the present study, we investigated the rheological/mechanical properties of both ionic- (iGG-MA) and photo-crosslinked methacrylated gellan gum (phGG-MA) hydrogels. Steady shear analysis, injectability and confined compression stress-relaxation tests were carried out. The injectability of the reactive solutions employed for the preparation of iGG-MA and phGG-MA hydrogels was first studied, then the zero-strain compressive modulus and permeability of the acellular hydrogels were evaluated. In addition, human intervertebral disc (hIVD) cells encapsulated in both iGG-MA and phGG-MA hydrogels were cultured in vitro, and its mechanical properties also investigated under dynamic mechanical analysis at 37°C and pH 7.4. After 21 days of culturing, hIVD cells were alive (Calcein AM) and the E′ of ionic-crosslinked hydrogels and photo-crosslinked was higher than that observed for acellular hydrogels. Our study suggests that methacrylated gellan gum hydrogels present promising mechanical and biological performance as hIVD cells were producing extracellular matrix. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3438-3446, 2013. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Keywords: hydrogels | injectability | mechanical properties | methacrylated gellan gum | rheology

[103] Gomez E., Dias J., D'Amora U., Rodríguez C.A., Gloria A., Bártolo P., Morphological and mechanical evaluation of hybrid scaffolds for bone regeneration, Advanced Materials Research, 749, 429-432, (2013). Abstract
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Abstract: Ideal scaffolds for tissue engineering should mimic the complex characteristics of natural tissues and their mechanical performance. This work presents a new concept of hybrid scaffolds produced through the combination of electrospinning and an additive bioextruder system. The obtained results have shown that the hybrid structures present improved mechanical properties. © (2013) Trans Tech Publications, Switzerland.

Keywords: Bioextrusion | Electrospinning | Hybrid scaffolds | Polycaprolactone | Tissue engineering

[104] De Santis R., Gloria A., Russo T., D'Amora U., D'Antò V., Bollino F., Catauro M., Mollica F., Rengo S., Ambrosio L., Advanced composites for hard-tissue engineering based on PCL/organic-inorganic hybrid fillers: From the design of 2D substrates to 3D rapid prototyped scaffolds, Polymer Composites, 34(9), 1413-1417, (2013). Abstract
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Abstract: The bioactivity of sol-gel synthesized poly(ε-caprolactone) (PCL)/TiO2 or poly(ε-caprolactone)/ZrO2 particles was already known. In designing innovative 2D composite substrates for hard-tissue engineering, the possibility to embed PCL/TiO2 or PCL/ZrO2 hybrid fillers into a PCL matrix was previously proposed. In the present study, the potential of 3D fiber-deposition technique to design morphologically controlled scaffolds consisting of PCL reinforced with PCL/TiO2 or PCL/ZrO2 hybrid fillers was demonstrated. Finite element analysis was initially carried out on 2D substrates to find a correlation between the previously obtained results from the small punch test and the Young's modulus of the materials, whilst mechanical and biological tests were suitably performed on rapid prototyped scaffolds to assess the effects of the inclusion of the hybrid fillers on the performances of the 3D porous structures. The role of the inclusion of the hybrid fillers in improving the compressive modulus (about 90 MPa) and the cell viability/proliferation was demonstrated. © 2013 Society of Plastics Engineers.

[105] Patrício T., Glória A., Bártolo P., PCL and PCL/PLA scaffolds for bone tissue regeneration, Advanced Materials Research, 683, 168-171, (2013). Abstract
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Abstract: This paper investigates the use of PCL and PCL/PLA scaffolds, produced using a novel additive biomanufacturing system called BioCell Printing, for bone tissue engineering applications. Results show that the BioCell Printing system produces scaffolds with regular and reproducible architecture, presenting no toxicity and enhancing cell attachment and proliferation. It was also possible to observe that the addition of PLA to PCL scaffolds strongly improves the biomechanical performance of the constructs. © (2013) Trans Tech Publications, Switzerland.

Keywords: Additive biomanufacturing | Bone tissue regeneration | Cells | Polymers | Scaffolds

[106] Dias J., Gloria A., Bártolo P., Mechanical and biological characteristics of electrospun PCL meshes - The influence of solvent type and concentration, Advanced Materials Research, 683, 137-140, (2013). Abstract
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Abstract: Non-woven scaffolds, with fiber dimensions at a nanometer scale, can mimic the physical structure of natural extracellular matrices, being ideal construts for Tissue Engineering applications. This research work explores solution electrospinning to produce nanoscale meshes. Different Poly (ε-caprolactone) (PCL) solutions were considered and the influence of both polymer concentration and type of solvent studied regarding the fabrication of polymeric meshes and their mechanical and biological properties. PCL solutions were prepared using two different solvents: glacial acetic acid with triethylamine (AA/TEA)) and Acetone (DMK) at different concentrations. PCL/AA/TEA meshes present better mechanical properties and good cell viability and proliferation. © (2013) Trans Tech Publications, Switzerland.

Keywords: Electrospinning | Nanofibers | Polycaprolacone | Tissue engineering

[107] Russo L., Gloria A., Russo T., D'Amora U., Taraballi F., De Santis R., Ambrosio L., Nicotra F., Cipolla L., Glucosamine grafting on poly(ε-caprolactone): A novel glycated polyester as a substrate for tissue engineering, RSC Advances, 3(18), 6286-6289, (2013). Abstract
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Abstract: Poly(ε-caprolactone), PCL, has been functionalized with a biologically relevant monosaccharide, i.e. glucosamine, in a single step process after material fabrication. Glucosamine-functionalised PCL showed enhanced cell density and spreading over the non-functionalised samples. © 2013 The Royal Society of Chemistry.

[108] Esposito A.R., Moda M., Cattani S.M.D.M., De Santana G.M., Barbieri J.A., Munhoz M.M., Cardoso T.P., Barbo M.L.P., Russo T., D'Amora U., Gloria A., Ambrosio L., Duek E.A.D.R., PLDLA/PCL-T scaffold for meniscus tissue engineering, BioResearch Open Access, 2(2), 138-147, (2013). Abstract
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Abstract: The inability of the avascular region of the meniscus to regenerate has led to the use of tissue engineering to treat meniscal injuries. The aim of this study was to evaluate the ability of fibrochondrocytes preseeded on PLDLA/PCL-T [poly(L-co-D,L-lactic acid)/poly(caprolactone-triol)] scaffolds to stimulate regeneration of the whole meniscus. Porous PLDLA/PCL-T (90/10) scaffolds were obtained by solvent casting and particulate leaching. Compressive modulus of 9.5±1.0 MPa and maximum stress of 4.7±0.9 MPa were evaluated. Fibrochondrocytes from rabbit menisci were isolated, seeded directly on the scaffolds, and cultured for 21 days. New Zealand rabbits underwent total meniscectomy, after which implants consisting of cell-free scaffolds or cell-seeded scaffolds were introduced into the medial knee meniscus; the negative control group consisted of rabbits that received no implant. Macroscopic and histological evaluations of the neomeniscus were performed 12 and 24 weeks after implantation. The polymer scaffold implants adapted well to surrounding tissues, without apparent rejection, infection, or chronic inflammatory response. Fibrocartilaginous tissue with mature collagen fibers was observed predominantly in implants with seeded scaffolds compared to cell-free implants after 24 weeks. Similar results were not observed in the control group. Articular cartilage was preserved in the polymeric implants and showed higher chondrocyte cell number than the control group. These findings show that the PLDLA/PCL-T 90/10 scaffold has potential for orthopedic applications since this material allowed the formation of fibrocartilaginous tissue, a structure of crucial importance for repairing injuries to joints, including replacement of the meniscus and the protection of articular cartilage from degeneration. © 2013, Mary Ann Liebert, Inc. 2013.

Keywords: fibrochondrocyte culture | meniscus regeneration | PLDLA/PCL-T scaffold

[109] Gloria A., Russo T., D'amora U., Zeppetelli S., D'Alessandro T., Sandri M., Bañobre-López M., Piñeiro-Redondo Y., Uhlarz M., Tampieri A., Rivas J., Herrmannsdörfer T., Dediu V.A., Ambrosio L., De Santis R., Magnetic poly(1-caprolactone)/irondoped hydroxyapatite nanocomposite substrates for advanced bone tissue engineering, Journal of the Royal Society Interface, 10(80), (2013). Abstract
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Abstract: In biomedicine, magnetic nanoparticles provide some attractive possibilities because they possess peculiar physical properties that permit their use in a wide range of applications. The concept of magnetic guidance basically spans from drug delivery and hyperthermia treatment of tumours, to tissue engineering, such as magneto-mechanical stimulation/activation of cell constructs and mechanosensitive ion channels, magnetic cell-seeding procedures, and controlled cell proliferation and differentiation. Accordingly, the aim of this study was to develop fully biodegradable and magnetic nanocomposite substrates for bone tissue engineering by embedding irondoped hydroxyapatite (FeHA) nanoparticles in a poly(1-caprolactone) (PCL) matrix. X-ray diffraction analyses enabled the demonstration that the phase composition and crystallinity of the magnetic FeHA were not affected by the process used to develop the nanocomposite substrates. The mechanical characterization performed through small punch tests has evidenced that inclusion of 10 per cent by weight of FeHA would represent an effective reinforcement. The inclusion of nanoparticles also improves the hydrophilicity of the substrates as evidenced by the lower values of water contact angle in comparison with those of neat PCL. The results from magnetic measurements confirmed the superparamagnetic character of the nanocomposite substrates, indicated by a very low coercive field, a saturation magnetization strictly proportional to the FeHA content and a strong history dependence in temperature sweeps. Regarding the biological performances, confocal laser scanning microscopy and AlamarBlue assay have provided qualitative and quantitative information on human mesenchymal stem cell adhesion and viability/proliferation, respectively, whereas the obtained ALP/DNA values have shown the ability of the nanocomposite substrates to support osteogenic differentiation. © 2013 The Authors.

