Methods for medical applications

Many foot pathologies are prevented or treated with Custom Made Insoles (CMIs). Although a strong computerization has characterized the shoe development process during the last decade, the CMI sector still lacks a software platform integrating the design and diagnosis tools used by the stakeholders of this area. Moreover, the prescription of CMIs is only based on the experience of skilled podiatrists rather than on a common and shared knowledge (e.g. guidelines, best practices, rules, etc.). This paper presents a multi-users and knowledge-based platform, called Smart Prescription Platform (SPP), covering the whole CMI development phases, from foot diagnosis to the production, involving clinicians, patients, manufacturers and controllers. The web-based platform is fully integrated with the technologies available in the orthopaedic sector, which are 3D/4D scanners, baropodometric platforms, footwear virtual catalogues, plantar pressure simulators, Augmented Reality devices and 3D CAD systems. The use of standard file formats (e.g.stl,.bmp,.xml) allows an electronic dataflow among the tools. The main module of the platform, called Prescription System (PS), is used for prescribing custom-made insoles for patients with different health conditions, satisfying the needs of all actors and optimizing the data exchange. PS is a knowledge-based prescription system integrating the best practices related to the prescription of CMIs. The PS output is a XML file representing the electronic order, used to exchange data with the other tools of the SPP. The proposed platform has been tested with a twofold aim: to validate the usability of the Prescription System and the inter-operability of the platform tools. The positive results gathered during the validation, led the experts to start using the web platform for their daily work.

Keywords: Collaborative platform , Custom Made Insole , Insole prescription , Knowledge-based platform , Web-based platform

Diagnosis and treatment of orbital wall fractures are based on both physical examination and computed tomography scan of the orbital cavity. The present paper reports on the secondary reconstruction of the skeletal orbit following untreated orbital floor fracture in a patient wearing an ocular prosthesis because of an orbital trauma. A computer-assisted approach, based on anatomical modelling and custom-made mould fabrication via selective laser sintering, is proposed for manufacturing a preformed orbital implant. Such a procedure offers precise and predictable results for orbital reconstructions. This protocol proved an effective reduction of operating time, patient morbidity and a fast and low-cost preoperative planning procedure. Such an approach can be used for immediate and in-office manufacturing of custom implants in trauma and reconstructive patients.

Keywords: computer aided surgery , ocular prosthesis , Orbital wall reconstruction , surgical tools

The custom-made insole is largely recognized as the most important orthotics for decreasing the foot plantar pressure, using additions or cutouts, which modify the geometry of the insole. This paper proposes a procedure for supporting the clinicians in prescribing innovative custom made insoles for offloading the plantar pressure by using specific combinations of materials for the foot peak-pressure areas, without modifying the geometry of the insole. The process starts with the acquisition of the plantar pressure map of the customer and ends with the definition of the customised insole. The aim of the procedure is choosing the best combination of materials for each foot anatomical area for reducing the plantar pressure peaks below a maximum admissible pressure value decided by the physician. The positions and dimensions of the inserts are defined through analyzing the customer plantar pressure while the inserts materials are defined using FEM simulations of the insole-foot interaction. The case study showed a plantar pressure reduction congruent with the FEM simulations results. This procedure is applicable both for subtractive and additive manufacture techniques.

Keywords: Biomedical design , Custom made insole , Design process , Pressure offloading , Simulation

Many diseases of the spine require surgical treatments that are currently performed based on the experience of the surgeon. For pedicle arthrodesis surgery, two critical factors must be addressed: Screws must be applied correctly and exposure to harmful radiation must be avoided. The incorrect positioning of the screws may cause operating failures that lead to subsequent reoperations, an increase in the overall duration of surgery and, therefore, more harmful, real-time X-ray checks. In this paper, the authors solve these problems by developing a method to realize a customized surgical template that acts as a drilling template. The template has two cylindrical guides that follow a correct trajectory previously calculated by means of an automatic algorithm generated on the basis of a vertebra CAD model for a specific patient. The surgeon sets the template (drilling guides) on the patient's vertebra and safely applies the screws. Three surgical interventions for spinal stabilization have been performed using the template. These have had excellent results with regard to the accuracy of the screw positioning, reduction of the overall duration of the intervention, and reduction of the number of times the patient was exposed to X-rays.

Keywords: Pedicle arthrodesis , Screw direction optimization , Spine surgery , Surgical template , X-ray minimization

This work shows the practical application and the experimental validation of a procedure based on an algorithm, running in a finite element environment, able to operate inside a convex three-dimensional solid by replacing the continuous mass with an appropriate cancellous bone-inspired space frame sharing, with the solid, the border and organized for having the fibres oriented according to the boundary conditions. The purpose is to reach the maximum mechanical efficiency realizing a load adaptive space frame optimized in terms of weight. Young's moduli of a cubic virtual specimen were numerically estimated. Fifteen specimens were printed by a 3D printer using a titanium alloy. Numerical results were compared with experimental ones obtained by tensile tests. The simulation results confirmed the validity of the FEM “beam element-based” space frame.

