Cleft Alveolar Bone Graft Materials: Literature Review.

INTRODUCTION: Since the early stages of alveolar bone grafting development, multiple types of materials have been used. Iliac cancellous bone graft (ICBG) remains the gold standard. DESIGN/METHODS: A review of literature is conducted in order to describe the different bone filling possibilities, autologous or not, and to assess their effectiveness compared to ICBG. This review focused on studies reporting volumetric assessment of the alveolar cleft graft result (by computed tomography scan or cone beam computed tomography). RESULTS: Grafting materials fall into 3 types: autologous bone grafts, ICBG supplementary material, and bone substitutes. Among autologous materials, no study showed the superiority of any other bone origin over iliac cancellous bone. Yet ICBG gives inconsistent results and presents donor site morbidity. Concerning supplementary material, only 3 studies could show a benefit of adding platelet-rich fibrin (1 study) or platelet-rich plasma (2 studies) to ICBG, which remains controversial in most studies. There is a lack of 3-dimensional (3D) assessment in most articles concerning the use of scaffolds. Only one study showed graft improvement when adding acellular dermal matrix to ICBG. Looking at bone substitutes highlights failures among bioceramics alone, side-effects with bone morphogenetic protein-2 composite materials, and difficulties in cell therapy setup. Studies assessing cell therapy-based substitutes show comparable efficacy with ICBG but remain too few. CONCLUSION: This review highlights the lack of 3D assessments in the alveolar bone graft materials field. Nothing dethroned ICBG from its position as the gold standard treatment at this time.

A New Software Suite in Orthognathic Surgery : Patient Specific Modeling, Simulation and Navigation.

Orthognathic surgery belongs to the scope of maxillofacial surgery. It treats dentofacial deformities consisting in discrepancy between the facial bones (upper and lower jaws). Such impairment affects chewing, talking, and breathing and can ultimately result in the loss of teeth. Orthognathic surgery restores facial harmony and dental occlusion through bone cutting, repositioning, and fixation. However, in routine practice, we face the limitations of conventional tools and the lack of intraoperative assistance. These limitations occur at every step of the surgical workflow: preoperative planning, simulation, and intraoperative navigation. The aim of this research was to provide novel tools to improve simulation and navigation. We first developed a semiautomated segmentation pipeline allowing accurate and time-efficient patient-specific 3D modeling from computed tomography scans mandatory to achieve surgical planning. This step allowed an improvement of processing time by a factor of 6 compared with interactive segmentation, with a 1.5-mm distance error. Next, we developed a software to simulate the postoperative outcome on facial soft tissues. Volume meshes were processed from segmented DICOM images, and the Bullet open source mechanical engine was used together with a mass-spring model to reach a postoperative simulation accuracy <1 mm. Our toolset was completed by the development of a real-time navigation system using minimally invasive electromagnetic sensors. This navigation system featured a novel user-friendly interface based on augmented virtuality that improved surgical accuracy and operative time especially for trainee surgeons, therefore demonstrating its educational benefits. The resulting software suite could enhance operative accuracy and surgeon education for improved patient care.

Investigation of the human bridging veins structure using optical microscopy.

In this paper, we investigated the brain-sinus junction and especially the bridging veins linking these two organs. Two types of optical microscopy were used: conventional optical microscopy and digital microscopy. We used thin histological sections prepared from a human brain, and stained with Masson's trichrome, hemalun and orcein. Finally we observed the path of the bridging vein inside the brain-skull interface. At smaller scales, wavy collagen fiber bundles were found and characterized inside the vein walls. Taking into account the orientations of the different sections with reference to frontal planes, we found that the bridging vein has a very complex geometry, which increases the difficulty to determine fiber orientations in its walls. Nevertheless, we found that collagen fiber bundles are mainly circumferentially oriented in the superior sagittal sinus walls. In this paper, we were able to characterize precisely the path of the bridging vein from the brain to the sinus, with different magnifications.

Prediction of osteoporotic degradation of tibia human bone at trabecular scale.

A theoretical numerical model is proposed to predict patient dependent osteoporotic bone degradation. The model parameters are identified through a particle swarm optimization algorithm and based on individual patient high resolution peripherical quantitative computer tomography (HRpQCT) scan data. The degradation model is based on cellular activity initiated by the elastic strain energy developed in the bone microstructure through patient's body weight. The macro (organ scale) and meso (trabecular scale) scale analyses are carried out and predicted bone volume fraction and microstructure evolution are compared with in-vivo experimental bone degradation for four elderly women over a period of 10 years. A significant correlation (r > 0.9) is observed between the model predictions and in-vivo experiments in all cases with an average deviation error of 1.46%. The model can easily be extended to other patients and provide good predictions for different population categories such as ethnicity, gender, age, etc.

