A mechano-regulation model to design and optimize the surface microgeometry of titanium textured devices for biomedical applications.

In a technological context where, thanks to the additive manufacturing techniques, even sophisticated geometries as well as surfaces with specific micrometric features can be realized, we propose a mechano-regulation algorithm to determine the optimal microgeometric parameters of the surface of textured titanium devices for biomedical applications. A poroelastic finite element model was developed including a portion of bone, a portion of a textured titanium device and a layer of granulation tissue separating the bone from the device and occupying the space between them. The algorithm, implemented in the Matlab environment, determines the optimal values of the root mean square and the correlation length that the device surface must possess to maximize bone formation in the gap between the bone and the device. For low levels of compression load acting on the bone, the algorithm predicts low values of root mean square and high values of correlation length. Conversely, high levels of load require high values of root mean square and low values of correlation length. The optimal microgeometrical parameters were determined for various thickness values of the granulation tissue layer. Interestingly, the predictions of the proposed computational model are consistent with the experimental results reported in the literature. The proposed algorithm shows promise as a valuable tool for addressing the demands of precision medicine. In this approach, the device or prosthesis is no longer designed solely based on statistical averages but is tailored to each patient's unique anthropometric characteristics, as well as considerations related to their metabolism, sex, age, and more.

Optimization of Cobalt-Chromium (Co-Cr) Scaffolds for Bone Tissue Engineering in Endocrine, Metabolic and Immune Disorders.

Approximately 50% of the adult global population is projected to suffer from some form of metabolic disease by 2050, including metabolic syndrome and diabetes mellitus. At the same time, this trend indicates a potential increase in the number of patients who will be in need of implant-supported reconstructions of specific bone regions subjected to inflammatory states. Moreover, physiological conditions associated with dysmetabolic subjects have been suggested to contribute to the severity of bone loss after bone implant insertion. However, there is a perspective evidence strengthening the hypothesis that custom-fabricated bioengineered scaffolds may produce favorable bone healing effects in case of altered endocrine or metabolic conditions. This perspective review aims to share a comprehensive knowledge of the mechanisms implicated in bone resorption and remodelling processes, which have driven researchers to develop metallic implants as the cobalt-chromium (Co-Cr) bioscaffolds, presenting optimized geometries that interact in an effective way with the osteogenetic precursor cells, especially in the cases of perturbed endocrine or metabolic conditions.

Ceramic Materials for Biomedical Applications: An Overview on Properties and Fabrication Processes.

A growing interest in creating advanced biomaterials with specific physical and chemical properties is currently being observed. These high-standard materials must be capable to integrate into biological environments such as the oral cavity or other anatomical regions in the human body. Given these requirements, ceramic biomaterials offer a feasible solution in terms of mechanical strength, biological functionality, and biocompatibility. In this review, the fundamental physical, chemical, and mechanical properties of the main ceramic biomaterials and ceramic nanocomposites are drawn, along with some primary related applications in biomedical fields, such as orthopedics, dentistry, and regenerative medicine. Furthermore, an in-depth focus on bone-tissue engineering and biomimetic ceramic scaffold design and fabrication is presented.

Metals Biotribology and Oral Microbiota Biocorrosion Mechanisms.

During the last decades, metal-based biomaterials have been extensively explored to be used as biocompatible metals for biomedical applications, owing to their superior mechanical properties and corrosion resistance. Consequently, for long-term implanted medical devices, to assure the biomaterials' reliability, functionality, and biocompatibility, studying the various bio-tribological damage mechanisms to obtain the optimum properties is one of the most important goals. In this review, we consider the most important metal-based biomaterials such as stainless steel, alloys of titanium (Ti), cobalt-chromium (Co-Cr), and Nichel-Titatium (Ni-Ti), as well Magnesium (Mg) alloys and with Tantalum (Ta), emphasizing their characteristics, clinical applications, and deterioration over time. The influence of metal elements on biological safety, including significant effects of metal-based biomaterials in dentistry were discussed, considering the perspectives of surface, mechanical properties, corrosion behaviors, including interactions, bio-mechanisms with tissues, and oral environments. In addition, the role of the oral microbiota was explored due to its role in this erosion condition, in order to further understand the mechanism of metal-based biomaterials implanted on the microflora balance of aerobic and anaerobic bacteria in an oral environment.

