<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>

Prostate cancer (PCa) bone metastases have been reported in ~90% of patients with advanced disease. Bone metastases disrupt tissue homeostasis and weaken the skeleton, resulting in an increased risk of bone fractures and morbidity. Specifically, PCa cells disrupt the crosstalk between critical cells within the tumor/bone microenvironment (osteoblasts, osteoclasts, and immune cells), and utilize this effector-rich environment for cancer survival and growth. Therefore, a key therapeutic objective in malignant skeletal disease management is to eliminate tumors while restoring bone homeostasis. Current treatments include palliative radiotherapy, chemotherapy, or anti-RANK treatments, all of which have considerable side effects such as osteonecrosis of the jaw or enhanced tumor invasion. There remains a critical gap in therapies than can reduce tumor burden and simultaneously restore bone homeostasis. To address this gap, our work explores emerging gene therapy approaches for treating skeletal malignancies by utilizing multifunctional cytokine-based agents that can simultaneously combat tumor growth and promote bone regeneration.<div><br></div><div>We hypothesize that rationally designed cytokine-based gene therapies that can be secreted from skeletal muscle and targeted to the bone/tumor microenvironment, could effectively reduce tumor growth and restore bone cell homeostasis. To test this hypothesis, we adopted two strategies: 1) a second-generation targeted IL-27 cytokine, and 2) a de novodesign of a cytokine-like therapeutic agent (Propeptide) that includes anti-tumorigenic and pro-osteogenic domains. Both strategies share modules with overlapping therapeutic functions, rendering them complementary in their therapeutic application. In this work, we examined the proof of principle for propeptide gene therapy in muscle cells (in vitro models) and assessed the therapeutic efficacy of our cytokine-based biologics in reducing prostate tumor growth and rebalancing bone cell proliferation and differentiation. Our studies resulted in a propeptide construct representative of a cytokine structure comprised of a bundle of helices that we were able to express in cells. Additionally, our work demonstrated the targeting and anti-tumor efficacy of our therapeutic cytokines in cancer and bone cell models. Ultimately, this will provide the framework for innovative peptide and cytokine-based therapeutics that target and treat both the tumor metastases and bone. This approach will facilitate improvement of morbidity and quality of life of prostate cancer patients with bone metastases and could be applicable to other diseases with bone/tumor pathologies. <br><div><br></div></div>

Meniscal tears are the most common intra-articular injury of the knee joint. Due to the avascular zone with limited blood supply, treatment of the injury is a complex process. Today, research on the development of efficient treatments and meniscal replacements is of increasing interest. However, there are few alternatives of meniscal replacements available on the market and research has shown uncertain results in their ability to restore the natural biomechanics of the knee joint or prevent development of osteoarthritis. Furthermore there is no comparable method to evaluate tensile stresses caused by axial compressional load on a whole meniscus replacement. Therefore the possibility of knitted casing to contain, fixate and mechanically stabilize a cell seeded bioprinted gel and develop a methodology to characterize its compressional behaviour was analysed. By interlock knitting with segments of partial knit a 3D crescent-shaped biodegradable casing was produced mimicking the dimension of the medial meniscus. In the casing design, an Artelon® Flexband™ was incorporated functioning both as reinforcement at the peripheral rim and as fixation method. Moreover radial threads were added to the casing design by inclusion of weft inlays in the knitting pattern. In the non-destructive characterization of the compressional behaviour of the prototype, axial compressional forces of 10.82 N and 29.77 N were achieved. However the forces achieved were significantly lower if compared to the high force that is applied to the menisci in the knee joint. Furthermore a high influence of the coefficient of friction of the casing in the axial compressional force was concluded. Nevertheless refinements of the methodology are required to perform evaluation with comparable and reliable results.