Decisive structural elements in water and ion permeation through mechanosensitive channels of large conductance: insights from molecular dynamics simulation.

In this paper, a series of equilibrium molecular dynamics simulations (EMD), steered molecular dynamics (SMD), and computational electrophysiology methods are carried out to explore water and ion permeation through mechanosensitive channels of large conductance (MscL). This research aims to identify the pore-lining side chains of the channel in different conformations of MscL homologs by analyzing the pore size. The distribution of permeating water dipole angles through the pore domains enclosed by VAL21 and GLU104 demonstrated that water molecules are oriented toward the charged oxygen headgroups of GLU104 from their hydrogen atoms to retain this interaction in a stabilized fashion. Although, this behavior was not perceived for VAL21. Numerical assessments of the secondary structure clarified that, during the ion permeation, in addition to the secondary structure alterations, the structure of Tb-MscL would also undergo significant conformational changes. It was elucidated that VAL21, GLU104, and water molecules accomplish a fundamental task in ion permeation. The mentioned residues hinder ion permeation so that the pulling SMD force is increased remarkably when the ions permeate through the domains enclosed by VAL21 and GLU102. The hydration level and potassium diffusivity in the hydrophobic gate of the transmembrane domain were promoted by applying the external electric field. Furthermore, the implementation of an external electric field altered the distribution pattern for potassium ions in the system while intensifying the accumulation of Cl- in the vicinity of ARG11 and ARG98.

Prediction of Cortical Bone Thickness Variations in the Tibial Diaphysis of Running Rats.

A cell-mechanobiological model is used for the prediction of bone density variation in rat tibiae under medium and high mechanical loads. The proposed theoretical-numerical model has only four parameters that need to be identified experimentally. It was used on three groups of male Wistar rats under sedentary, moderate intermittent and continuous running scenarios over an eight week period. The theoretical numerical model was able to predict an increase in bone density under intermittent running (medium intensity mechanical load) and a decrease of bone density under continuous running (higher intensity mechanical load). The numerical predictions were well correlated with the experimental observations of cortical bone thickness variations, and the experimental results of cell activity enabled us to validate the numerical results predictions. The proposed model shows a good capacity to predict bone density variation through medium and high mechanical loads. The mechanobiological balance between osteoblast and osteoclast activity seems to be validated and a foreseen prediction of bone density is made available.

A Microfabrication Method of PCL Scaffolds for Tissue Engineering by Simultaneous Two PDMS Molds Replication.

Not very far away, "tissue engineering" will become one of the most important branches of medical science for curing many types of diseases. This branch needs the cooperation of a wide range of sciences like medicine, chemistry, cellular biology, and genetic and mechanical engineering. Different parameters affect the final produced tissue, but the most important one is the quality and biocompatibility of the scaffold with the desired tissue which can provide the functionality of "native ECM" as well. The quality of the scaffold is directly dependent on its materials, design, and method of fabrication. As to the design and fabrication, there are two main categories: (a) random microporosity such as phase separation, electrospinning, and fused deposition modeling (3D printing) and (b) designed microporosity mostly achievable by stereo lithography and soft lithography. The method of fabrication implemented in this research is a novel method in soft lithography employing a type of "replica molding" with one pair of polydimethylsiloxane (PDMS) molds in contrast to traditional replica molding with just one single mold. In this operation, the solution of polycaprolactone in chloroform is initially prepared, and one droplet of the solution is placed between the molds while a preset pressure is applied to maintain the molds tightly together during the solidification of the polymer layer and vaporization of the solvent. Thus, a perfect warp and woof pattern is created. In this research, it has been approved that this is a feasible method for creating complex patterns and simple straight fiber patterns with different spacings and pore sizes. Cell attachment and migration was studied to find the optimum pore size. It was shown that the small pore size improves the cells' adhesion while reducing cell migration capability within the scaffold.

A novel machine learning based computational framework for homogenization of heterogeneous soft materials: application to liver tissue.

