Calculating femoral bone density changes after hip arthroplasty is of interest to researchers and clinicians for predicting the longevity of the prosthetic implant and the surrounding bone. Recently clinicians have been administering bisphosphonate drugs in an attempt to reduce the bone resorption due to stress shielding caused by these implants. Current strain-adaptive computational models with bisphosphonate treatment don’t predict the long term effects or look at treatment with hip resurfacing implants. The main goal of this study was to create and validate a computer model of the human femur incorporating a bone remodeling algorithm based on biological remodeling processes and bisphosphonate drug treatment. A secondary objective was to then create various bisphosphonate drug treatment scenarios and evaluate differences in bone density, damage, and activation frequency. Experimental studies were used to validate the model and the effects of bisphosphonates. A finite element model created from a CT scan of a cadaveric femur, a bone remodeling algorithm, and a bisphosphonate algorithm were incorporated into the model with loading conditions representative of walking and stair climbing. The model was allowed to evolve from an initial state of homogenous density to a steady state form with a density similar to that of the femur. Reduced loading representative of decreased muscle forces were applied to the steady state form to simulate preoperative conditions of a patient with hip osteoarthritis. Both a femoral hip resurfacing component and an uncemented, tapered stem were then integrated in the computer model representative of a postoperative state. Bisphosphonate treatment was applied to both the preoperative and postoperative states in several scenarios after untreated simulations. Bone loss was predicted over a six year postoperative period for both implants and varying treatments. Femoral bone loss in bisphosphonate treatment scenarios matched results seen clinically. Bone volume fraction (BVF) showed little change between one year preoperative to one year postoperative Alendronate treatment and one year postoperative Alendronate treatment for a specific implant type. Both treatment scenarios increase the BVF over no treatment. Pretreating with Alendronate appears to help against femoral neck fracture. This study successfully created a three-dimensional finite element model able to simulate long term effects of the remodeling process in bone with Alendronate treatment. The results show an importance of treatment timing for both types of implants especially when potentially requiring a revision surgery.

archives@tulane.edu / Tendons transmit loads from muscle to bone. Tendon injuries result in degenerative changes, including increased inflammatory response and poor healing. Tendon mechanical function is dictated by the composition and organization of the underlying extracellular matrix. Damage to the tendon extracellular matrix results in permanent functional decline. Provisional matrix deposition, which occurs during early tendon healing, may be influenced by sex and age. The effects of sex and age in patellar tendon injuries as well as the mechanisms that impede total restoration and therefore tendon mechanics following injury are unknown. Therefore, there is need to determine the role of age and sex on early tendon matrix deposition. Thus, the objective of this study was to examine age- and sex-dependent early tendon healing. An established patellar tendon biopsy procedure was used to evaluate changes in mechanical properties at 3-, 7-, and 14-days post injury in male and female mice. Significant differences with respect to sex and injury were found in tendon linear region elastic modulus and percent relaxation for 120-day mature mice. Mechanical properties appeared to decrease with increasing age; however, statistics could not evaluate this decrease due to low sample sizes for the 270- and 540-day mice. Sex differences in mechanical properties may be due to prolonged inflammatory response in injured female mice. Such prolonged exposure may result in increased deposition of type III collagen and thus exhibit altered mechanical function. These results provide valuable information to improve tendinopathy treatment options and to develop finite element models of tendon healing to inform surgical outcomes. / 1 / Richard Urbanowski