<p>Embryonic development is a complicated phenomenon influenced by genetic regulation and biomechanical cellular behaviors. However, the relative influence of these factors on spatiotemporal morphogen distributions is not well understood. Bone Morphogenetic Proteins (BMPs) are the primary morphogen guiding the dorsal-ventral (DV) patterning of the early zebrafish embryo, and BMP signaling is regulated by a network of extracellular and intracellular factors that impact the range and signaling of BMP ligands.  Recent advances in understanding the mechanism of pattern formation support a source-sink mechanism, however, it is not clear how the source-sink mechanism shapes patterns in 3D, nor how sensitive the pattern is to biophysical rates and boundary conditions along both the anteroposterior (AP) and DV axes of the embryo.</p><p> Throughout blastulation and gastrulation, major cell movement, known as epiboly, happens along with the BMP mediated DV patterning. The layer of epithelial cells begins to thin as it spreads toward the vegetal pole of the embryo until it has completely engulfed the yolk cell. This dynamic domain may influence the distributions of BMP network members. This project aims to investigate the multiscale regulatory network of the BMP signaling dynamics along with the biophysical deformation of the embryo tissue during epiboly. </p><p> In this study, we present a three-dimensional (3D) growing domain mathematical modeling framework to simulate the BMP patterning and epiboly process during the blastula to gastrula stage zebrafish embryo, with both finite difference and finite element approaching. These models provide a starting point to elucidate how different mechanisms and components work together in 3D to create and maintain the BMP gradient in the zebrafish embryo. We are interested in how the cellular movements impact the formation of gradients by contributing an advective term whereby the morphogens are swept with the moving cells as they move vegetally. Dynamic cell imaging data are used to quantify the cell movement during the epiboly. We evaluated the accuracy of the mesh updating compared to the advection caused by cell movement and its role in embryonic patterning. Quantitative whole-mount RNA scope data of BMP2b, Chordin, Noggin, Sizzled, and phosphorylated-SMAD data are collected and analyzed precisely to test the hypotheses of the gradient formation mechanism in our model. We also present a novel approach of Neuro Network model to accelerate the computationally intensive PDE simulations. Our goal is to develop a complete advection-diffusion-reaction model that incorporates all stages of zebrafish embryonic development data. By combining the biophysics of epiboly with the regulatory dynamics of the BMP network, we can test complex models to investigate the consistent spatiotemporal DV patterning in the early zebrafish embryo.</p>

<div><div><div><p>The aorta has many complex features including valve and vessel wall geometry, blood flow, and wall composition. Diseases such as aortic aneurysms and aortic valve lesions affect vessel function and may even lead to rupture, which can be fatal. However, current clinical diagnoses of aortopathies mainly rely on simple parameters such as diameter and growth rate. To better understand aortopathies and ultimately improve patient diagnoses and treatments, it is important to investigate disease progression as well as the effect of vessel wall composition changes and hemodynamic forces on aortic biomechanics, such as strain and wall shear stress distribution. Preclinical research using small animals allows for disease progression to be studied while controlling outside factors. The next important step is to apply the methods used in the preclinical studies to human patient data. Both preclinical and clinical studies often focus on noninvasive, patient-specific methods for further characterizing the biomechanics of the aorta using advanced techniques such as 4D flow magnetic resonance imaging, 4D ultrasound, computational fluid dynamics (CFD), and fluid structure interaction (FSI) modeling. Yet the challenge of bridging these research techniques to a clinical setting remains. Factors such as financial costs, acquisition time, and ease of analysis must be considered. Therefore, the following document highlights two specific aims to extend our knowledge about the effects of aneurysms and aortic valve lesions. We will 1) characterize the regional effects of murine abdominal aortic aneurysms on strain over time, and 2) use CFD and FSI to simulate the hemodynamic effects on the thoracic aorta using both murine and human patient imaging data. Conducting research using clinically translatable methods of biomechanical characterization that consider the complexity of the aorta on a patient-specific basis will contribute to our understanding and lead to better patient outcomes.</p></div></div></div>