Keywords: Bone tissue regeneration | Magnetic hydroxyapatite | Nanocomposite | Poly(ε-caprolactone) | Scaffold

[110] Guarino V., Gloria A., de Santis R., Ambrosio L., Manufacturing multifunctional scaffolds for tissue engineering, Polymeric Biomaterials: Medicinal and Pharmaceutical Applications, Volume 2, 507-532, (2013). Abstract
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Abstract: The basic principle of tissue engineering entails the guided application and the control of cells, materials, and the microenvironment into which they are delivered [1]. In a tissue engineering process, tissues or organs may be created in vivo, in vitro, or ex vivo and implanted into the patient [2]. In this direction, the selection of three elements rstly concurs to satisfy the basic tissue engineering principles on fabricating biological tissues: (i) viable, responsive cells; (ii) a scaffold to support tissue formation; and (iii) a growth-inducing stimulus.

[111] Albani D., Gloria A., Giordano C., Rodilossi S., Russo T., D'Amora U., Tunesi M., Cigada A., Ambrosio L., Forloni G., Hydrogel-based nanocomposites and mesenchymal stem cells: A promising synergistic strategy for neurodegenerative disorders therapy, The Scientific World Journal, 2013, (2013). Abstract
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Abstract: Hydrogel-based materials are widely employed in the biomedical field. With regard to central nervous system (CNS) neurodegenerative disorders, the design of injectable nanocomposite hydrogels for in situ drug or cell release represents an interesting and minimally invasive solution that might play a key role in the development of successful treatments. In particular, biocompatible and biodegradable hydrogels can be designed as specific injectable tools and loaded with nanoparticles (NPs), to improve and to tailor their viscoelastic properties upon injection and release profile. An intriguing application is hydrogel loading with mesenchymal stem cells (MSCs) that are a very promising therapeutic tool for neurodegenerative or traumatic disorders of the CNS. This multidisciplinary review will focus on the basic concepts to design acellular and cell-loaded materials with specific and tunable rheological and functional properties. The use of hydrogel-based nanocomposites and mesenchymal stem cells as a synergistic strategy for nervous tissue applications will be then discussed. © 2013 Diego Albani et al.

[112] Russo T., D'Amora U., Gloria A., Tunesi M., Sandri M., Rodilossi S., Albani D., Forloni G., Giordano C., Cigada A., Tampieri A., De Santis R., Ambrosio L., Systematic analysis of injectable materials and 3D rapid prototyped magnetic scaffolds: From CNS applications to soft and hard tissue repair/regeneration, Procedia Engineering, 59, 233-239, (2013). Abstract
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Abstract: Over the past years, polymer-based materials have attracted research interest in the field of tissue repair and regeneration. As reported in literature, different injectable systems have been proposed, trying to reduce surgical invasiveness. In a first step of the current research, the rheological and functional features of injecatble hydrogel-based materials for central nervous system applications or soft tissue regeneration (collagen/PEG semi-IPNs) as well as for hard tissue engineering (alginate/iron-doped hydroxyapatite) were evaluated. Then, the study was also devoted to the development of 3D nanocomposite poly(s-caprolactone)/iron-doped hydroxyapatite scaffolds for bone tissue engineering, providing a preliminary approach to assess magnetic attraction forces. © 2013 The Authors.

Keywords: Injectable Materials | Magnetic Scaffolds | Nanocomposites | Rapid Prototyping | Rheology

[113] Tunesi M., Batelli S., Rodilossi S., Russo T., Grimaldi A., Forloni G., Ambrosio L., Cigada A., Gloria A., Albani D., Giordano C., Development and analysis of semi-interpenetrating polymer networks for brain injection in neurodegenerative disorders, International Journal of Artificial Organs, 36(11), 762-774, (2013). Abstract
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Abstract: Purpose: Our aim was to assess the use of injectable, biocompatible and resorbable, hydrogel-based tools for innovative therapies against brain-related neurodegenerative disorders like Alzheimer's (AD) and Parkinson's (PD) diseases. Methods: Two compositions of semi-interpenetrating polymer networks (semi-IPNs) based on collagen and poly(ethylene glycol) (PEG) were investigated. We examined their viscoelastic properties, flow behavior, functional injectability, as well as in vitro biocompatibility with SH-SY5Y human neuroblastoma cells and murine primary neurons. We also evaluated the in vivo biological performance after subcutaneous and brain injection in mice. Results: The selected semi-IPNs showed a gel-like behavior and were injectable through a 30 G needle, with the maximum load ranging from 3.0 to 3.9 N. In vitro results showed that immortalized cells kept their proliferative potential and neurons maintained their viability after embedding in both materials, with better performances for the gel with the higher collagen content. For both semi-IPNs, after subcutaneous injection, the inflammatory response was negligible; after brain injection, the tissue did not show any signs of damage or degeneration. Conclusions: The results suggest that the selected semi-IPNs not only represent a proper environment for cells, but also, once injected in vivo, do not induce damage/inflammation in the surrounding brain tissue. These findings represent a crucial starting point for the development of minimally invasive and injectable hydrogel-based tools for innovative drug/cell-based therapeutic strategies against AD, PD, or other severe brain-related neurodegenerative pathologies. © 2013 Wichtig Editore.

Keywords: Brain | Hydrogels | Neurodegenerative diseases | Semi-interpenetrating polymer networks

[114] Patrício T., Domingos M., Gloria A., Bártolo P., Characterisation of PCL and PCL/PLA scaffolds for tissue engineering, Procedia CIRP, 5, 110-114, (2013). Abstract
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Abstract: This paper investigates the use of PCL and PCL/PLA scaffolds produced using a novel additive biomanufacturing system called BioCell Printing. PCL/PLA blends were prepared using melt blend and solvent casting techniques. Scaffolds with 0/90° architecture and 350 μm of pore size were morphologically evaluated using scanning electron microscopy and atomic force microscopy. Biological tests, using osteosarcoma cell line G-63, were performed using the Alamar Blue Assay and Alkaline Phosphatase Activity. Results show that the BioCell Printing system produces scaffolds with regular and reproducible architecture, presenting no toxicity and enhancing cell attachment and proliferation. It was also possible to observe that the addition of PLA to PCL scaffolds strongly improves the biomechanical performance of the constructs. © 2013 The Authors.

Keywords: Biomanufacturing | Polymer blends | Scaffolds | Tissue Engineering

[115] Patrício T., Glória A., Bártolo P., Mechanical and biological behaviour of PCL and PCL/PLA scaffolds for tissue engineering applications, Chemical Engineering Transactions, 32, 1645-1650, (2013). Abstract
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Abstract: A new biomanufacturing system allowing to produce three-dimensional matrices (scaffolds) with well defined internal geometries, uniform pore distribution and good adhesion among different adjacent layers. Polymers selected are Poly ε-caprolactone (PCL) and Poly Lactic Acid (PLA), both these polymers are used in medical applications. These two polymers are interesting biomaterials because they are complementary on their physical properties and biodegradability. This work aims to assess the temperature evaluation during the extrusion process and the influences of the temperatures on the PCL and PCL/PLA scaffolds with lay down pattern 90° and pore size 350μm. The results demonstrated that extrusion process not modified the thermal properties of the scaffolds and these structures are able to sustain MG-63cells. Copyright © 2013, AIDIC Servizi S.r.l.

[116] Domingos M., Intranuovo F., Gloria A., Gristina R., Ambrosio L., Bártolo P.J., Favia P., Improved osteoblast cell affinity on plasma-modified 3-D extruded PCL scaffolds, Acta Biomaterialia, 9(4), 5997-6005, (2013). Abstract
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Abstract: Cellular adhesion and proliferation inside three-dimensional synthetic scaffolds represent a major challenge in tissue engineering. Besides the surface chemistry of the polymers, it is well recognized that scaffold internal architecture, namely pore size/shape and interconnectivity, has a strong effect on the biological response of cells. This study reports for the first time how polycaprolactone (PCL) scaffolds with controlled micro-architecture can be effectively produced via bioextrusion and used to enhance the penetration of plasma deposited species. Low-pressure nitrogen-based coatings were employed to augment cell adhesion and proliferation without altering the mechanical properties of the structures. X-ray photoelectron spectroscopy carried out on different sections of the scaffolds indicates a uniform distribution of nitrogen-containing groups throughout the entire porous structure. In vitro biological assays confirm that plasma deposition sensitively promotes the activity of Saos-2 osteoblast cells, leading to a homogeneous colonization of the PCL scaffolds. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Keywords: Biofabrication | Osteoblast cells | Scaffolds | Surface modification | Tissue engineering

[117] Guarino V., Gloria A., Raucci M.G., Ambrosio L., Hydrogel-based platforms for the regeneration of osteochondral tissue and intervertebral disc, Polymers, 4(3), 1590-1612, (2012). Abstract
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Abstract: Hydrogels currently represent a powerful solution to promote the regeneration of soft and hard tissues. Primarily, they assure efficient bio-molecular interactions with cells, also regulating their basic functions, guiding the spatially and temporally complex multi-cellular processes of tissue formation, and ultimately facilitating the restoration of structure and function of damaged or dysfunctional tissues. In order to overcome basic drawbacks of traditional synthesized hydrogels, many recent strategies have been implemented to realize multi-component hydrogels based on natural and/or synthetic materials with tailored chemistries and different degradation kinetics. Here, a critical review of main strategies has been proposed based on the use of hydrogels-based devices for the regeneration of complex tissues, i.e., osteo-chondral tissues and intervertebral disc. © 2012 by the authors.

Keywords: Disc nucleus | Hydrogels | Osteochondral tissue | Scaffolds | Tissue regeneration

[118] Puppi D., Mota C., Gazzarri M., Dinucci D., Gloria A., Myrzabekova M., Ambrosio L., Chiellini F., Additive manufacturing of wet-spun polymeric scaffolds for bone tissue engineering, Biomedical Microdevices, 14(6), 1115-1127, (2012). Abstract
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Abstract: An Additive Manufacturing technique for the fabrication of three-dimensional polymeric scaffolds, based on wet-spinning of poly(ε-caprolactone) (PCL) or PCL/hydroxyapatite (HA) solutions, was developed. The processing conditions to fabricate scaffolds with a layer-by-layer approach were optimized by studying their influence on fibres morphology and alignment. Two different scaffold architectures were designed and fabricated by tuning inter-fibre distance and fibres staggering. The developed scaffolds showed good reproducibility of the internal architecture characterized by highly porous, aligned fibres with an average diameter in the range 200-250 μm. Mechanical characterization showed that the architecture and HA loading influenced the scaffold compressive modulus and strength. Cell culture experiments employing MC3T3-E1 preosteoblast cell line showed good cell adhesion, proliferation, alkaline phosphatase activity and bone mineralization on the developed scaffolds. © 2012 Springer Science+Business Media, LLC.