The lack of long term patency of small diameter synthetic vascular grafts currently available on the market has directed research towards improving the performance of these grafts. Improved radial compliance matching and appropriate tissue ingrowth into the graft structure are main goals for an ideal vascular graft. In addition, the use of biodegradable materials offers the promising prospect of leaving behind a near native vessel with no synthetic material remaining. Tissue ingrowth into grafts alters their mechanics. This, combined with a loss of mechanical integrity over time, in the case of biodegradable scaffolds, brings the need to investigate how these changes play out and how to tailor them for optimal graft healing. This project set out to investigate the mechanics of electrospun Pellethane® 2363-80AE (Dow Chemicals) and DegraPol® (ab medica S.p.A) biostable DegraPol® DP0 and biodegradable DegraPol® DP30 scaffolds during in vivo animal studies. DegraPol® DP30 findings were used to investigate the scaffolds' potential use for vascular grafts by means of a finite element graft model. Porous, electrospun scaffolds were manufactured and implanted into two subcutaneous and one circulatory rat models. All studies consisted of four time points, namely 0, 7, 14 and 28 days. Scaffold morphology was characterised, and tissue ingrowth was quantified by histological analysis of explanted samples. Orthogonal, uni-axial tensile testing measured scaffold mechanical response of in-fibre and cross-fibre deformation. Tissue ingrowth brought about considerable changes in biostable DegraPol® DP0 scaffold mechanics. Tensile testing of degradable DegraPol® DP30 scaffolds in their load bearing circumferential direction showed a balance between a loss in mechanical strength and an increase in strength by tissue ingrowth. This resulted in constant radial compliance of 4.47 ± 0.14%/100 mmHg between 80 and 120 mmHg for the four week period predicted with the numerical models. The finite element model based on DegraPol® DP30 scaffold mechanics for 6 mm grafts showed better, i.e. higher, radial compliance than current grafts used clinically (polyethylene terephthalate and expanded polytetrafluoroethylene grafts). This stability in compliance, coupled with good tissue ingrowth is of scientific importance as it shows that highly aligned, porous electrospun DegraPol® DP30 scaffolds are a viable option for vascular grafting to achieve long term graft patency

Cardiovascular diseases account for one third of all deaths worldwide, more than 33% of which are related to ischemic heart disease, including myocardial infarction (MI). This thesis seeks to provide insight and understanding of mechanisms during different stages of MI by utilizing finite element (FE) modelling. Three-dimensional biventricular rat heart geometries were developed from cardiac magnetic resonance images of a healthy heart and a heart with left ventricular (LV) infarction two weeks and four weeks after infarct induction. From these geometries, FE models were established. To represent the myocardium, a structure-based constitutive model and a rule-based myofibre distribution were developed to simulate both passive mechanics and active contraction.

Emphysema is a type of Chronic Obstructive Pulmonary Disease (COPD) characterized by breathing difficulties due to airflow obstruction, and results in structural and functional changes of the lungs. Structural changes include alveolar wall destruction and the formation of enlarged alveoli, or bullae, which appear as low attenuation areas in the CT image of emphysematous lungs. Functional changes include increased lung compliance and decreased bulk modulus in emphysematous lungs. Previous mathematical and computational models have attempted to explain either general lung structure or function, but have not linked the two to explore patient-specific lung mechanics. We propose that we can link the structure and function by creating CT-based spring network models of the lung parenchyma and manipulating these networks to predict the regional tissue stiffness and global pressure-volume relationship of the lung during disease progression. The goal of this thesis is to predict these patient-specific changes during emphysema progression by approximating the lung tissue stiffness distribution from CT densities and predicting parenchymal destruction over time from high-strain regions of a non-linear elastic spring network representing lung tissue. First, we used simple spring network models to determine the appropriate non-linear spring force-extension equation to implement into the full lung network. We then mapped a spring network onto a CT image to create a lung network, applied the non-linear force-extension equation to the network springs, and developed a lung deflation model to capture the quasi-static pressure-volume curve of the lung. Finally, we reduced the stiffness of high-strain regions of the lung network and deflated the model to predict the loss of tissue elastance and the reduced bulk modulus over time. Our method shows evidence of a reduced bulk modulus and similar tissue destruction between predicted and actual lung networks, but further development and testing are necessary to create more accurate prediction network models.