<p>  </p> <p>Congenital diseases of the kidney are the leading cause of chronic kidney disease in pediatric patients. Tissue engineering models used to investigate these diseases are limited by an immature phenotype. Models cultured in an extracellular matrix (ECM), a network of proteins and glycosaminoglycans surrounding cells and providing structural support that mimic the matrix found in development will be likely more mature. However, developing kidney ECM composition and structural dynamics are unknown. To address this gap, we studied ECM composition using mass spectrometry and organization by visualizing the ECM in 3D.</p> <p>In this work, we used mass spectrometry to resolve ECM basement membrane and interstitial matrix dynamics between embryonic, perinatal, and adult kidneys. Surprisingly, we observed a transient upregulation of interstitial matrix structures that corresponded to dynamic 3D structures in the cortex (vertical fibers) and at the corticomedullary junction (medullary ray sheath fibers). Notably, in a model of abnormal <em>Foxd1</em>+ stromal cells, the vertical fibers were disorganized, and medullary ray sheath fibers were no longer associated with blood vessels, suggesting the dynamic 3D structures depended on stromal cell modulation.</p> <p>One of the effects of abnormal kidney development is decreased amniotic fluid, which limits embryonic movement and subsequent limb development. In additional studies, we looked at the implications of the lost motility in the muscular dysgenesis (<em>mdg</em>) mouse on the development of the myotendinous junction (MTJ). The MTJ links contractile muscle with tendon. We found the ECM protein COL22A1 was specific to the developing MTJ as early as embryonic day (E)13.5. The development of the MTJ from a linear structure to a cap-like structure with invaginations in adolescent mice depended on muscle contraction. Furthermore, we used a model to decouple the muscle-tendon-bone complex at an ectopic lateral triceps insertion (<em>Prrx1Cretg/+; Tbx3fl/fl</em>). We observed disorganized tendon and MTJ markers at the termination of the ectopic lateral triceps muscle but negligible cartilage markers. Together, this indicated MTJ maturation depended on motility but not on the enthesis.</p> <p>The information gleaned from our studies on how stromal cells affect dynamic 3D interstitial ECM structures and composition change during kidney development can be used as a template for 3D kidney culture systems. Combined with forelimb MTJ development, our results indicate the importance of the interstitial matrix in tissue morphogenesis.</p>

Cartilage fatigue may be a factor in the precocious development of degenerative changes in the temporomandibular joint (TMJ). This cross-sectional study estimated potential for cartilage fatigue via TMJ energy densities (ED) and jaw muscle duty factors (DF), which were combined to calculate mechanobehavioral scores (MBS) in women with (+) and without (-) bilateral TMJ disc displacement (DD). All subjects gave informed consent to participate and were examined using Diagnostic Criteria (DC) for Temporomandibular Disorders (TMD) and magnetic resonance (MR) and computed tomography (CT) images. Forty-seven subjects were categorized into +DD (n = 29) and -DD (n = 18) groups. Dynamic stereometry (MR images combined with jaw-tracking data) characterized individual-specific data of TMJ stress-field mechanics to determine ED (ED = W/Q mJ/mm3, where W = work done, Q = volume of cartilage) during 10 symmetrical jaw-closing cycles with a 20-N mandibular right canine load. Subjects were trained to record masseter and temporalis electromyography over 3 days and 3 nights. Root mean square electromyography/bite-force calibrations determined subject-specific masseter and temporalis muscle activities per 20-N bite-force (T20 N, μV), which defined thresholds. Muscle DF (DF = % duration of muscle activity/total recording time) were determined for a range of thresholds, and MBS (ED2 × DF) were calculated. Intergroup differences in ED, DF, and MBS were assessed via analyses of variance with Bonferroni and Tukey honest significant difference post hoc tests. Average ED for contralateral TMJs was significantly larger (P = 0.012) by 1.4-fold in +DD compared to -DD subjects. Average DF were significantly larger (all P < 0.01) for +DD compared to -DD subjects by 1.7-, 2.5-, and 1.9-fold for day, night, and overall, respectively. Daytime MBS were significantly larger (all P < 0.04) by up to 8.5-fold in +DD compared to -DD subjects. Significantly larger ED, DF, and MBS were shown in women with compared to women without bilateral TMJ DD.

This thesis presents an improved oscillotonometric system for the measurement of human blood pressure. The study included: 1. The design of a hydraulic occlusive cuff, 2. The investigation of the wave forms taken from the blood pressure measurements, and 3. The design of a mechanism for the simulation of human blood pressure pulse. In this study, an experimental system consisting of a rigid shell occlusive cuff, a constant volume displacement pump, a transducer, and a chart recorder was designed and used for data collection.

