Biomedical Engineering and Bioengineering Commons^™

Computational Analysis Of Oxidative Stress In Endothelial Dysfunction: Insights On The Role Of Tetrahydrobiopterin, Ascorbate And Glutathione, Sheetal Kedar Panday

Wayne State University Dissertations

Oxidative stress and endothelial dysfunction are reported in the cardiovascular and neurovascular diseases. Oxidative stress is caused due to an increase in the generation of reactive oxygen (ROS) and nitrogen species (RNS) and incapacity of antioxidant systems to eliminate ROS and RNS. Endothelial dysfunction is characterized by a reduction in nitric oxide (NO) bioavailability. NO is constitutively produced by enzyme endothelial nitric oxide synthase (eNOS). A reduction in tetrahydrobiopterin (BH4), which is an essential cofactor of eNOS, can lead to eNOS uncoupling. There is complex interplay between the ROS/RNS and antioxidant system underlying pathophysiologies of vascular diseases, however our quantitative …

Development Of Rat Head Finite Element Model And Tissue Level Biomechanical Threshold For Traumatic Axonal Injury, Runzhou Zhou

Wayne State University Dissertations

Traumatic brain injury (TBI) is caused by local tissue deformation at the time of trauma, leading to neurological dysfunction. In the United States alone, 2.87 million people sustain a TBI each year, of which one-fifth results in death. Traumatic axonal injury (TAI) is a well-recognized consequence of every fatal head injury and more than 85% of vehicular crash-related blunt head injuries. The most common and important pathologic feature of TBIs are multifocal changes to axons in the white matter produced by rapid head acceleration/deceleration during a traumatic event with consequent local shear/tension on neural tissue and axons contributing to secondary …

Development Of A Novel Cardiac Ischemia-Reperfusion Model In The Axolotl, Jeremy Tolentino Llaniguez

Wayne State University Dissertations

The Center for Disease Control’s National Center for Health Statistics data for mortality from diseases of the heart show the age-adjusted death rate has fallen from almost 600 deaths in the 1950s to just over 190 deaths per 100,000 U.S. residents today. With the recognized limitations of pharmacotherapy of myocardial infarction (MI), cell-based therapies have been undergoing rapid development and clinical testing. However, there is still no consensus about cell types, delivery routes, dosing and treatment schedules and pretreatment conditioning of cells prior to administration. Furthermore, a fundamental question remains unanswered about the reasons for the poor capacity for myocardial …

Utilizing Immunopet To Measure Tumor Response To Treatment In Breast Cancer, Brooke Mcknight

Wayne State University Dissertations

With a broad spectrum of therapies available for treating breast cancer, the need for personalized medicine tailoring the cure according to phenotype is evident. Such an approach may be fully realized with the development of quantitative imaging technologies for disease detection, staging and diagnosis, without increasing patient burden. Immuno-positron emission tomography (PET) combines the targeted specificity of antibodies with the sensitivity of PET for whole body imaging by targeting molecular features amplified in lesions. ImmunoPET probes targeting different antigens and their utility to measure response to treatment were explored. 89Zr-trastuzumab was employed as a surrogate readout of Src inhibition after …

Optimization Of Underbody Blast Energy-Attenuating Seat Mechanisms Using Modified Madymo Hybrid Iii And Human Body Models, Kelly Erin Bryan Bosch

Wayne State University Dissertations

Energy attenuating (EA) blast seats, although not new to the market, have not been fully characterized with respect to energy attenuation capability and the resulting effects on occupant protection. EA seats utilize stroking mechanisms to absorb energy and reduce the vertical forces imparted on the occupant’s pelvis and lower spine complex. Although a variety of EA seats are available on the market, the fundamental question behind how to optimize the force and deflection rates of the EA mechanisms to effectively reduce occupant injury has not yet been answered. Using modeling and simulation techniques, this research developed a tool to determine …