Real-time simulation of organs increases comfort and safety for patients during the surgery. Proper generalized decomposition (PGD) is an efficient numerical method with coordinate errors below 1 mm and response time below 0.1 s that can be used for simulated surgery. For input of this approach, nonlinear mechanical properties of each segment of the liver need to be calculated based on the geometries of the patient's liver extracted using medical imaging techniques. In this research work, a map of the mechanical properties of the liver tissue has been estimated with a novel combined method of the finite element (FE) optimization. Due to the existence of major-size vessels in the liver that makes the surrounding tissue anisotropic, the simulation of hyperelastic material with two different sections is computationally expensive. Thus, a homogenized, anisotropic, and hyperelastic model with the nearest response to the real heterogeneous model was developed and presented. Because of various possibilities of the vessel orientation, position, and size, homogenization has been carried out for adequate samples of heterogeneous models to train artificial neural networks (ANNs) as machine learning tools. Then, an unknown sample of heterogeneous material was categorized and mapped to its homogenized material parameters with the trained networks for the fast and low-cost generalization of our combined FE optimization method. The results showed the efficiency of the proposed novel machine learning based technique for the prediction of effective material properties of unknown heterogeneous tissues.

Homogenization of heterogeneous brain tissue under quasi-static loading: a visco-hyperelastic model of a 3D RVE.

Researches, in the recent years, reveal the utmost importance of brain tissue assessment regarding its mechanical properties, especially for automatic robotic tools, surgical robots and helmet producing. For this reason, experimental and computational investigation of the brain behavior under different conditions seems crucial. However, experiments do not normally show the distribution of stress and injury in microscopic scale, and due to various factors are costly. Development of micromechanical methods, which could predict the brain behavior more appropriately, could highly be helpful in reducing these costs. This study presents computational analysis of heterogeneous part of the brain tissue under quasi-static loading. Heterogeneity is created by irregular distribution of neurons in a representative volume element (RVE). Considering time-dependent behavior of the tissue, a visco-hyperelastic constitutive model is developed to predict the RVE behavior more realistically. The RVE is studied in different loads and load rates; 1, 2, 3, 10 and 15% strain load are applied at 0.03 and 0.2 s on the RVE as tensile and shear loads. Due to complexity in geometry, self-consistent approximation method is employed to increase the volume fraction of neurons and analyze RVE behavior in various NVFs. The results show increasing the load rate leads to a raise in the maximum stress that indicates the tissue is more vulnerable at higher rates. Moreover, stiffness of the tissue is enhanced in higher NVFs. Additionally, it is found that axons undergo higher stresses; hence, they are more sensitive in accidents which lead to axonal death and would cause TBI and DAI.

A model order reduction approach to create patient-specific mechanical models of human liver in computational medicine applications.

BACKGROUND AND OBJECTIVE: This paper focuses on computer simulation aspects of Digital Twin models in the medical framework. In particular, it addresses the need of fast and accurate simulators for the mechanical response at tissue and organ scale and the capability of integrating patient-specific anatomy from medical images to pinpoint the individual variations from standard anatomical models. METHODS: We propose an automated procedure to create mechanical models of the human liver with patient-specific geometry and real time capabilities. The method hinges on the use of Statistical Shape Analysis to extract the relevant anatomical features from a database of medical images and Model Order Reduction to compute an explicit parametric solution for the mechanical response as a function of such features. The Sparse Subspace Learning, coupled with a Finite Element solver, was chosen to create low-rank solutions using a non-intrusive sparse sampling of the feature space. RESULTS: In the application presented in the paper, the statistical shape model was trained on a database of 385 three dimensional liver shapes, extracted from medical images, in order to create a parametrized representation of the liver anatomy. This parametrization and an additional parameter describing the breathing motion in linear elasticity were then used as input in the reduced order model. Results show a consistent agreement with the high fidelity Finite Element models built from liver images that were excluded from the training dataset. However, we evidence in the discussion the difficulty of having compact shape parametrizations arising from the extreme variability of the shapes found in the dataset and we propose potential strategies to tackle this issue. CONCLUSIONS: A method to represent patient-specific real-time liver deformations during breathing is proposed in linear elasticity. Since the proposed method does not require any adaptation to the direct Finite Element solver used in the training phase, the procedure can be easily extended to more complex non-linear constitutive behaviors - such as hyperelasticity - and more general load cases. Therefore it can be integrated with little intrusiveness to generic simulation software including more sophisticated and realistic models.

Constitutive Modeling of the Tensile Behavior of Recycled Polypropylene-Based Composites.

