Biomedical Engineering and Bioengineering Commons^™

Three-Dimensional Endothelial Spheroid-Based Investigation Of Pressure-Sensitive Sprout Formation, Min Song

Theses and Dissertations--Biomedical Engineering

This study explored hydrostatic pressure as a mechanobiological parameter to control in vitro endothelial cell tubulogenesis in 3-D hydrogels as a model microvascular tissue engineering approach. For this purpose, the present investigation used an endothelial spheroid model, which we believe is an adaptable microvascularization strategy for many tissue engineering construct designs. We also aimed to identify the operating magnitudes and exposure times for hydrostatic pressure-sensitive sprout formation as well as verify the involvement of VEGFR-3 signaling. For this purpose, we used a custom-designed pressure system and a 3-D endothelial cell spheroid model of sprouting tubulogenesis. We report that an exposure …

The Rheological Impact Of Cell Activation On The Flow Behavior Of Neutrophils, Nolan M. Horrall

Theses and Dissertations--Biomedical Engineering

Previously, it was reported that the morphological changes (pseudopod projection) that circulating neutrophils adopt due to cell activation raises peripheral vascular resistance by disrupting microvascular rheology. Studies utilized murine muscle preparations to link neutrophil pseudopod formation to cell activation and a viscous impact on hemodynamic resistance. But because of the complexity associated with the organization of the vasculature and microvasculature in tissues, it was unclear whether the effects of neutrophil activation on hemodynamic resistance were associated with the macro-/micro- circulation. This research describes an in vitro analysis using viscometry and microvascular network mimics (microporous membranes) to assess the rheological impact …

The Influence Of Cholesterol-Related Membrane Fluidity On The Shear Stress Control Of Neutrophil Adhesion And Its Implications In Hypercholesterolemia, Michael L. Akenhead

Theses and Dissertations--Biomedical Engineering

Hypercholesterolemia is a significant risk factor in the development of cardiovascular disease and is associated with chronic leukocyte adhesion in the microvasculature. While the underlying mechanisms behind this have yet to be determined, it may be possible that hypercholesterolemia impairs the fluid shear stress (FSS) inactivation of neutrophils through the rigidifying effect of cholesterol on membrane fluidity. FSS restricts surface expression of CD18 integrins through cathepsin B (ctsB) proteolysis, which minimizes neutrophil adhesivity. If hypercholesterolemia blocks FSS mechanotransduction, then the inhibition of CD18 cleavage may link pathologic blood cholesterol elevations with dysregulated neutrophil adhesion. We hypothesized that elevated cholesterol contributes …

Recent Advances In Optical Spectroscopic And Imaging Methods For Medicine And Biology, Yu Shang, Zhiyu Qian, Rickson C. Mesquita, Mathieu Dehaes

Biomedical Engineering Faculty Publications

No abstract provided.

Reference Point Indentation Of Human Trabecular Bone Treated With Bisphosphonates For Varying Durations, Drew Jones

Theses and Dissertations--Biomedical Engineering

Reference point indentation (RPI), a novel form of micro-indentation, quantifies RPI material parameters which correlate with modulus, yield stress, strength, or toughness. Information linking bisphosphonate treatment length with the material properties of osteoporotic trabecular bone is needed to improve patient treatment. The objectives of this study were to: 1) determine if RPI can be used to successfully evaluate human trabecular bone and if so, determine an optimized test method for using RPI on trabecular bone, and 2) use this method to determine if any RPI parameters are related to the duration of bisphosphonate treatment.

Indentation using a 4 N applied …

Closed-Loop Afferent Nerve Electrical Stimulation For Rehabilitation Of Hand Function In Subjects With Incomplete Spinal Cord Injury, Christopher J. Schildt

Theses and Dissertations--Biomedical Engineering

Peripheral nerve stimulation (PNS) is commonly used to promote use-dependent cortical plasticity for rehabilitation of motor function in spinal cord injury. Pairing transcranial magnetic stimulation (TMS) with PNS has been shown to increase motor evoked potentials most when the two stimuli are timed to arrive in the cortex simultaneously. This suggests that a mechanism of timing-dependent plasticity (TDP) may be a more effective method of promoting motor rehabilitation. The following thesis is the result of applying a brain-computer interface to apply PNS in closed-loop simultaneously to movement intention onset as measured by EEG of the sensorimotor cortex to test whether …

