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Angiogenesis, the development of new blood capillaries, is crucial for the wound healing process. This biological process allows the proper blood supply to the tissue, essential for cell proliferation and viability. Several biological factors modulate angiogenesis, however the vascular endothelial growth factor (VEGF) is the main one. Given the complexity of angiogenesis, in the last years, computational modelling aroused the interest of scientists since it allows to model this process with different, more economic and faster methodologies, comparatively to experimental approaches. In this work, a mathematical model motivated by the analysis of the effect of VEGF diffusion gradient in endothelial cell migration is presented. This is the process that allows capillary formation and it is essential for angiogenesis. The proposed mathematical model is combined with the Radial Point Interpolation Method, being the area discretized considering an unorganized nodal cloud and a background mesh of integration points, without predefined relations. The nodal connectivity was achieved using the "influence-domain" approach. The interpolation functions were constructed using the Radial Point Interpolators techniques. This method combines a radial basis functions with a polynomial functions to obtain the approximation. This preliminary work does not account for the whole complexity of cell and tissue biology, and numerical results are presented for an idealised two-dimensional setting. Nevertheless, the developed RPIM software is a valid numerical tool that can be adjusted to biological problems and may also be able to complement the biological and medical subjects., (© 2020 John Wiley & Sons Ltd.)

Purpose: Bone is a hierarchical material that can be characterized from the microscale to macroscale. Multiscale models make it possible to study bone remodeling, inducing bone adaptation by using information of bone multiple scales. This work proposes a computationally efficient homogenization methodology useful for multiscale analysis. This technique is capable to define the homogenized microscale mechanical properties of the trabecular bone highly heterogeneous medium., Methods: In this work, a morphology- based fabric tensor and a set of anisotropic phenomenological laws for bone tissue was used, in order to define the bone micro-scale mechanical properties. To validate the developed methodology, several examples were performed in order to analyze its numerical behavior. Thus, trabecular bone and fabricated benchmarks patches (representing special cases of trabecular bone morphologies) were analyzed under compression., Results: The results show that the developed technique is robust and capable to provide a consistent material homogenization, indicating that the homogeneous models were capable to accurately reproduce the micro-scale patch mechanical behavior., Conclusions: The developed method has shown to be robust, computationally less demanding and enabling the authors to obtain close results when comparing the heterogeneous models with equivalent homogenized models. Therefore, it is capable to accurately predict the micro-scale patch mechanical behavior in a fraction of the time required by classic homogenization techniques.

Bone remodeling remains a highly researched topic investigated by many strands of science. The main purpose of this work is formulating a new computational framework for biological simulation, extending the version of the bone remodeling model previously proposed by Komarova. Thus, considering only the biological aspect of the remodeling process, the action of osteoclasts and osteoblasts is taken into account as well as its impact on bone mass. It is conducted a spatiotemporal analysis of a remodeling cycle obtaining a dynamic behavior of bone cells very similar to the biological process already described in the literature. The numerical example used is based on bone images obtained with scanning electron microscopy. During simulation, it is possible to observe the variation of bone's architecture through isomaps. These maps are obtained through the combination of biological bone remodeling models with three distinct numerical techniques-finite element method (FEM), radial point interpolation method (RPIM), and natural neighbor radial point interpolation method (NNRPIM). A study combining these numerical techniques allows to compare their performance. Ultimately, this work supports the inclusion of meshless methods due to their smoother results and its easiness to be combined with medical images from CT scans and MRI., (© 2019 John Wiley & Sons, Ltd.)

Purpose: Bone tissue is a dynamic tissue, possessing different functional requirements at different scales. This layered organization indicates the existence of a hierarchical structure, which can be characterized to distinguish macro-scale from micro-scale levels. Structurally, both scales can be linked by the use of classic multiscale homogenization techniques. Since in bone tissue each micro-scale domain is distinct form its neighbour, applying a classic multiscale homogenization technique to a complete bone structure could represent an inadmissible computational cost. Thus, this work proposes a homogenization methodology that is computationally efficient, presenting a reduced computational cost, and is capable to define the homogenized microscale mechanical properties of the trabecular bone highly heterogeneous medium., Methods: The methodology uses the fabric tensor concept in order to define the material principal directions. Then, using an anisotropic phenomenological law for bone tissue correlating the local apparent density with directional elasticity moduli, the anisotropic homogenized material properties of the micro-scale patch are fully defined. To validate the developed methodology, several numerical tests were performed, measuring the sensitivity of the technique to changes in the micro-patch size and preferential orientation., Results: The results show that the developed technique is robust and capable to provide a consistent material homogenization. Additionally, the technique was combined with two discrete numerical techniques: the finite element method and radial point interpolation meshless method., Conclusions: Structural analyses were performed using real trabecular patches, showing that the proposed methodology is capable to accurately predict the micro-scale patch mechanical behavior in a fraction of the time required by classic homogenization techniques.

