Recently, a constituent based cartilage growth finite element model (CGFEM) was developed in order to predict articular cartilage (AC) biomechanical properties before and after growth. Previous research has noted limitations in the CGFEM such as model convergence with growth periods greater than 12 days. The main aims of this work were to address these limitations through (1) implementation of an exact material Jacobian matrix definition using the Jaumann-Kirchhoff (J-K) method and (2) quantification of elastic material parameters based upon research findings of the Cal Poly Cartilage Biomechanics Group (CPGBG). The J-K method was successfully implemented into the CGFEM and exceeded the maximum convergence strains for both the “pushed forward, then differentiated” (PFD) and “differentiated, then pushed forward” (DPF) methods, while maintaining correct material stress responses. Elastic parameters were optimized for confined compression (CC), unconfined compression (UCC), and uniaxial tension (UT) protocols. This work increases the robustness of the CGFEM through the J-K method, as well as defines an accurate starting point for AC growth based on the optimized material parameters.

Articular cartilage degeneration, called osteoarthritis, in the hip joint is a serious condition that affects millions of individuals yearly, with limited clinical solutions available to prevent or slow progression of damage. Additionally, the effects of high-risk factors (e.g. obesity, soft and hard tissue injuries, abnormal joint alignment, amputations) on the progression of osteoarthritis are not fully understood. Therefore, the objective of this thesis is to generate a finite element model for predicting osteochondral tissue stress and strain in the human hip joint during gait, with a future goal of using this model in clinically relevant studies aimed at prevention, treatment, and rehabilitation of OC injuries. A subject specific finite element model (FEM) was developed from computerized tomography images, using rigid bones and linear elastic isotropic material properties for cartilage as a first step in model development. Peak contact pressures of 8.0 to 10.6 MPa and contact areas of 576 to 1010 mm2 were predicted by this FEM during the stance phase of gait. This model was validated with in vitro measurements and found to be in good agreement with experimentally measured contact pressures, and fair agreement with measured contact areas.

<p>  </p> <p>The disruption of homeostasis in tendon extracellular matrix and altered biomechanical properties lead to poor tendon healing, creating a significant clinical challenge for millions of diabetics. Furthermore, improving blood glucose levels doesn't normalize tendon properties in diabetics. Diabetes-related tendon complications are often associated with advanced glycation end products (AGEs) crosslinking with collagen. However, recent studies have found no evidence of higher collagen crosslinking in diabetics and no correlation between tendon AGE content and tensile strength. The interaction between serum AGEs and AGE receptors (RAGE) is a less explored mechanism of AGE-mediated effects. People with diabetes are more likely to accumulate AGEs in their serum as a result of hyperglycemia, the consumption of AGE-rich foods, and diminished kidney clearance of AGEs. In previous studies, advanced glycation end-products (AGEs) have been shown to inhibit cell proliferation and migration, both of which are critical to tendon healing. We hypothesized that serum AGEs and activation of RAGE represent a mechanism underlying impaired tendon properties with diabetes. The increasing serum AGE levels would impair tendon biomechanical properties and tendon healing, while inhibition of RAGE [Azeliragon (AZ)] would improve tendon mechanics.</p> <p>Db/db mice with naturally elevated serum AGEs and impaired tendon function were treated daily with a RAGE inhibitor [Azeliragon (AZ), n=9] or vehicle (n=10) for three weeks. Patellar tendon stiffness and modulus were greater (p<0.05) in mice receiving AZ (stiffness: 9.6±1.2 N/mm, modulus: 78.2±8.2 MPa) compared to vehicle (5.8±0.9 N/mm, modulus: 49.0±8.3 MPa). Maximum strain (vehicle: 0.9±0.1, AZ: 0.8±0.05) and toughness (vehicle: 6.1±1.4, AZ: 6.5±1.2 J·m−3) were not different between groups (p>0.05). Maximum stress tended to be greater in the AZ group (vehicle: 14.6±2.4, AZ: 23.3±2.9 N/mm2, p=0.156).</p> <p>Ten-week-old non-diabetic mice were assigned to receive daily injections of bovine serum albumin (BSA-only, n=6), BSA and AZ (BSA-AZ, n=5), 200 mg/ml glycated BSA (AGE-BSA, n=4), and AGE with AZ (AGE-AZ, n=6). A full-thickness, partial-width defect was created in both patellar tendons. Treatments were started one week before surgery and continued for three weeks after surgery. Three Tendon stiffness was lower in mice treated with AGEs (p<0.05, 10.8±1.4 N/mm) compared to BSA-only (17.6±1.3 N/mm). Further, tendon stiffness in AGE-treated mice given AZ was not different from AGE-BSA (p<0.05, 12.7±1.8 N/mm). Tendon modulus was lower in mice treated with AGEs (p<0.05, 28.0±7.0 MPa) compared to BSA-only (63.5±9.0 MPa). Additionally, modulus in AGE-treated mice given AZ was not different from AGE-BSA (p>0.05, 47.6±10.4 N/mm). </p> <p>We demonstrate that administering a RAGE inhibitor improves tendon properties in an established mouse model for type 2 diabetes. In healthy mice, serum AGE levels inhibit the recovery of tendon biomechanical properties after injury; RAGE inhibitors did not have an effect on mice given AGEs. Based on these data, we suggest elevated serum AGEs, as seen with diabetes, are associated with poor mechanical properties and delayed tendon healing.</p>

