<p>The purpose of this thesis was to evaluate musculoskeletal contributions to joint stiffness in the distal upper extremity. An <em>in-vitro</em> and <em>in-vivo</em> approach was used to examine muscle and ligament contributions to mechanical joint stiffness at the elbow and wrist. In Chapters 2 and 3 an <em>in-vitro</em> approach was used to evaluate ligament contributions to carpal tunnel mechanics. Chapter 2 documented transverse carpal ligament (TCL) mechanical properties and provided a calculation of TCL length when stretched, which confirmed the ligaments importance in carpal tunnel mechanics and carpal bone stability. Chapter 3 quantified mechanical properties of the TCL at six different locations using a biaxial tensile testing method. It was found that the complex TCL fibre arrangement makes the tissue properties location dependent. The TCL contributes to carpal tunnel mechanics and carpal stability and the ligament contributions are different depending on the tissue location tested. Chapters 4 and 5 focused on the effects of hand loads and arm postures on the muscular response to sudden arm perturbations. The elbow flexors demonstrated stiffness contributions immediately prior to a perturbation and were influenced by posture and hand loading. The forearm muscles provided a small contribution to elbow joint stiffness. Chapter 6 also found muscular contributions that increased wrist joint stiffness immediately prior to a sudden perturbation. Additionally, for a small grip-demanding task, forearm muscle co-contraction resulted in large increases in wrist joint stiffness.</p> <p>This thesis has provided a detailed analysis of the TCL which improves our understanding of the carpal tunnel and specific mechanisms of injury. It is the first to document individual muscle contributions to elbow and wrist joint stiffness. The comprehensive analysis of ligament and muscular contributions to joint stiffness has provided insight into joint stability in the distal upper extremity. This can improve our understanding of injury caused by sudden joint loading.</p> / Doctor of Philosophy (PhD)

<p>Computational fluid dynamic (CFD) models of aortic blood flow have developed over the past decade from rigid one dimensional models to three dimensional models that include wall flexibility. Although anatomically correct, these models have been significantly idealized as compared to their physiologic in vivo conditions. This thesis investigates the effect of addition of four dimensional MRI inlet flow, motion of the heart at the aortic inlet and addition of wall elasticity coupled with tissue backing support. Results show that the addition of MRI inlet data and aortic inlet motion of the heart significantly change flow in the aorta and should be included in future aortic CFD simulations.</p> / Master of Applied Science (MASc)

Mechanical conditioning has been shown to promote tissue formation in a wide variety of tissue engineering efforts. However the underlying mechanisms by which external mechanical stimuli regulate cells and tissues are not known. This is particularly relevant in the area of heart valve tissue engineering (HVTE) owing to the intense hemodynamic environments that surround native valves. Some studies suggest that oscillatory shear stress (OSS) caused by steady flow and scaffold flexure play a critical role in engineered tissue formation derived from bone marrow derived stem cells (BMSCs). In addition, scaffold flexure may enhance nutrient (e.g. oxygen, glucose) transport. In this study, we computationally quantified the i) magnitude of fluid-induced shear stresses; ii) the extent of temporal fluid oscillations in the flow field using the oscillatory shear index (OSI) parameter, and iii) glucose and oxygen mass transport profiles. Noting that sample cyclic flexure induces a high degree of oscillatory shear stress (OSS), we incorporated moving boundary computational fluid dynamic simulations of samples housed within a bioreactor to consider the effects of: 1) no flow, no flexure (control group), 2) steady flow-alone, 3) cyclic flexure-alone and 4) combined steady flow and cyclic flexure environments. We also coupled a diffusion and convention mass transport equation to the simulated system. We found that the coexistence of both OSS and appreciable shear stress magnitudes, described by the newly introduced parameter OSI-t , explained the high levels of engineered collagen previously observed from combining cyclic flexure and steady flow states. On the other hand, each of these metrics on its own showed no association. This finding suggests that cyclic flexure and steady flow synergistically promote engineered heart valve tissue production via OSS, so long as the oscillations are accompanied by a critical magnitude of shear stress. In addition, our simulations showed that mass transport of glucose and oxygen is enhanced by sample movement at low sample porosities, but did not play a role in highly porous scaffolds. Preliminary in-house in vitro experiments showed that cell proliferation and phenotype is enhanced in OSI-t environments.