Detection Of Electrical Alternans In Ventricular Depolarization Phase Of Human Electrocardiogram, David R. Wasemiller

Theses and Dissertations--Biomedical Engineering

T-wave Alternans (TWA) in an electrocardiogram (ECG) has received considerable interest as a potential predictor of sudden cardiac death (SCD). However, large clinical trials have shown that while TWA has a very high negative predictive value, its positive predictive value is poor. Results of previous studies suggest that arrhythmia onset can be affected by the phase relationship of alternans of the depolarization and repolarization phase of the action potentials of the ventricles. To assess this relationship, one would first need to establish that depolarization alternans can be detected and then develop methods to determine its relationship with repolarization alternans, which …

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds …

Biventricular Finite Element Modeling And Quantification Of 3d Langragian Strains And Torsion Using Dense Mri, Zhanqiu Liu

Theses and Dissertations--Mechanical and Aerospace Engineering

Statistical data suggests that increased use of evidence-based medical therapies has largely contributed to the decrease in American death rate caused by heart disease. And my studies are about two applications of magnetic resonance imaging (MRI) as a non-invasive approach in evidence-based health care research. In my first study, the achievement of a pulmonary valve replacement surgery was assessed on a patient with tetralogy of Fallot (TOF). In order to evaluate the remodeling of right ventricle, two biventricular finite element models were built up for pre-surgical images and post-surgical images. In my second study, 3D Lagrangian strains and torsion in …

Diffusion-Mediated Deposition Of Proteins, Ruiqian Zhan

Theses and Dissertations--Mechanical and Aerospace Engineering

Gradients of proteins play a prominent role in many biological processes, from development of multicellular organisms to chemical signaling in the immune system. Deposition of surface gradients is a way to permanently modifying a surface’s properties, resulting in the creation of novel materials which have widespread applications in biologically relevant fields, such as directed cell growth, production of biocompatible implantable materials, and creation of functional biosensors. These types of surfaces can also be used as an ex vivo tool to help understand many biological processes by mimicking the environment in gradient-related phenomena in a controllable way. However, despite the large …

Development And Application Of Gadolinium Free Cardiac Magnetic Resonance Fibrosis Imaging For Multiscale Study Of Heart Failure In Patients With End Stage Renal Disease, Tori A. Stromp

Theses and Dissertations--Physiology

Cardiac magnetic resonance (CMR) is a powerful tool to noninvasively image ventricular fibrosis. Late gadolinium enhancement (LGE) CMR identifies focal and, with T1 mapping, diffuse fibrosis. Despite prevalent cardiac fibrosis and heart failure, patients with end stage renal disease (ESRD) are excluded from LGE. Absence of a suitable diagnostic has limited the understanding of heart failure and obstructed development of therapies in the setting of ESRD. A quantitative, gadolinium free fibrosis detection method could overcome this critical barrier, propelling the advancement of diagnostic, monitoring, and therapy options. This project describes the development of a gadolinium free CMR technique and application …

Automated Solid-Substrate Cultivation Of The Anaerobic Bacterium Clostridium Thermocellum, Mathew J. Ruwaya

Theses and Dissertations--Biosystems and Agricultural Engineering

The organism Clostridium thermocellum grows on cellulosic substrates and produces ethanol, acetate, lactate, formic acid, and CO₂. The organic acids produced alter the growth environment in which the bacteria grows and ultimately inhibit bacterial growth. One method which has been used successfully to maintain the system at acceptable growth conditions is to intermittently flush out the spent media and metabolic products and replace with new fermentation media. Our goal was to design and build an automated system that will automatically flush the spent media from the growing culture and resupply new media without manual intervention. An automated control …

Analysis Of Vocal Fold Kinematics Using High Speed Video, Harikrishnan Unnikrishnan

Theses and Dissertations--Electrical and Computer Engineering

Vocal folds are the twin in-folding of the mucous membrane stretched horizontally across the larynx. They vibrate modulating the constant air flow initiated from the lungs. The pulsating pressure wave blowing through the glottis is thus the source for voiced speech production. Study of vocal fold dynamics during voicing are critical for the treatment of voice pathologies. Since the vocal folds move at 100 - 350 cycles per second, their visual inspection is currently done by strobosocopy which merges information from multiple cycles to present an apparent motion. High Speed Digital Laryngeal Imaging(HSDLI) with a temporal resolution of up to …

