Computational joint models provide insight into the biomechanical function of human joints. Through both deformable and rigid body modeling, the structure-function relationship governing joint behavior is better understood, and subsequently, knowledge regarding normal, diseased, and/or injured function is garnered. Given the utility of these computational models, it is imperative to supply them with appropriate inputs such that model function is representative of true joint function. In these models, Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) scans and literature inform the bony anatomy and mechanical properties of muscle and ligamentous tissues, respectively. In the case of the latter, literature reports a wide range of values or average values with large standard deviations due to the inability to measure the mechanical properties of soft tissues in vivo. This makes it difficult to determine which values within the published literature to assign to computational models, especially patient-specific models. Therefore, while the use of published literature serves as a reasonable first approach to set up a computational model, a means of improving the supplied input data was sought. This work details the application of artificial neural networks (ANNs), specifically feedforward and radial basis function networks, to the optimization of ligament stiffnesses for the improved performance of pre- and post-operative, patient-specific foot/ankle computational models. ANNs are mathematical models that utilize learning rules to determine relationships between known sets of inputs and outputs. Using knowledge gained from these training data, the ANN may then predict outputs for similar, never‑before-seen inputs. Here, an optimal network of each ANN type was found, per mean square error and correlation data, and then both networks were used to predict optimal ligament stiffnesses corresponding to a single patient’s radiographic measurements. Both sets of predictions were ultimately supplied to the patient-specific computational models, and the resulting kinematics illustrated an improvement over the existing models that utilized literature-assigned stiffnesses. This research demonstrated that neural networks are a viable means to hone in on ligament stiffnesses for the overall objective of improving the predictive ability of a patient-specific computational model.

Diseases involving fibrosis cause tens of thousands of deaths per year in the US alone. These diseases are characterized by a large amount of extracellular matrix, causing stiff abnormal tissues that may not function correctly. To take steps towards curing these diseases, a fundamental understanding of how cells interact with their substrate and how mechanical forces alter signaling pathways is vital. Studying the mechanobiology of cells and the interaction between a cell and its extracellular matrix can help explain the mechanisms behind stem cell differentiation, cell migration, and metastasis. Due to the correlation between force, extracellular matrix assembly, and substrate stiffness, it is vital to make in vitro models that more accurately simulate biological stiffness as well as measure the amount of force and extracellular matrix assembly. To accomplish this, blends of two types of poly(dimethylsiloxane) (PDMS) were made and the material properties of these polymer blends were characterized. A field of 5µm or 7µm microscopic pillars (referred to as posts) with a diameter of 2.2µm were fabricated from these blends. Each combination of PDMS blend and post height were calibrated and the stiffness was recorded. Additionally, polymer attachment experiments were run to ensure cells survived and had a normal phenotype on the different blends of PDMS when compared to pure PDMS. Finally, cells were placed onto a field of posts and their forces were calculated using the new stiffness found for each blend of post. Varying the PDMS material stiffness using blends allow posts to be much more physiologically relevant and help to create more accurate in vitro models while still allowing easy and accurate force measurement. More biologically relevant in vitro models can help us acquire more accurate results when testing new drugs or examining new signaling pathways.

Abnormal lumbar movement has been observed in individuals who have a history of low back pain (LBP). Affected individuals display a reduction in lumbar spine rotation during trunk movement tasks, while pelvic rotation increases to compensate. Reduced lumbar contribution to forward bending is associated with increased compressive forces and increased shearing demand of the task on the lower back. This abnormal lumbo-pelvic coordination (LPC) can persist beyond LBP symptom alleviation and may contribute to further occurrences or more severe cases of LBP. This study serves as a first step in investigating if abnormal LPC can be corrected with a hip orthosis by examining the effects of the device on the LPC of healthy individuals. Twenty participants without presence or history of LBP were recruited to participate in a repeated measures study, completing trunk motion tasks with and without a hip orthosis. In a random order, participants completed forward bending and backward return, lateral bending to the left and right, and axial twisting to the left and right. Thoracic, lumbar, and pelvic rotation along with lumbar-thoracic ratio (LTR) were calculated for each of the movement tasks. Thoracic rotation (total trunk movement) was not significantly altered (p > 0.05, F=0.633) by the application of the hip orthosis. LTR was significantly increased (p < 0.001, F=2.96) with the orthosis by 32%, 22%, 12%, 4%, and 12% for axial twisting left, axial twisting right, lateral bending left, lateral bending right, and forward bending, respectively. This indicates lumbar contributions were increased by physically restricting the pelvis. The effects of a hip orthosis should be further investigated in LBP patients to verify correction of an abnormal LPC.