To alleviate the poor ergonomics which surgeons suffer during knee arthroscopy, a semi-robotic device with braking mechanism is created for intraoperative assistance. A slitted ball joint assembly is developed to transmit the clamping force to the arthroscope inside. Ball deformation and stress at various angles to the vertical and clamping forces is recorded through Abaqus Finite Element Analysis (FEA). Contact forces between the scope and inner surfaces of the ball is also computed in FEA at different clamping forces. The von Mises stress occurring in the ball joint is under the yield stress limit for polyethylene, and there is noticeable force preventing the scope from sliding along the ball through-hole under clamping. A prototype of this device is constructed for proof-of-concept.

Indiana University-Purdue University Indianapolis (IUPUI) / The force-moment systems of orthodontic T-loops have been widely described and investigated. A simpler triangular loop spring design has been employed in the graduate orthodontic clinic at Indiana University School of Dentistry. To date, no investigators have specifically examined and compared the force systems generated by these two loop configurations. The objective of this study was to compare the force systems generated by a T-loop and two different geometric shapes of triangular loops. A sample of 20 T-loops and 40 triangular loop springs were studied. The triangular loops were constructed in two different geometric configurations (n = 20 in each group) utilizing the same linear amount of wire as used in the T-loop fabrication. One set of triangular loops was the same height as the T-loop (isosceles shape); the other set was the same width as the T-loop (equilateral shape). Force and moment components along three mutually perpendicular axes (x, y, and z) were analyzed, with particular emphasis on the force system generated in the sagittal plane. The force-moment systems generated upon mesio-distal (x axis) activation were measured by a transducer connected to a computer for data collection and analysis. Statistical analysis utilized repeated measures of variance models (ANOVA). Multiple comparisons were made using Fisher's Protected Least Significant Differences at a 95-percent overall confidence level. On initial ligation, there were no significant differences between the loops in the M/F ratios in the sagittal plane (p = 0.75). For all other activation distances, the equilateral triangular loops produced greater M/F ratios than both the isosceles and T-loops (p = 0.0001), and the isosceles triangular loops generated greater M/F ratios than the T-loops (p < 0.0035).

