<p> Intramuscular pressure (IMP), which is closely correlated with both active and passive muscle tension, may become a useful supplement to current clinical tools as a means to quantify individual muscle-generated force. A continuing challenge associated with this measure is its non-uniform distribution, which is not yet fully understood. Several studies have observed that pressure increases with muscle depth. Conservation of mass suggests that these regional pressure differences may result from non-uniformly distributed changes in local tissue volume. Therefore, the overarching goal of this work was to characterize volumetric strain distribution in skeletal muscle as a means to better understand the mechanism driving the non-uniform IMP distribution. </p><p> Three-dimensional volumetric strain distribution had not been previously quantified in skeletal muscle; therefore the bulk of this thesis work revolved around developing and validating a method for this purpose using cine Phase Contrast (CPC) magnetic resonance imaging (MRI). CPC MRI has been previously used to quantify 2D strain distribution in skeletal muscle. Fortunately, the method lends itself to 3D measurements using multiple slice data collection, but this requires a lengthy data acquisition time. We chose to develop the method during passive tension of the human tibialis anterior (TA), because passive tension is closely correlated with IMP and the motion repeatability is more readily controlled and maintained for an extended duration than active tension. </p><p> As hypothesized, volumetric strain was found to be non-uniformly distributed during passive tension of the human TA with a decreasing trend from the anterior (superficial) to the posterior (deep) muscle regions. These data align with previously observed trends of decreasing IMP near the muscle surface and may provide important insight into ideal sensor placement regions to maximize measurement repeatability. These results advance our understanding of the tension-IMP relationship in muscle by providing insight into the mechanism behind the non-uniform distribution of IMP. Furthermore, this work has strong potential to contribute to a computational model relating IMP to muscle tension by way of volumetric strain.</p>

<p> The esophagus is critical for passage of oral bolus into the gastrointestinal tract. Diseases of the esophagus, such as malignancy, can necessitate resection of esophageal tissue. To maintain esophageal continuity with the remainder of the gastrointestinal tract, reconstruction is mandatory. Current reconstructive options are morbid and involve autologous conduits such as stomach, small bowel, or colon. An alternative tissue engineered conduit that facilitates esophageal regrowth to reduce the need for these morbid reconstructions would have significant clinical utility. Several critical challenges must be addressed in order to make these conduits a clinical reality. First, scaffolds should be designed to ideally mimic mechanical behavior of the native esophagus. To accomplish this, a non-destructive method to mechanically assess these constructs benchmarked to native esophagi is necessary before and after implantation. Second, scaffolds should be both biocompatible and mechanically stable <i> in vitro</i>; this would allow selection of desirable candidates for subsequent <i>in vivo</i> testing. Finally, <i>in vivo</i> testing of the esophageal conduit requires development of an analogous large animal model to human disease. <i>In vivo</i> large animal model testing is required as proof of concept for esophageal regeneration as a critical step toward future human use.3</p><p>

<p> Determining natural inner knee mechanics is a longstanding goal for researchers with applications to prevention and treatment of knee trauma and osteoarthritis. Physical testing has only provided limited information of knee mechanics due to technical challenges and cost. Modeling has been used for decades to obtain some of this otherwise inaccessible information, and recently finite element analysis (FEA) has become a popular means to this end. However, FEA requires time intensive mesh-creation and has large computational requirements. Ideally, model creation should be easy and simulations should be fast to allow for sensitivity analysis. Although allowing easier model creation and offering over an order of magnitude more computational efficiency than FEA, current rigid body modeling of the knee is limited by imprecise methodologies for defining material properties. Cartilage and meniscus are particular points of weakness. </p><p> The following thesis develops an improved methodology for cartilage contact which is user-friendly and allows for precise definition of contact via user-supplied material properties while accounting for changes in stiffness due to discretization. Additionally, meniscus modeling is improved by developing and implementing equations which directly define stress-strain relationships to match values reported in literature or those selected by the user. Results from two implemented knee models are compared to experimental results in literature and sensitivity to material properties and driving kinematics is investigated.</p>