Engineering Hyaluronic Acid Carbon Nanotube Nanofibers: A Peripheral Nerve Interface To Electrically Stimulate Regeneration, Elisabeth M. Steel

Wayne State University Dissertations

Peripheral nerve injuries annually affect hundreds of thousands of people globally. Current treatments like the gold standard autograft and commercially available nerve guide conduits (NGC) are insufficient to repair long gap peripheral nerve injuries. NGCs can aid recovery but lack key microenvironment cues that promote nerve regeneration. We hypothesized that providing topographical, mechanical, and electrical guidance cues through a nanofibrous composite biopolymer would result in improved neuron growth metrics using an in vitro model. We embedded hydrophilic carbon nanotubes (CNT) within hyaluronic acid (HA) nanofibers by electrospinning. The aims of this study were (1) to define the topographical, nanomechanical, and …

Pet Imaging Of Early Therapeutic Response In Solid Tumors, Stephanie J. Blocker

Wayne State University Dissertations

An important pillar of precision medicine for oncology is the ability to identify patients who respond to treatment early into their therapy. Positron emission tomography (PET) allows physicians and researchers to measure changes in tumor behavior prior to noticeable differences in morphology.

Objective: Determine the utility of multiple tracers for PET in assessing early changes in tumor activity that result from treatment.

Methods: Two tracers for PET were studied. 64Cu-labeled liposomes were used to assess changes in liposome delivery two solid colon tumors early into treatment with bevacizumab (Bev). 18F-FMAU thymidine analog (1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine), was utilized to detect early response to …

Biomechanics Of Concussion: The Importance Of Neck Tension, Ron Jadischke

Wayne State University Dissertations

Linear and angular velocity and acceleration of the head are typically correlated to concussion. Despite improvements in helmet performance to reduce accelerations, a corresponding reduction in the incidence of concussion has not occurred (National Football League [NFL] 1996 – present).

There is compelling research that forces on and deformation to the brain stem are related to concussion. The brain stem is the center of control for respiration, blood pressure and heart rate and is the root of most cranial nerves. Injury to the brain stem is consistent with most symptoms of concussion reported in the National Football League and the …

Development Of A Finite Element Pelvis And Lower Extremity Model With Growth Plates For Pediatric Pedestrian Protection, Ming Shen

Wayne State University Dissertations

Finite element (FE) model is a useful tool frequently used for investigating the injury mechanisms and designing protection countermeasures. At present, no 10 years old (YO) pedestrian FE model has been developed from appropriate anthropometries and validated against limitedly available impact response data. A 10 YO child FE pelvis and lower extremities (PLEX) model was established to fill the gap of lacking such models in this age group. The baseline model was validated against available pediatric postmortem human subjects (PMHS) test data and additional scaled adult data, then the PLEX model was integrated to build a whole-body FE model representing …

Biomaterials Approaches For Utilizing The Regenerative Potential Of The Peripheral Nerve Injury Microenvironment, Melissa Renee Wrobel

Wayne State University Dissertations

Clinically available treatments are insufficient to achieve full functional recovery in large (>3cm) peripheral nerve injuries (PNI). The objectives in this thesis were 1) to study often overlooked elements of intrinsic PNI repair including release of inhibitory CSPGs and post-injury responses of inflammatory macrophages and dedifferentiated Schwann cells; 2) to create biomaterial scaf-folds featuring topographical and adhesive cues to enhance neurite outgrowth; and 3) to test the ability of those cues to direct macrophages and Schwann cells towards a pro-regenerative phe-notype. It is hypothesized that recapitulating the positive and negative cues of the PNI microenvi-ronment can better improve regeneration. …

An Investigation Of The Relationship Between Axonal Injury, Biomarker Expression And Mechanical Response In A Rodent Head Impact Acceleration Model, Yan Li

Wayne State University Dissertations

In the United States 1.4 million people sustain traumatic brain injury (TBI) each year, resulting in 235,000 hospitalizations and 50,000 fatalities annually. Traumatic axonal injury (TAI) is a serious outcome of TBI that accounts for 40-50% of hospitalizations due to head injury and one third of the mortality due to TBI, and it is difficult to diagnose and evaluate. The purpose of this dissertation is to determine mechanical injury predictors for TAI and identify potential biomarkers to evaluate TAI.

