Endothelial cells (ECs) form the innermost layer of all vasculature and constantly receive both biochemical and biomechanical signals, yielding a plethora of biomechanical responses. In response to various biochemical or biomechanical cues, ECs have been documented to generate biomechanical responses such as tractions and intercellular stresses between the cell and substrate and between adjacent cells in a confluent monolayer, respectively. Thus far, the ability of endothelial tight junctions and adherens junctions to transmit intercellular stresses has been actively investigated, but the role of gap junctions is currently unknown. In addition, there is no report of the independent influence of hyperglycemia on endothelial biomechanics present in the literature. To fill these gaps, we conducted a two-fold study where we investigated the influence of endothelial gap junction Cx43 and hyperglycemia in endothelial tractions and intercellular stress generation. In the first study, we selectively disrupted and enhanced EC gap junction Cx43 by using 2',5'-dihydroxychalcone and retinoic acid, respectively and in the second study, we cultured ECs in both normal glucose and hyperglycemic condition for 10 days. In both studies, tractions and intercellular stresses were calculated using traction force microscopy (TFM) and monolayer stress microscopy (MSM), respectively. Our results reveal that Cx43 downregulation increased as well as decreased endothelial avg. normal intercellular stresses in response to a low (0.83 µM) and a high dose (8.3 µM) chalcone treatment, respectively, while Cx43 upregulation decreases avg. normal intercellular stresses in both treatment conditions (2.5 µM and 25 µM) compared to control. In addition, we observed a decrease in intercellular stresses with hyperglycemic condition compared to control. The results we present here represent, for the first time, detailed and comprehensive biomechanical analysis of endothelial cells under the influence of glucose and the gap junction Cx43. We believe our results will provide valuable insights into endothelial permeability, barrier strength as well as leading to a greater understanding of overall endothelial mechanics.

Hypoplastic left heart syndrome (HLHS) is a type of heart defect where the left ventricle is underdeveloped or not developed, resulting in only a single functioning right ventricle. Approximately 7.5% of patients with congenital heart disease are born with a single ventricle (SV) which is accompanied by a spectrum of other malformations such as atrophied ascending aorta, atrial septal defects, and ventricular septal defects (VSD). The existing three-hybrid staged surgical approach serving as a palliative treatment for this anomaly entails multiple complications and achieves a survival rate of only 50%. To reduce the trauma associated with the second stage of the hybrid procedure the hybrid comprehensive stage 2 (HCSII) operation can be a novel palliation alternative for a select subset of SV patients with adequate antegrade aortic flow. The procedure reduces surgical trauma in newborns by introducing a stented intrapulmonary baffle to avoid dissection of the pulmonary arteries and reconstruction of the aortic arch while obviating the dissection of the ductal continuation and distal arch. It is the purpose of this dissertation to undertake a computational investigation to elucidate the complex hemodynamics of patients who have undergone HCS II. This was accomplished in a multiscale manner coupling a 0D lumped parameter model (LPM) of the peripheral circulation with 3D pulsatile Computational Fluid Dynamics (CFD) model providing the details and enabling investigation of the HCS II complex hemodynamics. The use of CFD allows modeling of blood flow, the study of the effect of different surgical procedures, suggestion of potential improvements from investigation of areas of concern which are: the pressure drop across the baffle, the loading of the baffle itself, shear stress and shear rates that might lead to thrombus formation, as well as oxygen transport and particle residence time. A 3D anatomical model representative of a patient having undergone the HCSII was rendered utilizing the solid modeling software Solidworks based on anatomical landmarks from CT scans, and a 0D LPM was tuned to produce flowrates and waveforms that matched catheter data. The pulsatile CFD computations were carried out using the commercial STARCCM+ solver. Several cases of baffle strictures relevant to surgical implementations were considered and results showed that the largest pressure drop across the baffle reported was about 3 mmHg while for the same narrowing size and accounting for the distal arch kink, a four-fold increase is observed yielding a 12.15 mmHg drop. Moreover, the analysis showed that for averaged blood flow velocity of 0.5 m/s, no vortex shedding from the baffle was observed in the computational model due to the short distance from the baffle to the aortic arch apex. The velocity and pressure-flow fields were examined at different points throughout the cardia cycle: late diastole, early systole, peak systole, and early diastole. Reverse flow was observed towards late diastolic phase due to the presence of an adverse pressure gradient, and a stagnant flow in the aortic arch apex was also noticed. For the pulmonary circulation and due to the low flow velocity and low pulsatility, the T-junction shape of the SVC presented no risk of recirculation or swirling that may promote thrombogenesis. The wall shear stress on the baffle surface was also reported in pulsatile flow. It was observed that the flow detaches in systole and subsequently reattaches to the baffle surface. Moreover, the baffle surface experiences high wall shear stress magnitudes during systole and uneven distribution of WSS during diastole. The variation in the baffle related narrowing had a little impact on the flow hemodynamics, as shown by the nearly constant oxygen transport across the models. The geometrical modification applied to the models had little effect on the oxygen delivery for up to a 15% change between a 4 mm increment of MPA minimum diameter. The results showed consistency with the published data of Glenn patients. Particle residence time was also reported to identify any blood recirculation or flow stagnation that may lead to platelet activation leading to clot formation rate. On average particles take about 0.5(s) to exit the fluid domain. This time span is equal to the time of one cardiac cycle. Finally, the energy loss and energy efficiency were calculated as a function of split ratio and baffle related narrowing. Across all models, the efficiency was shown to be high.

