Methods for medical applications

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.

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

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

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

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

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

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

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

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

Recently, 3D landmark extraction has been widely researched and experimented in medical field, for both corrective and aesthetic purposes. Automation of these procedures on three-dimensional face renderings is something desirable for the specialists who work in this field. In this work we propose a new method for accurate landmark localization on facial scans. The method relies on geometrical descriptors, such as curvatures and Shape Index, for computing candidate and initial points, and on a statistical model based on Procrustes Analysis and Principal Component Analysis, which is fitted to candidate points, for extracting the final landmarks. The elaborated method is independent on face pose. © 2012 Elsevier Ireland Ltd.

Keywords: 3D face , Differential Geometry , Landmark extraction , PCA , Procrustes Analysis

Distance measures and geometrical features are widely used to describe faces. Generally, they are extracted punctually from landmarks, namely anthropometric reference points. The aims are various, such as face recognition, facial expression recognition, face detection, study of changes in facial morphology due to growth, or dysmorphologies. Most of the time, landmarks were extracted with the help of an algorithm or manually located on the faces. Then, measures are computed or geometrical features are extracted to perform the scope of the study. This paper is intended as a survey collecting and explaining all these features, in order to provide a structured user database of the potential parameters and their characteristics. Firstly, facial soft-tissue landmarks are defined and contextualized; then the various measures are introduced and some results are given; lastly, the most important measures are compared to identify the best one for face recognition applications. © 2012 Elsevier B.V. All rights reserved.

Keywords: 3D models , 3D scanners , Face morphology , Soft tissue landmarks

In the field of oral rehabilitation, innovative methodologies based on the combined use of 3D imaging technologies and computer-guided approaches, have been developed with the aim at defining reliable tools for the virtual preoperative assessment of implant placement. The accurate and reliable transfer of the virtual planning into the surgical field represents the main challenge for modern implantology. This paper aims at defining and verifying the clinical applicability of an innovative CAD/CAM framework for the accurate planning of dental implant surgeries based on the integration of Computed Tomography (CT) and surface optical scanning. The higher accuracy and resolution of optical scanning allows a more accurate reconstruction of dentition structures and mouth soft tissues, thus guaranteeing a better fitting of the designed prosthetic structures with respect to the patient oral cavity. © 2012 IEEE.

Keywords: 3D virtual model reconstruction , computer-assisted dental implantology , oral rehabilitation

This work is aimed at designing and constructing a loading rig for the synthetic hemi-pelvis; this system has been conceived with the goal of applying differently oriented articular forces in order to experimentally test the stress distribution and the stability of surgical reconstructions like, for example, hip arthroplasty or pelvic fixation. This device can be interfaced with a usual loading machine; it preserves the anatomy of the hemi-pelvis; it is simply constrained and it allows the simulation of all physiologic activities. Moreover, the visual accessibility of the peri-acetabular area has been guaranteed and this is imperative in order to be able to perform full-field analyses like a thermoelastic or photoelastic stress analysis. First experimental trials have shown a good repeatability of loading-unloading cycles (<1.2%), a low hysteresis (<2.4%) and a good dynamic behaviour (up to 10 Hz loading frequencies).

Keywords: Dynamical loading , Hip arthroplasty , Mechanical test , Pelvic fractures , Pelvis , Thermoelastic stress analysis

The fundamental passive mechanical properties of the bladder need to be known in order to design the most appropriate long-term surgical repair procedures and develop materials for bladder reconstruction. This study has focused on the bladder tissue viscoelastic behavior, providing a comprehensive analysis of the effects of fibers orientation, strain rate and loading history. Whole bladders harvested from one year old fat pigs (160 kg approximate weight) were dissected along the apex-to-base direction and samples were isolated from the lateral region of the wall, as well as along apex-to-base and transverse directions. Uniaxial monotonic (stress relaxation) and cyclic tests at different frequencies have been performed with the Bose Electroforce ® 3200. Normalized stress relaxation functions have been interpolated using a second-order exponential series and loading and unloading stress-strain curves have been interpolated with a non-linear elastic model. The passive mechanical behavior of bladder tissue was shown to be heavily influenced by frequency and loading history, both in monotonic and cyclic tests. The anisotropy of the tissue was evident in monotonic and in cyclic tests as well, especially in tests performed on an exercised tissue and at high frequencies. In contrast, transverse and apex-to-base samples demonstrated an analogous relaxation behavior. © 2012 - IOS Press and the authors. All rights reserved.

Keywords: cycle number , damping , Dynamic , relaxation , stiffness , viscoelastic

Objective: In restored teeth, stresses at the tooth-restoration interface during masticatory processes may fracture the teeth or the restoration and cracks may grow and propagate. The aim was to apply numerical methodologies to simulate the behavior of a restored tooth and to evaluate fatigue lifetimes before crack failure. Materials and methods: Using a CAD-FEM procedure and fatigue mechanic laws, the fatigue damage of a restored molar was numerically estimated. Tessellated surfaces of enamel and dentin were extracted by applying segmentation and classification algorithms, to sets of 2D image data. A user-friendly GUI, which enables selection and visualization of 3D tessellated surfaces, was developed in a MatLab® environment. The tooth-boundary surfaces of enamel and dentin were then created by sweeping operations through cross-sections. A class II MOD cavity preparation was then added into the 3D model and tetrahedral mesh elements were generated. Fatigue simulation was performed by combining a preliminary static FEA simulation with classical fatigue mechanical laws. Results: Regions with the shortest fatigue-life were located around the fillets of the class II MOD cavity, where the static stress was highest. Significance: The described method can be successfully adopted to generate detailed 3D-FE models of molar teeth, with different cavities and restorative materials. This method could be quickly implemented for other dental or biomechanical applications. © 2010 Academy of Dental Materials.

