<p dir="ltr">Murine, or small rodent, models can provide valuable and translatable insights into human pathophysiology. Specifically, we are looking to combine murine models and high-frequency ultrasound to non-invasively investigate microrobot drug delivery systems, cardiac effects of lactation on the mother during postpartum, and cardiac remodeling due to the combination of pregnancy and hypertension.</p><p dir="ltr">Currently, we are looking at the applications of microrobots within the colon to provide targeted treatment for patients suffering from inflammatory bowel disease (IBD). IBD is an overarching term encompassing chronic inflammation of the digestive tract tissue. The standard treatment of IBD includes oral and injectable treatments depending on disease severity. The drawbacks of these therapeutics are the associated systemic toxicity, non-specific treatment allocation, and degradation of the treatment in proximal portions of the gastrointestinal (GI) system. The goal of this research is to use an external magnetic torque to cause the microrobots to tumble to targeted areas of inflammation and release a drug payload. Retroactive locomotion of these microrobots can avoid degradation in the proximal GI tract. Therefore, these microrobots need a smaller drug payload to provide the same efficacy as traditional treatments.</p><p dir="ltr">The cardiovascular system adapts to meet the growing physiological demands of pregnancy. Although this change has been greatly studied, it is unclear if this change in shape and function returns to prepregnant values during postpartum. Previous research has also shown that lactation affects the mother’s hemodynamics during postpartum, but its impact on cardiac morphology is still not completely understood. To study this further, we longitudinally tracked cardiovascular changes using ultrasound and blood pressure measurements in C57BL6/J mice during pregnancy and postpartum that were either lactating or not.</p><p dir="ltr">Chronic hypertension affects approximately 1 in 20 pregnancies and its prevalence in pregnancies continues to increase. The maternal cardiovascular system goes through dynamic changes during pregnancy to meet the demands of perfusing the gestation, especially during the exponential growth seen later in pregnancy. Studies with female C57BL6/J mice demonstrate comparable cardiovascular changes during pregnancy to those observed in humans. Additionally, a study using rats showed the cardioprotective properties of pregnancy against angiotensin II-induced fibrosis. The objective of this study is to characterize non-invasive cardiac remodeling in a small animal model of hypertensive disorders in pregnancy. We used a combination of ultrasound imaging and noninvasive blood pressure measurements to longitudinally monitor the physiological adaptations that occur during pregnancy with superimposed hypertension.</p>

<p dir="ltr">Diabetes has become an international health crisis with type 2 diabetes composing the majority of cases. Along with a variety of other systemic effects, type 2 diabetes increases fracture risk. This aspect of type 2 diabetes has become a topic of interest in preclinical research and has been investigated using rodent models of type 2 diabetes. Of these models, the Yellow Kuo Kondo (KK-A^y) mouse model has shown promise as an obese model of type 2 diabetes. In the KK-A^y model, mice heterozygous for a mutation in the agouti gene (A^y) are treated as an obese model of type 2 diabetes. Those that are homozygous (no mutation) are treated as non-diabetic, obese controls. While this model has been indicated to be non-diet dependent, recent data has revealed the efficacy of this model may be reliant on diet. Following approval from the Indiana University-Purdue University at Indianapolis School of Science Institutional Animal Care and Use Committee, mice of each sex and genotype were placed on separate diets. Half on a standard chow diet and the other half on a diet recommended by Jackson Laboratory for this strain. Animals were aged to 16 weeks of age with blood glucose and body weight monitored every other week. Animals were then sacrificed to collect whole blood, blood serum, the pancreas, bilateral tibiae, and bilateral femora. End-point metabolic impacts were assessed through hemoglobin A1c and serum insulin measures while skeletal measures were quantified using microcomputed tomography scanning and analysis. Through this research, it was determined diet did have a significant impact on the skeletal and metabolic phenotype associated with type 2 diabetes in the KK-A^ymodel. </p>

