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arXiv2018

Micromechanical Experimental and Numerical Studies of Collagen Fibers Failure in Arterial Tissue

Arterial tissue failures lead to a number of clinical conditions that develop rapidly and unpredictably in vivo. Structural components and their interfacial mechanical strength of arterial tissue play a critical role in the process of arterail delamination. Therefore, there is a pressing need to understand the micromechanical mechanisms of arterial delamination. The objective of this study was to investigate various failure mechanisms (e.g. failure of collagen fibers) responsible for arterial interfacial delamination. In-situ tensile tests of fibers were performed on a micro-tester in the scanning electron microscope. A 3D unit cell model containing an individual fiber bridging two arterial tissue layers was constructed. An exponential cohesive zone model (CZM) was used to assess the stiffening and softening mechanical behaviors of collagen fiber bundles between the two arterial layers. An anisotropic constitutive model was implemented for characterizing the mechanical properties of the amorphous matrix which includes the fibrous cap and the underlying plaque tissue and a nonlinear elastic model was adopted for characterizing the mechanical properties of the fibers. The CZM and elastic parameter values of fibers were identified through an inverse boundary value approach that matches the load-displacement curves from simulation predictions of tensile test of collagen fibers with experimental measurements. The identified parameter values were then used as input in the 3D unit cell model, through which micromechanical factors affecting the resultant traction-separation relation for the unit cell were investigated via a parametric analysis. Results of the parametric analysis showed the applicability of the 3D unit cell model approach for evaluating the micromechanical mechanisms of arterial tissue failure processes.

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arXiv2018

Optimal mechanical operation in the vicinity of curved vasculature

It has been shown that geometrical, structural properties vary along the length of the aortic arch. There is a scarcity of studies focus on the variation in the vessel wall thickness of aortic arch. The central premise of this study is that considering the variation in the vessel wall thickness along the circumference of the aortic arch to be governed by the uniform stress distribution across the vessel wall, meeting the principle of optimal mechanical operation of which the distribution of stress across the vessel wall is assumed to be uniform so as to create a favorable mechanical environment for the mechanosensitive resident vascular cells. Aortic arch was created with image-derived three-dimensional (3D) reconstruction technique. A structure-motivated constitutive model was utilized in the numerical modeling and direct boundary value problem was solved. Stress distribution across the vessel wall under physiological loading condition was predicted in circumferential direction to test the role of the wall thickness. The results showed the variation of the vessel wall thickness in the circumferential direction and uniform distribution of the circumferential stress in the aortic wall which implies a favorable mechanical environment for the resident mechano-sensitive vascular smooth muscle cells. Correlation of geometrical and simulation data support the proposed principle of optimal mechanical operation for the aortic arch.

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arXiv2023

Exact traveling wave solutions of one-dimensional models of cancer invasion

In this paper we consider continuous mathematical models of tumour growth and invasion based on the model introduced by Chaplain and Lolas \cite{Chaplain&Lolas2006}, for the case of one space dimension. The models consist of a system of three coupled nonlinear reaction-diffusion-taxis partial differential equations describing the interactions between cancer cells, the matrix degrading enzyme and the tissue. For these models under certain conditions on the model parameters we obtain exact analytical solutions in terms of traveling wave variables. These solutions are smooth positive definite functions for some of which whose profiles agree with those obtained from numerical computations \cite{Chaplain&Lolas2006} for not very large time intervals.

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arXiv2018

Morphogenesis of the Sternum in Quail Embryos

The flat bone develops through intramembranous ossification, in which the mesenchymal cells are directly driven towards osteogenic lineage without the formation of cartilage template. While long bone develops through endochondral ossification, where cartilage template act as an intermediate stage between mesenchymal and bone tissues. Although the avian sternum is a flat bone, some studies describe formation of a cartilage template during its development. The aim of the current study was to observe the mechanism of ossification in quail sternum during embryonic development. Thirty quail embryos were collected for the current study (5 embryos/ day) during the period between Day (D) 5 and D10 of embryonic development and processed for light microscopy. The differentiation of mesenchymal condensation in to the chondrogenic cells was observed at D5 whereas the secretion of extracellular matrix could be evident at D6. The cartilage primordia were observed by D7 which were consisted of chondrocytes, embedded in matrix and surrounded by perichondrium. Later these primordia were developed in to cartilage template by D8 where the chondrocytes were present in their lacuna. This template attained the shape of future sternum by D9, which was more distinct at D10. These preliminary observations suggested that the quail sternum grows through endochondral ossification. The future study will further explore the histological changes of quail sternum during post-hatching development.