Keywords: Additive manufacturing | Polycaprolactone | Scaffolds | Tissue engineering | Wet-spinning

[119] Santis R.D., Gloria A., Russo T., D'Amora U., D'Antò V., Bollino F., Catauro M., Mollica F., Rengo S., Ambrosio L., PCL loaded with sol-gel synthesized organic-inorganic hybrid fillers: From the analysis of 2D substrates to the design of 3D rapid prototyped composite scaffolds for tissue engineering, AIP Conference Proceedings, 1459(1), 26-29, (2012). Abstract
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Abstract: As reported in the literature, scaffolds for soft and hard tissue regeneration should satisfy several requirements. In the present work, the potential of 3D fiber deposition technique to design morphologically controlled scaffolds consisting of poly(ε-caprolactone) reinforced with sol-gel synthesized organic-inorganic hybrid fillers was demonstrated, also benefiting from a basic study carried out on 2D composite substrates. Finite element analysis, biological and mechanical tests were properly performed to assess the effects of the inclusion of the hybrid fillers on the performances of 2D substrates and 3D structures. © 2012 American Institute of Physics.

Keywords: Alamar Blue™ assay | Composite scaffolds | Finite element analysis | Mechanical properties | Organic-inorganic hybrid | Poly(e-caprolactone) | Tissue engineering

[120] Gloria A., Causa F., Russo T., Battista E., Della Moglie R., Zeppetelli S., De Santis R., Netti P.A., Ambrosio L., Three-dimensional poly(ε-caprolactone) bioactive scaffolds with controlled structural and surface properties, Biomacromolecules, 13(11), 3510-3521, (2012). Abstract
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Abstract: The requirement of a multifunctional scaffold for tissue engineering capable to offer at the same time tunable structural properties and bioactive interface is still unpaired. Here we present three-dimensional (3D) biodegradable polymeric (PCL) scaffolds with controlled morphology, macro-, micro-, and nano-mechanical performances endowed with bioactive moieties (RGD peptides) at the surface. Such result was obtained by a combination of rapid prototyping (e.g., 3D fiber deposition) and surface treatment approach (aminolysis followed by peptide coupling). By properly designing process conditions, a control over the mechanical and biological performances of the structure was achieved with a capability to tune the value of compressive modulus (in the range of 60-90 MPa, depending on the specific lay-down pattern). The macromechanical behavior of the proposed scaffolds was not affected by surface treatment preserving bulk properties, while a reduction of hardness from 0.50-0.27 GPa to 0.1-0.03 GPa was obtained. The penetration depth of the chemical treatment was determined by nanoindentation measurements and confocal microscopy. The efficacy of both functionalization and the following bioactivation was monitored by analytically quantifying functional groups and/or peptides at the interface. NIH3T3 fibroblast adhesion studies evidenced that cell attachment was improved, suggesting a correct presentation of the peptide. Accordingly, the present work mainly focuses on the effect of the surface modification on the mechanical and functional performances of the scaffolds, also showing a morphological and analytical approach to study the functionalization/bioactivation treatment, the distribution of immobilized ligands, and the biological features. © 2012 American Chemical Society.

[121] Reitmaier S., Wolfram U., Ignatius A., Wilke H.J., Gloria A., Martín-Martínez J.M., Silva-Correia J., Miguel Oliveira J., Luís Reis R., Schmidt H., Hydrogels for nucleus replacement-Facing the biomechanical challenge, Journal of the Mechanical Behavior of Biomedical Materials, 14, 67-77, (2012). Abstract
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Abstract: Hydrogels are considered promising for disc regeneration strategies. However, it is currently unknown whether the destruction of the natural interface between nucleus and surrounding structures caused by nucleotomy and an inadequate annulus closure diminishes the mechanical competence of the disc. This in vitro study aimed to clarify these mechanisms and to evaluate whether hydrogels are able to restore the biomechanical behaviour of the disc.Nucleus pressure in an ovine intervertebral disc was measured in vivo during day and night and adapted to an in vitro axial compressive diurnal (15min) and night (30min) load. Effects of different defects on disc height and nucleus pressure were subsequently measured in vitro using 30 ovine motion segments. Following cases were considered: intact; annulus incision repaired by suture and glue; annulus incision with removal and re-implantation of nucleus tissue; and two different hydrogels repaired by suture and glue.The intradiscal pressure in vivo was 0.75. MPa during day and 0.5. MPa during night corresponding to an in vitro axial compressive force of 130 and 58. N, respectively. The compression test showed that neither the implantation of hydrogels nor the re-implantation of the natural nucleus, assumed as being the ideal implant, was able to restore the mechanical functionality of an intact disc.Results indicate the importance of the natural anchorage of the nucleus with its surrounding structures and the relevance of an appropriate annulus closure. Therefore, hydrogels that are able to mimic the mechanical behaviour of the native nucleus may fail in restoring the mechanical behaviour of the disc. © 2012 Elsevier Ltd.

Keywords: Compression test | Disc regeneration | Hydrogels | In vitro | In vivo | Intervertebral disc | Nucleus replacement

[122] Guarino V., Gloria A., Raucci M.G., De Santis R., Ambrosio L., Bio-inspired composite and cell instructive platforms for bone regeneration, International Materials Reviews, 57(5), 256-275, (2012). Abstract
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Abstract: Biological studies indicate that numerous materials present in living tissues owe their success to an optimal combination of properties and adaptive structures, rather than to extreme properties per se. Through studying natural tissues and by biomimesis, new polymer and composite materials may be designed to emulate the structural and functional responses of bone. These materials must ensure biochemical affinity with host tissue through judicious mixing of specific chemical cues. Also, they must mimic the response under load exhibited by natural bone through complex organisation of material phases, i.e. embedding of collagen fibres in the extracellular substance. Fibre and particulate reinforced polymers are increasingly significant in the development of new biomedical materials, since they can be engineered more accurately than monolithic structures. Meanwhile, design of nanocomposites with specific morphological and chemical signals is emerging as a powerful approach to the mimesis of extracellular matrix of natural bone. In both cases, the manipulation of the main materials features at the micro- and nano-metric scale offers an intriguing strategy for improvement of biological and mechanical response. Several biodegradable and bioresorbable materials, as well as technologies and scaffold designs, will be critically reviewed, illustrating the potential of bio-inspired composites and multicomponent platforms for bone tissue engineering. © 2012 Institute of Materials, Minerals and Mining and ASM International Published by Maney for the Institute and ASM International.

Keywords: Biocompatibility | Biomedical materials | Biomimesis | Bone regeneration | Electrospun fibres | Hierarchical structures | Polymer composites | Polymer processing | Review | Tissue scaffolds

[123] Reitmaier S., Shirazi-Adl A., Bashkuev M., Wilke H.J., Gloria A., Schmidt H., In vitro and in silico investigations of disc nucleus replacement, Journal of the Royal Society Interface, 9(73), 1869-1879, (2012). Abstract
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Abstract: Currently, numerous hydrogels are under examination as potential nucleus replacements. The clinical success, however, depends on how well the mechanical function of the host structure is restored. This study aimed to evaluate the extent to and mechanisms by which surgery for nucleus replacements influence the mechanical behaviour of the disc. The effects of an annulus defect with and without nucleus replacement on disc height and nucleus pressure were measured using 24 ovine motion segments. The following cases were considered: intact; annulus incision repaired by suture and glue; annulus incision with removal and re-implantation of nucleus tissue repaired by suture and glue or plug. To identify the likely mechanisms observed in vitro, a finite-element model of a human disc (L4-L5) was employed. Both studies were subjected to physiological cycles of compression and recovery. A repaired annulus defect did not influence the disc behaviour in vitro, whereas additional nucleus removal and replacement substantially decreased disc stiffness and nucleus pressure. Model predictions demonstrated the substantial effects of reductions in replaced nucleus water content, bulk modulus and osmotic potential on disc height loss and pressure, similar tomeasurements. In these events, the compression load transfer in the disc markedly altered by substantially increasing the load on the annulus when compared with the nucleus. The success of hydrogels for nucleus replacements is not only dependent on the implantmaterial itself but also on the restoration of the environment perturbed during surgery. The substantial effects on the disc response of disruptions owing to nucleus replacements can be simulated by reduced nucleus water content, elastic modulus and osmotic potential. © 2012 The Royal Society.

Keywords: Disruptions | Finite-element method | Hydrogels | In vitro | Interface | Intervertebral disc

[124] Raucci M.G., Gloria A., De Santis R., Ambrosio L., Tanner E., Introduction to biomaterials for spinal surgery, Biomaterials for Spinal Surgery, 1-38, (2012). Abstract
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Abstract: Spinal disease is one of the most common causes of low back pain. This chapter will consider the wide range of materials employed in the field of spinal surgery to overcome drawbacks related to normal aging, trauma and pathology that could compromise the quality of life. Although 'conventional' materials such as metals, ceramics and polymers have been considered for spinal applications, over the past years research has focused on the development of polymer-based composite materials to design advanced devices. Accordingly, this chapter will first deal with the different classes of conventional materials, starting from their structure and properties, highlighting their specific applications in the field of disc arthroplasty and nucleus pulposus replacement. Finally, basic concepts and considerations regarding the importance of designing and developing polymer-based composite materials will be briefly discussed. © 2012 Woodhead Publishing Limited. All rights reserved.