Bioactive Poly(Beta-Amino Ester) Biomaterials For Treatment Of Infection And Oxidative Stress, Andrew L. Lakes

Theses and Dissertations--Chemical and Materials Engineering

Polymers have deep roots as drug delivery tools, and are widely used in clinical to private settings. Currently, however, numerous traditional therapies exist which may be improved through use of polymeric biomaterials. Through our work with infectious and oxidative stress disease prevention and treatment, we aimed to develop application driven, enhanced therapies utilizing new classes of polymers synthesized in-house. Applying biodegradable poly(β-amino ester) (PBAE) polymers, covalent-addition of bioactive substrates to these PBAEs avoided certain pitfalls of free-loaded and non-degradable drug delivery systems. Further, through variation of polymer ingredients and conditions, we were able to tune degradation rates, release profiles, cellular …

Synthesis And Characterization Of Antioxidant Conjugated Poly(Βeta-Amino Ester) Micro/Nanogels For The Suppression Of Oxidative Stress, Prachi Gupta

Theses and Dissertations--Chemical and Materials Engineering

Oxidative stress is a pathophysiological condition defined by an increased production of reactive oxygen species (ROS), which can result in the growth arrest of cells followed by cell disintegration or necrosis. A number of small molecule antioxidants (e.g. curcumin, quercetin and resveratrol) are capable of directly scavenging ROS, thereby short-circuiting the self-propagating oxidative stress state. However, poor solubility and rapid 1^st pass metabolism results in overall low bioavailability and acts as a barrier for its use as a drug to suppress oxidative stress efficiently.

To overcome this limitation, these small molecule antioxidants were covalently conjugated into poly(β-amino ester) (PβAE) …

2d Cine Dense With Low Encoding Frequencies Accurately Quantifies Cardiac Mechanics With Improved Image Characteristics, Gregory J. Wehner, Jonathan D. Grabau, Jonathan D. Suever, Christopher M. Haggerty, Linyuan Jing, David Powell, Sean M. Hamlet, Moriel H. Vandsburger, Xiaodong Zhong, Brandon K. Fornwalt

Biomedical Engineering Faculty Publications

BACKGROUND: Displacement Encoding with Stimulated Echoes (DENSE) encodes displacement into the phase of the magnetic resonance signal. The encoding frequency (k_e) maps the measured phase to tissue displacement while the strength of the encoding gradients affects image quality. 2D cine DENSE studies have used a k_e of 0.10 cycles/mm, which is high enough to remove an artifact-generating echo from k-space, provide high sensitivity to tissue displacements, and dephase the blood pool. However, through-plane dephasing can remove the unwanted echo and dephase the blood pool without relying on high k_e. Additionally, the high sensitivity comes …

Noncontact Diffuse Correlation Tomography Of Human Breast Tumor, Lian He, Yu Lin, Chong Huang, Daniel Irwin, Margaret M. Szabunio, Guoqiang Yu

Biomedical Engineering Faculty Publications

Our first step to adapt our recently developed noncontact diffuse correlation tomography (ncDCT) system for three-dimensional (3-D) imaging of blood flow distribution in human breast tumors is reported. A commercial 3-D camera was used to obtain breast surface geometry, which was then converted to a solid volume mesh. An ncDCT probe scanned over a region of interest on the mesh surface and the measured boundary data were combined with a finite element framework for 3-D image reconstruction of blood flow distribution. This technique was tested in computer simulations and in vivo human breasts with low-grade carcinoma. Results from computer simulations …

Noncontact Diffuse Optical Assessment Of Blood Flow Changes In Head And Neck Free Tissue Transfer Flaps, Chong Huang, Yu Lin, Yu Shang, Guoqiang Yu, Jeffrey Radabaugh, Rony Aouad, Thomas J. Gal, Amit B. Patel, Joseph Valentino

Biomedical Engineering Faculty Publications

Knowledge of tissue blood flow (BF) changes after free tissue transfer may enable surgeons to predict the failure of flap thrombosis at an early stage. This study used our recently developed noncontact diffuse correlation spectroscopy to monitor dynamic BF changes in free flaps without getting in contact with the targeted tissue. Eight free flaps were elevated in patients with head and neck cancer; one of the flaps failed. Multiple BF measurements probing the transferred tissue were performed during and post the surgical operation. Postoperative BF values were normalized to the intraoperative baselines (assigning “1”) for the calculation of relative BF …