Hollow fiber membranes are widely used in blood oxygenators to remove carbon dioxide and add oxygen during cardiopulmonary bypass operations. These devices are now widely used off-label by physicians to perform extracorporeal blood oxygenation for patients with lung failure. Unfortunately, the hollow fiber membranes used in these devices fail prematurely due to blood plasma leakage and gas emboli formation. This project formed ultrathin (~100nm) polymer coatings on polymer hollow fiber membranes. The coatings were intended to “block” existing pores on the exterior surfaces while permitting high gas fluxes. This coating is synthesized using surface imitated control radical polymerization. The coating was durable and did not peel or degrade. Fibers modified using this coating technique did not substantially degrade the mechanical properties of the membrane. This coating technique prevented blood plasma leakage and gas emboli formation. The coating permitted blood oxygenation and carbon dioxide removal from in a mock circulation module. Coating formation on polymeric hollow fiber membranes using surface initiated controlled radical polymerization allows for the formation of membranes that have the potential for long term blood oxygenation. This coating technique would allow these long term blood membranes to be produced more inexpensively than currently existing membranes used for long term use.

Osteoporosis is a significant healthcare issue due to the increasing elderly population. Bisphosphonates are used to treat osteoporosis by reducing the rate of resorption, increasing bone mineral density (BMD) and thereby reducing fracture risk. Long-term bisphosphonate treatment, however, has been associated with low-energy fractures. Bone microdamage may provide a partial explanation for one of the mechanisms responsible for these fractures since it has been shown to reduce bone toughness, fracture resistance, and bone strength. The goal of this study was to quantify the changes in bone microdamage parameters with the duration of bisphosphonate treatment. This study selected, stained, and histomorphometrically analyzed 40 iliac crest bone biopsies from controls and female patients with osteoporosis treated with bisphosphonates for varying durations (up to 12 years). All subjects were matched for age and low turnover. The results showed that microcrack density and microcrack surface density were significantly greater in patients who took bisphosphonates for at least 5 years compared to those who took bisphosphonates for less than 5 years or not at all. These results reveal novel, clinically relevant information linking microdamage accumulation to long-term bisphosphonate treatment without influences from age or turnover.

Oral bisphosphonate drug therapy is a common and effective treatment for osteoporosis. Little is known about the long-term effects of bisphosphonates on bone quality. This study examined the structural and mechanical properties of trabecular bone following 0-16 years of bisphosphonate treatment. Fifty-three iliac crest bone samples of Caucasian women diagnosed with low turnover osteoporosis were identified from the Kentucky Bone Registry. Forty-five were treated with oral bisphosphonates for 1 to 16 years while eight were treatment naive. A section of trabecular bone was chosen from a micro-computed tomography (Scanco µCT 40) scan of each sample for a uniaxial linearly elastic compression simulation using finite element analysis (ANSYS 14.0). Morphometric parameters (BV/TV, SMI, Tb.Sp., etc.) were computed using µCT. Apparent modulus, effective modulus and estimated failure stress were calculated. Biomechanical and morphometric parameters improved with treatment duration, peaked around 7 years, and then declined independently of age. The findings suggest a limit to the benefits associated with bisphosphonate treatment and that extended continuous bisphosphonate treatment does not continue to improve bone quality. Bone quality, and subsequently bone strength, may eventually regress to a state poorer than at the onset of treatment. Treatment duration limited to less than 7 years is recommended.