<p> Over one&ndash;third of Americans over the age of 65 fall each year, costing more than $19 billion in health care costs in 2000. Many adults 65+ who have not experienced a fall still fear falling, and fear can decrease quality of life and increase the likelihood of falls. Several factors such as muscle strength, power, stiffness and tendon properties change in the human body with age affecting balance, which has been tagged as a fall risk predictor. Additionally, balance recovery strategies also differ between young and older adults, with young adults primarily utilizing their ankle joint and older adults utilizing their hip. The role of passive ankle joint power in balance recovery is unknown. Therefore, we conducted three studies. In Study 1, we investigated the role of passive ankle joint power in balance recovery of young subjects and tested if the contribution of passive power to net ankle joint power changed with perturbation speed. In Study 2, we explored the factor of age in the contribution of passive ankle joint power to net ankle joint power. In Study 3, we searched for a link between the contribution of passive ankle joint power to net ankle joint power and balance recovery strategy. Passive joint torque through the full range of motion was collected for each subject. Each subject performed 5 stepping tasks at two speeds, fast and slow. Joint kinematics and kinetics were collected for each trial. Inverse dynamics were performed and net ankle joint torque and net ankle joint work were computed. Passive ankle joint torque models were optimized for each subject, and passive ankle joint powers were determined. In Study 1, there appeared to be no difference in net or passive joint powers with respect to perturbation speed. In Study 2, age affected net ankle joint powers and passive uniarticular plantar- and dorsiflexor powers. In Study 3, we noted a change in balance recovery strategy between young and older adults. We were unable to predict balance recovery strategy index based off of the percent contribution of passive ankle joint work to net ankle joint work. These studies bring greater clarity to the role of passive ankle joint power with respect to balance recovery. </p>

<p> The mechanical properties of the extracellular matrix (ECM) have shown to regulate key cellular processes. However, current tools studying cell-ECM biophysical interactions revolve around cell-mediated traction forces, which, as I will show, are not appropriate in natural matrices due to matrix remodeling. I used active microrheology (AMR) to, instead, measure ECM stiffness in order to quantify these interactions in various cell-ECM systems. </p><p> In the first system, I evaluated a commonly used 3D cell-culture method in breast cancer research. I show that this model produces a large physical asymmetry in ECM stiffness, which resulted in altered cellular morphology, adhesion-mediated signaling, and phenotype. Importantly, a hallmark result obtained in this culture method was not repeatable once the asymmetry was removed, highlighting the importance of considering biophysical interactions in cell-culture models. </p><p> In the second system, my work, in collaboration with Dr. Stephen Weiss, led to the discovery that stem cells are not passive recipients of ECM stiffness signals as previously thought. Rather they can deliberately alter local (pericellular) stiffness with matrix metalloproteinases as a control for cellular functions. In particular, we found that skeletal stem cells competent in their ability to degrade collagen, increased pericellular stiffness via matrix remodeling to activate ?1 integrin signaling pathways and thus controlled their own lineage commitment to osteogenic fates. Cells without the ability to degrade their local matrix lost this functionality and were restricted in lineage commitment to adipogenic or chondrogenic fates. </p><p> For the third system, I quantified the contributions of cell contractility and matrix metalloproteinases in matrix remodeling for developing a normal mechanical topography in smooth muscle cells. I also provide evidence that it is the distribution of pericellular stiffness rather than a bulk value that instructs cellular behavior. In order to accomplish this task, I automated the AMR system (aAMR) for a tenfold decrease in measurement time. Importantly, aAMR reduces the complexity of AMR to a few mouse clicks, can create stiffness maps over large distances and provides metrics to assess the distribution of stiffness in the pericellular space within the volume of a natural, fibrous hydrogel.</p>