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arXiv2018

Computer Assisted Localization of a Heart Arrhythmia

We consider the problem of locating a point-source heart arrhythmia using data from a standard diagnostic procedure, where a reference catheter is placed in the heart, and arrival times from a second diagnostic catheter are recorded as the diagnostic catheter moves around within the heart. We model this situation as a nonconvex feasibility problem, where given a set of arrival times, we look for a source location that is consistent with the available data. We develop a new optimization approach and fast algorithm to obtain online proposals for the next location to suggest to the operator as she collects data. We validate the procedure using a Monte Carlo simulation based on patients' electrophysiological data. The proposed procedure robustly and quickly locates the source of arrhythmias without any prior knowledge of heart anatomy.

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arXiv2018

A CT image based finite element modelling to predict the mechanical behaviour of human arm

In the present work, complex irregular bones and joints of the complete human arm were developed in a computer-aided design environment. Finite element analysis of an actual human arm was done to identify the distribution of stress using von-Mises stress and maximum principal stress measures. The results obtained from the present study revealed the region where, maximum stress was developed for different loading and boundary conditions with different joint rotations as obtained in the actual human arm. This subject specific analysis helps to analyse the region of the arm in which the risk is more.

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arXiv2018

Modelling and analysis of biological joints of a human arm in different movements

In the present work, irregular complex joints of the human arm are modelled in the computer-aided design environment. Accurately the geometric models of the joints and surrounding bony regions are developed from computed tomography data set and the range of movements are analysed. In this present work, biological joints are approximated into the mechanical joint without losing any kinematic behaviour and degrees of freedom. Then the analysis is done to determine the importance of joint geometries with different loading and boundary conditions. The present study helps to predict the behavior of joint configuration in the design stage.

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arXiv2018

Entrainment of Lymphatic Contraction to Oscillatory Flow

Lymphedema, a disfiguring condition characterized by the asymmetrical swelling of the limbs, is suspected to be caused by dysfunctions in the lymphatic system. Lymphangions, the spontaneously contracting units of the lymphatic system, are sensitive to luminal wall shear stress. In this study, the response of the lymphangions to dynamically varying wall shear stress is characterized in isolated rat thoracic ducts in relation to their shear sensitivity. The critical shear stress above which the thoracic duct shows substantial inhibition of contraction was found to be significantly negatively correlated to the diameter of the lymphangion. The entrainment of the lymphangion to an applied oscillatory shear stress was found to be significantly dependent on the difference between the applied frequency and intrinsic frequency of contraction of the lymphangion. The strength of entrainment was also positively correlated to the applied shear stress when this shear was below the critical shear stress. The results suggest an adaptation of the lymphangion contractility to the existing oscillatory mechanical shear stress as a function of its intrinsic contractility and shear sensitivity. These adaptations might be crucial to ensure synchronized contraction of adjacent lymphangions through mechanosensitive means and might help explain the lymphatic dysfunctions that result from impaired mechanosensitivity.

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arXiv2018

Ionic-heterogeneity-induced spiral- and scroll-wave turbulence in mathematical models of cardiac tissue

Spatial variations in the electrical properties of cardiac tissue can occur because of cardiac diseases. We introduce such gradients into mathematical models for cardiac tissue and then study, by extensive numerical simulations, their effects on reentrant electrical waves and their stability in both two and three dimensions. We explain the mechanism of spiral- and scroll-wave instability, which entails anisotropic thinning in the wavelength of the waves because of anisotropic variation in its electrical properties.

physics.bio-ph↗

arXiv2018

Patient-specific and physiological load sustaining synthetic graft substitutes for fusion of critically sized segmental bone defects