Airborne diseases transmitted through tiny respiratory droplets such as the Coronavirus disease can not only rapidly infect others but also worsen the symptoms in already affected individuals. People with COVID-19 are more likely to develop severe acute respiratory syndrome or SARS through aspiration pneumonia, which refers to when some virus-laden droplets are inhaled into the airway and lungs. This project aims to study droplet behavior in the upper airway in order to investigate methods to reduce the risk of infected droplets entering the upper airway in a patient. The project involves the design and development of a cough emulator that can simulate a human cough accurately, build a physical model of the upper airway using a material similar in texture to the human windpipe, and measure and track the generated particles as they transverse through the upper airway and exit the mouth. The criteria needed to be met to design, manufacture, and evaluate a cough emulator reproducing a human-like cough include the volume, pressure, and flow rate of a cough. To evaluate the validity and accuracy of the device, the number, size, and spread of cough droplets are compared to that of a real cough. The upper airway is fabricated using Elastic 50A resin due to its flexible and durable properties, and texture similarity to the tissue of the human trachea. In addition, particles are tracked in the upper airway using a Charged Couple Device (CCD) Camera.

Surgical robots are increasingly becoming an integral part of an operating room to assist surgeons in performing dexterous surgical procedures and improve surgical precision. Research and development of novel and innovative surgical devices have become essential to further the frontiers of knowledge in this field and enable enhanced surgical outcomes. Precise and accurate positioning of tools is a key requirement during the design of a surgical robot, and this often demands design of new mechanisms. This dissertation explores development of two robotic surgical devices to improve the current surgical procedure of an osteochondral autograft transplantation and transperineal prostate biopsy needle insertion. We design and develop a robotically assisted novel graft removal mechanism to harvest a personalized autologous graft of any shape and size for osteochondral autograft transplantation. To provide robotic precision, greater access, and compact design, we design and develop a robotic mechanism that can provide four Degrees of Freedom manipulation in a compact form comparable to size of manual templates for transperineal prostate biopsy.

Prostate cancer is one of the most commonly diagnosed cancers among men and a major area of concern for healthcare system. Magnetic Resonance Imaging (MRI) that has superior soft tissue imaging capability, enables higher cancer detection rate. MRI guided intervention devices that require device-to-image registration, essential for accurate and precise targeting, complicates the overall process while increasing total time for intervention. We design and develop a simplified, MRI guided, registration-free transperineal prostate biopsy needle guide and perform experiments. A preliminary simulation is performed to understand whether the interaction between guide hole and biopsy needle during the firing step affects the needle motion characteristics. The proposed device could be incorporated for rapid adoption into the clinical environment.

Medical Robots are transforming the healthcare landscape by applying robotic technologies across several aspects of patient care. Though medical robots can be classified based on several aspects such as field of application, target anatomical region or surgical and non-surgical robots, an important classification is based on the compliant nature of the robotic systems i.e., soft robotics and robots with rigid structures. Through this dissertation we present the development of two medical robotic devices, each falling under two separate categories i.e., a soft robotic device applied to tele-palpation and training and a rigid robotic device for orthognathic surgery. We design and develop a novel tactile display apparatus to facilitate medical palpation and enable early diagnosis of a possibly cancerous tumor or thyroid lump. We also design and develop a prototype of a surgical robotic device for orthognathic surgery, that can eliminate the intra-operative device registration, thereby simplifying the robotic procedure with a smaller footprint.