Computational modeling is increasingly necessary to the biomechanics and biophysics communities in order to model the solid, fluid, and solute mechanics of biological systems of interest, spanning across the molecular, cellular, tissue, organ, and whole-body levels. However, most commercial and custom codes are not suitable for biomechanical applications. Many such problems require either the use of specialized boundary conditions and material models or multiphysics simulations to obtain sufficiently accurate results and predictions. Verifying and sharing results from available software can be problematic as they are typically compatible only within the same program and their specific implementation details are not well documented. In addition, the source codes of these software are generally unavailable. As a result, there is a need for a computational modeling tool for biomechanical applications that has robust multiphysics capabilities while also allowing for both customizability and accessibility. To address these needs, FEBio, a free, open-source finite element software, was developed specifically for the computational modeling requirements of the biomechanics and biophysics communities. FEBio has a large collection of novel computational algorithms and methodologies with detailed documentation and new user tutorials, and source code that is freely available and customizable. However, prior to the studies presented in this dissertation, FEBio only had solvers for analyzing the structural mechanics of deformable and rigid solids, as well as standard multiphasic mixtures. It did not yet have a dedicated computational fluid dynamics (CFD) solver, which is a crucial tool for many applications in biomechanics. In this dissertation, a “standard multiphasic” material refers to the existing FEBio framework for modeling a mixture of solid, fluid, and solute constituents where dynamic effects and intrinsic solvent viscosity are neglected, and where all the constituents are assumed to be intrinsically incompressible. One of the main contributions of the studies presented here is the formulation and finite element implementation of a multiphasic-fluid-structure interaction (MFSI) domain where the dynamics of solid and fluid constituents, and the viscosity of the fluid are taken into account. The term “multiphasic” may be used as shorthand for “standard multiphasic mixture,” whereas the multiphasic-fluid-structure interaction mixture is always described explicitly, or abbreviated as MFSI. Many biological fluids interact with surrounding tissues or contain solutes and other constituents, which would require such fluid solvers to be coupled with the structural mechanics and multiphasic mixture solvers. Fluid solvers that can account for interactions with deformable multiphasic mixtures, while also accommodating reactive processes, are currently unavailable in any finite element code, and their formulation and implementation would represent a major milestone that greatly expands modeling capabilities and problem configurations. Consequently, the objective of this thesis is to formulate and implement a novel and fully general MFSI finite element solver into FEBio that allows for dynamic fluid flow, dynamic and finite deformation solid mechanics, fluid-structure interactions (FSI), porous media mechanics, and reactive and charged solute transport simultaneously. To do so, for each of the components, we propose to systematically formulate the governing equations using the mixture framework and implement them as finite element code into FEBio before combining all of these features together into one solver. In particular: (1) We formulate and implement an isothermal and compressible CFD solver in FEBio that is combined with its solid mechanics solver to allow for FSI. (2) We extend biphasic theory by developing a biphasic-fluid-structure interaction (BFSI) formulation that allows for dynamic and viscous fluid flow and implement it in FEBio. (3) We formulate and implement a CFD-solute transport solver in FEBio that accommodates diffusion, convection, chemical reactions, osmotic effects, body forces, and frictional drag between the solvent and the solutes. (4) We finally combine all of the features from these solvers (CFD, FSI, BFSI, and CFD-solute) to develop the MFSI solver, in FEBio. We develop the CFD solver using a solid mechanics approach to solve the governing equations in order to circumvent the need for stabilization methods. The fluid dilatation is used as a degree of freedom to represent the compressibility of the fluid, and as a kinematic quantity, may further serve as a state variable for functions of state such as the fluid pressure. Using the CFD solver, an FSI solver derived from mixture theory is developed to model the deformation of the fluid domain mesh and allow interactions with any of the hyperelastic materials available in FEBio. Here, the FSI material is a special case of a biphasic medium, where the fluid flows relative to the solid constituent, which is defined on the mesh. We formulate a novel biphasic mixture that includes dynamics and models a viscous interstitial fluid that can interface with a dynamic viscous fluid domain, such that the fluid can flow across the interface and into or out of the biphasic mixture. The new biphasic material formulation employs a hybrid approach, where the porous solid skeleton is intrinsically incompressible but the interstitial fluid is compressible, such that the overall biphasic mixture is compressible due to changes in pore volume. The speed of sound in each medium (compressible porous solid and compressible fluid) remains finite. This framework is then implemented into FEBio as the BFSI solver. Then, we develop a CFD-solute transport formulation derived from the mixture framework, as an extension of the CFD solver. In addition to modeling convection, diffusion, and reactions for solutes, the CFD-solute formulation can also consider body forces for the solutes, frictional drag between the fluid and solutes, and osmotic effects. Like the CFD solver, the CFD-solute solver can model both viscous Newtonian or non-Newtonian solvents. It can also include any number of reactive and charged solute species like the existing standard multiphasic solver in FEBio. The CFD-solute solver does not require any stabilization method, neither for the fluid nor the solute equations, unlike standard methods that assume intrinsic fluid incompressibility. Finally we formulate and implement the MFSI solver by using the mixture framework to combine the capabilities of the previous solvers, namely the CFD, FSI, CFD-solute, standard biphasic, BFSI, and standard multiphasic solvers in FEBio, where solvent and solutes may be exchanged across the fluid-structure interfaces, while also allowing for chemical reactions and the presence of charged solute species. The MFSI solver forms the foundation of a fully general multiphysics finite element code that can, in principle, be used in almost any FEBio scenario to obtain the most physiological results possible for a wide range of biomechanics problems. All of the solvers developed in this thesis encompass innovative formulations based on the framework of mixture theory, greatly expanding the modeling capabilities available to the biomechanics and biophysics communities. By being open-source, the FEBio project encourages verification and sharing of results through the availability of the source code and modular code structure. The MFSI finite element solver in particular can also potentially act as a foundation for further extension by being amenable the addition of new capabilities that are currently not considered here.

