Transtibial amputees are at increased risk of contralateral hip and knee joint osteoarthritis, likely due to abnormal biomechanics. Biomechanical challenges exist for transtibial amputees in gait and cycling; particularly, asymmetry in ground/pedal reaction forces and joint kinetics is well documented and state-of-the-art passive and powered prostheses do not fully restore natural biomechanics. Elliptical training has not been studied as a potential exercise for rehabilitation, nor have any studies been published that compare joint kinematics and kinetics and ground/pedal reaction forces for the same group of transtibial amputees in gait, cycling, and elliptical training. The hypothesis was that hip and knee joint kinematics and kinetics and ground and pedal reaction forces would differ due to exercise (gait, cycling, elliptical) amputee status (amputated, control [non-amputated]), and leg (dominant [intact], non-dominant [amputated]). Ten unilateral transtibial amputees and ten control participants performed the three exercises while kinematic and kinetic data were collected. Hip and knee joint flexion angle, resultant forces, and resultant moments were calculated by inverse dynamics for the dominant and non-dominant legs of both participant groups. Joint biomechanics and measured ground/pedal reaction forces were then compared between exercises, between the dominant and non-dominant legs within each participant group, and across participant groups. Significant differences in hip and knee joint flexion angles and timing, compressive forces, extension-flexion (EF) and adduction-abduction (AddAbd) moments, and anterior-posterior (AP) and lateral-medial (LM) reaction forces were found. Particularly, transtibial amputees showed maximum knee flexion angle asymmetry as compared to controls in all three exercises. Maximum hip and knee compressive forces, EF moments, and AddAbd moments were lowest in cycling and highest in gait. Asymmetry in amputee midstance knee flexion and timing in v gait, coupled with low maximum EF moment for the non-dominant leg, suggests that amputees avoid contraction of the non-dominant quadriceps muscle. Knee flexion angle and EF moment asymmetry in elliptical training suggests that a similar phenomenon occurs. Asymmetry in AP and LM reaction forces in gait, but not other exercises, suggests that exercises that constrain kinematics reduce loading imbalances. The results suggest that cycling and elliptical training should be recommended to transtibial amputees for rehabilitation due to reduced hip and knee joint forces and moments. Elliptical training may be preferred over gait due to decreased joint loading and loading asymmetry, but some asymmetry and differences from control participants still exist. Non-weight bearing exercises such as cycling may be best at reducing overall joint loading and joint load asymmetry but do not eliminate all kinematic and temporal asymmetries. Current state-of-the-art prosthetic leg design is insufficient in restoring natural biomechanics not only in gait but also in cycling and elliptical training. Improved prosthesis kinematics that restore non-dominant knee flexion in amputees to normal levels could help reprogram quadriceps muscle patterns in gait and elliptical training and hip and knee joint biomechanical asymmetries. Further work in comparing contralateral and prosthesis ankle joint biomechanics would help to elucidate the relationship between prosthesis design and its impact on lower limb joint biomechanics.

The goal of this study is to design and manufacture a microfluidic device capable of measuring changes in impedance valuesof microfluidic cell cultures. Tocharacterize this, an interdigitated array of electrodes was patterned over glass, where it was then bonded to a series of fluidic networks created in PDMS via soft lithography. The device measured ethanol impedance initially to show that values remain consistent over time. Impedance values of water and 1% wt. saltwater were compared to show that the device is able to detect changes in impedance, with up to a 60% reduction in electrical impedance in saltwater. Cells were introduced into the device, where changes in impedance were seen across multiple frequencies, indicating that the device is capable of detecting the presence of biologic elements within a system. Cell measurements were performed using NIH-3T3 fibroblasts.

The goal of this project was to determine whether i) fused deposition modeling could be employed to manufacture molds for vascular constructs, ii) whether vascular constructs could be created from these molds, and iii) to verify practical equivalence between observed fluid velocities. Dye tracking was to be employed to characterize fluid velocity profiles through the in vitro vascular constructs, including a half-vessel model and a full vessel model of an iliac artery aneurysm. A PDMS half-vessel construct was manufactured, and the movement of dye through the construct was tracked by a cellphone camera. Thresholds were applied to each video in HSB or YUV mode in ImageJ, and analyzed to determine the velocity of the fluid through the construct. COMSOL simulations of the half-vessel were conducted for comparison to the empirical observations. Plots describing the flow velocities along the maximum streamline path length were generated, and a one sample t-test was conducted at a 5% significance level to determine whether there was a significant difference between velocity values obtained by dye tracking and the COMSOL simulations. It was determined that the empirical dye tracking trials failed to demonstrate agreement between the measured and predicted flow rates. A full vessel construct was not completed due to unforeseen time constraints. Dye tracking was not determined to be reliable as a means of measuring the maximum velocity of fluid. Discrepancies between the empirical observations and the COMSOL simulation are discussed. The discrepancy was attributed to limitations in the experimental protocol; low frame rate, poor control over lighting conditions, and the subjectivity involved in image processing. Methods of improving upon the manufacturing and experimental protocols used for the half-vessel are proposed for future work, such as improving control over lighting conditions, choosing a camera with a higher frame rate, constructing a more stable fixture, exploring PIV. Additionally, the technical problems leading to the failure to complete the full vessel model are discussed, and changes in the manufacturing process are proposed to allow dissolution or removal of the aneurysm model.