Humeral fractures in veterinary patients are challenging to stabilize. This study is a biomechanical in vitro comparison of the performance of two locking plate constructs used to stabilize a canine distal humeral metaphyseal gap model. Two groups of canine cadaveric humeri were prepared. One group consisted of a unilateral medially placed locking plate (UNI). The second group consisted of bilateral locking plates (BI). Constructs were tested in torsion and axial compression. The UNI constructs had significantly lower stiffness in torsion and axial compression than the BI group. However, UNI constructs had a significantly higher ultimate strength than BI constructs. All UNI constructs failed by bending of the transcondylar screw and SOP plate. All BI constructs failed by axial pullout of the distal most screws. The clinical significance is that in stabilizing canine supracondylar humeral fractures as modeled here, both the UNI model and the BI model demonstrated biomechanical advantages.

The goal of this project is to advance the understanding of tendon disease and injury through the design and validation of a new model of tendon injury. Controlled, mechanically-induced traction injury was created in rat Achilles’ tendons with a tensioning apparatus through a minimally invasive surgical approach. Tendons were tensioned to subailure loads. Assessments of damage to tendons included gross morphology, evaluation of biomechanical of load strain curves, histopathology under light microscopy (H&E), collagen fibril structure and disruption under scanning electron microscopy, and immunohistochemical study of MMP-13 expression under confocal laser microscopy. Tendon injuries were found to be more severe with respect to loads placed upon them. Differences between treatment groups were identified subjectively in microscopic appearance (H&E), in collagen fibril organization (SEM), and in MMP-13 expression. However, analysis of the numerical data did not provide definitive evidence that this model for acute tendon injury is consistent and repeatable.

The complexity of the human musculoskeletal system presents challenges in accurately identifying its characteristics, particularly due to the presence of redundant actuators on a single joint. Non-invasive measures are necessary to overcome these challenges. Optimization algorithms have emerged as a crucial tool to advance subject-specific musculoskeletal modeling allows a more realistic representation of biomechanical behaviors, enhancing our understanding of human movement and enabling better clinical decision-making. Furthermore, optimization algorithms play a vital role in customizing rehabilitation and assistive devices, such as orthoses and prostheses. The current ankle-foot orthosis (AFO) stiffness measurement methods require bulky, complex designs, and often permanent modification of the AFO. To address this, we proposed the Ankle Assistive Device Stiffness (AADS) test method, which utilizes a simple design jig and motion capture system. In our method we employed a static optimization algorithm to estimate external forces and AFO torque, providing reliable stiffness quantification. The AADS test demonstrated high precision among different operators and trials, with an overall percent error within ±6%. In the pursuit of accurately measuring muscle-tendon parameters, various techniques, including shear waves, have been utilized. However, these techniques often are invasive or lack the ability to provide quantitative measurements. In our second study, we introduced a noninvasive method for estimating passive muscle-tendon parameters (PMPs) in knee flexors/extensors and the Achilles tendon. We employed a direct collocated optimal control algorithm and evaluated the precision of the proposed method through simulation, replica leg experiments, and in-vivo experiments involving 10 subjects. The estimated range for tendon slack length was reported between 0.59 and 1.13, while the median of tendon stiffness was 421 KN/m. Muscle stiffness ranged between 473 N/m and 1200 N/m. The average root mean square error (RMSE) between experimentally collected joint kinematics and kinetics and forward dynamic verification was less than 0.56° and 12 mN.m/Kg, respectively.

Stress fractures are common overuse injuries that have plagued athletes for many years. Often referred to as fatigue fractures, they are formed when the skeletal muscles fatigue and can no longer absorb the shock of repetitive pounding activities such as running. Stress fractures are most common in the weight-bearing bones of the lower extremities and are usually preceded by sudden increases or changes in training routines. Because they are most common in athletes who are least fit, it has been hypothesized that freshmen athletes who are not prepared for the increased physical demands of college athletics have the greatest risk for developing stress fractures compared to other academic classes. As of yet however, there have been very few studies that have examined the interaction of different variables such as academic class, on the formation of stress fractures. Therefore, the purpose of this study was to look at the incidence, frequency and pattern of stress fractures among the female athletes at Virginia Polytechnic Institute and State University. A retrospective analysis of 28 injury cases over four years revealed that 67% of the injuries occurred in freshmen athletes. The majority of these were in the lower leg and occurred in mid-season rather than pre-season. There were no relationships found between the variables sport, class, site and season and thus it was concluded that the incidence of injury was not affected by the interaction of these variables. However, the variables themselves did influence the formation of stress fractures. Ultimately, this study provided insight on what factors should be carefully examined in order to prevent future stress fracture injuries in collegiate athletes. / Master of Science