Hypercholesterolemia is a risk factor for osteoporosis but the underlying mechanism is unknown. Previous evidence suggests that osteoporosis results from an impaired regulation of osteoblasts by fluid pressure fluctuations in the bone matrix. Recently, our laboratory showed that enhanced cholesterol in the cell membrane, due to hypercholesterolemia, alters leukocyte mechanosensitivity. We predict a similar link between osteoblasts and hypercholesterolemia leading to osteoporosis. Specifically, we hypothesize that extracellular cholesterol modifies the osteoblast sensitivity to pressure. MC3T3-E1 cells were exposed to hydrodynamic pressures regimes (mean=40mmHg, amplitude=0-20mmHg, frequency=1Hz) for 1-12 hours. To assess the impact of membrane cholesterol enrichment, cells were pre-treated with 0-50 µg/mL cyclodextran:cholesterol conjugates. We assessed the pressure effects on mitosis and F-actin stress fiber formation (SFF) of cells. Exposure of cells to 50/30 mmHg pressure transiently increased the number of cells in the S- and G2M-phases of mitosis after 6 and 12 hours, respectively. Relative to controls, osteoblast-like cells exposed to all pressures exhibited significantly (p

While military body armor is used among warfighters for protection on and off the battlefield, it has been suggested to impede performance and act as a risk factor for the development of musculoskeletal disorders, especially low back pain. Apart from personal suffering, low back pain in soldiers is a great economic burden on the US economy. The objective of this study was to quantify the changes in trunk mechanical and neuromuscular behavior following prolonged exposure to body armor compared to exposure without. A crossover study design was used where 12 sex-balanced participants completed a series of tests before and after 45 minutes of treadmill walking with and without body armor. The tests included range of motion, isometric trunk tests, sudden perturbations, and stress relaxation. As a whole, exposure duration considered in this study resulted in no significant differences in performance between armor and no armor conditions. However, comparing the effects of body armor among the sex-differentiated groups showed a body armor -induced increase in range of trunk motion in the sagittal plane among females (p = 0.0018) and a decrease in pelvic range of motion in the transverse plane among both males (p=0.025) and females (p=0.004).

The prevalence of asymmetry in performance research has increased in recent years with mixed results. Much of the performance research has focused on unilateral jumping activities attempting to show relationships to other performance variables. However, bilateral ground reaction forces (bGRF) from jumps are more frequently assessed in athlete monitoring programs and the asymmetry from those jumps could be a simple addition to data already being collected. Research into bGRF asymmetries is lacking and no studies have addressed longitudinal changes. Additionally, research into the relationship of asymmetries to performance have infrequently used athletes. For these reasons, this dissertation will focus on bGRFs by assessing reliability, determining the relationship to performance, and tracking longitudinal changes among collegiate athletes. These data indicate that impulse has high absolute (ICC > 0.87) and relative (CV < 3.22) reliability values and should be the preferred metric for assessing jumping asymmetry. As well, a combination of the braking and propulsive phase above body mass has higher correlations (r = -0.25 to -0.49) to jumping performance compared to the propulsive phase alone (r = -0.09 to 0.26). Males and female soccer players have differing relationships with asymmetry as males had the greatest correlations between weighted countermovement jump (CMJ) asymmetry and weighted CMJ performance (r = -0.49), whereas females produced their greatest correlations with unweighted CMJs (r = -0.43). Additionally, all statistically significant correlations between asymmetry and performance were negative. Athletes with higher asymmetry values typically realize improvements over time without specific interventions, whereas athletes with lower values may not experience many fluctuations. Overall, asymmetry has negligible relationships to strength lev els (r = 0.30 to with strength training. 0.22) but seems to be associated with the improved motor coordination Indeed, athletes with higher asymmetry values involved even displayed trends of greater performance gains over time.

Subclinical atherosclerosis is an important area of research to evaluate stroke risk and predict localization of plaque. The current methods for detecting atherosclerosis risk are insufficient because it is based on The Framingham Risk Score and carotid intima media thickness, therefore an engineering detection model based on quantifiable data is needed. Laminar and turbulent flow, dictated by Reynolds number and relative roughness, was modeled through the carotid artery bifurcation to compare shear stress and shear rate. Computer-aided design and fluid flow software were used to model hemodynamics through the carotid artery. Data from the model was derived from governing equations programmed in COMSOL for both laminar and turbulent flow. A carotid artery model is accurate enough to describe how relative roughness, flow profiles, and shear rate can be a good prediction of subclinical atherosclerosis.