Keywords: Ceramic | Composite | Hydrogel | Metal | Polymer | Spinal applications

[125] Gloria A., De Santis R., Ambrosio L., Tanner E., Artificial intervertebral discs, Biomaterials for Spinal Surgery, 295-312, (2012). Abstract
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Abstract: Over recent years, several models of the artificial intervertebral disc (IVD) have been designed and developed to restore the normal kinematics and load-bearing behaviour of the natural IVD, involving the use of metals, ceramics and polymers. This chapter first describes the structure-properties relationship of the natural IVD, and deals with the state of the art of artificial discs made of conventional materials. Then, it highlights the role of polymer-based composite biomaterials, underlining the possibility to design multifunctional devices with tailored mechanical properties. Accordingly, a biomimetic approach and the engineering of a pilot-scale device production process for a total, customized, artificial IVD with appropriate biological, transport and mechanical properties, have also been reported. Finally, future trends and strategies are discussed, emphasizing the importance of designing advanced materials and customized implants. © 2012 Woodhead Publishing Limited. All rights reserved.

Keywords: Artificial intervertebral disc | Biomimetic approach | Design | Mechanical behaviour | Polymer-based composite materials | Technologies

[126] Gloria A., Russo T., De Santis R., Ambrosio L., Nucleus regeneration, Biomaterials for Spinal Surgery, 563-581, (2012). Abstract
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Abstract: The intervertebral disc is a complex structure consisting of different tissues (nucleus pulposus, annulus fibrosus and cartilage endplate) that differ chemically, histologically and physiologically. Its degeneration represents a serious medical problem which affects many people worldwide. Discectomy and spinal fusion compromise the biomechanics of the spine, whilst current disc prostheses do not properly reproduce the static mechanical behaviour, as well as the viscoelastic, transport and biological properties of the natural structure. This clearly stresses the importance of biological approaches to disc repair. Considering the structure-function relationship, biomimetic structures able to mimic the multi-scale structural hierarchy of complex tissues are extremely important for tissue engineering applications. This chapter first describes the structure, anatomy and function of the intervertebral disc, then it briefly introduces the mechanics-biology interrelation. In particular, the chapter underlines the several approaches considered in the field of tissue engineering of annulus, nucleus and entire intervertebral disc, also trying to evidence key functional features. Injectable materials, polymers, electrospun scaffolds and several cell sources are also discussed alone or in combination. © 2012 Woodhead Publishing Limited. All rights reserved.

Keywords: Annulus fibrosus | Intervertebral disc | Nucleus pulposus | Polymers | Scaffolds | Tissue engineering

[127] Laino G., De Santis R., Gloria A., Russo T., Quintanilla D.S., Laino A., Martina R., Nicolais L., Ambrosio L., Calorimetric and thermomechanical properties of titanium-based orthodontic wires: DSC-DMA relationship to predict the elastic modulus, Journal of Biomaterials Applications, 26(7), 829-844, (2012). Abstract
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Abstract: Orthodontic treatment is strongly dependent on the loads developed by metal wires, and the choice of an orthodontic archwire should be based on its mechanical performance. The desire of both orthodontists and engineers would be to predict the mechanical behavior of archwires. To this aim, Gum Metal (Toyota Central R&L Labs., Inc.), TMA (ORMCO), 35°C Copper NiTi (SDS ORMCO), Thermalloy Plus (Rocky Mountain), Nitinol SE (3M Unitek), and NiTi (SDS ORMCO) were tested according to dynamic mechanical analysis and differential scanning calorimetry. A model was also developed to predict the elastic modulus of superelastic wires. Results from experimental tests have highlighted that superelastic wires are very sensitive to temperature variations occurring in the oral environment, while the proposed model seems to be reliable to predict the Young's modulus allowing to correlate calorimetric and mechanical data. Furthermore, Gum Metal wire behaves as an elastic material with a very low Young's modulus, and it can be particularly useful for the initial stage of orthodontic treatments. © The Author(s), 2010.

Keywords: differential scanning calorimetry | DSC-DMA relationship | dynamic mechanical analysis | orthodontic wires | superelasticity | thermomechanical behavior

[128] Gloria A., Borzacchiello A., Causa F., Ambrosio L., Rheological characterization of hyaluronic acid derivatives as injectable materials toward nucleus pulposus regeneration, Journal of Biomaterials Applications, 26(6), 745-759, (2012). Abstract
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Abstract: Nucleus pulposus (NP) is the soft center of the intervertebral disc (IVD), able to resist compressive loads, while the annulus fibrosus withstands tension and gives mechanical strength.NP function may be altered as consequence of several pathologies or injury and when a damaged IVD does not properly play its role. In the past years, a great effort has been devoted to the design of injectable systems as NP substitutes. The different synthetic- and natural hydrogel-based materials proposed, present many drawbacks and, in particular, they do not seem to mimic the required behavior. In the search for natural-based systems a dodecylamide of hyaluronic acid (HA), HYADD3, has been proved as bioactive and suitable vehicle to carry cells for NP tissue engineering, while a crosslinked HA ester, HYAFF120 showed interesting results if used as injectable acellular material. Even though these derivatives showed appropriate biological behavior up to now, data on mechanical behavior of these derivatives are still missing. In this frame, the aim of this study was to provide a rheological characterization of these HA derivatives to asses their biomechanical compatibility with the NP tissue. To this, the rheological properties of these derivatives were studied through dynamic shear tests before and after injection through needles used in the current surgical procedure. Both HA derivatives showed a 'gel-like' rheological behavior similar to the native NP tissue and this behavior was not altered by injection. © 2010 The Author(s) Reprints and permissions.

Keywords: hyaluronic acid derivatives | hydrogels | injectable materials | nucleus pulposus | viscoelastic properties

[129] Domingos M., Chiellini F., Gloria A., Ambrosio L., Bartolo P., Chiellini E., Effect of process parameters on the morphological and mechanical properties of 3D Bioextruded poly(1-caprolactone) scaffolds, Rapid Prototyping Journal, 18(1), 56-67, (2012). Abstract
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Abstract: Purpose - This paper aims to report a detailed study regarding the influence of process parameters on the morphological/mechanical properties of poly(1-caprolactone) (PCL) scaffolds manufactured by using a novel extrusion-based system that is called BioExtruder. Design/methodology/approach - In this study the authors focused investigations on four parameters, namely the liquefier temperature (LT), screw rotation velocity (SRV), deposition velocity (DV) and slice thickness (ST). Scaffolds were fabricated by employing three different values of each parameter. Through a series of trials, scaffolds were manufactured varying iteratively one parameter while maintaining constant the other ones. The morphology of the structures was investigated using a scanning electron microscope (SEM), whilst the mechanical performance was assessed though compression tests. Findings - Experimental results highlight a direct influence of the process parameters on the PCL scaffolds properties. In particular, DV and SRV have the highest influence in terms of road width (RW) and consequently on the porosity and mechanical behaviour of the structures. Research limitations/implications - The effect of process and design parameters on the biological response of scaffolds is currently under investigation. Originality/value - The output of this work provides a major insight into the effect of process parameters on the morphological/mechanical properties of PCL scaffolds. Moreover, the potential and feasibility of this novel extrusion-based system open a new opportunity to study how structural features may influence the characteristics and performances of the scaffolds, enabling the development of integrated biomechanical models that can be used in CAD systems to manufacture customized structures for tissue regeneration. © Emerald Group Publishing Limited.

Keywords: Biomanufacturing | Biotechnology | Mechanical properties of materials | Morphological properties | Process parameters | Scaffolds

[130] De Santis R., Gloria A., Russo T., D'Amora U., Zeppetelli S., Dionigi C., Sytcheva A., Herrmannsdörfer T., Dediu V., Ambrosio L., A basic approach toward the development of nanocomposite magnetic scaffolds for advanced bone tissue engineering, Journal of Applied Polymer Science, 122(6), 3599-3605, (2011). Abstract
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Abstract: Magnetic scaffolds for bone tissue engineering based on a poly(ω-caprolactone) (PCL) matrix and iron oxide (Fe3O 4) magnetic nanoparticles were designed and developed through a three-dimensional (3D) fiber-deposition technique. PCL/Fe3O 4 scaffolds were characterized by a 90/10 w/w composition. Tensile and magnetic measurements were carried out, and nondestructive 3D imaging was performed through microcomputed tomography (Micro-CT). Furthermore, confocal analysis was undertaken to investigate human mesenchymal stem cell adhesion and spreading on the PCL/Fe3O4 nanocomposite fibers. The results suggest that nanoparticles mechanically reinforced the PCL matrix; the elastic modulus and the maximum stress increased about 10 and 30%, respectively. However, the maximum strain decreased about 50%; this suggested an enhanced brittleness. Magnetic results evidenced a superparamagnetic behavior for these nanocomposite scaffolds. Micro-CT suggested an almost uniform distribution of nanoparticles. Confocal analysis highlighted interesting results in terms of cell adhesion and spreading. All of these results show that a magnetic feature could be incorporated into a polymeric matrix that could be processed to manufacture scaffolds for advanced bone tissue engineering and, thus, provide new opportunity in terms of scaffold fixation and functionalization. © 2011 Wiley Periodicals, Inc.

Keywords: biocompatibility | nanocomposites | nanoparticles | polyesters

[131] Antunes J.C., Pereira C.L., Molinos M., Ferreira-Da-Silva F., Dessi M., Gloria A., Ambrosio L., Gonca̧lves R.M., Barbosa M.A., Layer-by-layer self-assembly of chitosan and poly(γ-glutamic acid) into polyelectrolyte complexes, Biomacromolecules, 12(12), 4183-4195, (2011). Abstract
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Abstract: Chitosan (Ch) is a nontoxic and biocompatible polysaccharide extensively used in biomedical applications. Ch, as a polycation, can be combined with anionic polymers by layer-bylayer (LbL) self-assembly, giving rise to multilayered complexed architectures. These structures can be used in tissue engineering strategies, as drug delivery systems, or artificial matrices mimicking the extracellular microenvironment. In this work, Ch was combined with poly(γ-glutamic acid) (γ-PGA). γ-PGA is a polyanion, which was microbially produced, and is known for its low immunogenic reaction and low cytotoxicity. Multilayered ultrathin films were assembled by LbL, with a maximum of six layers. The interaction between both polymers was analyzed by: ellipsometry, quartz crystal microbalance with dissipation, Fourier transform infrared spectroscopy, atomic force microscopy, and zeta potential measurements. Ch/γ-PGA polyelectrolyte multilayers (PEMs) revealed no cytotoxicity according to ISO 10993-5. Overall, this study demonstrates that Ch can interact electrostatically with γ-PGA forming multilayered films. Furthermore, this study provides a comprehensive characterization of Ch/γ-PGA PEM structures, elucidating the contribution of each layer for the nanostructured films. These model surfaces can be useful substrates to study cell-biomaterial interactions in tissue regeneration. © 2011 American Chemical Society.