Design of Materials for Bone Tissue Scaffolds.

The strong impulse recently experienced by the manufacturing technologies as well as the development of innovative biocompatible materials has allowed the fabrication of high-performing scaffolds for bone tissue engineering. The design process of materials for bone tissue scaffolds represents, nowadays, an issue of crucial importance and the object of study of many researchers throughout the world. A number of studies have been conducted, aimed at identifying the optimal material, geometry, and surface that the scaffold must possess to stimulate the formation of the largest amounts of bone in the shortest time possible. This book presents a collection of 10 research articles and 2 review papers describing numerical and experimental design techniques definitively aimed at improving the scaffold performance, shortening the healing time, and increasing the success rate of the scaffold implantation process.

Nanoindentation of mesenchymal stem cells using atomic force microscopy: effect of adhesive cell-substrate structures.

The procedure commonly adopted to characterize cell materials using atomic force microscopy neglects the stress state induced in the cell by the adhesion structures that anchor it to the substrate. In several studies, the cell is considered as made from a single material and no specific information is provided regarding the mechanical properties of subcellular components. Here we present an optimization algorithm to determine separately the material properties of subcellular components of mesenchymal stem cells subjected to nanoindentation measurements. We assess how these properties change if the adhesion structures at the cell-substrate interface are considered or not in the algorithm. In particular, among the adhesion structures, the focal adhesions and the stress fibers were simulated. We found that neglecting the adhesion structures leads to underestimate the cell mechanical properties thus making errors up to 15%. This result leads us to conclude that the action of adhesion structures should be taken into account in nanoindentation measurements especially for cells that include a large number of adhesions to the substrate.

A Body Tracking-Based Low-Cost Solution for Monitoring Workers' Hygiene Best Practices during Pandemics.

Since its beginning at the end of 2019, the pandemic spread of the severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) caused more than one million deaths in only nine months. The threat of emerging and re-emerging infectious diseases exists as an imminent threat to human health. It is essential to implement adequate hygiene best practices to break the contagion chain and enhance society preparedness for such critical scenarios and understand the relevance of each disease transmission route. As the unconscious hand-face contact gesture constitutes a potential pathway of contagion, in this paper, the authors present a prototype system based on low-cost depth sensors able to monitor in real-time the attitude towards such a habit. The system records people's behavior to enhance their awareness by providing real-time warnings, providing for statistical reports for designing proper hygiene solutions, and better understanding the role of such route of contagion. A preliminary validation study measured an overall accuracy of 91%. A Cohen's Kappa equal to 0.876 supports rejecting the hypothesis that such accuracy is accidental. Low-cost body tracking technologies can effectively support monitoring compliance with hygiene best practices and training people in real-time. By collecting data and analyzing them with respect to people categories and contagion statistics, it could be possible to understand the importance of this contagion pathway and identify for which people category such a behavioral attitude constitutes a significant risk.

An Algorithm to Optimize the Micro-Geometrical Dimensions of Scaffolds with Spherical Pores.

Despite the wide use of scaffolds with spherical pores in the clinical context, no studies are reported in the literature that optimize the micro-architecture dimensions of such scaffolds to maximize the amounts of neo-formed bone. In this study, a mechanobiology-based optimization algorithm was implemented to determine the optimal geometry of scaffolds with spherical pores subjected to both compression and shear loading. We found that these scaffolds are particularly suited to bear shear loads; the amounts of bone predicted to form for this load type are, in fact, larger than those predicted in other scaffold geometries. Knowing the anthropometric characteristics of the patient, one can hypothesize the possible value of load acting on the scaffold that will be implanted and, through the proposed algorithm, determine the optimal dimensions of the scaffold that favor the formation of the largest amounts of bone. The proposed algorithm can guide and support the surgeon in the choice of a "personalized" scaffold that better suits the anthropometric characteristics of the patient, thus allowing to achieve a successful follow-up in the shortest possible time.

Mechanobiological Approach to Design and Optimize Bone Tissue Scaffolds 3D Printed with Fused Deposition Modeling: A Feasibility Study.