Several surgically corrective procedures are considered to treat Adult Acquired Flatfoot Deformity (AAFD) patients, relieve pain, and restore function. Procedure selection is based on best practices and surgeon preference. Recent research created patient specific models of Adult Acquired Flatfoot Deformity (AAFD) to explore their predictive capabilities and examine effectiveness of the surgical procedure used to treat the deformity. The models’ behavior was governed solely by patient bodyweight, soft tissue constraints, and joint contact without the assumption of idealized joints. The current work expanded those models to determine if an alternate procedure would be more effective for the individual. These procedures included one hindfoot procedure, the Medializing Calcaneal Osteotomy (MCO), and one of three lateral column procedures: Evans osteotomy, Calcaneocuboid Distraction Arthrodesis (CCDA), Z osteotomy and the combination procedures MCO & Evans osteotomy, MCO & CCDA, and MCO & Z osteotomy all used in combination with a tendon transfer. The combination MCO & Evans and MCO & Z procedures were shown to provide the greatest amount of correction for both forefoot abduction and hindfoot valgus. However, these two procedures significantly increased the joint contact force, specifically at the calcaneocuboid joint, and ground reaction force along the lateral column. With exception to the lateral bands of the plantar fascia and middle spring ligament, the strain present in the plantar fascia, spring, and deltoid ligaments decreased after all procedures. The use of patient specific computational models provided the ability to investigate effects of alternate surgical corrections on restoring biomechanical function in flatfoot patients.

Heart failure is expected to ail over 8 million people in America by 2030 leaving many in need of cardiac replacement. To accommodate this large volume of people, ventricular assist devices (VADs) are necessary to provide mechanical circulatory support. Current VADs exhibit issues such as thrombosis and hemolysis caused by large local pressure drops and turbulent flow within the pump. Multiple disk centrifugal pumps (MDCPs) use shearing and centrifugal forces to produce laminar flow patterns and eliminate large pressure drops within the pump which greatly reduce risks that are in current VADs. The MDCP has a shaft drive system (SDS) that causes leakage between the motor and housing that when implanted can cause blood loss, infection, thrombosis and hemolysis. To eliminate these adverse effects, a magnetic external motor-driven system (MEMDS) was implemented. An efficiency study was performed to examine the efficacy of the MEMDS by comparing the hydraulic work of the MDCP to the power required to run the pump. This was done by measuring inlet and outlet pressures, outlet flow rate and input current at various input voltages and resistances. The results showed the MDCP could produce physiologic flow characteristics with a flow rate of 4.90 L/min and outlet pressure of 61.33 mmHg at an impeller speed of 989.79 rpm. Other VADs generate flow rates around 5 L/min at rotational speeds of 2400 rpm for centrifugal pumps and 12000 rpm for axial pumps. When compared to the SDS, the MEMDS exhibited similar efficiencies of 3.89% and 3.50% respectively. This study shows promise in the advancement of MDCP.

This research utilizes CFD to analyze blood flow through pathways representative of central shunts, commonly used as part of the Fontan procedure to treat cyanotic heart disease. In the first part of this research, a parametric study of steady, Newtonian blood flow through parabolic pathways was performed to demonstrate the effect that flow pathway curvature has on wall shear stress distribution and flow energy losses. In the second part, blood flow through two shunts obtained via biplane angiograms is simulated. Pressure boundary conditions were obtained via catheterization. Results showed that wall shear stresses were of sufficient magnitude to initiate platelet activation, a precursor for thrombus formation. Steady results utilizing time-averaged boundary conditions showed excellent agreement with the time-averaged results obtained from pulsatile simulations. For the points of interest in this research, namely wall shear stress distribution and flow energy loss, the Newtonian viscosity model was found to yield acceptable results.