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The hands are essential for our ability to complete tasks. Quantifying the many forces acting on the entire hand is important to improve our understanding of hand function and hand-related musculoskeletal disorders. Biomechanical models of the hand used to compute internal tissue loads typically simplify the applied forces into a single point of force applied at the centre of mass of the distal phalanx. Accounting for the distributed loads across the hands and fingers is a needed step in understanding the loads acting on and inside the body. Therefore, the purpose of this thesis was to use a pressure mapping system to examine the effects of distributed loads on net joint moments and muscle activations in the hands during common tasks. Twenty-three right-handed participants completed a series of finger presses, power grips, and pinch tasks. A pressure mapping system measured pressure on 17 regions of the hand. Three- dimensional hand kinematics was collected using a 72-marker setup. Forces were also measured with a six degrees of freedom force transducer to ensure participants matched specified exertion levels. Pressure distribution, kinematics, and kinetics were used to calculate internal net joint moments at the fingers (distal phalangeal flexion, proximal phalangeal flexion, metacarpal flexion, metacarpal abduction) and muscle activations for 22 forearm and hand muscles using an OpenSim model. External loads were represented in three manners: (1) Centre of Mass Model (COM) distributed the forces over segments that contributed to the force production and placed loads at the centre of mass; (2) Centre of Pressure Model (COP) distributed the forces over segments that contributed to the force production and placed loads at the centre of pressure; (3) Single Point Model (SP) placed a single load at the distal phalanx or the centre of mass of the hand. Results of equivalence tests indicate differences in all net joint moments between COM-SP and COP-SP comparisons. There were no differences between COM and COP. COM and COP moments during all tasks were larger in digits with a larger percentage of total force compared to SP. Due to the larger moments in those conditions, COM and COP calculated larger muscle activities compared to SP. Both internal net joint moments and muscle activations were most affected by the pressure distribution and hand posture. Overall, these findings indicate that representing external forces using distributed loads provide increased fidelity of forces at the hand and fingers. Distributed loads provide more information on internal loads of the hand and digits, and in turn, quantify individual differences that can lead to injury in occupational settings. / Thesis / Master of Science in Kinesiology

Manual material handling (MMH) tasks are associated with the development of work-related musculoskeletal disorders (WMSDs). Minimizing the frequency and intensity of handling objects is an ideal solution, yet MMH remains an integral part of many industry sectors, including manufacturing, construction, warehousing, and distribution. Physical exposure assessment can help identify high-risk tasks, guide the development and evaluation of ergonomic interventions, and contribute to understanding exposure-risk relationships. Physical exposure can be evaluated using self-assessment, observational methods, and direct measurements. Nevertheless, implementing these methods in situ can be challenging, time consuming, expensive, and infeasible or inaccurate in many cases. Thus, there is a critical need to improve physical exposure assessments to protect workers and save costs. This dissertation assessed the accuracy of a markerless motion capture system (MMC) to quantify physical exposures during MMH tasks using three studies. Specifically, the first study investigated the performance of an MMC system, together with machine learning algorithms, for classifying diverse MMH tasks during a simulated complex job. In the second study, the feasibility of predicting dynamic hand forces was determined, using alternative measures, such as kinematics from MMC and/or in-sole pressure systems, coupled with a machine learning algorithm. Finally, in the third study, we systematically evaluated MMC for assessing biomechanical demands, by comparing outputs from a full-body musculoskeletal model driven by kinematic and kinetics from gold standard input and estimates derived from the MMC and in-sole pressure measurement system. Overall, the findings of these studies demonstrated the potential of using MMC to classify several common occupational tasks and to estimate the associated biomechanical demands for a given worker (automatically and with minimal physical contact). Additionally, the methods developed here can help stakeholders rapidly assess an individual worker's exposure to physical demands during diverse tasks. / Doctor of Philosophy / Manual material handling (MMH) tasks expose workers to known risk factors for work-related musculoskeletal disorders (WMSDs) such as back and shoulder pain. Accurately quantifying workplace exposures to these risk factors is an essential aspect of identifying high-risk working conditions and for developing/evaluating workplace interventions to reduce WMSD risks. Current physical exposure assessment tools are labor-intensive, offer crude measures, and have limited application due to costs or feasibility. Using markerless motion capture (MMC) systems in the workplace could enable full or partial automation for the collection of critical measures such as the tasks a worker performs, the hand forces involved, and their biomechanical demands. New approaches are needed, though, since such automation is challenging due to variations in the type of input data required for different physical exposure assessments. In this dissertation, our goal was to assess the accuracy of MMC as a tool to quantify physical exposures during MMH tasks. In support of our goal, three studies were completed. In the first study, we investigated the accuracy of using data from MMC together with machine learning algorithms to classify diverse MMH tasks, and distinguish among different task conditions. Our results emphasized that classification performance was satisfactory, though it differed between feature sets, MMH tasks, and between males and females. The second study explored combining MMC and IPM data with machine learning algorithms to predict hand forces during MMH tasks. Our results were encouraging overall, but predictions were less accurate in pushing and pulling tasks. In the third study, we evaluated an approach for estimating biomechanical demands on data obtained from MMC and in-sole pressure measurement systems. We compared estimates from a musculoskeletal model driven by kinematics from a whole-body inertial measurement unit and kinetics from direct measures of hand loads, and kinematics from MMC. Our findings support using MMC and kinetics from predicted hand forces as input for estimating biomechanical demands. Overall, findings from these studies show that MMC can automatically classify common occupational tasks, predict dynamic hand forces, and estimate biomechanical demands with minimal physical contact. This new approach could allow stakeholders to assess worker's exposure and the efficiency of ergonomic interventions.