[132] Gloria A., Dessì M., De Santis R., Ambrosio L., Injectable collagen-LMW HA gels loaded with gelatin microspheres as nucleus pulposus substitutes, 24th European Conference on Biomaterials - Annual Conference of the European Society for Biomaterials, (2011).
[133] Russo L., Lupo C., Gloria A., De Santis R., Cipolla L., Nicotra F., PCL grafting with small biomolecules, 24th European Conference on Biomaterials - Annual Conference of the European Society for Biomaterials, (2011).
[134] Tsaryk R., Gloria A., De Santis R., Ghanaati S., Landes C., Unger R.E., Ambrosio L., Kirkpatrick C.J., Cell-loaded semi-interpenetrating collagen-LMW HA gel for nucleus pulposus regeneration, 24th European Conference on Biomaterials - Annual Conference of the European Society for Biomaterials, (2011).
[135] Serroni G., Bitondo C., Astarita A., Scala A., Gloria A., Prisco U., Squillace A., Bellucci F., A comparison between mechanical and electrochemical tests on Ti6Al4V welded by LBW, AIP Conference Proceedings, 1353, 1391-1396, (2011). Abstract
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Abstract: Titanium and its alloys are nowadays widely used in many sectors: in the medical field (orthopedic and dental ones), in the architectural field, in the chemical plants field and in aeronautic. In this last field it is more and more used both for its contribution to make lightweight and time durable structures and for its compatibility with new materials, first of all Carbon Fiber Reinforced Plastics (CFRP). To this aim, lots of researches are now focusing on new and emerging technologies capable to make titanium objects and, at the same time, reducing the scrap, since titanium alloys for aeronautic application are very expensive. This paper examines Grade 5 Titanium Alloy (Ti6Al4V) welded by Laser Beam (LBW) in butt-joint configuration. The source was Nd:YAG laser, moreover two inert gases were used, in order to provide a shield both on the top and on the bottom of the weld bead. The joints were studied by varying two process parameters: welding speed and power of the laser beam. It was not possible to realize a full experimental plan, due to technological limits in making titanium laser beam welds. The joints were tested to measure their mechanical properties and the corrosion resistance. The process parameters do not significantly affect the maximum static strength of the joints. Microscopic analysis showed that welds made with high power and low welding speed have a uniform weld bead, and no macroscopic defect occurs. Fatigue test results, instead, show a marked influence of the morphology of the weld bead: the occurrence of some defects, such as the undercut, both on the top and on the bottom of the weld bead, dramatically reduced fatigue resistance of the joints. Corrosion resistance was studied using the electrochemical micro cell technique, which allows to distinguish electrochemical properties of each zone of the weld bead, even when, as in this case, they are very narrow. By a general point of view, it has been demonstrated that the joints showing the best mechanical performances also possess better electrochemical properties. What's more, in these cases, the weld bead shows a cathodic behavior with respect to the parent material. © 2011 American Institute of Physics.

Keywords: electrochemical micro cell | fatigue tests | Laser | Titanium | Welding

[136] de Santis R., Gloria A., Russo T., D'Amora U., Zeppetelli S., Tampieri A., Herrmannsdörfer T., Ambrosio L., A route toward the development of 3D magnetic scaffolds with tailored mechanical and morphological properties for hard tissue regeneration: Preliminary study: A basic approach toward the design of 3D rapid prototyped magnetic scaffolds for hard-tissue regeneration is presented and validated in this paper, Virtual and Physical Prototyping, 6(4), 189-195, (2011). Abstract
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Abstract: A basic approach toward the design of three-dimensional (3D) rapid prototyped magnetic scaffolds for hard-tissue regeneration has been proposed. In particular, 3D scaffolds consisting of a poly(ε-caprolactone) (PCL) matrix and iron oxide (Fe 3O 4) or iron-doped hydroxyapatite (FeHA) nanoparticles were fabricated through a 3D fibre deposition technique. As a first approach, a polymer to nanoparticle weight ratio of 90/10 (wt/wt) was used. The effect of the inclusion of both kinds of nanoparticles on the mechanical, magnetic, and biological performances of the scaffolds was studied. The inclusion of Fe 3O 4 and FeHA nanoparticles generally improves the modulus and the yield stress of the fibres if compared to those of neat PCL, as well as the modulus of the scaffolds. Micro-computed tomography has confirmed the possibility to design morphologically-controlled structures with a fully interconnected pore network. Magnetisation analyses performed at 378C have highlighted M-H curves that are not hysteretic; values of saturation magnetisation (M s) of about 3.9 emu/g and 0.2 emu/g have been evaluated for PCL/Fe 3O 4 and PCL/FeHA scaffolds, respectively. Furthermore, results from confocal laser scanning microscopy (CLSM) carried out on cell-scaffold constructs have evidenced that human mesenchymal stem cells (hMSCs) better adhered and were well spread on the PCL/Fe 3O 4 and PCL/FeHA nanocomposite scaffolds in comparison with the PCL structures. © 2011 Taylor & Francis.

Keywords: Biological and mechanical analyses | Hard tissue regeneration | Magnetic scaffold | Nanocomposite | Rapid prototyping

[137] Guarino V., Gloria A., Alvarez-Perez M., Raucci M.G., Cirillo V., Ronca A., De Santis R., Ambrosio L., Design of functional polymer and composite scaffolds for the regeneration of bone, menisci, osteochondral and peripheral nervous tissues, Advanced Materials Research, 324, 8-13, (2011). Abstract
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Abstract: In order to mimic the behaviors of natural tissue, the optimal approach for designing novel biomaterials has to be inspired to nature guidelines. One of the major challenge consists in the development of well-organized structures or scaffolds with controlled porosity in terms of pore size, pore shape and interconnection degree able to guide new tissue formation during the in vivo degradation following the scaffold implantation. Scaffolds endowed with molecular cues together to a controlled degradation profile should contribute to cell proliferation and differentiation, controlled vascularization, promoting the remodeling of neo tissue through a gradual transmission of biochemicals and biophysical signals as performed by the extracellular matrix (ECM). Here, different polymers and composites have been investigated to design scaffolds with peculiar micro and/or nanometric morphological features in order to satisfy all these requirements: a) bioactive scaffolds, with tailored porosity and high pores interconnectivity were developed by integrating PLA fibres, Calcium Phosphates particles or Hyaff11 phases into a Poly(ε-caprolactone) (PCL) matrix by the combination of filament winding technology and phase inversion/salt leaching technique as mineralised ECM analogue for bone regeneration; b) custom made PCL/hydroxyapatite scaffolds were designed by imaging and rapid prototyping technologies for the osteochondral defect. c) Ester of Hyaluronic Acid reinforced with degradable fibres were processed by composite technology, phase inversion and salt leaching technique, to obtain scaffolds for meniscus regeneration. d) PCL and gelatin nanofibres were obtained by highly customized fibre deposition via electrospinning to guide the nerve outgrowth in nerve regeneration. All the proposed approaches offer the chance of realizing tailor-made platforms with micro/nanoscale architecture and chemical composition suitable for the regeneration of the extracellular matrix of a large variety of natural tissues (i.e, bone, menisci, osteochondral and peripheral nervous tissues). © (2011) Trans Tech Publications, Switzerland.

Keywords: Composite | Polycaprolactone | Scaffold | Tissue engineering

[138] Borzacchiello A., Gloria A., Mayol L., Dickinson S., Miot S., Martin I., Ambrosio L., Natural/synthetic porous scaffold designs and properties for fibro-cartilaginous tissue engineering, Journal of Bioactive and Compatible Polymers, 26(5), 437-451, (2011). Abstract
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Abstract: The goal of this study was to produce and characterize the scaffolds by combining the advantages of both natural and synthetic polymers for engineering fibro-cartilaginous tissues. Porous three-dimensional composite scaffolds were produced based on glycosaminoglycans and hyaluronic acid (HYAFF11) reinforced with polycaprolactone. The mechanical properties of scaffolds were evaluated as a function of time and compared with those of scaffolds seeded with human chondrocytes (constructs) and cultured in vitro up to 6 weeks. The composite scaffolds had a porosity of 68% with interconnected macropores with average pore sizes of 200 μm, an equilibrium swelling of 350%, and a predominant elastic behavior, typical of a macromolecular gel. The composite constructs maintained chondrocyte phenotype and degraded with the deposition of macromolecules synthesized by the cells. The scaffold presented mechanical properties and the ability to dissipate energy similar to the fibro-cartilaginous tissue. © The Author(s) 2011.

Keywords: cartilage tissue engineering | hyaluronic acid derivatives | mechanical properties | PCL | scaffolds

[139] Bartolo P., Domingos M., Gloria A., Ciurana J., BioCell Printing: Integrated automated assembly system for tissue engineering constructs, CIRP Annals - Manufacturing Technology, 60(1), 271-274, (2011). Abstract
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Abstract: The production methodology of 3D constructs for tissue regeneration is usually a complex discontinuous process involving three different stages: (1) production of 3D matrices; (2) matrix sterilisation and cell seeding; (3) in vitro dynamic cell culture. This paper presents a novel automated bench-top manufacturing system called BioCell Printing, designed for the integrated, continuous and fully automated production and in vitro dynamic culture of tissue engineering constructs. The BioCell aims at the rapid production of tissue-engineered substitutes with low risk of contamination, increasing the chances of direct clinical application. © 2011 CIRP.

