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.

Real time RULA assessment using Kinect v2 sensor.

The evaluation of the exposure to risk factors in workplaces and their subsequent redesign represent one of the practices to lessen the frequency of work-related musculoskeletal disorders. In this paper we present K2RULA, a semi-automatic RULA evaluation software based on the Microsoft Kinect v2 depth camera, aimed at detecting awkward postures in real time, but also in off-line analysis. We validated our tool with two experiments. In the first one, we compared the K2RULA grand-scores with those obtained with a reference optical motion capture system and we found a statistical perfect match according to the Landis and Koch scale (proportion agreement index = 0.97, k = 0.87). In the second experiment, we evaluated the agreement of the grand-scores returned by the proposed application with those obtained by a RULA expert rater, finding again a statistical perfect match (proportion agreement index = 0.96, k = 0.84), whereas a commercial software based on Kinect v1 sensor showed a lower agreement (proportion agreement index = 0.82, k = 0.34).

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.

Geometry Design Optimization of Functionally Graded Scaffolds for Bone Tissue Engineering: A Mechanobiological Approach.

Functionally Graded Scaffolds (FGSs) are porous biomaterials where porosity changes in space with a specific gradient. In spite of their wide use in bone tissue engineering, possible models that relate the scaffold gradient to the mechanical and biological requirements for the regeneration of the bony tissue are currently missing. In this study we attempt to bridge the gap by developing a mechanobiology-based optimization algorithm aimed to determine the optimal graded porosity distribution in FGSs. The algorithm combines the parametric finite element model of a FGS, a computational mechano-regulation model and a numerical optimization routine. For assigned boundary and loading conditions, the algorithm builds iteratively different scaffold geometry configurations with different porosity distributions until the best microstructure geometry is reached, i.e. the geometry that allows the amount of bone formation to be maximized. We tested different porosity distribution laws, loading conditions and scaffold Young's modulus values. For each combination of these variables, the explicit equation of the porosity distribution law-i.e the law that describes the pore dimensions in function of the spatial coordinates-was determined that allows the highest amounts of bone to be generated. The results show that the loading conditions affect significantly the optimal porosity distribution. For a pure compression loading, it was found that the pore dimensions are almost constant throughout the entire scaffold and using a FGS allows the formation of amounts of bone slightly larger than those obtainable with a homogeneous porosity scaffold. For a pure shear loading, instead, FGSs allow to significantly increase the bone formation compared to a homogeneous porosity scaffolds. Although experimental data is still necessary to properly relate the mechanical/biological environment to the scaffold microstructure, this model represents an important step towards optimizing geometry of functionally graded scaffolds based on mechanobiological criteria.

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.

Effect of Text Outline and Contrast Polarity on AR Text Readability in Industrial Lighting.

Text readability with augmented reality head-worn displays is critical and at present time, there are no standard guidelines to follow. The readability depends mainly on background lighting, display technology (i.e., OST: optical see-through or VST: video see-through), and text style (e.g., plain text, outline or billboard). In this work, we addressed the readability limits for industrial activities. We experimented the effects of two background illuminances levels (1,000 lx for very fine basic industrial tasks and 4,000 lx for fine machining), two commercially available head-worn display technologies, variable outline widths and contrast polarity of text. We analyzed the performance of 12 subjects by collecting about 3,400 measurements using a specific test application and followed by qualitative interviews. With high illuminances, VST performed better than OST, regardless of contrast polarity and outline width. We found that negative contrast polarity is preferable with VST, and that just a minimum outline (1 px) around black text is optimal. On the contrary, positive contrast polarity should be used with OST and outline is not effective. Therefore, we evaluated the usage limits of the OST by sampling its contrast sensitivity function.

Roughness Analysis on Composite Materials (Microfilled, Nanofilled and Silorane) After Different Finishing and Polishing Procedures.

The finishing and polishing of composite materials affect the restoration lifespan. The market shows a variety of finishing and polishing procedures and the choice among them is conditioned by different factors such as the resulting surface roughness. In the present study, 156 samples were realized with three composite materials, -microfilled, nanofilled and silorane-, and treated with different finishing and polishing procedures. Profilometric analyses were carried out on the samples' surface, the measured roughness values were submitted to statistical analysis. A complete factorial plan was drawn up and two-way analysis of variance (ANOVA) was carried out to investigate whether the following factors affect the values of roughness: (i) material; (ii) polishing/finishing procedure. Tukey post-hoc test was also conducted to evaluate any statistically significant differences between the material/procedure combinations. The results show that the tested materials do not affect the resulting surface quality but roughness values depend on the finishing/polishing procedure adopted. The procedures that involve: (a) the finishing with medium Sof-Lex discs and (b) the finishing with two tungsten carbide multi-blade milling cutters Q series and UF series are those that allow the lowest values of roughness to be obtained.

Text readability in head-worn displays: color and style optimization in video versus optical see-through devices.

Efficient text visualization in head-worn augmented reality (AR) displays is critical because it is sensitive to display technology, text style and color, ambient illumination and so on. The main problem for the developer is to know the optimal text style for the specific display and for applications where color coding must be strictly followed because it is regulated by laws or internal practices. In this work, we experimented the effects on readability of two head-worn devices (optical and video see-through), two backgrounds (light and dark), five colors (white, black, red, green, and blue), and two text styles (plain text and billboarded text). Font type and size were kept constant. We measured the performance of 15 subjects by collecting about 5,000 measurements using a specific test application and followed by qualitative interviews. Readability turned out to be quicker on the optical see-through device. For the video see-through device, background affects readability only in case of text without billboard. Finally, our tests suggest that a good combination for indoor augmented reality applications, regardless of device and background, could be white text and blue billboard, while a mandatory color should be displayed as billboard with a white text message.