Heart failure (HF) is one of the leading causes of death and impacts millions of people throughout the world. Recently, injectable hydrogels have been developed as a potential new therapy to treat myocardium infarction (MI). This dissertation is focused on two main topics: 1) to gain a better understanding the transmural contractility in the healthy left ventricle (LV) wall and 2) investigate the efficacy of the hydrogel injection treatment on LV wall stress and function. The results indicate that a non-uniform distribution of myocardial contractility in the LV wall provide a better representation of normal LV function. The other important study explored the influence altering the stiffness of the biomaterial hydrogel injections. These results show that a larger volume and higher stiffness injection reduce myofiber stress the most and maintaining the wall thickness during loading. The computational approach developed in this dissertation could be used in the future to evaluate the optimal properties of the hydrogel. The last study used a combination of MRI, catheterization, finite element (FE) modeling to investigate the effects of hydrogel injection on borderzone (BZ) contractility after MI. The results indicate that the treatment with hydrogel injection significantly improved BZ function and reduce LV remodeling, via altered MI properties. Additionally, the wall thickness in the infarct and BZ regions were significantly higher in the treated case. Conclusion: hydrogel injection could be a valuable clinical therapy for treating MI.

The blood flow through the Bidirectional Glenn shunt (BGS) and modified Blalock-Taussig shunt (mBTS) to the pulmonary arteries (PAs) was analyzed using Computational Fluid Dynamics. This study consisted of the steady and pulsatile cases. In case one, the results of blood flow through the BGS for the Newtonian and non-Newtonian viscosity models were compared. Case two focused on having an additional pulsatile blood flow through the mBTS using the non-Newtonian Carreau viscosity model. The geometries were created based on the angiograms. In case one, boundary conditions to be specified at the inlets were obtained from the flow rate measurements via Doppler flow studies in children and young adults. The averaged velocities were obtained from these flow rates and specified as parabolic velocity profiles at the inlets. The average PA pressures were obtained from the catheterization data and specified at the branches of the PA outlets. In case two, boundary conditions at the same inlets were constant during the cardiac cycle. The pulsatile PA and aortic pressure tracings obtained from the catheterization data were specified at the outlets and mBTS inlet, respectively. A comparison is made between the first and second case results.

<div>Pancreatic cancer is the present third leading cause of all cancer-associated deaths with a under 9% 5-year survival rate. Aggressive tumor progression and lack of early detection technique lead to the fact that most patients are diagnosed at terminal stage - pancreatic ductal adenocarcinoma (PDAC). Despite that numerous therapeutic approaches have been introduced, most options cannot advance to or fail at the clinical trials. It has been suggested that previous failure is due to insufficient understanding of PDAC tumor microenvironment (TME). Human PDAC is composed of severely fibrotic tissue (i.e., desmoplasia) that harbors a variety of malignant cells (e.g., pancreatic stellate cells, cancer-associated fibroblasts, macrophages, etc.), excessive extracellular matrices (ECM), as well as abnormal expression of growth factors, cytokines, and chemokines. Multiple cell-cell and cell-ECM interactions jointly result in a stiffened, hypoxic, and fluid pressure-elevated PDAC tissue. The resulting pancreatic TME not only physically hinders penetration of therapeutics, but also dynamically interacts with the residing cells, regulating their behaviors.</div><div><br></div><div>Increasing tumor tissue stiffness in PDAC is not only a passive outcome from desmoplasia, but an active environmental factor that promotes tumor survival, growth, and invasion. However, traditional in vitro cell culture systems such as two-dimensional (2D) culture plate and animal models are not ideal for mechanistic understanding of specific cell-matrix interactions. Therefore, dynamic hydrogels have been introduced as a category of advanced biomaterials that exhibit biomimetic, adaptable, and modularly tunable physiochemical property. Dynamic hydrogels can be precisely engineered to recapitulate a variety of aspects in TME, from which to investigate the role of dynamic tumor-stroma interaction in PDAC progression. The goal of this dissertation was to exploit synthetic polymers (i.e., poly(ethylene glycol) (PEG)) or natural ECM (i.e., gelatin and hyaluronic acid (HA)) as precursors to prepare the dynamic cancer-cell laden gels. The design utilized the orthogonal thiol-norbornene photopolymerization to prepare the primary homogenous xxvi</div><div><br></div><div>gel network. Next, through further functionalizing gel precursors with phenolic derivatives, enzymatic reaction (i.e., tyrosinase) or flavin mononucleotide (FMN)-mediated photochemistry could be harnessed to manipulate the dynamic changes of substrate mechanics. Experimentally, a computational model and the associated validation were presented to investigate the process of gel stiffening. Finally, these techniques were integrated to prepare cell-laden gels with spatial-temporally tunable properties that were instrumental in exploring the synergistic effects of dynamical matrix stiffening and presence of HA in promoting epithelial-mesenchymal transition (EMT) in PDAC cancer and stromal cells.</div>