<p> Above elbow prosthesis control has trended toward increasing the number of control channels in the human-prosthetic system, to provide simultaneous joint control. Several methods have had varying success, such as Targeted-Muscle-Reinnervation (TMR) and Electromyograph (EMG) pattern recognition. While the number of control channels is increased, the fundamental control loop is still based on amputees placing the prosthetic end effector through visual feedback. In most clinical uses prosthetic joints are driven with a standard proportional EMG antagonistic muscle controller (S). The S controller can be difficult for the amputee as nonintuitive muscle contractions are needed to overcome internal joint and induced external torques, in particular from gravity. To address these issues, two new controllers, which use gravity and friction compensation techniques, have been developed to share the control of the prosthetic elbow joint and reduce control effort on prosthetic users. The new controllers were tested against the S proportional control by having 10 test subjects reach to 6 targets in their user workspace utilizing a Utah Arm 2 testbed. Motion capture cameras recorded the reaching motions. The controllers were compared using quantitative metrics which define the approach, time to target and smoothness (jerk), and holding, steady state error and variance, stages of a reaching motion. A qualitative metric was also used which surveys a test subject's effort in performing a reach. It was found that when considering the new controllers using the combined data for all test subjects at all targets they outperformed the S controller, except in smoothness. It was also found that the new controllers statistically performed best over the S controller at target locations where the humerus was in flexion at approximately 45deg, except in smoothness. Smoothness is predicted to be more influenced by the joint friction in the elbow joint. Only one friction compensation method was tested. Further studies on friction affects by varying joint impedance is suggested. Considering these findings, including gravity compensation in the control for active prosthetic elbow joints is found to improve the control over the standard proportional control, as captured in the majority of the physical metrics and in test subject ratings. </p>

<p> Motion analysis allows for the collection and quantification of movement, and has long been used for the assessment of gait. In more recent years, models have been developed to accurately track the kinematics of the upper extremity, however, current methods are limited due to the small number of validated kinematic models. Over time, multiple models have developed for shoulder joint center (SJC) calculation, however, few are validated, with most difficult to implement. </p><p> Currently, approximately 3.7 million wheelchair users reside in the USA. The repetitive cyclic propulsion pattern required for wheelchair mobility places high loads on the wrist, elbow, and shoulder and often results in overuse injuries with an estimated 30% to 69% prevalence. Quantification of the shoulder complex using 3D kinematics allows for the assessment of ranges of motion, forces, and moments which may allow for better prescription and training, and propulsion biomechanics in wheelchair users. </p><p> Schnorenberg et al. developed and validated a wheelchair model whereby the SJC was calculated using multiple linear regression of the positions of the scapula, clavicle, and humerus. While this model more accurately tracks the glenohumeral joint center as compared to previous models, it requires advanced training and custom Matlab code which limit application for adoption by low resourced clinics and facilities. A simplified model using Visual 3D was developed to allow for local and international clinical and research applications in conjunction with a previously develop low-cost motion tracking system. Motion data during the wheelchair stroke cycle, was obtained using 12 Vicon cameras and Vicon Nexus software. The 3D motion files were processed using both models. </p><p> The wrist joint center and glenohumeral joint center yielded sub 2 mm mean error. While the wrist, elbow, and glenohumeral joints had an average error of less than 10&deg; during the grasp and vertical events. Through the development and validation of a simplified model utilizing Visual3D, upper extremity motion analysis may be easily applied in international and outreach clinics. This work presents new methodology to augment current paradigms for evaluation of wheelchair biomechanics.</p><p>