The occurrence of wounds is a main health concern in Western society due to their high frequency and treatment cost. During wound healing, the formation of a functional blood vessel network through angiogenesis is an essential process. Angiogenesis allows the reestablishment of the normal blood flow, the sufficient exchange of oxygen and nutrients and the removal of metabolic waste, necessary for cell proliferation and viability. Mathematical and computational models provide new tools to improve the healing process. In fact, over the last thirty years, in silico models have been continuously formulated to describe the effect of several biological and mechanical factors in angiogenesis during wound healing. Additionally, with different levels of complexity, these models allow coupling the human skin structure, to distinct cell types and growth factors, to study extracellular matrix composition and to understand its deformation. This paper discusses how in silico models, which are more economical and less time-consuming comparatively to laboratory methodologies, can help test new strategies to promote/optimize angiogenesis. The continuum, cell-based and hybrid mathematical models of wound healing angiogenesis are reviewed in the present paper, in order to identify possible improvements. Accordingly, the development of higher dimension models incorporating multiscale analysis at molecular, cellular and tissue level remains a challenge that future models should consider., (Copyright © 2018. Published by Elsevier Ltd.)

Vertiginous symptoms are one of the most common symptoms in the world, therefore investing in new ways and therapies to avoid the sense of insecurity during the vertigo episodes is of great interest. The classical maneuvers used during vestibular rehabilitation consist in moving the head in specific ways, but it is not fully understood why those steps solve the problem. To better understand this mechanism, a three-dimensional computational model of the semicircular ducts of the inner ear was built using the finite element method, with the simulation of the fluid flow being obtained using particle methods. To simulate the exact movements performed during rehabilitation, data from an accelerometer were used as input for the boundary conditions in the model. It is shown that the developed model responds to the input data as expected, and the results successfully show the fluid flow of the endolymph behaving coherently as a function of accelerometer data. Numerical results at specific time steps are compared with the corresponding head movement, and both particle velocity and position follow the pattern that would be expected, confirming that the model is working as expected. The vestibular model built is an important starting point to simulate the classical maneuvers of the vestibular rehabilitation allowing to understand what happens in the endolymph during the rehabilitation process, which ultimately may be used to improve the maneuvers and the quality of life of patients suffering from vertigo.

This work has the objective to compare the mechanical behaviour of a brain impact using an alternative numerical meshless technique. Thus, a discrete geometrical model of a brain was constructed using medical images. This technique allows to achieve a discretization with realistic geometry, allowing to define locally the mechanical properties according to the medical images colour scale. After defining the discrete geometrical model of the brain, the essential and natural boundary conditions were imposed to reproduce a sudden impact force. The analysis was performed using the finite element analysis and the radial point interpolation method, an advanced discretization technique. The results of both techniques are compared. When compared with the finite element analysis, it was verified that meshless methods possess a higher convergence rate and that they are capable of producing smoother variable fields.

Purpose: The vestibular system is the part of the inner ear responsible for balance. Vertigo and dizziness are generally caused by vestibular disorders and are very common symptoms in people over 60 years old. One of the most efficient treatments at the moment is vestibular rehabilitation, permitting to improve the symptoms. However, this rehabilitation therapy is a highly empirical process, which needs to be enhanced and better understood., Methods: This work studies the vestibular system using an alternative computational approach. Thus, part of the vestibular system is simulated with a three dimensional numerical model. Then, for the first time using a combination of two discretization techniques (the finite element method and the smoothed particle hydrodynamics method), it is possible to simulate the transient behavior of the fluid inside one of the canals of the vestibular system., Results: The obtained numerical results are presented and compared with the available literature. The fluid/solid interaction in the model occurs as expected with the methods applied. The results obtained with the semicircular canal model, with the same boundary conditions, are similar to the solutions obtained by other authors., Conclusions: The numerical technique presented here represents a step forward in the biomechanical study of the vestibular system, which in the future will allow the existing rehabilitation techniques to be improved.

In this work the maxillary central incisor is numerically analysed with an advance discretization technique--Natural Neighbour Radial Point Interpolation Method (NNRPIM). The NNRPIM permits to organically determine the nodal connectivity, which is essential to construct the interpolation functions. The NNRPIM procedure, based uniquely in the computational nodal mesh discretizing the problem domain, allows to obtain autonomously the required integration mesh, permitting to numerically integrate the differential equations ruling the studied physical phenomenon. A numerical analysis of a tooth structure using a meshless method is presented for the first time. A two-dimensional model of the maxillary central incisor, based on the clinical literature, is established and two distinct analyses are performed. First, a complete elasto-static analysis of the incisor/maxillary structure using the NNRPIM is evaluated and then a non-linear iterative bone tissue remodelling analysis of the maxillary bone, surrounding the central incisive, is performed. The obtained NNRPIM solutions are compared with other numerical methods solutions available in the literature and with clinical cases. The results show that the NNRPIM is a suitable numerical method to analyse numerically dental biomechanics problems.

In this work, a novel anisotropic material law for the mechanical behaviour of the bone tissue is proposed. This new law, based on experimental data, permits to correlate the bone apparent density with the obtained level of stress. Combined with the proposed material law, a biomechanical model for predicting bone density distribution was developed, based on the assumption that the bone structure is a gradually self-optimising anisotropic biological material that maximises its own structural stiffness. The strain and the stress field required in the iterative remodelling process are obtained by means of an accurate meshless method, the Natural Neighbour Radial Point Interpolation Method (NNRPIM). Comparing with other numerical approaches, the inclusion of the NNRPIM presents numerous advantages such as the high accuracy and the smoother stress and strain field distribution. The natural neighbour concept permits to impose organically the nodal connectivity and facilitates the analysis of convex boundaries and extremely irregular meshes. The viability and efficiency of the model were tested on several trabecular benchmark patch examples. The results show that the pattern of the local bone apparent density distribution and the anisotropic bone behaviour predicted by the model for the microscale analysis are in good agreement with the expected structural architecture and bone apparent density distribution.