In spite of the rather large use of the fused deposition modeling (FDM) technique for the fabrication of scaffolds, no studies are reported in the literature that optimize the geometry of such scaffold types based on mechanobiological criteria. We implemented a mechanobiology-based optimization algorithm to determine the optimal distance between the strands in cylindrical scaffolds subjected to compression. The optimized scaffolds were then 3D printed with the FDM technique and successively measured. We found that the difference between the optimized distances and the average measured ones never exceeded 8.27% of the optimized distance. However, we found that large fabrication errors are made on the filament diameter when the filament diameter to be realized differs significantly with respect to the diameter of the nozzle utilized for the extrusion. This feasibility study demonstrated that the FDM technique is suitable to build accurate scaffold samples only in the cases where the strand diameter is close to the nozzle diameter. Conversely, when a large difference exists, large fabrication errors can be committed on the diameter of the filaments. In general, the scaffolds realized with the FDM technique were predicted to stimulate the formation of amounts of bone smaller than those that can be obtained with other regular beam-based scaffolds.

A neural network-based software to recognise blepharospasm symptoms and to measure eye closure time.

Blepharospasm (BSP) is an adult-onset focal dystonia with phenomenologically heterogeneous effects, including, but not limited to, blinks, brief or prolonged spasms, and a narrowing or closure of the eyelids. In spite of the clear and well-known symptomatology, objectively rating the severity of this dystonia is a rather complex task since BSP symptoms are so subtle and hardly perceptible that even expert neurologists can rate the gravity of the pathology differently in the same patients. Software tools have been developed to help clinicians in the rating procedure. Currently, a computerised video-based system is available that is capable of objectively determining the eye closure time, however, it cannot distinguish the typical symptoms of the pathology. In this study, we attempt to take a step forward by proposing a neural network-based software able not only to measure the eye closure, time but also to recognise and count the typical blepharospasm symptoms. The software, after detecting the state of the eyes (open or closed), the movement of specific facial landmarks, and properly implementing artificial neural networks with an optimised topology, can recognise blinking, and brief and prolonged spasms. Comparing the software predictions with the observations of an expert neurologist allowed assessment of the sensitivity and specificity of the proposed software. The levels of sensitivity were high for recognising brief and prolonged spasms but were lower in the case of blinks. The proposed software is an automatic tool capable of making objective 'measurements' of blepharospasm symptoms.

Irregular Load Adapted Scaffold Optimization: A Computational Framework Based on Mechanobiological Criteria.

By combining load adaptive algorithms with mechanobiological algorithms, a computational framework was developed to design and optimize the microarchitecture of irregular load adapted scaffolds for bone tissue engineering. Skeletonized cancellous bone-inspired lattice structures were built including linear fibers oriented along the internal flux of forces induced by the hypothesized boundary conditions. These structures were then converted into solid finite element models, which were optimized with mechanobiology-based optimization algorithms. The design variable was the diameter of the beams included in the scaffold, while the design objective was the maximization of the fraction of the scaffold volume predicted to be occupied by neo-formed bony tissue. The performance of the designed irregular scaffolds, intended as the capability to favor the formation of bone, was compared with that of the regular ones based on different unit cell geometries. Three different boundary and loading conditions were hypothesized, and for all of them, it was found that the irregular load adapted scaffolds perform better than the regular ones. Interestingly, the numerical predictions of the proposed framework are consistent with the results of experimental studies reported in the literature. The proposed framework appears to be a powerful tool that can be utilized to design high-performance irregular load adapted scaffolds capable of bearing complex load distributions.

Recent Advances in Endocrine, Metabolic and Immune Disorders: Mesenchymal Stem Cells (MSCs) and Engineered Scaffolds.

BACKGROUND: New sources of stem cells in adult organisms are constantly emerging. Postnatal Mesenchymal Stem Cells (MSCs), are the most promising support to perform an effective regenerative medicine: such cells have the ability to differentiate into several lineages, such as osteoblasts and chondroblasts, providing novel strategies to improve different complex treatments, during bone regeneration. 3D-printed biomaterials can be designed with geometry aimed to induce stem cells to differentiate towards specific lineage. OBJECTIVE: The interaction between stem cells easy to isolate and engineered 3D-printed scaffolds can translate the tissue bio-engineering into bone regenerative surgery. For those reasons, to better identify the complexity represented by the activities and responses of MSCs requires the advance of new target therapies which are not current in endocrine, metabolic and immune disorders and yet to be developed. METHOD: This topical review briefly focuses on the new approaches of translational medicine with the use of MSCs and scaffolds engineered with the aid of 3D-printing technology, highlights the osteogenic functions and addresses their applications across the breadth of regenerative medicine. RESULTS: The application of bone constructs consisting of the engineered scaffold and MSCs as well as the aspects related to the optimal scaffold geometry that favours the best MSCs differentiation and the improvement of concepts as "sensing surface" were also discussed. CONCLUSION: Regenerative surgery is largely growing in the field of translational medicine. The use of new sources of MSCs and the improvement of new concepts of bio-engineered scaffolds will certainly be the next step of customized medicine.