Critically sized defects are currently treated via autologous or allograft bone grafting, distraction osteogenesis, and membrane induction. However, these methods have major weaknesses which encourage the development of synthetic bone graft substitutes. A bioresorbable and physiologically load sustaining graft substitute was fabricated from polylactic acid using 3D printing, a versatile method which enables parameters to be customizable in a patient-specific manner. The internal architecture consists of vertical and horizontal conduits that are organized to achieve gradients in porosity and pore size in the radial direction to emulate cortical bone encapsulating cancellous bone. A diameter of 30mm and height of 10mm was designed to target the repair of critically sized long bone defects. The compressive properties of these graft substitutes were determined to be comparable to adult human femurs. Furthermore, dynamic fatigue testing at twice the human torso weight (800N) indicated that the bone graft substitute achieved stability as quickly as 200,000 cycles, suggesting its ability to support weight bearing loads while it gradually degrades as bone cells proliferate and mineralize. Additionally, the graft substitutes were seeded with human fetal osteoblasts to validate homogenous cellular attachment and cytocompatibility. Graft substitutes were also dynamically cultured for 28 days under various loading regimens using human mesenchymal stem cell differentiated osteoblasts, and these resulting tissue constructs were subjected to fatigue testing. The frequency of loading during dynamic culturing had a profound effect on the rate of mineralization which was particularly high at 2Hz, confirmed by Alizarin Red staining of the calcium deposits. Taken together, these bone graft substitutes have potential for use as orthopaedic implants to facilitate the repair of critically sized bone defects.

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arXiv2018

An Open-Source OpenSim Oculomotor Model for Kinematics and Dynamics Simulation

Physics-based modeling and dynamic simulation of human eye movements has significant implications for improving our understanding of the oculomotor system and treating various visuomotor disorders. We introduce an open-source biomechanical model of the human eye that can be used for kinematics and dynamics analysis. This model is based on the passive pulley hypothesis, constructed based on the data reported in literature regarding physiological measurements of the human eye and made publicly available. The model is implemented in OpenSim, which is an open-source framework for modeling and simulation of musculoskeletal systems. The model incorporates an eye globe, orbital suspension tissues and six extraocular muscles. The excitation and activation patterns for a variety of targets can be calculated using the proposed closed-loop fixation controller that drives the model to perform saccadic movements in a forward dynamics manner. The controller minimizes the error between the desired saccadic trajectory and the predicted movement. Consequently, this model enables the investigation muscle activation patterns during static fixation and analyze the dynamics of eye movements.

physics.bio-ph↗

arXiv2018

Chromatin Laser Imaging Reveals Abnormal Nuclear Changes for Early Cancer Detection

We developed and applied rapid scanning laser-emission microscopy to detect abnormal changes in cell nuclei for early diagnosis of cancer and cancer precursors. Regulation of chromatins is essential for genetic development and normal cell functions, while abnormal nuclear changes may lead to many diseases, in particular, cancer. The capability to detect abnormal changes in apparently normal tissues at a stage earlier than tumor development is critical for cancer prevention. Here we report using LEM to analyze colonic tissues from mice at-risk for colon cancer by detecting prepolyp nuclear abnormality. By imaging the lasing emissions from chromatins, we discovered that, despite the absence of observable lesions, polyps, or tumors under stereoscope, high-fat mice exhibited significantly lower lasing thresholds than low-fat mice. The low lasing threshold is, in fact, very similar to that of adenomas and is caused by abnormal cell proliferation and chromatin deregulation that can potentially lead to cancer. Our findings suggest that conventional methods, such as colonoscopy, may be insufficient to reveal hidden or early tumors under development. We envision that this work will provide new insights into LEM for early tumor detection in clinical diagnosis and fundamental biological and biomedical research of chromatin changes at the biomolecular level of cancer development.

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arXiv2018

The importance and impact of discoveries about neural crest fates

We review here some of the historical highlights in exploratory studies of the vertebrate embryonic structure known as the neural crest. The study of the molecular properties of the cells that it produces, their migratory capacities and plasticity, and the still-growing list of tissues that depend on their presence for form and function, continue to enrich our understanding of congenital malformations, pediatric cancers but also of evolutionary biology.

q-bio.CB↗

arXiv2020

Parameter identifiability of a respiratory mechanics model in an idealized preterm infant