The effect of reprocessing on the quasi-static uniaxial tensile behavior of two commercial polypropylene (PP)-based composites is experimentally investigated and modeled. In particular, the studied materials consist of an unfilled high-impact PP and a talc-filled high-impact PP. These PP composites are subjected to repeated processing cycles, including a grinding step and an extrusion step to simulate recycling at the laboratory level, the selected reprocessing numbers for this study being 0, 3, 6, 9, and 12. Because the repeated reprocessing leads to thermo-mechanical degradation by chain scission mechanisms, the tensile behavior of the two materials exhibits a continuous decrease of elastic modulus and failure strain with the increasing amount of reprocessing. A physically consistent three-dimensional constitutive model is used to predict the tensile response of non-recycled materials with strain rate dependence. For the recycled materials, the reprocessing effect is accounted by incorporating the reprocessing sensitive coefficient into the constitutive model for Young's modulus, failure strain, softening, and hardening equations. Our predictions of true stress-true strain curves for non-recycled and recycled 108MF97 and 7510-are in good agreement with experimental data and can be useful for industries and companies which are looking for a model able to predict the recycling effect on mechanical behavior of polymer-based materials.

Determinative factors in inhibition of aquaporin by different pharmaceuticals: Atomic scale overview by molecular dynamics simulation.

The inhibition of water permeation through aquaporins by ligands of pharmaceutical compounds is considered as a method to control the cell lifetime. The inhibition of aquaporin 1 (AQP1) by bacopaside-I and torsemide, was explored and its atomistic nature was elucidated by molecular docking and molecular dynamics (MD) simulation collectively along with Poisson-Boltzmann surface area (PBSA) method. Docking results revealed that torsemide has a lower level of docking energy in comparison with bacopaside-I at the cytoplasmic side. Furthermore, the effect of steric constraints on water permeation was accentuated. Bacopaside-I inhibits the channel properly due to the strong interaction with the channel and larger spatial volume, whereas torsemide blocks the cytoplasmic side of the channel imperfectly. The most probable active sites of AQP1 for the formation of hydrogen bonds between the inhibitor and the channel were identified by numerical analysis of the bonds. Eventually, free energy assessments indicate that binding of both inhibitors is favorable in complex with AQP1, and van der Waals interaction has an important contribution in stabilizing the complexes.

Optimization of Taylor spatial frame half-pins diameter for bone deformity correction: Application to femur.

Using external fixtures for bone deformity correction takes advantages of less soft tissue injury, better bone alignment and enhances strain development for bone formation on cutting section, which cause shorter healing time. Among these fixtures, Taylor spatial frame is widely used and includes two rings and six adjustable struts developing 6 degrees of freedom, making them very flexible for this type of application. The current study describes a method to optimize Taylor spatial frame pin-sizes currently chosen from the surgeon's experiences. A three-dimensional model of femur was created from computed tomography images; segmentation of the medical images was made based on the Hounsfield unit (gray scale) in order to allocate adequate mechanical properties into cortical and trabecular bone sections. Both the cortical and trabecular sections were assumed to be isotropic and homogeneous. The diameter optimization of Taylor spatial frame's half-pins was carried out by coupling genetic algorithm and finite element analysis. The finite element analysis was based on a static mechanical load corresponding to a standing person's body weight. Finite element analysis results were validated with experimentally measured strains obtained from bone compression tests. A cost function, based on the developed bone stresses, was defined close to the Taylor spatial frame's half-pins. The calculated cost function showed a decrease of over 33% from the initial half-pin selection by the surgeon and the genetic algorithm optimization. Consequently, the maximum stresses experienced by the bone in the connected location of the half-pins decreased from 121.4 MPa in the surgeon's selection to 73.07 MPa as a result of the optimization process.

Mechanical equilibrium of forces and moments applied on orthodontic brackets of a dental arch: Correlation with literature data on two and three adjacent teeth.

Although orthodontics have greatly improved over the years, understanding of its associated biomechanics remains incomplete and is mainly based on two dimensional (2D) mechanical equilibrium and long-time clinical experience. Little experimental information exists in three dimensions (3D) about the forces and moments developed on orthodontic brackets over more than two or three adjacent teeth. We define here a simplified methodology to quantify 3D forces and moments applied on orthodontic brackets fixed on a dental arch and validate our methodology using existing results from the literature by means of simplified hypotheses.

Experimental quantification of the mechanical forces and moments applied on three adjacent orthodontic brackets.