Comparison of the mechanobiological performance of bone tissue scaffolds based on different unit cell geometries.

Enhancing the performance of scaffolds for bone regeneration requires a multidisciplinary approach involving competences in the fields of Biology, Medicine and Engineering. A number of studies have been conducted to investigate the influence of scaffolds design parameters on their mechanical and biological response. The possibilities offered by the additive manufacturing techniques to fabricate sophisticated and very complex microgeometries that until few years ago were just a geometrical abstraction, led many researchers to design scaffolds made from different unit cell geometries. The aim of this work is to find, based on mechanobiological criteria and for different load regimes, the optimal geometrical parameters of scaffolds made from beam-based repeating unit cells, namely, truncated cuboctahedron, truncated cube, rhombic dodecahedron and diamond. The performance, -expressed in terms of percentage of the scaffold volume occupied by bone-, of the scaffolds based on these unit cells was compared with that of scaffolds based on other unit cell geometries such as: hexahedron and rhombicuboctahedron. A very intriguing behavior was predicted for the truncated cube unit cell that allows the formation of large amounts of bone for low load values and of very small amounts for the medium-high ones. For high values of load, scaffolds made from hexahedron unit cells were predicted to favor the formation of the largest amounts of bone. In a clinical context where medical solutions become more and more customized, this study offers a support to the surgeon in the choice of the best scaffold to be implanted in a patient-specific anatomic region.

Optimal Load for Bone Tissue Scaffolds with an Assigned Geometry.

Thanks to the recent advances of three-dimensional printing technologies the design and the fabrication of a large variety of scaffold geometries was made possible. The surgeon has the availability of a wide number of scaffold micro-architectures thus needing adequate guidelines for the choice of the best one to be implanted in a patient-specific anatomic region. We propose a mechanobiology-based optimization algorithm capable of determining, for bone tissue scaffolds with an assigned geometry, the optimal value Lopt of the compression load to which they should be subjected, i.e. the load value for which the formation of the largest amounts of bone is favoured and hence the successful outcome of the scaffold implantation procedure is guaranteed. Scaffolds based on hexahedron unit cells were investigated including pores differently dimensioned and with different shapes such as elliptic or rectangular. The algorithm predicted decreasing values of the optimal load for scaffolds with pores with increasing dimensions. The optimal values predicted for the scaffolds with elliptic pores were found higher than those with rectangular ones. The proposed algorithm can be utilized to properly guide the surgeon in the choice of the best scaffold type/geometry that better satisfies the specific patient requirements.

Rhombicuboctahedron unit cell based scaffolds for bone regeneration: geometry optimization with a mechanobiology - driven algorithm.

In a context more and more oriented towards customized medical solutions, we propose a mechanobiology-driven algorithm to determine the optimal geometry of scaffolds for bone regeneration that is the most suited to specific boundary and loading conditions. In spite of the huge number of articles investigating different unit cells for porous biomaterials, no studies are reported in the literature that optimize the geometric parameters of such unit cells based on mechanobiological criteria. Parametric finite element models of scaffolds with rhombicuboctahedron unit cell were developed and incorporated into an optimization algorithm that combines them with a computational mechanobiological model. The algorithm perturbs iteratively the geometry of the unit cell until the best scaffold geometry is identified, i.e. the geometry that allows to maximize the formation of bone. Performances of scaffolds with rhombicuboctahedron unit cell were compared with those of other scaffolds with hexahedron unit cells. We found that scaffolds with rhombicuboctahedron unit cell are particularly suited for supporting medium-low loads, while, for higher loads, scaffolds with hexahedron unit cells are preferable. The proposed algorithm can guide the orthopaedic/surgeon in the choice of the best scaffold to be implanted in a patient-specific anatomic region.

Experiencing the Sights, Smells, Sounds, and Climate of Southern Italy in VR.