Keywords: 3-Dimensional printing , Directional orientation , Fibres , Finite element analysis (FEA) , Mechanical testing

The associated risk for a patient taking advantage of Helicopter Emergency Medical Services (HEMS) mainly relates to vibrations. To this aim, especially in case of trauma and serious illness and long travels, aspects related to the vibrations effects on the patient needs to be properly investigated, taking into account the particular features of the helicopter used for HEMS. The purpose of this paper is the integrated simulation of vertical vibration at the supine patient's body, lying down on a rescue litter, in HEMS. Here, a 3D structural model of a reference helicopter, the Aerospatiale Gazelle, has been developed in ABAQUS and integrated with a dynamic model where aerodynamic forcing functions due to rotor are modelled. The accelerations at the litter location in the helicopter structural model are recorded and used as inputs to the supine patient's body model in MATLAB. The Multi-Body (MB) model of the patient's body consists of three interconnected masses of the head-neck, torso-arms and pelvis-legs. The simulation is carried out for single manoeuvre and the vibration information is extracted at the three body segments. This predictive approach of integrated simulation of the helicopter-patient is an effective tool in investigating of biodynamic response of the patient in HEMS. The benefits of this approach are reducing the risk and costs of running the experiments, providing suggestions on redesigning of litters and controlling the vibration on the litters in HEMS.

Keywords: Helicopter Emergency Medical Service , HEMS , Simulation , Structural model , Supine patient's body , Vertical vibration

HoloLens technology enables mixed reality experiences that integrate holographic objects into the real world in which the mixed reality head-mounted device is used. Since HoloLens' launch in March 2016, some mixed-reality applications of this technology have been announced or showcased, addressing different fields, including education, data visualization, tourism, entertainment, and professional training e.g., in medicine, architecture, manufacturing, and engineering. Still, a limited number of reported research provide examples of user experience designs and evaluations for applications using HoloLens. We are interested in the use of HoloLens as therapeutic tool for people with the Alzheimer's Disease. The paper describes a set of therapeutic activities that have been designed in cooperation with neurologists and aim at stimulating short term memory and spatial memory in this target group. We also report a preliminary study of the usability of these activities among the elderly subjects.

Keywords: Alzheimer's , Augmented reality , Cognitive training , Hologram , HoloLens , Memory , Mixed reality , Rehabilitation

The aim of regenerative medicine is replacing missing or damaged bone tissues with synthetic grafts based on porous interconnected scaffolds, which allow adhesion, growth, and proliferation of the human cells. The optimal design of such scaffolds, in the Bone Tissue Engineering field, should meet several geometrical requirements. First, they have to be customized to replicate the skeletal anatomy of the patient, and then they have to provide the proper trabecular structure to be successfully populated by the cells. Therefore, for modelling such scaffolds, specific design methods are needed to conceive extremely complex structures by controlling both macro and micro shapes. For this purpose, in the last years, the Computer Aided Design of Triply Periodic Minimal Surfaces has received considerable attention, since their presence in natural shapes and structures. In this work, we propose a method that exploit Triply Periodic Minimal Surfaces as unit cell for the development of customized trabecular scaffolds. The aim is to identify the mathematical parameters of these surfaces in order to obtain the target requirements of the bone grafts. For that reason, the method is implemented through a Generative Design tool that allow to interactively controlling both the porosity and the pores size of the scaffolds.

Keywords: Bone tissue engineering , Generative design , Scaffold design , Triple periodic minimal surfaces

Titanium and its alloys are widely used in cranioplasty because they are biocompatible with excellent mechanical properties and favor the osseointegration with the bone. However, when Titanium alloys have to be worked several problems occurred from a manufacturing point of view: the standard procedure for obtaining Titanium prostheses is represented by the machining processes, which result time and cost consuming. The aim of this research consist to introduce alternative flexible sheet forming processes, i.e. Super Plastic Forming (SPF) and Single Point Incremental Forming (SPIF), for the manufacturing of patient-oriented titanium prostheses. The research activities have already highlighted the potentiality of the investigated forming processes that can be alternatively used taking into account both the damage morphology and the need of urgency operation. In the present work, the way of manufacturing the Ti prostheses by SPF and SPIF is described. A comparative analysis has been performed, thus highlighting the peculiarities of the investigated processes and the prostheses feasibility.