Orthodontic appliances deliver forces and moments that will determine movement of teeth. To analyze this latter, we developed an experimental setup to measure the mechanical forces applied on the teeth and to calculate, through a simplified theoretical analysis, the reactive forces and corresponding moments onto the brackets of three adjacent teeth. To validate the theoretical and experimental results, we use a simplified clinical situation of a maxillary canine in infraclusion and surrounded by its corresponding upper lateral incisor and first premolar. Forces are then measured experimentally and compared with the calculated results. From this, we show the specific dissymmetry of the mechanical forces on each side of the maxillary canine due to the applied mechanical forces and the undesirable induced generated moments occurring on each tooth that will directly impact the bone remodeling process and the final tooth repositioning.

Examples of multiscale and multiphysics numerical modeling of biological tissues.

Predictive theoretical-numerical modeling of the behavior and evolution of biological tissue is a difficult task since many of the required knowledge tools (experimental, theoretical and numerical) are still not well understood. We present here some methodologies and results specific to multiscale and multiphysics numerical modeling of biological tissues applied to the predictive behavior of cortical veins depending on their local constituents' microstructure and for bone remodeling and reconstruction as a function of the local mechanobiology. Although further work is required to improve the accuracy of the developed models, the proposed approaches highlight their potential usefulness for understanding the mechanical-biological couplings, short and long term predictions of biological evolutions as well as possible further transfer to medical applications.

Numerical simulation and identification of macroscopic vascularised liver behaviour: Case of indentation tests.

Mini-invasive surgery restricts the surgeon information to two-dimensional digital representation without the corresponding physical information obtained in previous open surgery. To overcome these drawbacks, real time augmented reality interfaces including the true mechanical behaviour of organs depending on their internal microstructure need to be developed. For the case of tumour resection, we present here a finite element numerical study of the liver mechanical behaviour including the effects of its own vascularisation through numerical indentation tests in order extract the corresponding macroscopic behaviour. The obtained numerical results show excellent correlation of the corresponding force-displacement curves when compared with macroscopic experimental data available in the literature.

Evolution of the three-dimensional collagen structure in vascular walls during deformation: an in situ mechanical testing under multiphoton microscopy observation.

The collagen fibers' three-dimensional architecture has a strong influence on the mechanical behavior of biological tissues. To accurately model this behavior, it is necessary to get some knowledge about the structure of the collagen network. In the present paper, we focus on the in situ characterization of the collagenous structure, which is present in porcine jugular vein walls. An observation of the vessel wall is first proposed in an unloaded configuration. The vein is then put into a mechanical tensile testing device. As the vein is stretched, three-dimensional images of its collagenous structure are acquired using multiphoton microscopy. Orientation analyses are provided for the multiple images recorded during the mechanical test. From these analyses, the reorientation of the two families of collagen fibers existing in the vein wall is quantified. We noticed that the reorientation of the fibers stops as the tissue stiffness starts decreasing, corresponding to the onset of damage. Besides, no relevant evolutions of the out of plane collagen orientations were observed. Due to the applied loading, our analysis also allowed for linking the stress relaxation within the tissue to its internal collagenous structure. Finally, this analysis constitutes the first mechanical test performed under a multiphoton microscope with a continuous three-dimensional observation of the tissue structure all along the test. It allows for a quantitative evaluation of microstructural parameters combined with a measure of the global mechanical behavior. Such data are useful for the development of structural mechanical models for living tissues.

Assessing the three-dimensional collagen network in soft tissues using contrast agents and high resolution micro-CT: Application to porcine iliac veins.

The assessment of the three-dimensional architecture of collagen fibers inside vessel walls constitutes one of the bases for building structural models for the description of the mechanical behavior of these tissues. Multiphoton microscopy allows for such observations, but is limited to volumes of around a thousand of microns. In the present work, we propose to observe the collagenous network of vascular tissues using micro-CT. To get a contrast, three staining solutions (phosphotungstic acid, phosphomolybdic acid and iodine potassium iodide) were tested. Two of these stains were showed to lead to similar results and to a satisfactory contrast within the tissue. A detailed observation of a small porcine iliac vein sample allowed assessing the collagen fibers orientations within the medial and adventitial layers of the vein. The vasa vasorum network, which is present inside the adventitia of the vein, was also observed. Finally, the demonstrated micro-CT staining technique for the three-dimensional observation of thin soft tissues samples, like vein walls, contributes to the assessment of their structure at different scales while keeping a global overview of the tissue.