This article explores what it takes to make interactive computer graphics and VR attractive as a promotional vehicle, from the points of view of tourism agencies and the tourists themselves. The authors exploited current VR and human-machine interface (HMI) technologies to develop an interactive, innovative, and attractive user experience called the Multisensory Apulia Touristic Experience (MATE). The MATE system implements a natural gesture-based interface and multisensory stimuli, including visuals, audio, smells, and climate effects.

Nanoindentation characterisation of human colorectal cancer cells considering cell geometry, surface roughness and hyperelastic constitutive behaviour.

Characterisation of the mechanical behaviour of cancer cells is an issue of crucial importance as specific cell mechanical properties have been measured and utilized as possible biomarkers of cancer progression. Atomic force microscopy certainly occupies a prominent place in the field of the mechanical characterisation devices. We developed a hybrid approach to characterise different cell lines (SW620 and SW480) of the human colon carcinoma submitted to nanoindentation measurements. An ad hoc algorithm was written that compares the force-indentation curves experimentally retrieved with those predicted by a finite element model that simulates the nanoindentation process and reproduces the cell geometry and the surface roughness. The algorithm perturbs iteratively the values of the cell mechanical properties implemented in the finite element model until the difference between the experimental and numerical force-indentation curves reaches the minimum value. The occurrence of this indicates that the implemented material properties are very close to the real ones. Different hyperelastic constitutive models, such as Arruda-Boyce, Mooney-Rivlin and Neo-Hookean were utilized to describe the structural behaviour of indented cells. The algorithm was capable of separating, for all the cell lines investigated, the mechanical properties of cell cortex and cytoskeleton. Material properties determined via the algorithm were different with respect to those obtained with the Hertzian contact theory. This demonstrates that factors such as: the cell geometry/anatomy and the hyperelastic constitutive behaviour, which are not contemplated in the Hertz's theory hypotheses, do affect the nanoindentation measurements. The proposed approach represents a powerful tool that, only on the basis of nanoindentation measurements, is capable of characterising material at the subcellular level.

An Optical System to Monitor the Displacement Field of Glass-fibre Posts Subjected to Thermal Loading.

Endocanalar posts are necessary to build up and retain coronal restorations but they do not reinforce dental roots. It was observed that the dislodgement of post-retained restorations commonly occurs after several years of function and long-term retention may be influenced by various factors such as temperature changes. Temperature changes, in fact, produce micrometric deformations of post and surrounding tissues/materials that may generate high stress concentrations at the interface thus leading to failure. In this study we present an optical system based on the projection moiré technique that has been utilized to monitor the displacement field of endocanalar glass-fibre posts subjected to temperature changes. Measurements were performed on forty samples and the average displacement values registered at the apical and middle region were determined for six different temperature levels. A total of 480 displacement measurements was hence performed. The values of the standard deviation computed for each of the tested temperatures over the forty samples appear reasonably small which proves the robustness and the reliability of the proposed optical technique. The possible implications for the use of the system in the applicative context were discussed.

A Mechanobiology-based Algorithm to Optimize the Microstructure Geometry of Bone Tissue Scaffolds.

Complexity of scaffold geometries and biological mechanisms involved in the bone generation process make the design of scaffolds a quite challenging task. The most common approaches utilized in bone tissue engineering require costly protocols and time-consuming experiments. In this study we present an algorithm that, combining parametric finite element models of scaffolds with numerical optimization methods and a computational mechano-regulation model, is able to predict the optimal scaffold microstructure. The scaffold geometrical parameters are perturbed until the best geometry that allows the largest amounts of bone to be generated, is reached. We study the effects of the following factors: (1) the shape of the pores; (2) their spatial distribution; (3) the number of pores per unit area. The optimal dimensions of the pores have been determined for different values of scaffold Young's modulus and compression loading acting on the scaffold upper surface. Pores with rectangular section were predicted to lead to the formation of larger amounts of bone compared to square section pores; similarly, elliptic pores were predicted to allow the generation of greater amounts of bone compared to circular pores. The number of pores per unit area appears to have rather negligible effects on the bone regeneration process. Finally, the algorithm predicts that for increasing loads, increasing values of the scaffold Young's modulus are preferable. The results shown in the article represent a proof-of-principle demonstration of the possibility to optimize the scaffold microstructure geometry based on mechanobiological criteria.