<p> The purpose of this research was to identify limitations people with arm amputations face completing daily living tasks and to design a new prosthesis which alleviates these deficiencies. State of the art prosthetic devices can mimic many of the motions of an intact limb but are controlled by a limited number of signals from the muscles in the residual limb. The majority of current research is focused on improving the control of these devices by increasing the number of inputs or using software to interpret the limited inputs in a more meaningful way. This research instead determined that the mechanics of the prosthesis could be simplified while maintaining functionality and a simple control system. Specifically, this research tested the hypothesis that the three degrees of freedom in the wrist (flexion-extension, radial-ulnar deviation, and rotation), could be combined into a single degree of freedom, known as the Dart Thrower&rsquo;s Motion, in a way that preserves most of the wrist&rsquo;s motion and functionality and could be controlled with a simple input method. There are currently no commercially available wrist flexion devices which utilize this motion. The studies presented in this dissertation surveyed people with upper limb amputations and found that they are less satisfied performing tasks that utilize the Dart Thrower&rsquo;s Motion with their prosthesis. The major angle of the Dart Thrower&rsquo;s Motion was identified in able-bodied individuals to be 22 degrees offset from the anatomical flexion-extension plane. Finally, a new prosthetic wrist device was developed based on this angle. This new prosthesis improved functionality over a traditional flexion wrist and was no more difficult to use than a device without a wrist. This research helps to alleviate many of the barriers to inclusion which people living with upper limb deficiency regularly face.</p><p>

<p> The lack of adequate equipment and measurement tools in whole-body vibration has imposed significant constraints on what can be measured and what can be investigated in the field. Most current studies are limited to single direction measurements while focusing on simple postures. Besides the limitation in measurement, most of the current biomechanical measures, such as the seat-to-head transmissibility, have discrepancies in the way they are calculated across different labs. Additionally, this field lacks an important measure to quantify the subjective discomfort of individuals, especially when sitting with different postures or in multiple-axis vibration. </p><p> This work begins by explaining discrepancies in measurement techniques and uses accelerometers and motion capture to provide the basis for more accurate measurement during single- and three-dimensional human vibration responses. Building on this concept, a new data collection method is introduced using inertial sensors to measure the human response in whole-body vibration. The results indicate that measurement errors are considerably reduced by utilizing the proposed methods and that accurate measurements can be gathered in multiple-axis vibration. </p><p> Next, a biomechanically driven predictive model was developed to evaluate human discomfort during single-axis sinusoidal vibration. The results indicate that the peak discomfort can be captured with the predictive model during multiple seated postures. The predictive model was then modified to examine human discomfort to whole-body vibration on a larger scale with random vibrations, multiple postures, and multiple vibration directions. The results demonstrate that the predictive measure can capture human discomfort in random vibration and during varying seated postures. </p><p> Lastly, a new concept called effective seat-to-head transmissibility is introduced, which describes how to combine the human body's biodynamic response to vibration from multiple directions. This concept is further utilized to quantify the human response using many different vibration conditions and seated postures during 6D vibration. The results from this study demonstrate how complicated vibrations from multiple-input and multiple-output motions can be resolved into a single measure. The proposed effective seat-to-head transmissibility concept presents an objective tool to gain insights into the effect of posture and surrounding equipment on the biodynamic response of the operators. </p><p> This thesis is timely as advances in seat design for operators are increasingly important with evolving armrests, backrests, and seat suspension systems. The utilization of comprehensive measurement techniques, a predictive discomfort model, and the concept of effective seat-to-head transmissibility, therefore, would be beneficial to the fields of seat/equipment design as well as human biomechanics studies in whole-body vibration.</p>

<p> With Athletes and individuals developing osteoarthritis and chondral defects at younger ages, long term treatments are in high demand. Total knee replacements only last for 10-15 years, so younger individuals would need to have multiple knee replacements within their lifetime. Allograft transplantation has shown to last long term and have high success rates, but the lack of donors and the possibility of damaging other areas of the knee to obtain tissue grafts has become a large concern. &nbsp;Xenografts derived from porcine cartilage is cost effective and the supply is abundant. Two antigen removal processes were examined: a short term antigen removal process to maintain the mechanical stability of the tissue, and a long antigen removal process to minimize the risk of triggering an immune response. The antigen removal processes were compared, and the future precautions were determined to enhance the probability of creating a viable osteochondral xenograft preparation technique. </p>