Aortic aneurysms are the 14th leading cause of death in the United States. Annually, abdominal aortic aneurysm (AAA) ruptures are responsible for 4500 deaths. There are another 45,000 repair procedures performed to prevent rupture, and of these approximately 1400 lead to deaths. With proper detection, the aneurysm may be treated using endovascular aneurysm repair (EVAR). Understanding how the flow of the blood within the artery is affected by the aneurysm is important in determining the growth of the aneurysm, as well as how to properly treat the aneurysm. The goal of this project was to develop a physical construct of the AAA, and use this construct to validate a computational model of the same aneurysm through flow visualization. The hypothesis was that the fluid velocities within the physical construct would accurately mimic the fluid velocities used in the computational model. The physical model was created from a CT scan of an AAA using 3D printing and polymer casting. The result was a translucent box containing a region in the shape of the aneurysm. Fluid was pumped through the construct to visualize and quantify the velocity of the fluid within the aneurysm. COMSOL Multiphysics® was used to create a computational model of the same aneurysm, as well as obtain velocity measurements to statistically compare to those from the physical construct. There was no significant difference between the velocity values for the physical construct and the COMSOL Multiphysics® model, confirming the hypothesis. This study used a CT scan to create an anatomically accurate model of an AAA that was used to validate a computational model using a novel technique of flow visualization. As EVAR technologies continue to progress, it will become increasingly important to understand how the blood flow within the aneurysm affects the growth and treatment of AAAs.

Current research suggests that femoroacetabular impingement can be a cause of osteoarthritis. Femoroacetabular impingement is a condition that can affect both the femur and the pelvis of an individual. Femoroacetabular impingement can cause damage to the hip joint and its surrounding tissues. The articular cartilage and the labrum are both affected by this condition. A cam impingement is where a bony protrusion develops at the femoral head/neck junction. A pincer impingement is where a bony protrusion develops at the acetabular rim. Often, patients are seen with a combination of both impingements. The main goal of this study was to computationally model and analyze acetabular stresses in a healthy hip, a hip with a cam impingement, a hip with a pincer impingement, and a hip with a combination of the two impingements. The bone models were taken from CT scans. The impingements were created by using Autodesk Maya to modify the surfaces of the models. The hip models were set up to model the single-leg stance phase of the walking cycle. For the most part, the impingements reduce the stress experienced by the femur. The only exception to this is that the cam femur paired with the pincer pelvis experienced the highest maximum principal stress in the proximomedial region. The pincer impingements increase both the maximum and minimum principal stresses experienced in the acetabulum. Overall, the two types of femoroacetabular impingement change the stress experienced by both the femur and the pelvis. The results of this study demonstrate that acetabular stresses can increase as a result of femoroacetabular impingements. These increased stresses can lead to damage in the hip joint which presents a clinical problem.

With more young adults requiring total hip arthroplasties the need for bone saving implants becomes more important. The Zimmer Fitmore is a new bone saving implant that utilizes an implantation technique that reduces the damage to the muscle tissue allowing for patients to have a short recovery time as well as a new design that allows it to rest on the medial cortex. There has been anecdotal evidence that this device leads to early revision within six months of implantation due to failures occurring in the medial cortex. The main goal of this study was to computationally model the Zimmer Fitmore and compare it to the ML Taper to see if the failures are due to the design of the implant. The models were created using CT scans of the implants and the same implantation process was simulated for each. Two sizes for the cortical bone thickness, 4mm and 10mm, were used and contrasted with each other. The 10mm cortical thickness model showed that v the strains experienced by the Zimmer Fitmore femur were higher than that of the ML Taper. The 4mm model did not fully complete the simulation, but the results that were obtained showed an increased strain in Gruen zone 7. These results show that the design, not implantation method, could be to blame for the need for early revision when using the Zimmer Fitmore.

Experimental results show that collagen fibers exhibit stress relaxation under tension and a highly anisotropic distribution. To further develop the earlier model of Stender [1], the collagen constituent was updated to reflect its intrinsic viscoelasticity and anisotropic distribution, and integrated with an existing mixture model with glycosaminoglycans and ground substance matrix. A two-term Prony series expansion of the quasi-linear viscoelastic model was chosen to model the viscoelastic properties of the collagen fibers. Material parameters were determined by using the simplex method to minimize the sum of squared errors between model results and experimental stress relaxation data of tissue in tension. Collagen elastic fiber modulus was calculated by fitting to the equilibrium data and viscoelastic parameters were determined by fitting to the relaxation curve. Results of newborn (~1-3 week old) untreated bovine articular cartilage explants from the patellar femoral groove as well as explants cultured in transforming growth factor-β1 (TGF-β1), from both the superficial (~0-0.5 mm from the articular surface) and middle (~0.5-1.0 mm from the articular surface) layers were compared to examine the effects of TGF- β1. TGF-β1 has been shown to maintain or even enhance mechanical properties of articular cartilage in compression and tension [2, 3] and this study continues with the hope that it may be used to improve tissue engineering of mature cartilage to better survive implantation in vivo for the successful repair of articular cartilage defects. Results show that TGF-β1 has a maturational effect on collagen, causing the tissue to become stiffer through an increase in elastic collagen fiber modulus and less viscous through shorter relaxation time and less stress relaxation (tissue retained a higher percentage of residual stress). The results of this study further advance the understanding of the effects of location and treatment with TGF-β1.