Keywords: Biomedical | Extrusion | Rapid prototyping

[140] Gloria A., Ronca D., Russo T., D'Amora U., Chierchia M., de Santis R., Nicolais L., Ambrosio L., Technical features and criteria in designing fiber-reinforced composite materials: From the aerospace and aeronautical field to biomedical applications, Journal of Applied Biomaterials and Biomechanics, 9(2), 151-163, (2011). Abstract
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Abstract: Polymer-based composite materials are ideal for applications where high stiffness-to-weight and strength-to-weight ratios are required. From aerospace and aeronautical field to biomedical applications, fiber-reinforced polymers have replaced metals, thus emerging as an interesting alternative. As widely reported, the mechanical behavior of the composite materials involves investigation on micro- and macro-scale, taking into consideration micromechanics, macromechanics and lamination theory. Clinical situations often require repairing connective tissues and the use of composite materials may be suitable for these applications because of the possibility to design tissue substitutes or implants with the required mechanical properties. Accordingly, this review aims at stressing the importance of fiber-reinforced composite materials to make advanced and biomimetic prostheses with tailored mechanical properties, starting from the basic principle design, technologies, and a brief overview of composites applications in several fields. Fiber-reinforced composite materials for artificial tendons, ligaments, and intervertebral discs, as well as for hip stems and mandible models will be reviewed, highlighting the possibility to mimic the mechanical properties of the soft and hard tissues that they replace. © 2011 Società Italiana Biomateriali.

Keywords: Applications | Basic principles | Fiber-reinforced composite materials | Prosthetic implants and models | Tailored properties | Technologies

[141] Gloria A., De Santis R., Ambrosio L., Causa F., Tanner K.E., A multi-component fiber-reinforced PHEMA-based hydrogel/HAPEX<sup>TM</sup> device for customized intervertebral disc prosthesis, Journal of Biomaterials Applications, 25(8), 795-810, (2011). Abstract
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Abstract: Spinal disease due to intervertebral disc degeneration represents a serious medical problem which affects many people worldwide. Disc arthroplasty may be considered the future "gold standard" of back pain treatment, even if problems related to available disc prostheses are considered. Hence, the aim of the present study was to improve the artificial disc technology by proposing the engineering of a pilot-scale device production process for a total multi-component intervertebral disc prosthesis. The device is made up of a poly(2-hydroxyethyl methacrylate)/poly(methyl methacrylate) (PHEMA/PMMA) (80/20 w/w) semi-interpenetrating polymer network (s-IPN) composite hydrogel reinforced with poly(ethylene terephthalate) (PET) fibers as annulus/nucleus substitute, and two hydroxyapatite-reinforced polyethylene composite (HAPEXTM) endplates in order to anchor the multi-component device to the vertebral bodies. Static and dynamic-mechanical characterization show appropriate mechanical behavior. An example of engineering of a suitable pilot-scale device production process is also proposed in order to manufacture custom made implants. © 2010 The Author(s).

Keywords: customized prosthesis | fiber-reinforced hydrogel | intervertebral disc | mechanical testing. | multi-component model | reverse engineering | technologies

[142] Bañobre-López M., Piñeiro-Redondo Y., De Santis R., Gloria A., Ambrosio L., Tampieri A., Dediu V., Rivas J., Poly(caprolactone) based magnetic scaffolds for bone tissue engineering, Journal of Applied Physics, 109(7), (2011). Abstract
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Abstract: Synthetic scaffolds for tissue engineering coupled to stem cells represent a promising approach aiming to promote the regeneration of large defects of damaged tissues or organs. Magnetic nanocomposites formed by a biodegradable poly(caprolactone) (PCL) matrix and superparamagnetic iron doped hydroxyapatite (FeHA) nanoparticles at different PCL/FeHA compositions have been successfully prototyped, layer on layer, through 3D bioplotting. Magnetic measurements, mechanical testing, and imaging were carried out to calibrate both model and technological processing in the magnetized scaffold prototyping. An amount of 10% w/w of magnetic FeHA nanoparticles represents a reinforcement for PCL matrix, however, a reduction of strain at failure is also observed. Energy loss (absorption) measurements under a radio-frequency applied magnetic field were performed in the resulting magnetic scaffolds and very promising heating properties were observed, making them very useful for potential biomedical applications. © 2011 American Institute of Physics.

[143] Borzacchiello A., Gloria A., De Santis R., Ambrosio L., Spinal disc implants using hydrogels, Biomedical Hydrogels: Biochemistry, Manufacture and Medical Applications, 103-117, (2011). Abstract
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Abstract: Low back pain, a common cause of disability in individuals - especially between 20 and 50 years old - with enormous socioeconomic consequences, may be strongly associated with the degeneration of the intervertebral disc (IVD). The traditional IVD treatments, such as spinal fusion, even though they provide amelioration of the pain, present different drawbacks; consequently there is a lot of research interest in replacing the damaged disc with an artificial one. In this chapter, after an introductory part on IVD and the pathologies and treatment related to it, an overview of the IVD traditional prostheses is given, followed by the presentation of new hydrogels-based prostheses designed according to a biomimetic approach. Finally, the hydrogels-based systems aimed to replace the nucleus pulposus (NP) and to act as scaffolds to carry cells to engineer the IVD tissues are described.

Keywords: Hydrogels | Intervertebral disc prostheses | Nucleus pulposus | Tissue engineering

[144] Giordano C., Albani D., Gloria A., Tunesi M., Rodilossi S., Russo T., Forloni G., Ambrosio L., Cigada A., Nanocomposites for neurodegenerative diseases: Hydrogel-nanoparticle combinations for a challenging drug delivery, International Journal of Artificial Organs, 34(12), 1115-1127, (2011). Abstract
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Abstract: Neurodegenerative disorders are expected to strike social and health care systems of developed countries heavily in the coming decades. Alzheimer's and Parkinson's diseases (AD/PD) are the most prevalent neurodegenerative pathologies, and currently their available therapy is only symptomatic. However, innovative potential drugs are actively under development, though their efficacy is sometimes limited by poor brain bioavailability and/or sustained peripheral degradation. To partly overcome these constraints, the development of drug delivery devices made by biocompatible and easily administrable materials might be a great adjuvant. In particular, materials science can provide a powerful tool to design hydrogels and nanoparticles as basic components of more complex nanocomposites that might ameliorate drug or cell delivery in AD/PD. This kind of approach is particularly promising for intranasal delivery, which might increase brain targeting of neuroprotective molecules or proteins. Here we review these issues, with a focus on nanoparticles as nanocomponents able to carry and tune drug release in the central nervous system, without ignoring warnings concerning their potential toxicity. © 2011 Wichtig Editore.

Keywords: Alzheimer's disease | Hydrogels | Intranasal delivery | Nanocomposites | Nanoparticles | Nanotoxicity | Parkinson's disease

[145] Domingos M., Chiellini F., Gloria A., Ambrosio L., Bartolo P., Chiellini E., BioExtruder: Study of the influence of process parameters on PCL scaffolds properties, Innovative Developments in Design and Manufacturing - Advanced Research in Virtual and Rapid Prototyping, 67-73, (2010). Abstract
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Abstract: The success of regenerative medicine is strongly dependent on the ability to produce biomimetic scaffolds that closely mimic the biomechanical properties of the native tissues. Additive biomanufacturing techniques have been recently introduced in the medical field and are increasingly being recognized as ideal methods to produce 3D porous structures with an effective control over pore size/shape and spatial distribution. The BioExtruder is an additive biomanufacturing system under development for Tissue Engineering (TE) applications. The working principle is based on the extrusion of thin filaments of low melting point materials in a layer-by-layer fashion, controlled by a computer model. There are several parameters that control the BioExtruder and that have a direct influence on the morphological and mechanical properties of the extruded scaffolds. In this study we have focused our investigations on four parameters, namely the Liquefier Temperature (LT), Screw Rotation Velocity (SRV), Deposition Velocity (DV) and Slice Thickness (ST). © 2010 Taylor & Francis Group, London.

[146] Russo T., Gloria A., D'Antò V., D'Amora U., Ametrano G., Bollino F., De Santis R., Ausanio G., Catauro M., Rengo S., Ambrosio L., Poly(ε-caprolactone) reinforced with sol-gel synthesized organic-inorganic hybrid fillers as composite substrates for tissue engineering, Journal of Applied Biomaterials and Biomechanics, 8(3), 146-152, (2010). Abstract
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Abstract: Purpose: The importance of polymer-based composite materials to make multifunctional substrates for tissue engineering and the strategies to improve their performances have been stressed in the literature. Bioactive features of sol-gel synthesized poly(ε-caprolactone)/TiO2 or poly(ε-caprolactone)/ZrO2 organic-inorganic hybrid materials are widely documented. Accordingly, the aim of this preliminary research was to develop advanced composite substrates consisting of a poly(ε-caprolactone) matrix reinforced with sol-gel synthesized PCL/TiO2 or PCL/ZrO 2 hybrid fillers. Methods: Micro-computed tomography and atomic force microscopy analyses allowed to study surface topography and roughness. On the other hand, mechanical and biological performances were evaluated by small punch tests and Alamar Blue™ assay, respectively. Results: Micro-computed tomography and atomic force microscopy analyses highlighted the effect of the preparation technique. Results from small punch tests and Alamar Blue™ assay evidenced that PCL reinforced with Ti2 (PCL=12, TiO2=88 wt%) and Zr2 (PCL=12, ZrO2=88 wt%) hybrid fillers provided better mechanical and biological performances. Conclusions: PCL reinforced with Ti2 (PCL=12, TiO2=88 wt%) and Zr2 (PCL=12, ZrO2=88 wt%) hybrid fillers could be considered as advanced composite substrates for hard tissue engineering. © 2010 Società Italiana Biomateriali.