Many people with multiple sclerosis (MS) have difficulty with walking, which can decrease their sense of mobility. Gait stability was investigated by studying stride parameters and head movements at preferred and fixed speeds in those with MS. First, walking gait data were recorded at preferred and fixed walking speeds from 19 individuals with MS and 19 controls. Traditional gait parameters were compared, as was swing foot to center of mass (CoM) timing at mid-swing. Second, walking gait data in healthy young adults (n=20) were recorded at preferred speed and while stepping over an obstacle. Study 2 developed novel swing definitions, measures of coordination between the swing foot and body CoM, and head movements as they pertain to field of view orientation during walking. Third, these novel measures were used to study the swing phase of walking in people with MS. The first investigation revealed that the MS group walked with lengthened dual support times across all speeds, but shortened swing time and altered swing foot timing at fixed speeds in comparison to controls. Those with MS adopted a gait strategy with increased dual support time, despite forcing changes to swing that may reduce gait stability. In the second investigation, novel measures of swing showed alterations to phases of swing and in coordination between the swing foot and CoM under different gait tasks. This study also showed that the field of view was closer to the body during obstacle condition steps compared with unobstructed gait. In the third study, these novel measures showed that at all speeds the MS group shortened early swing and lengthened mid swing while late swing remained unchanged compared with controls. Coordination measures illustrated adaptations in swing foot dynamics that may partially ameliorate altered swing foot timing. The MS group oriented the field of view closer to the body earlier in swing compared with controls. Those with MS have functionally adapted swing to increase time over the stance foot and rely more on visual perception, yet shorter early swing may afford fewer opportunities to plan a step or cope with gait disturbances while walking.