Keywords: Single Point Incremental Forming , Super Plastic Forming , Titanium alloy

Blepharospasm is characterized by bilateral, synchronous, and symmetric involuntary orbicularis oculi muscle spasms leading to partial/total eyelid closure. We proposed a comprehensive method for assessing the severity of blepharospasm cases, based on expert observation of fixed-length video recordings and natural feature detection algorithms. The developed software detects involuntary spasms and blinks in order to evaluate BSP severity. In this work we have considered a new BSP severity scale to realize an objective evaluation of BSP severity.

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(É›-caprolactone)/iron-doped hydroxyapatite (PCL/FeHA) nanocomposite scaffolds.

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

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.

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

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

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

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

Ultrasound scans, Computed Axial Tomography, Magnetic Resonance Imaging are only few examples of medical imaging tools boosting physicians in diagnosing a wide range of pathologies. Anyway, no standard methodology has been defined yet to extensively exploit them and current diagnoses procedures are still carried out mainly relying on physician's experience. Although the human contribution is always fundamental, it is self-evident that an automatic procedure for image analysis would allow a more rapid and effective identification of dysmorphisms. Moving toward this purpose, in this work we address the problem of feature extraction devoted to the detection of specific diseases involving facial dysmorphisms. In particular, a bounded Depth Minimum Steiner Trees (D-MST) clustering algorithm is presented for discriminating groups of individuals relying on the manifestation/absence of the labio-schisis pathology, commonly called cleft lip. The analysis of three-dimensional facial surfaces via Differential Geometry is adopted to extract landmarks. The extracted geometrical information is furthermore elaborated to feed the unsupervised clustering algorithm and produce the classification. The clustering returns the probability of being affected by the pathology, allowing physicians to focus their attention on risky individuals for further analysis.

Keywords: Artificial intelligence , Clustering , D-MST , Decision support , Diagnosis , Facial dysmorphism , Feature extraction , Labio-schisis , Landmarking

3D face was recently investigated for various applications, including biometrics and diagnosis. Describing facial surface, i.e. how it bends and which kinds of patches is composed by, is the aim of studies of Face Analysis, whose ultimate goal is to identify which features could be extracted from three-dimensional faces depending on the application. In this study, we propose 105 novel geometrical descriptors for Face Analysis. They are generated by composing primary geometrical descriptors such as mean, Gaussian, principal curvatures, shape index, curvedness, and the coefficients of the fundamental forms, and by applying standard functions such as sine, cosine, and logarithm to them. The new descriptors were mapped on 217 facial depth maps and analysed in terms of descriptiveness of facial shape and exploitability for localizing landmark points. Automatic landmark extraction stands as the final aim of this analysis. Results showed that some newly generated descriptors were sounder than the primary ones, meaning that their local behaviours in correspondence to a landmark position is thoroughly specific and can be registered with high similarity on every face of our dataset.

Keywords: 3D face , Face analysis , Face expression recognition , Face recognition , Geometry , Landmarks

This work proposes a methodology to automatically diagnose and formalize prenatal cleft lip with representative key points and identify the type of defect (unilateral, bilateral, right, or left) in three-dimensional ultrasonography (3D US). Differential Geometry has been used as a framework for describing facial shapes and curvatures. Then, descriptors coming from this field are employed for identifying the typical key points of the defect and its dimensions. The descriptive accurateness of these descriptors has allowed us to automatically extract reference points, quantitative distances, labial profiles, and to provide information about facial asymmetry. Seventeen foetal faces, nine of healthy foetuses and eight with different types of cleft lips, have been obtained through a Voluson system and used for testing the algorithm. In case no defect is present, the algorithm detects thirteen standard facial soft-tissue landmarks. This would help ultrasonographists and future mothers in identifying the most salient points of the forthcoming baby. This algorithm has been designed to support practitioners in identifying and classifying cleft lips. The gained results have shown that differential geometry may be a valuable tool for describing faces and for diagnosis.

Keywords: 3D ultrasound , Cleft lip , Dysmorphisms , Landmarking , Syndrome diagnosis

As the interest in human face grows, facial landmarks become more and more important for a large variety of fields and applications. Multipurpose medical is evidently leading in this sense, but others such as skull study for crime scenes, sex estimation, and attractiveness quantification, morphological and cephalometric analyses are present. A cluster analysis of the examined papers is performed depending on scope, landmarking method, and facial database features. The purpose is to face these topics by providing the reader with a comprehensive view of what 3D facial landmarks are and what "they have been up to" in 2014 and 2015. The aim is to offer to users the very up-todate scenario, the best outcomes, i.e., the latest frontier of landmarks' talents and skills. The third dimension allowed to select the most prominent contributions, especially in terms of scientific advance innovativeness.

Keywords: 3D face , Cluster analysis , Fiducial point , Landmarks , Soft-tissue landmark, hard-tissue landmark