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The development of a robotic slit-lamp for remote ophthalmology is the primary purpose of this work. In addition to novel mechanical designs and implementation, it was also a goal to develop a control system that was flexible enough to be adapted with minimal user adjustment to various styles and configurations of slit-lamps. The system was developed with intentions of commercialization, so common hardware was used for all components to minimize the costs. In order to improve performance using this low-cost hardware, investigations were made to attempt to achieve better performance by applying control theory algorithms in the system software. Ultimately, the controller was to be flexible enough to be applied to other areas of human-robot interaction including pediatric rehabilitation via the use of humanoid robotic aids. This application especially requires a robust controller to facilitate safe interaction. Though all of the prototypes were successfully developed and made to work sufficiently with the control hardware, the application of advanced control did not yield notable gains as was hoped. Further investigations were made attempting to alter the performance of the control system, but the components selected did not have the physical capabilities for improved response above the original software implemented. Despite this disappointment, numerous novel advances were made in the area of teleoperated ophthalmic technology and pediatric physical rehabilitation tools. This includes a system that is used to remote control a slit-lamp and lens for examinations and some laser procedures. Secondly, a series of of humanoid systems suitable for both medical research and therapeutic modeling were developed. This included a robotic face used as an interactive system for ophthalmic testing and training. It can also be used as one component in an interactive humanoid robotic system that includes hands and arms to allow use of teaching sign language, social skills or modeling occupational therapy tasks. Finally, a humanoid system is presented that can serve as a customized surrogate between a therapist and client to model physical therapy tasks in a realistic manner. These systems are all functional, safe and low-cost to allow for feasible implementation with patients in the near future.

<div><p>The cellular protein pool exists in a state of dynamic equilibrium, such that a balance between protein synthesis and degradation is maintained to sustain protein homeostasis. This equilibrium is essential for normal cellular functions and hence alteration in protein dynamics has several pathological implications in developing and adult tissues. Recent progress in mass spectrometry (MS) and metabolic labeling techniques has advanced our understanding of the mechanisms of protein regulation in cultured cells and less complicated multicellular organisms. However, methods for the analysis of the dynamics of intra- and extra-cellular proteins in embryonic and adult tissues remain lacking.</p><p>To address this gap, we developed a metabolic labeling technique that enables labeling the nascent murine proteome via injection of non-canonical amino acids (ncAAs), which can be selectively enriched by “clickable” tags for identification and quantification. Using this technique, we developed a MS-based method for the selective identification and quantification of the intra- and extra-cellular newly synthesized proteins in developing murine tissues. We then applied this technique to study the dynamic regulation of extracellular matrix (ECM) proteins during embryonic and adolescent musculoskeletal development. We show that the applied technique enables resolving differences in the nascent proteome of different developmental time points with high temporal resolution. The technique can also reveal protein dynamic information that cannot be captured by the traditional proteomic techniques. Additionally, we identified key ECM components that play roles in musculoskeletal development to provide insights into the mechanisms of musculoskeletal tissue regeneration.</p><p>To fully characterize our labeling technique, we developed a mathematical model to describe the biodistribution kinetics of azidohomoalanine (Aha), the most widely used ncAA, in murine tissues. The model enabled measuring the relative rates of protein synthesis and turnover in different tissues and predicting the effect of different dosing regimens of Aha on the degree of protein labeling. Finally, we analyzed the plasma metabolome of Aha-injected mice to investigate the impact of Aha incorporation on normal physiology. The analysis revealed that Aha administration into mice does not significantly perturb metabolic functions. Taken together, the findings presented in this dissertation demonstrate the utility of the ncAA labeling technique in mapping protein dynamics in mammalian tissues. This will ultimately have a significant impact on our understanding of protein regulation in health and disease. </p></div><br>

Osteoarthritis (OA) is a debilitating disease affecting roughly 31 million Americans. The incidence of OA is significantly higher for persons who have suffered a transtibial amputation. Abnormal cartilage stress can cause higher OA risk, however it is unknown if there is a connection between exercise type and cartilage stress. To help answer this, a tibiofemoral FEA model was created. Utilizing linear elastic isotropic materials and non-linear springs, the model was validated to experimental cadaveric data. In a previous study, 6 control and 6 amputee subjects underwent gait and cycling experiments. The resultant knee loads were analyzed to find the maximum compressive load and the respective shear forces and rotation moments for each trial, which were then applied to the model. Maximum tibial contact stress values were extracted for both the medial and lateral compartments. Only exercise choice in the lateral compartment was found to be a significant interaction (p<0.0001). No other interactions in either compartment were significant. This suggests that cycling reduces the risk for lateral OA regardless of amputation status and medial OA risk is unaffected. This study also developed a process for creating subject-specific FEA models.