In this dissertation, a modified Marmarou impact acceleration injury model was developed to allow the monitoring of velocity of the impactor …

How Atomic Level Interactions Drive Membrane Fusion: Insights From Molecular Dynamics Simulations, Navendu Bhatnagar

Wayne State University Dissertations

This project is focused on identifying the role of key players in the membrane fusion process at the atomic level with the use of molecular dynamics simulations. Membrane fusion of apposed bilayers is one of the most fundamental and frequently occurring biological phenomena in living organisms. It is an essential step in several cellular processes such as neuronal exocytosis, sperm fusion with oocytes and intracellular fusion of organelles to name a few. Membrane fusion is a frequent process in a living organism but is still not fully understood at the atomic level in terms of the role of various factors …

Computational Simulation Of Skull Fracture Patterns In Pediatric Subjects Using A Porcine Model, Christina Devito Wagner

Wayne State University Dissertations

In cases of suspected child abuse with skeletal trauma, it is often the role of the injury biomechanist, forensic pathologist, clinical radiologist, and forensic anthropologist to determine the mechanism of injury when the child victims cannot speak for themselves. This is a challenging task, especially for the head, as comprehensive biomechanical data on skull fracture in infants and children do not currently exist, and frequently the determination regarding cause of injury is based on anecdotal evidence from the medical literature and unsubstantiated eyewitness accounts. The current process may result in unreliable autopsy interpretation and miscarriages of justice due to a …

Finite Element Reconstruction Of Real World Aortic Injury In Near-Side Lateral Automotive Crashes With Conceptual Countermeasures, Aditya Neelakanta Belwadi

Wayne State University Dissertations

Traumatic rupture of the aorta (TRA) remains the second most common cause of death associated with motor vehicle crashes after brain injury. On an average, nearly 8,000 people die annually in the United States due to blunt injury to the aorta. It is observed that more than 80% of occupants who suffer an aortic injury die at the scene due to exsanguination into the chest. With the advent of more accurate and established human body finite element (FE) models, FE crash reconstruction methods may become a valuable tool when assessing crash scenarios and occupant injury mechanisms.

The current study is …

Longissimus Muscle Fatigue And Injury Response Due To Electrical Stimulation With Varied Work/Rest Ratios, Peter Wawrow

Wayne State University Dissertations

LONGISSIMUS MUSCLE FATIGUE AND INJURY RESPONSE DUE TO ELECTRICAL STIMULATION WITH VARIED WORK/REST RATIOS

BY

PETER WAWROW

May 2011

Advisor: John Cavanaugh, MD

Major: Biomedical Engineering

Degree: Doctor of Philosophy

The estimated yearly cost of lost-time work injuries and illnesses is $140 billion. The average cost of musculoskeletal disorders (MSDs) exceeds all other claims. These injuries persist in spite of ergonomic interventions addressing known risk factors. Work/rest ratios have not received a significant amount of attention, particularly in low back disorders, and it is hypothesized that the lack of adequate rest within a work cycle may contribute to muscle fatigue …

A Multi-Species Analysis Of Biomechanical Responses Of The Head To A Shock Wave, Richard Bolander

Wayne State University Dissertations

Shock wave induced brain injury remains a field of research that has great consequences for the rehabilitation of soldiers and civilians that are exposed to an explosion. As such, for the research to be successful in developing strategies to mitigate the effects of these injuries, appropriate research methods need to be developed. Animal models are currently employed to understand the brain's response to a shock wave exposure. Unfortunately no criteria have been established that indicates in what way the mechanical inputs that the cells in an animal's brain are subjected to are similar to a human. The purpose of this …