The currently accepted methods for measuring systemic blood pressure are either highly accurate but invasive in nature or clinically convenient but prone to observer-related errors. A new oscillometric method uses sensitive signal conditioning and sensing equipment with a non-invasive arm cuff to record arterial pulsations. The goal of this study is to establish more reliable criteria for the identification of systolic and diastolic pressures from oscillometric data.

In a recent in vitro biomechanical stability study by F.J. Jacobs, a unique, patented inclined screw insertion (I.S.I.) mandibular angle, intra-oral trauma-plate was evaluated for torsion and compression stability and compared to conventional plating of simulated angle fractures in polyurethane mandibular replicas. This in vitro comparative pilot study is an extension of the above-mentioned study. Similar I.S.I. mini-plates with 45º inclined screw holes in quadrant 3 (Fig 1), were used but in the one sample 13mm-long lag screws were used to transect the fracture lines where in the other group non-lagging screws of similar length were used to fixate simulated mandibular angle fractures in polyurethane mandible replicas. A uniquely designed and manufactured jig, incorporated in a Zwick machine, was utilized to apply torsion forces within clinical relevant load values. The load-displacement values for torsion forces was determined and compared for the two groups. It was established that 5 lag screws significantly improved the torsion stability of the lag-plate group to that of the non-lag group. During the stability testing, two factors were identified, which had a critical influence on the compression generated by the lag screw between the fracture fragments. An adequate amount of bone must be maintained between the first screw hole, directly distal to the fracture line, and the fracture line. All screws must be inserted in the correct sequence in order to insure sufficient compression between the fracture fragments as a result of the lag-effect. AFRIKAANS : In `n onlangse in vitro studie deur F.J. Jacobs, is `n gepatenteerde, unieke geanguleerde miniplate, waarvan die skroefgate geanguleer is, die sg. Inklineerde Skroef Inplasing (I.S.I.) kaak-hoek, intra-orale traumaplaat geevalueer vir torsie en kompressie stabiliteit en vergelyk met konvensionele plate op gesimuleerde kaakhoek frakture in poli-uretaan mandibular replikas. In hierdie in vitro loodstudie, is I.S.I. miniplate met skroefgate wat teen 45º geanguleer is, gebruik in kombinasie met `n enkele 13mm lange grypskroef (“lag screw”) om gesimuleerde kaakhoek frakture in poli-uretaan mandibula replikas te fikseer. Deur gebruik te maak van `n spesiaal ontwerpte en vervaardigde monterings-apparaat wat binne in `n Zwick masjien geïnkorporeer word, is die I.S.I gefikseerde replikas onderwerp aan torsie kragte, binne klinies relevante ladingswaardes. Die verplasings en ladingswaardes is geregistreer en vergelyk met identiese I.S.I miniplate sonder `n grypskroef. Die loodstudie resultate het getoon dat die frakture wat gefikseerd is met die I.S.I. miniplaat-grypskroef kombinasie betekenisvol beter stabiliteit toon as die frakture wat met slegs die miniplaat, sonder `n grypskroef, gefikseerd is vir klinies relevante ladingsen verplasingswaardes. Tydens biomeganiese toetsing van die mandibula replikas, is twee faktore wat `n kardinale rol speel in die stabiliteit wat verkry word deur `n miniplaat grypskroef kombinasie te gebruik, geïdentifiseer. Voldoende hoeveelheid been tussen die eerste skroefgat, direk distaal van die fraktuurlyn, en die fraktuurlyn asook die korrekte volgorde waarin die skroewe geplaas word, moet gehandhaaf word om maksimale kompressie van die fragmente deur die grypskroef te verseker. Deur `n I.S.I miniplaat, met geanguleerde skroefgate van 45º, te kombineer met `n grypskroef, kan die stabiliteit van die gefikseerde mandibulere kaakhoek betekenisvol verbeter word en verleen dit meer stabiliteit wanneer vergelyk word met frakture gereduseer met `n I.S.I miniplaat sonder grypskroef plasing. / Dissertation (MSc)--University of Pretoria, 2010. / Maxillo-Facial and Oral Surgery / unrestricted