The complexity of mathematical models describing respiratory mechanics has grown in recent years to integrate with cardiovascular models and incorporate nonlinear dynamics. However, additional model complexity has rarely been studied in the context of patient-specific observable data. This study investigates parameter identification of a previously developed nonlinear respiratory mechanics model (Ellwein Fix, PLoS ONE 2018) tuned to the physiology of 1 kg preterm infant, using local deterministic sensitivity analysis, subset selection, and gradient-based optimization. The model consists of 4 differential state equations with 31 parameters to predict airflow and dynamic pulmonary volumes and pressures generated under six simulation conditions. The relative sensitivity solutions of the model state equations with respect to each of the parameters were calculated with finite differences and a sensitivity ranking was created for each parameter and simulation. Subset selection identified a set of independent parameters that could be estimated for all six simulations. The combination of these analyses produced a subset of 6 independent sensitive parameters that could be estimated given idealized clinical data. All optimizations performed using pseudo-data with perturbed nominal parameters converged within 40 iterations and estimated parameters within ~8% of nominal values on average. This analysis indicates the feasibility of performing parameter estimation on real patient-specific data set described by a nonlinear respiratory mechanics model for studying dynamics in preterm infants.

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arXiv2018

Frontiers in Pigment Cell and Melanoma Research

We identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology. Significantly, this document encapsulates important advances in melanocyte and melanoma research including emerging frontiers in melanoma immunotherapy, medical and surgical oncology, dermatology, vitiligo, albinism, genomics and systems biology, epidemiology, pigment biophysics and chemistry, and evolution.

q-bio.TO↗

arXiv2018

A Structural Model For Simulating the Mechanical Response of Fingertip to Tactile Stimuli

Response of the mechanoreceptors underlying the skin is greatly affected by its mechanical properties. Knowledge of this response is essential in designing artificial tactile devices such as minimally invasive tools and tactile displays. The purpose of present research is to simulate the biomechanics of tactile sensation during indentation tests. A two-dimensional finite element model has been used for the analysis incorporating the essential anatomical structures of a finger (i.e., skin, subcutaneous tissue, bone, and nail). The skin and subcutaneous tissue are assumed to be hyperelastic and viscoelastic. We obtained the stress, strain and deformation fields in indentation tests. It was noted that the skin away from the indenter was experiencing considerable amount of strain energy density. Also, the response of SAI afferents could be predicted from the proposed model. These results were in agreement with the results mentioned in other published experimental data.

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arXiv2018

Computational Modeling of the Effects of Inflammatory Response and Granulation Tissue Properties on Human Bone Fracture Healing

Bone healing process includes four phases: inflammatory response, soft callus formation, hard callus development, and remodeling. Mechanobiological models have been used to investigate the role of various mechanical and biological factors on the bone healing. However, the initial phase of healing, which includes the inflammatory response, the granulation tissue formation and the initial callus formation during the first few days post-fracture, are generally neglected in such studies. In this study, we developed a finite-element-based model to simulate different levels of diffusion coefficient for mesenchymal stem cell (MSC) migration, Young's modulus of granulation tissue, callus thickness and interfragmentary gap size to understand the modulatory effects of these initial phase parameters on bone healing. The results showed that faster MSC migration, stiffer granulation tissue, thicker callus and smaller interfragmentary gap enhanced healing to some extent. After a certain threshold, a state of saturation was reached for MSC migration rate, granulation tissue stiffness and callus thickness. Therefore, a parametric study was performed to verify that the callus formed at the initial phase, in agreement with experimental observations, has an ideal range of geometry and material properties to have the most efficient healing time. Findings from this paper quantified the effects of the healing initial phase on healing outcome to better understand the biological and mechanobiological mechanisms and their utilization in the design and optimization of treatment strategies. Simulation outcomes also demonstrated that for fractures, where bone segments are in close proximity, callus development is not required. This finding is consistent with the concepts of primary and secondary bone healing.

q-bio.TO↗

arXiv2018

Quantification of Alveolar Recruitment for the Optimization of Mechanical Ventilation using Quasi-static Pressure Volume Curve

Quasi-static, pulmonary pressure-volume (P-V) curves over an inflation-deflation cycle are analyzed using a respiratory system model (RSM), which had been developed for quantitative characterization of the mechanical behavior of the total respiratory system. Optimum mechanical ventilation setting of Positive End Expiratory Pressure (PEEP) for total alveolar recruitment is quantified based on the existing P-V curves of healthy and injured animal models. Our analytical predictions may contribute to the optimization of mechanical ventilation settings for the Acute Respiratory Distress Syndrome (ARDS) patients.

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