A polyconvex continuum-level proteoglycan Cauchy stress function was developed based on the continuum electromechanical Poisson-Boltzmann unit cell model for proteoglycan interactions. The resulting proteoglycan model was combined with a novel collagen fibril model and a ground substance matrix material to create a polyconvex constitutive finite element model of articular cartilage. The true collagen fibril modulus , and the ground substance matrix shear modulus , were varied to obtain the best fit to experimental tension, confined compression, and unconfined compression data for native explants and explants cultured in insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). Results indicate that culture in IGF-1 results in a weakening of the COL fibers compared to native explants, and culture in TGF-β1 results in a strengthening of the COL fibers compared to native explants. These results elucidate the biomechanical changes in collagen fibril modulus, and ground matrix shear modulus following in vitro culture with IGF-1 and TGF-β1. Understanding the constitutive effects of growth factor stimulated culture may have applications in AC repair and tissue engineering.

A poroelastic finite element model of a heterogeneous articular cartilage disc was created to examine the tissue response to low amplitude (± 2% strain), low frequency (0.1 Hz) dynamic unconfined compression (UCC). A strong correlation has been made between the relative fluid velocity and stimulation of glycosaminoglycan synthesis. A contour plot of the model shows the relative fluid velocity during compression exceeds a trigger value of 0.25 μm/s at the radial periphery. Dynamic UCC biochemical results have also reported a higher glycosaminoglycan content in this region versus that of day 0 specimens. Fluid velocity was also found not to be the dominant physical mechanism that stimulates collagen synthesis; the heterogeneity of the fluid velocity contour plot conflicts with the homogeneous collagen content from the biochemical results. It was also found that a Tresca (shear) stress trigger of 0.07 MPa could provide minor stimulation of glycosaminoglycan synthesis. A feasibility study on modeling a heterogeneous disc was conducted and found convergence issues with the jump in properties from the superficial to middle layers of the disc. It is believed that the superficial layer contains material properties that allow the tissue to absorb much of the compressive strain, which in turn increases pressure and causes convergence issues in ABAQUS. The findings in this thesis may help guide the development of a growth and remodeling routine for articular cartilage.

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.

Here we describe a finite element model of the mechanical stresses and strains involved in the growth and development of epithelial cancers, specifically pancreatic ductal adenocarcinoma (PDAC). We model a growing tumor swelling over time, modeled as fluid influx in response to changing solute concentrations. Stresses and strains are computed in surrounding material regions in response to this swelling. Further studies are conducted into the relative impacts of factors such as basement membrane thickness, stiffness, and duct radius. We observe that normal stresses are confined mostly to the basement membrane layer and hypothesize that there exists some threshold for axial stress beyond which the basement membrane ruptures and cancer is able to invade into the surrounding tissue.

<p>With a stable center of mass, pneumatic-aided movement, and the ability to scale multiple terrain types, the uniquely efficient and lightweight form of spiders has changed the way we think about robotic design. While the number of papers on arachnid biomechanics and spider-based biomimetic robots has been increasing in recent years, the style of analysis and the motion-types analyzed have barely changed since the 1980s. Current analyses are based on a force plate and treadmill design, in which the spider is induced into an escape run. This environmental change can affect the movements of the spider. Here I propose a novel method of testing the biomechanical and kinematic properties of spiders using a tank with a built-in sensor matrix which allows for a more natural environment for the specimens and provides force data from individual legs. The system detects a minimum force of .0196 N and has a sampling rate of 1,000 samples /second, which allows for the analysis of forces during the step. <i>Aphonopelma seemanni</i>, a tarantula commonly used in such research, but whose forces during movement have to date not been analyzed, was recorded walking across the matrix, and the forces, step patterns, joint angles, and center of mass deviations were recorded. Walking indicated significantly different step pattern traits than current literature, and forces per leg (.07281 N±.0235) recorded were much smaller than expected in comparison to other spiders. Statistical analysis also indicated no changes in walking movement over a range of temperatures, which also varies from literature. These findings indicate that further research on spiders should be done with respect to walking gaits in order to improve upon current biomimetic models. </p> <br>