This thesis successfully integrates laminate microfluidic devices with an analytic Surface Plasmon Resonance (SPR) instrument. Integration was accomplished at low-cost using materials such as polydimethylsiloxane (PDMS), Poly(methyl methacrylate) (PMMA), Tygon tubing, and a 3-way stopcock. The main components of this thesis are the design and fabrication of the low-cost, in-house fluidics that can integrate with upstream microfluidics and the validation of the in-house fluidics using the Biosensing Instruments BI-2000 SPR instrument. The low-cost fluidics was designed and fabricated “in-house” using a novel investment casting technique that required the use of laser cutting technology to make a master cast, and candle wax to make the fluidic flow gasket. Integration of upstream microfluidic devices is the next step towards fully integrated point-of-care (POC) diagnostics. Development of low-cost POC diagnostics will enable physicians to diagnosis patients outside of clinical settings, granting treatment access to a much wider population. Surface Plasmon Resonance is used for its detection abilities combined with its ability to perform real-time sample analysis. Validation of the in-house fluidics was accomplished by conducting (2) experiments: (1) to compare the angular shift elicited by ethanol solutions between in-house fluidics, factory fluidics, and the literature, and (2) to compare the angular shift between in-house fluidics and factory fluidics caused by the cleaving of fibroblasts from the SPR sensor chip. Successful comparisons made in both experiments proved successful development of low-cost fluidics that could integrate upstream microfluidic devices.

With the high mortality rate of cardiovascular disease, it is important to study the early signs. The early detection of cardiovascular disease can lead to saved lives. Currently the most prevalent detection methods are the Framingham Risk Score and the carotid intima media thickness, both of which are insufficient. The necessary tool for early detection requires a uniform quantification system. The stimulus leading to endothelial dysfunction, the most significant predictor of a major adverse cardiovascular event (MACE)—and subsequently subclinical atherosclerosis—is reduced shear stress. Increased surface relative roughness affects the flow profile transition from laminar to turbulent resulting in reduced shear rate. The relationship between the shear stress and the relative roughness was studied using a computer model for fluid flow. A model of the brachial artery was generated to study its hemodynamics. Roughness values for both laminar and turbulent flow were calculated to use with the governing equations programmed in COMSOL Multiphysics. With all other factors remaining constant in the model, the roughness values were changed. From the model profile plots, line graphs, and numeral data are generated. This data provides information about how the shear stress and the shear rate change with respect to the relative roughness value. The models with different wall boundary conditions—slip versus Navier slip—were unable to be directly compared due to the differences in value magnitude. When the flow profile transitions from laminar to turbulent, there is a corresponding drop in both the shear stress and the shear rate values. Additional testing is required to determine a critical relative roughness value for this change in cumulative shear.

ABSTRACT Skier’s Edge: Biomechanical Analysis Benjamin T. Johannes The Skier’s Edge trainer can be used by novice or expert skiers. Testing was performed to analyze if the use of the Skier’s Edge could reduce in shear forces of the valgus moment on the knee joint and anterior cruciate ligament (ACL) due to lesser fatigue of muscle and a higher hamstring to quadricep (H/Q) ratio activity. This leads to a reduction of improper form and an increase in balance. Experiments performed observed the change in muscle activity with the use of the Skier’s Edge over time when compared to other forms of workout (elliptical and or a traditional ski conditioning workout). Comparison of the three workout methods was completed by collecting kinematic, kinetic and electromyographic (EMG) data. Each participant, 9 male skiers (22±3 years old, 70.56±3.44 inches, 206±54 lbs.) and 6 female skiers (22±4 years old, 66.25±3.25 inches, 148±72 lbs.), were separated into even groups between the workout types. Data was collected initially and after a four-week period of exercise for each respective workout group. A relative valgus moment was found with the force and valgus angle data and an H/Q ratio was created using the vastus medialis and semitendinosus EMG data for the respective muscles. The findings of this study show that there were no significant differences between the workout types for either reduction of valgus moment or an increase in H/Q ratio which are indicators of reduced ACL injury. Trends in the data indicate that the elliptical workout may have a positive impact on H/Q when compared to the Skier’s Edge workout. Recommendation for future study includes having participants complete a more intense and longer workout period or to focus on the elliptical and Skier’s Edge workout to test for significant differences to aid in ACL injury reduction.