Management and control of the low back pain as an important health problem in the industrial societies necessitates to investigate how the risk of this disease is affected by aging. Since the abnormalities of the lumbopelvic kinematics are related to the existence or risk of low back injuries, the objective of this dissertation was set to find the age-related differences in lumbopelvic kinematics when performing basic trunk motions reaching to range of motion in different anatomical planes. A cross-sectional study was designed where sixty asymptomatic individuals between 20–70 years old with no confounding health condition, no current or previous highly physically demanding occupation and a body mass index between 22 and 30, were divided in five equally-sized and gender-balanced age groups, and attended two sessions of data collection to perform three repetitions of self-selected slow and fast trunk forward bending and backward return, as well as one left and right lateral bending and axial twist. Following an extensive literature review, the lumbar contribution (LC) to the trunk motion, the mean absolute relative phase (MARP) between the thoracic and pelvic motions as well as variation in MARP under repetitive motions, denoted by deviation phase (DP) were selected and used for the assessment of age-related differences in lumbopelvic kinematics during forward bending and backward return tasks. Lumbopelvic kinematics during the lateral bending and axial twist tasks were assessed using the lumbar and pelvic ranges of motion (ROMs) and coupled motion ratios (CMRs) as respectively the maximum flexion/rotation in the primary (i.e., intended) and the secondary (i.e., coupled) planes of trunk motion, where the latter was normalized to the conjugate ROM for better comparison. The results showed age-related differences between the age groups above and under 50 years of age generally. A smaller LC during the forward bending and backward return tasks were observed in the older versus younger age groups, suggesting that the synergy between the active and passive lower back tissues is different between the older and younger people, which may affect the lower back mechanics. Also, smaller MARP and DP suggesting a more in-phase and more stable lumbopelvic rhythm were observed in the older versus younger age groups, which may be a neuromuscular strategy to protect the lower back tissues from excessive strain, in order to reduce the risk of injury. Furthermore, the coupled motion of lumbar spine in the transverse plane during the lateral bending to the left, and the coupled motion of pelvis in the sagittal plane during the axial twist to the right were larger in older versus younger age groups. In summary, the lumbopelvic kinematics changes with aging, especially after the age of 50 which implies alterations in the active and passive tissue responses to the task demands, as well as the neuromuscular control patterns. Drawing a conclusion regarding ii the effect of aging on the risk of low back pain from these results requires a further detailed knowledge on age-related differences in spinal active and passive tissue properties.

Myocardial infarction (i.e., a heart attack) is the most common heart disease in the United States. Mitral valve regurgitation, or the backflow of blood into the atrium from the left ventricle, is one of the complications associated with myocardial infarction. In this dissertation, a validated model of a sheep heart that has suffered myocardial infarction has been employed to study mitral valve regurgitation. The model was rebuilt with the knowledge of geometrical changes captured with MRI technique and is assigned with anisotropic, inhomogeneous, nearly incompressible and highly non-linear material properties. Patch augmentation was performed on its anterior leaflet, using a simplified approach, and its posterior leaflet, using a more realistic approach. In this finite element simulation, we virtually installed an elliptical patch within the central portion of the posterior leaflet. To the best of the author’s knowledge, this type of simulation has not been performed previously. In another simulation, the effect of patch within the anterior leaflet was simulated. The results from the two different surgical simulations show that patch implantation helps the free edges of the leaflets come close to one another, which leads to improved coaptation. Additionally, the changes in chordal force distributions are also reported. Finally, this study answers a few questions regarding mitral valve patch augmentation surgeries and emphasizes the importance of further investigations on the influence of patch positioning and material properties on key outcomes. The ultimate goal is to use the proposed techniques to assess human models that are patient-specific.