The scale of the scholarly community complicates searches within scholarly databases, necessitating keywords to index the topics of any given work. As a result, an author’s choice in keywords affects the visibility of each publication; making the sum of these choices a key representation of the author’s academic profile. As such the underlying network of investigators are often viewed through the lens of their keyword networks. Current keyword networks connect publications only if they use the exact same keyword, meaning uncontrolled keyword choice prevents connections despite semantic similarity. Computational understanding of semantic similarity has already been achieved through the process of word embedding, which transforms words to numerical vectors with context-correlated values. The resulting vectors preserve semantic relations and can be analyzed mathematically. Here we develop a model that uses embedded keywords to construct a network which circumvents the limitations caused by uncontrolled vocabulary. The model pipeline begins with a set of faculty, the publications and keywords of which are retrieved by SCOPUS API. These keywords are processed and then embedded. This work develops a novel method of network construction that leverages the interdisciplinarity of each publication, resulting in a unique network construction for any given set of publications. Postconstruction the network is visualized and analyzed with topological data analysis (TDA). TDA is used to calculate the connectivity and the holes within the network, referred to as the zero and first homology. These homologies inform how each author connects and where publication data is sparse. This platform has successfully modelled collaborations within the biomedical department at Purdue University and provides insight into potential future collaborations.

<div>The eradication of yaws a neglected tropical disease caused by Treponema pallidum subsp. pertenue, which affects children living in very deprived hard to reach rural communities is constrained by the lack of rapid, accurate diagnosis. I sought to develop a molecular point-of-care test for the diagnosis of yaws. A Loop-mediated isothermal amplification (LAMP) assay with primers targeting the conserved gene, tp0967, with visual detection by lateral flow test strip was developed and optimized. The limit of detection was evaluated while 63 samples from clinical cases of yaws and 5 samples with PCR-confirmed syphilis were used to determine the sensitivity and specificity of the assay compared to the current molecular testing protocol. Reagents were dried in tubes and tested up to 14 days. The developed LAMP assay was found to be optimal when run at 65oC in a water bath for 30 minutes. The limit of detection was 2.7*104 DNA copies/ml. The sensitivity of the LAMP assay using unextracted and DNA extracted samples were 0.67 and 1.00 respectively. None of the syphilis samples tested positive in any of the assays. We show the development of a fast and sensitive LAMP assay for yaws detected by lateral flow test strip. Using extracted DNA, the assay sensitivity is at par with gold standard detection. The assay can be adapted to minimal sample processing required for in-field detection without DNA extraction.</div><div><br></div>

Two Systems were designed. The first permits tunable on-demand softening of a hydrogel network. The second permits reversible on demand ligand exchange within a hydrogel network. Both means were shown to be cytocompatible and their uses demonstrated in cell culture of mesenchymal stem cells and 3T3 fibroblast cells.

<p>Emotional regulation is how people manage their emotions especially anxiety, anger, and frustration, which are all negative emotions. It is critical to health, academic achievement, and work performance to have proper emotion regulation skills. In order to facilitate participants to manage emotions, we developed a series of training programs by using HTC^© Vive^TM headset and Neuracle. The HTC Vive is to improve immersion in presence to lead to more effective training, and the Neuracle is using Electroencephalography (EEG) techniques for reading user’s brainwave signals which provide real time input for the training programs. We focused on analyzing if emotion, which was reflected in brainwave signals, had changes when participants were exposed to positive/negative stimuli. The testing results indicated that there were noticeable changes in brainwave signals to stimuli. The findings from the testing provide a solid foundation to use brainwave signals as real-time input in our game development for improving emotion regulation skills in the future. </p>