Keywords: 3D fatigue simulation , 3D image acquisition , CAD-FEM modeling , Class II MOD restoration , Micro-CT

In this work a new method for symmetry line recognition, from 3D scanned data of a subject's back, is presented. The new method is validated by comparison with traditional techniques based on cutaneous marking. For this purpose, the upright standing and sitting postures of a sample of 75 subjects, who usually perform different sports activities, are analysed. Error in symmetry line detection is measured as the distance between the estimated symmetry line and the position of the markers. The proposed method is compared with another one described in literature which has been validated in clinical field. Results are analysed and critically discussed. © 2011 CAD Solutions, LLC.

Keywords: Back shape analysis , Posture prediction , Symmetry line

This paper concerns the usage of virtual humans to validate lower limb prosthesis design. In particular, we are developing an innovative design framework centered on digital models of the whole patient or of his/her anatomical districts, which constitute the backbone of the design process. The framework integrates a set of virtual "assistants" to guide the technicians during each design task providing specific knowledge and design rules. In this paper, we focus the attention on the last step of the prosthesis deign process, i.e., the final set-up with the patient using a biomechanical model of the amputee. First, we describe the state of art on virtual humans and main features of the new design framework. Then, the application of virtual humans for the prosthesis set-up is presented as well as preliminary results. Copyright © 2011 by ASME.

Keywords: Lower limb prosthesis , Product development , Virtual humans , Virtual prototyping

Modular lower limb prosthesis is composed by custom-fit parts, such as the socket containing the residual limb, and standard components available on market, such as knee or foot. For both custom and standard parts the support offered by existing design tools is not efficient or integrated enough and, as a result, most prosthetists do not use computer-aided tools and still rely only on their personal expertise. This paper presents an approach to design and configure complete lower limb prosthesis for transfemoral and transtibial amputees, using patient's digital data (e.g., residual limb model acquired by MRI) and specification sheets of components. The ultimate goal is to realise a virtual laboratory where the technicians can design lower limb prosthesis guided step by step by the system. We have identified key patient's characteristics guiding the prosthetist during the four main steps of the production process: acquiring patient's data, socket modelling, standard components selection and prosthesis assembly and check. The developed innovative framework integrates different tools to guide the technicians during each design task providing specific knowledge and rules. Thus, it allows a quicker and easier definition of the virtual prosthesis, on which virtual test could be performed (e.g., pressure distribution on residual limb, gait evaluation) in order to be able to realize the definitive prosthesis at the first attempt. The results have been evaluated and validated with the technical staff of a certified orthopaedic laboratory. © 2011 by ASME.

This paper introduces a virtual laboratory to design prosthetic socket, which integrates a 3D CAD module, named Socket Modelling Assistant (SMA), specifically developed to create the socket digital model, and a CAE system to analyze the stumpsocket interaction. Software tool, named Virtual Socket Lab (VSL), is part of a knowledge-based framework to design lower limb prosthesis centered on digital models of the patient or of his/her anatomical districts. The focus of this paper is on the definition of an automatic simulation procedure to study the stump-socket interaction and validate socket design. We first introduce the new design framework and main features of VSL. Then, we present a state of art on FE models adopted for residual lower-limb and prosthetic socket during last two decades highlighting key issues. Finally, the identified procedure and the integration strategy within SMA are described as well as preliminary results of the experimentation. © 2011 CAD Solutions, LLC.

Keywords: Physics-based modelling and simulation , Socket , Socket-stump interaction

Background: A precise placement of dental implants is a crucial step to optimize both prosthetic aspects and functional constraints. In this context, the use of virtual guiding systems has been recognized as a fundamental tool to control the ideal implant position. In particular, complex periodontal surgeries can be performed using preoperative planning based on CT data. The critical point of the procedure relies on the lack of accuracy in transferring CT planning information to surgical field through custom-made stereo-lithographic surgical guides.Methods: In this work, a novel methodology is proposed for monitoring loss of accuracy in transferring CT dental information into periodontal surgical field. The methodology is based on integrating 3D data of anatomical (impression and cast) and preoperative (radiographic template) models, obtained by both CT and optical scanning processes.Results: A clinical case, relative to a fully edentulous jaw patient, has been used as test case to assess the accuracy of the various steps concurring in manufacturing surgical guides. In particular, a surgical guide has been designed to place implants in the bone structure of the patient. The analysis of the results has allowed the clinician to monitor all the errors, which have been occurring step by step manufacturing the physical templates.Conclusions: The use of an optical scanner, which has a higher resolution and accuracy than CT scanning, has demonstrated to be a valid support to control the precision of the various physical models adopted and to point out possible error sources. A case study regarding a fully edentulous patient has confirmed the feasibility of the proposed methodology. © 2011 Frisardi et al; licensee BioMed Central Ltd.