Change in papillary muscle motion as a result of left ventricular (LV) remodeling after posterolateral myocardial infarction is thought to contribute to ischemic mitral regurgitation. A finite element (FE) model of the LV was created from magnetic resonance images acquired immediately before myocardial infarction and 8 weeks later in a cohort of 12 sheep. Severity of mitral regurgitation was rated by two-dimensional echocardiography and regurgitant volume was estimated using MRI. Of the cohort, 6 animals (DC) received hydrogel injection therapy shown to limit ventricular remodeling after myocardial infarction while the control group (MI) received a similar pattern of saline injections. LV pressure was determined by direct invasive measurement and volume was estimated from MRI. FE models of the LV for each animal included both healthy and infarct tissue regions as well as a simulated hydrogel injection pattern for the DC group. Constitutive model material parameters for each region in the FE model were assigned based on results from previous research. Invasive LV pressure measurements at end diastole and end systole were used as boundary conditions to drive model simulations for each animal. Passive stiffness (C) and active material parameter (Tmax) were adjusted to match MRI estimations of LV volume at end systole and end diastole. Nodal positions of the chordae tendineae (CT) were determined by measurements obtained from the excised heart of each animal at the terminal timepoint. Changes in CT nodal displacements between end systole and end diastole at 0 and 8-week timepoints were used to investigate the potential contribution of changes in papillary muscle motion to the progression of ischemic mitral regurgitation after myocardial infarction. Nodal displacements were broken down into radial, circumferential, and longitudinal components relative to the anatomy of the individual animal model. Model results highlighted an outward radial movement in the infarct region after 8 weeks in untreated animals, while radial direction of motion observed in the treated animal group was preserved relative to baseline. Circumferential displacement decreased in the remote region in the untreated animal group after 8 weeks but was preserved relative to baseline in the treated animal group. MRI estimates of regurgitant volume increased significantly in the untreated animal group after 8 weeks but did not increase in the treated group. The results of this analysis suggest that hydrogel injection treatment may serve to limit changes in papillary muscle motion and severity of mitral regurgitation after posterolateral myocardial infarction.

The present research focuses on analyzing the possibility of implementing three dimensional woven composite (3DWC) materials in hip implants. The integration of 3DWCs in hip implants has the possibility to both extend the life-time and improve patient outcomes; by spatially varying mechanical properties to meet both biological needs as well as required mechanical loading. In this study, the bulk material properties of 3DWCs were varied based on woven composite architecture and determined using physics based models, which reflect the realistic geometries of fibers in compaction and preform. The multi-digital chain method combined with Extended Finite Elemental Analysis (XFEA) are adopted in this micro-analysis for composite design. Four different woven architectures with a combination of different existing biocompatible fiber and resins are considered in this study. The main objective is to assess the mechanical response of these biocompatible materials in the design of 3D woven architectures and determine their ability to match the required modulus at different regions of a hip implant. Results obtained show 3DWCs are viable candidates for this application. Multiple architectures and materials chosen, were able to achieve the desired mechanical response. Additional studies can use these results as a starting point and framework for further mechanical and biological testing.

<p>An abdominal aortic aneurysm (AAA), defined as a pathological expansion of the largest artery in the abdomen, is a relatively common disease that frequently leads to death if rupture occurs. Once diagnosed, clinicians often evaluate the rupture risk based on the maximum diameter of the aneurysm, a limited metric that is not accurate for all patients. In this study, we worked to provide additional distinguishing factors between growing and stable AAAs to aid in clinical rupture risk assessment. We utilized a relatively new murine model that uses surgical application of topical elastase to cause initial aortic expansion, and a lysyl oxidase inhibitor, β-aminopropionitrile (BAPN), in the drinking water to promote AAA growth. We further sought to develop and demonstrate applications of advanced imaging approaches, including four-dimensional ultrasound (4DUS), to obtain and evaluate alternative geometric and biomechanical parameters between 1) growing AAAs, 2) stable AAAs, and 3) non-aneurysmal control mice. Our study confirmed the reproducibility of the model and found reduced strain values, greater tortuosity, and decreased elastin health in mice with aneurysms. We also found expanding murine AAAs to have increased peak wall stress and surface area per length compared to stable aneurysms. The results from this work help provide a better understanding of the growth patterns associated with elastase-BAPN murine aneurysms and demonstrate the capabilities of high-frequency ultrasound. Eventually these data could help lay the groundwork for improving insight into clinical prediction of AAA expansion.</p>