Keywords: Alamar Blue™ | Assay | Atomic force microscopy | Composite substrate | Organic-inorganic hybrid | Poly(ε-caprolactone) | Small punch test

[147] De Santis R., Gloria A., Prisco D., Amendola E., Puppulin L., Pezzotti G., Rengo S., Ambrosio L., Nicolais L., Fast curing of restorative materials through the soft light energy release, Dental Materials, 26(9), 891-900, (2010). Abstract
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Abstract: Objective: The effect of a novel light curing process, namely soft light energy release (SLER®), on shrinkage, mechanical strength and residual stress of four dental restorative materials (DEI experience, Gradia Direct, Enamel Plus HFO and Venus) was investigated. Methods: Composite specimens were fast cured through high level of power density and soft light energy release. Temperature, linear shrinkage and light power measurements were acquired in parallel in order to assess the effect of light modulation on temperature and shrinkage profiles during the light curing process and the following dark reaction phase. The small punch test and Raman spectroscopy were adopted to investigate the effect of SLER® on mechanical strength and on internal stress, respectively. Results: The soft light energy release photo-polymerization allows to reduce of about 20% the shrinkage rate and to increase the strength of fast light cured specimens. In addition, a more relaxed and homogeneous internal stress distribution was observed. Significance: Properties of fast cured restorative materials can be improved by adopting the soft light energy release process. © 2010 Academy of Dental Materials.

Keywords: Composite | Contraction stress | Fast curing | Photo-polymerization | Shrinkage | Small punch test | Temperature

[148] De Santis R., Gloria A., Russo T., D'Amora U., Zeppetelli S., Ambrosio L., An approach in developing 3D fiber-deposited magnetic scaffolds for tissue engineering, AIP Conference Proceedings, 1255, 420-422, (2010). Abstract
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Abstract: Scaffolds should possess suitable properties to play their specific role. In this work, the potential of 3D fiber deposition technique to develop multifunctional and well-defined magnetic poly(ε-caprolactone)/iron oxide scaffolds has been highlighted, and the effect of iron oxide nanoparticles on the biological and mechanical performances has been assessed. © 2010 American Institute of Physics.

Keywords: 3D fiber deposition | Iron oxide nanoparticles | Poly(ε-caprolactone) | Scaffolds | Tissue engineering

[149] Gloria A., De Santis R., Ambrosio L., Polymer-based composite scaffolds for tissue engineering, Journal of Applied Biomaterials and Biomechanics, 8(2), 57-67, (2010). Abstract
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Abstract: Tissue engineering may be defined as the application of biological, chemical and engineering principles toward the repair, restoration or regeneration of living tissue using biomaterials, cells and biologically active molecules alone or in combinations. The rapid restoration of tissue biomechanical function represents a great challenge, highlighting the need to mimic tissue structure and mechanical behavior through scaffold designs. For this reason, several biodegradable and bioresorbable materials, as well as technologies and scaffold designs, have been widely investigated from an experimental and/or clinical point of view. Accordingly, this review aims at stressing the importance of polymer-based composite materials to make multifunctional scaffolds for tissue engineering, with a special focus on bone, ligaments, meniscus and cartilage. Moreover, polymer-based nanocomposites will also be briefly introduced as an interesting strategy to improve the biological and mechanical performances of polymer scaffolds, especially for bone tissue engineering. © 2010 Società Italiana Biomateriali.

Keywords: Bone | Cartilage | Composites | Ligaments | Meniscus | Polymers | Scaffolds

[150] Lee J., Guarino V., Gloria A., Ambrosio L., Tae G., Kim Y.H., Jung Y., Kim S.H., Kim S.H., Regeneration of Achilles' Tendon: The role of dynamic stimulation for enhanced cell proliferation and mechanical properties, Journal of Biomaterials Science, Polymer Edition, 21(8-9), 1173-1190, (2010). Abstract
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Abstract: The tissue engineering of tendon was studied using highly elastic poly(L-lactide-co-&epsi;-caprolactone) (PLCL) scaffolds and focusing on the effect of dynamic tensile stimulation. Tenocytes from rabbit Achilles tendon were seeded (1.0 × 106 cells/scaffold) onto porous PLCL scaffolds and cultured for periods of 2 weeks and 4 weeks. This was performed in a static system and also in a bioreactor equipped with tensile modulation which mimicked the environmental surroundings of tendons with respect to tensile extension. The degradation of the polymeric scaffolds during the culture was relatively slow. However, there was an indication that cells accelerated the degradation of PLCL scaffolds. The scaffold/cell adducts from the static culture exhibited inferior strength (at 2 weeks 350 kPa, 4 weeks 300 kPa) compared to the control without cells (at 2 weeks 460 kPa, 4 weeks 340 kPa), indicating that the cells contributed to the enhanced degradation. On the contrary, the corresponding values of the adducts from the dynamic culture (at 2 weeks 430 kPa, 4 weeks 370 kPa) were similar to, or higher than, those from the control. This could be explained by the increased quantity of cells and neo-tissues in the case of dynamic culture compensating for the loss in tensile strength. Compared with static and dynamic culture conditions, mechanical stimulation played a crucial role in the regeneration of tendon tissue. In the case of the dynamic culture system, cell proliferation was enhanced and secretion of collagen type I was increased, as evidenced by DNA assay and histological and immunofluorescence analysis. Thus, tendon regeneration, indicated by improved mechanical and biological properties, was demonstrated, confirming the effect of mechanical stimulation. It could be concluded that the dynamic tensile stimulation appeared to be an essential factor in tendon/ligament tissue engineering, and that elastic PLCL co-polymers could be very beneficial in this process. © 2010 Koninklijke Brill NV, Leiden.

Keywords: BIOREACTOR | MECHANICAL STIMULATION | PLCL | TENDON | TISSUE ENGINEERING

[151] Gloria A., Russo T., De Santis R., Ambrosio L., 3D fiber deposition technique to make multifunctional and tailor-made scaffolds for tissue engineering applications, Journal of Applied Biomaterials and Biomechanics, 7(3), 141-152, (2009). Abstract
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Abstract: Tissue engineering represents an interesting approach which aims to create tissues and organs de novo. In designing scaffolds for tissue engineering applications, the principal goal is to mimic the function of the natural extracellular matrix, providing a temporary template for the growth of target tissues. For this reason, scaffolds should possess suitable mechanical properties and architecture to play their specific role. In this paper, limitations of conventional scaffold fabrication methods will be briefly introduced, and rapid prototyping techniques will be described as advanced processing methods to realize customized scaffolds with controlled internal microarchitecture. Among the rapid prototyping techniques, the potential and challenges of 3D fiber deposition to create multifunctional and tailor-made scaffolds will be reviewed. © Società Italiana Biomateriali.

Keywords: 3D fiber deposition | Bioplotter | Rapid prototyping | Scaffolds | Tissue engineering

[152] De Santis R., Gloria A., Sano H., Amendola E., Prisco D., Mangani F., Rengo S., Ambrosio L., Nicolais L., Effect of light curing and dark reaction phases on the thermomechanical properties of a Bis-GMA based dental restorative material, Journal of Applied Biomaterials and Biomechanics, 7(2), 132-140, (2009). Abstract
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Abstract: Purpose: The effects of light curing units (LCU) and energy doses on the chemical and physical properties of a dental composite were investigated. Methods: The effects on the chemical and physical properties of a bisphenol A diglycidylether methacrylate (Bis-GMA) based dental restorative material were evaluated through photospectrometry, differential scanning calorimetry, and mechanical measurements. Results: The light curing conditions associated with direct and indirect restorations were replicated in vitro using optical investigation techniques. A slight attenuation resulted independently of the LCU and a strong attenuation was measured for the cement luting a thick inlay, as well as for the deepest layer of a composite filling increment. Calorimetric measurements indicated that the curing degree is very sensitive to the light energy dose rather than to the LCU. Mechanical testing showed a transient phase during which properties increased. The delay of the composite in reaching adequate properties is strongly dependent on the energy dose. Conclusions: It is recommended that composites subject to unfavorable light curing conditions undergo a prolonged light curing process. © Società Italiana Biomateriali.

Keywords: Composite | Differential scanning calorimetry | Light curing | Mechanical properties | Restorative materials

[153] de Santis R., Gloria A., Ambrosio L., Nicolais L., Recent patents on light curing of dental materials, Recent Patents on Biomedical Engineering, 2(2), 97-109, (2009). Abstract
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Abstract: In the last few decades photo-polymerization, the use of light for curing resins, has been a field of multidisciplinary research particularly involving advanced materials and technologies to restore a tooth. Polymers and composites used in the oral cavity in conjunction with light curing process represent the material and technology objective of this patent review article. The scenario related to polymers, composite formulations and light curing devices in relation to material performance in vitro and in vivo is presented. Current and future developments related to engineering of materials, technologies and clinical approaches to dental restoration will be considered and estimated. © 2009 Bentham Science Publishers Ltd.

Keywords: Bone | Composite | Dentin | Light curing | Mechanical properties | Polymers | Restorative materials

[154] Ambrosio L., Gloria A., Causa F., Composite materials for replacement of ligaments and tendons, Biomedical Composites, 234-254, (2009). Abstract
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Abstract: In this chapter, the role of composite biomaterials as a unique type of material able to reproduce the complexity of the hierarchical structure and the peculiar mechanical properties of ligaments and tendons is discussed. The fundamentals of fibre-reinforced composite materials are reviewed, highlighting critical aspects in designing devices for ligaments and tendons replacement. The various approaches for replacement and regeneration are explored, with the aim of benefiting from composite materials science. Prospective and future challenges for composite materials for ligaments and tendons replacement and regeneration are outlined. © 2010 Woodhead Publishing Limited All rights reserved.

[155] Gloria A., De Santis R., Ambrosio L., Causa F., Composite materials for spinal implants, Biomedical Composites, 178-200, (2009). Abstract
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Abstract: In this chapter, the state of the art of spinal implants such as interbody spacers and intervertebral disc (IVD) prostheses made of conventional materials, is described and the role of composite biomaterials for spine applications highlighted. In particular, the possibility of designing multifunctional devices with tailored mechanical properties is emphasized. A biomimetic approach to developing an IVD prosthesis with appropriate biological, transport and mechanical properties, is also presented. Finally, in the field of composite biomaterials for spine applications, future challenges and strategies are discussed. © 2010 Woodhead Publishing Limited All rights reserved.