The tumor microenvironment plays an important role in regulating cancer cell behavior. The tumor microenvironment describes the cancer cells, and the surrounding endothelial cells, fibroblasts, and mesenchymal stem cells, along with the extracellular matrix (ECM). The tumor microenvironment stiffens as cancer undergoes malignant progression, providing biophysical cues that promote invasive, metastatic cellular behaviors. This project investigated the influence of three dimensional (3D) chitosan-alginate (CA) scaffold stiffness on the morphology, growth, and migration of green fluorescent protein (GFP) – transfected MDA-MB-231 (231-GFP) breast cancer (BCa) cells. The CA scaffolds were produced by the freeze casting method at three concentrations, 2 wt%, 4 wt%, and 6 wt% to provide different stiffness culture substrates. The CA scaffold material properties were characterized using scanning electron microscopy imaging for pore structure and compression testing for Young's Modulus. The BCa cell cultures were characterized at day 1, 3, and 7 timepoints using Alamar Blue assay for cell number, fluorescence imaging for cell morphology, and single-cell tracking for cell migration. Pore size calculations using SEM imaging yielded pore sizes of 253.29 ± 52.45 µm, 209.55 ± 21.46 µm, and 216.83 ± 32.63 µm for 2 wt%, 4 wt%, and 6 wt%, respectively. Compression testing of the CA scaffolds yielded Young's Modulus values of 0.064 ± 0.008 kPa, 2.365 ± 0.32 kPa and 3.30 ± 0.415 kPa for 2 wt%, 4 wt%, and 6 wt% CA scaffolds, respectively. The results showed no significant difference in cell number among the 3D CA scaffold groups. However, the 231-GFP cells cultured in 2 wt% CA scaffolds possessed greater cellular size, area, perimeter, and lower cellular circularity compared to those in 4 wt% and 6 wt% CA scaffolds, suggesting a more prominent presence of cell clusters in softer substrates compared to stiffer substrates. The results also showed cells in 6 wt% CA having a higher average cell migration speed compared to those in 2 wt% and 4 wt% CA scaffolds, indicating a positive relationship between substrate stiffness and cell migration velocity. Findings from this experiment may contribute to the development of enhanced in vitro 3D breast tumor models for basic cancer research using 3D porous biomaterial scaffolds.

The intent of this thesis is to lay groundwork for examining the relationship between seismocardiography (SCG) and phonocardiography (PCG). Both are methods of measuring and describing heart mechanical function. SCG is described as chest vibrations while the heart beats, and PCG is described as acoustic chest surface signal believed to represent the heart valves opening or closing. SCG and PCG have both been used separately in clinical and research settings, but there is currently no clear comparison between the two. Therefore, there has been no way at the present to understand how one signal might inform the other. This study is an effort to fill that gap. SCG and PCG sensors were placed on subjects’ chests while sensor output was simultaneously recorded. The magnitudes of the signals and their trends were then compared against each other to see their similarities and differences. The comparisons demonstrated similar trends between the two sensor types, supporting the hypothesis that there is a relationship between the two that requires further research and insight.