Burrowing is most energy costly behavior. Many vertebrates burrow head-first into the sediment. Interestingly, head-first burial fishes differ in head shapes by having either a flatten or conical head shape. Head shape determines the penetration force magnitudes, but it is important for their neurocranium to avoid overwhelming cranial stresses from those burial forces. There is minimal research on the penetration force (N), rotational resistance (Nmm), and cranial stress (Pa) for different head shapes. Here, we selected four members with different head shapes: Tetraodon miurus (Bulky), Iniistius pavo (knife edge), Bunocephalus coracoideus (shovel), and Cheilio inermis (knife point). We constructed 3D head shape models and controlled the surface areas. We recorded penetration force (N) and torque (Nmm) for each model. We also constructed the neurocranium models and loaded them in Finite Element Analysis (FEA) to examine the stress magnitudes and concentrations. Our results show that bulky penetrated with highest penetration force, and knife point and shovel penetrated the minimum force. Knife edge experienced the greatest sediment resistance. Knife point succumbed to highest stress magnitude. The premaxillae and maxillae were the bones constraining burial for shovel. The parasphenoid bone constrained knife edge, knife point, and bulky during burial. From our results, having larger wide head dimensions and larger volumes generated greater penetration forces. Those with a flatten head succumbed to high sediment rotational resistance. Bone arrangements influences stress magnitudes because those with different skull shapes, yet same bone arrangements were constrained by the same bone. It seems there is a tradeoff between penetration force and cranial stress magnitudes. Fish use their parasphenoid for feeding and burial for those in our study, so there may be relationship between burial and feeding.

This study investigated reducing volumetric flowrate under steady flow conditions by varying lengths of compression with constant cross-sectional area and varying cross-sectional area reduction with constant length in order to better understand how to control junctional hemorrhaging. The hypotheses of this study were that length reduction will have little effect on volumetric flowrate and that cross-sectional area reduction would need to be approximately 80 percent in order to obtain bleeding control. The study found that length reduction has little effect on changing the flowrate. However, in order to obtain at least 80 percent reduction in flow, the area needs to be occluded by at least 95 percent. These results may help inform better tourniquet designs by using collapsible tube science.

Osteoporosis affects nearly 54 million people in the United States. The cost associated with treatment is estimated to be $19 billion per year and is expected to grow yearly. D-spacing is the staggering of collagen molecules found at the nanoscopic level. Previously thought to have a constant value, recent studies have found that D-spacing has a distribution of values throughout the tissue. As part of an ongoing effort in understanding the mechanisms that are affected by osteoporosis, a finite element model was developed to explore the effects of D-spacing distribution on the viscoelastic material properties of bone tissue. The goal of this computational model was to mimic the viscoelastic properties of different sectors of bone tissue that have been treated under different loading conditions (tension and compression). An appropriate animal model was required to allow for the development of an accurate computational model. Although they don't exhibit similar hormonal cycles as humans, sheep are an excellent animal model for bone research as they experience Haversian bone remodeling, are docile, relatively inexpensive, and have skeletons similar in size and mechanical properties to humans. For this study, six Rambouillet-cross ewes were either ovariectomized (OVX) or underwent a sham surgery (control). After twelve months post-surgery, the ewes were euthanized and rectangular beam bone samples were collected from different sectors of the ulna/radius bones. Dynamic mechanical analysis was performed on these samples and the viscoelastic property, tangent delta, was measured from each analysis at varying frequencies. Using experimental measurements, the Composite Model was developed on finite element analysis software, Abaqus. The model was generated through a Python script that uses experimental D-spacing mean and standard deviation data to create a large two-dimensional model composed of two hundred collagen and hydroxyapatite complexes with varying D-spacing lengths. Multiple security measurements were implemented to ensure biological relevance. Collagen was assigned viscoelastic material properties through a user subroutine material property. Four models for each sector of interest (caudal and cranial) were generated. Each model was loaded under appropriate loading conditions and tangent delta was recorded for each test frequency. Results from the Composite Model matched the experimental data more accurately than previous computational models, suggesting a superior model. The results implied that a large network of collagen and hydroxyapatite complexes in series and parallel are effective at modeling bone under different loading conditions. This computational model shows promise in the bone research field. A lot of flexibility was implemented in the model development process, making refinements easy to be performed. This study provides a stepping-stone in computational tooling on examining the effects of metabolic bone diseases on viscoelasticity.