[156] De Santis R., Gloria A., Ambrosio L., Composite materials for hip joint prostheses, Biomedical Composites, 276-295, (2009). Abstract
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Abstract: Composite hip prostheses have gained an increasingly important role in the development of prosthetic devices. These materials can be engineered more accurately than monolithic structures. Biomechanical properties of tissues composing the hip joint and the concept of composite material and anisotropy are introduced. The state of the art is reviewed for prosthetic components comprising monolithic and composite materials for hip arthroplasty. The final section shows the composite approach to develop the hip stem, including technology, modelling and testing. © 2010 Woodhead Publishing Limited All rights reserved.

[157] Nicolais L., Gloria A., Ambrosio L., The mechanics of biocomposites, Biomedical Composites, 411-440, (2009). Abstract
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Abstract: An overview is presented of the theoretical approach to the design of polymer composite materials. Composite materials with polymeric matrices are strong candidates for structural applications where high strength and stiffness to weight ratios are required. The fundamental analysis of the mechanical response of composite materials involves investigation on two levels, micro- and macro-scale. This approach encompasses micromechanics and macromechanics, extends to lamination theory and makes clear the physical significance of the basic concepts of composite material design. First, the mechanical behaviour is described of a unidirectional fibre-reinforced lamina as the basic building block of a laminate, showing stress-strain relationships in various coordinate systems. The design of laminates having suitable properties for a particular application is explained and short fibre-reinforced composites and particulate composites are examined. Finally, polymer nanocomposites are discussed as an interesting strategy to improve the mechanical properties of polymers. © 2010 Woodhead Publishing Limited All rights reserved.

[158] Giordano C., Albani D., Gloria A., Tunesi M., Batelli S., Russo T., Forloni G., Ambrosio L., Cigada A., Multidisciplinary perspectives for Alzheimer's and Parkinson's diseases: Hydrogels for protein delivery and cell-based drug delivery as therapeutic strategies, International Journal of Artificial Organs, 32(12), 836-850, (2009). Abstract
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Abstract: This review presents two intriguing multidisciplinary strategies that might make the difference in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The first proposed strategy is based on the controlled delivery of recombinant proteins known to play a key role in these neurodegenerative disorders that are released in situ by optimized polymer-based systems. The second strategy is the use of engineered cells, encapsulated and delivered in situ by suitable polymer-based systems, that act as drug reservoirs and allow the delivery of selected molecules to be used in the treatment of Alzheimer's and Parkinson's diseases. In both these scenarios, the design and development of optimized polymer-based drug delivery and cell housing systems for central nervous system applications represent a key requirement. Materials science provides suitable hydrogel-based tools to be optimized together with suitably designed recombinant proteins or drug delivering-cells that, once in situ, can provide an effective treatment for these neurodegenerative disorders. In this scenario, only interdisciplinary research that fully integrates biology, biochemistry, medicine and materials science can provide a springboard for the development of suitable therapeutic tools, not only for the treatment of Alzheimer's and Parkinson's diseases but also, prospectively, for a wide range of severe neurodegenerative disorders. © Wichtig Editore, 2009.

Keywords: Alzheimer's disease | Cell housing | Drug delivery | Engineered cells | Hydrogels | Parkinson's disease | Recombinant proteins

[159] Mollica F., De Santis R., Gloria A., Ambrosio L., Characterization and simulation of PCL scaffolds for bone tissue engineering, 8th World Biomaterials Congress 2008, 3, 1512, (2008).
[160] Gloria A., De Santis R., Ambrosio L., Novel polymer-based scaffolds and technologies for meniscus regeneration, 8th World Biomaterials Congress 2008, 1, 256, (2008).
[161] De Santis R., Prisco D., Gloria A., Rengo S., Ambrosio L., Development of light curing process to improve mechanical properties of dental composites, 8th World Biomaterials Congress 2008, 1, 109, (2008).
[162] Gloria A.N., Manto L., De Santis R., Ambrosio L., Biomechanical behavior of a novel composite intervertebral body fusion device, Journal of Applied Biomaterials and Biomechanics, 6(3), 163-169, (2008). Abstract
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Abstract: Purpose: Low back pain related to intervertebral disc (IVD) degeneration represents a socio-economic problem which affects quality of life. In order to solve this problem the current gold standard techniques such as spinal arthroplasty and arthrodesis (or fusion) are considered. As for spinal arthroplasty, over the past 40 yrs, IVD prostheses have been designed to maintain the correct IVD spacing and to allow for motion, while providing stability. However, there are many difficulties in incorporating important features such as viscoelastic and shock absorber behavior of natural IVDs in a prosthetic disc design. Moreover, in some cases, the use of IVD prostheses does not represent the ideal solution. Consequently, the aim of this study was to improve the design of alternative devices for spinal fusion, which overcome the problems related to metal ones currently available on the market, such as stress shielding, stress concentration effects and eventual bone corrosive or inflammatory reaction. Methods: Accordingly, a novel polyetherimide (PEI)-based cage reinforced with carbon fibers through filament winding and compression molding technologies was realized. Results: The characterization through a porcine model has produced very interesting results. The small values obtained from local compression tests have suggested that a reduction in mobility occurred, whereas distributed compression tests on IVDs prosthesized by employing the PEI-based cage reinforced with carbon fibers have highlighted a compressive stiffness of 100 MPa. This stiffness is lower than that of the IVD prosthesized through the titanium cage (146 MPa), and closer to the stiffness of natural porcine IVDs (90 MPa). Conclusions: Through a suitable composite cage design it is possible to control stress-strain distributions and the mechanical signals to bone, thus avoiding the stress-shielding phenomena, but also corrosion and metal ions release which are typical of the metallic implants. © Società Italiana Biomateriali.

Keywords: Composite interbody fusion device | Intervertebral disc | Mechanical behavior | Porcine model | Prosthesized segments

[163] Ronca A., Dessi M., Guarino V., Gloria A., Raucci M.G., Ambrosio L., Use of poly-ε-caprolactone as potential tissue engineering material, AIP Conference Proceedings, 1042, 199-200, (2008). Abstract
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Abstract: Morphological and mechanical properties of PCL porous scaffolds for bone tissue regeneration have been analyzed as function of two different preparation techniques : particulate leaching/phase inversion and rapid prototyping technique. © 2008 American Institute of Physics.

[164] Kyriakidou K., Lucarini G., Zizzi A., Salvolini E., Mattioli Belmonte M., Mollica F., Gloria A., Ambrosio L., Dynamic co-seeding of osteoblast and endothelial cells on 3D polycaprolactone scaffolds for enhanced bone tissue engineering, Journal of Bioactive and Compatible Polymers, 23(3), 227-243, (2008). Abstract
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Abstract: Tissue engineered scaffolds must have an organized and repeatable microstructure which enables cells to assemble in an ordered matrix that allows adequate nutriental perfusion. In this work, to evaluate the reciprocal cell interactions of endothelial and osteoblast-like cells, human osteoblast-like cells (MG63) and Human Umbilical Vein Endothelial Cells (HUVEC) were co-seeded onto 3D geometrically controlled porous poly(ε-caprolactone) (PCL) and cultured by means of a rotary cell culture system (RCCS-4DQ). In our dynamic co-culture system, the lack of significant enhancement of osteoblast ALP activity and ECM production indicated that the microgravity conditions of the rotary system affected the cells by favoring their proliferation and cellular cross-talk. These results emphasize how osteoblasts increase endothelial cell proliferate and endothelial cells amplify the growth of osteoblasts but decrease their differentiation. This dynamic seeding of osteoblasts and endothelial cells onto a 3D polymeric scaffold may represent a unique approach for studying the mechanisms of interaction of endothelial and osteoblast cells as well as achieve a functional hybrid in which angiogenesis, furnished by neo-vascular organization of endothelial cells may further support osteoblasts growth. Furthermore, this in vitro model may be useful in examining the applicability of novel material structures for tissue engineering. © SAGE Publications 2008.

Keywords: 3D scaffolds | Dynamic co-culture | Poly-ε- caprolactone | Rapid prototyping | Tissue engineering

[165] Gloria A., Causa F., De Santis R., Netti P.A., Ambrosio L., Dynamic-mechanical properties of a novel composite intervertebral disc prosthesis, Journal of Materials Science: Materials in Medicine, 18(11), 2159-2165, (2007). Abstract
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Abstract: Over the past years, a tremendous effort has been made to develop an intervertebral disc (IVD) prosthesis with suitable biological, mechanical and transport properties. However, it has been frequently reported that current prostheses undergo failure mainly due to the mismatch between the mechanical properties of the conventional device and the spine segment to be replaced. The aim of the present work was to develop a poly(2-hydroxyethyl methacrylate)/poly(methyl methacrylate) (PHEMA/PMMA) (80/20 w/w) semi-interpenetrating polymer network (s-IPN) composite hydrogel reinforced with poly(ethylene terephthalate) (PET) fibres, and to investigate the static and dynamic mechanical properties. Filament winding and moulding technologies were employed to obtain the composite IVD prostheses with the unique complex structure that is peculiar to the natural IVD. The compressive properties analysis showed the typical J-shaped stress-strain curve which is displayed by natural IVDs. Compressive modulus varied from 84 to 120 MPa, as a function of the strain rate, and stress was higher than 10 MPa. These values are in the range of those of the natural lumbar IVDs. No failure of the prostheses has occurred during fatigue test performed for ten million cycles in physiological solution. Dynamic mechanical tests have confirmed the composite IVD prostheses exhibited appropriate viscoelastic properties. © 2007 Springer Science+Business Media, LLC.

[166] De Santis R., Gloria A., Ronca D., Guida G., Nicolais L., Ambrosio L., Structural and mechanical properties of the cement-bone composite, Journal of Applied Biomaterials and Biomechanics, 4(3), 194, (2006).
[167] Gloria A., De Santis R., Ronca D., Guida G., Nicolais L., Ambrosio L., Biomechanical behavior of spongy bone: Dynamic-mechanical effects, Journal of Applied Biomaterials and Biomechanics, 4(3), 195-196, (2006).