Effects Of Individualized Centrifugation Training On Orthostatic Tolerance In Men And Women, Nandu Goswami, Joyce Evans, Stefan Schneider, Melanie Von Der Wiesche, Edwin Mulder, Andreas Rössler, Helmut Hinghofer-Szalkay, Andrew P. Blaber

Biomedical Engineering Faculty Publications

AIMS: Exposure to artificial gravity (AG) at different G loads and durations on human centrifuges has been shown to improve orthostatic tolerance in men. However, the effects on women and of an individual-specific AG training protocol on tolerance are not known.

METHODS: We examined the effects of 90 minutes of AG vs. 90 minutes of supine rest on the orthostatic tolerance limit (OTL), using head up tilt and lower body negative pressure until presyncope of 7 men and 5 women. Subjects were placed in the centrifuge nacelle while instrumented and after one-hour they underwent either: 1) AG exposure …

Treating Proximal Tibial Growth Plate Injuries Using Poly(Lactic-Co-Glycolic Acid) Scaffolds, Amanda Clark, J. Zach Hilt, Todd A. Milbrandt, David A. Puleo

Biomedical Engineering Faculty Publications

Growth plate fractures account for nearly 18.5% of fractures in children. Depending on the type and severity of the injury, inhibited bone growth or angular deformity caused by bone forming in place of the growth plate can occur. The current treatment involves removal of the bony bar and replacing it with a filler substance, such as a free fat graft. Unfortunately, reformation of the bony bar frequently occurs, preventing the native growth plate from regenerating. The goal of this pilot study was to determine whether biodegradable scaffolds can enhance native growth plate regeneration following a simulated injury that resulted in …

Collagen Crosslinking Reagent Utilized To Modify The Mechanical Properties Of The Soft Palate In Equine Snoring And Apnea Applications, Stephanie L. Hunt

Theses and Dissertations--Biomedical Engineering

Snoring is a sleep disruption that can lead to obstructive sleep apnea (OSA), which interrupts breathing by obstructing the airway. Injecting a protein crosslinker, such as genipin, into the soft palate could decrease the severity of snoring and OSA by stiffening the soft palate. Equine soft palates modeled human palates due to a high incidence of awake snoring and apnea.

The pilot in vivo study treated six horses with two 100 mM injections of the buffered genipin reagent. The efficacy phase horses underwent respiratory audio recordings to document snoring changes using Matlab and ImageJ in the time and frequency domains. …

Biomimetic Oral Mucin From Polymer Micelle Networks, Sundar Prasanth Authimoolam

Theses and Dissertations--Chemical and Materials Engineering

Mucin networks are formed by the complexation of bottlebrush-like mucin glycoprotein with other small molecule glycoproteins. These glycoproteins create nanoscale strands that then arrange into a nanoporous mesh. These networks play an important role in ensuring surface hydration, lubricity and barrier protection. In order to understand the functional behavior in mucin networks, it is important to decouple their chemical and physical effects responsible for generating the fundamental property-function relationship. To achieve this goal, we propose to develop a synthetic biomimetic mucin using a layer-by-layer (LBL) deposition approach. In this work, a hierarchical 3-dimensional structures resembling natural mucin networks was generated …

Noncontact Diffuse Correlation Tomography Of Breast Tumor, Lian He

Theses and Dissertations--Biomedical Engineering

Since aggressive cancers are frequently hypermetabolic with angiogenic vessels, quantification of blood flow (BF) can be vital for cancer diagnosis. Our laboratory has developed a noncontact diffuse correlation tomography (ncDCT) system for 3-D imaging of BF distribution in deep tissues (up to centimeters). The ncDCT system employs two sets of optical lenses to project source and detector fibers respectively onto the tissue surface, and applies finite element framework to model light transportation in complex tissue geometries. This thesis reports our first step to adapt the ncDCT system for 3-D imaging of BF contrasts in human breast tumors. A commercial 3-D …

Layered, Flexible Drug Delivery Films For The Prevention Of Fibrotic Scar Tissue Formation, Cheryl L. Rabek

Theses and Dissertations--Biomedical Engineering

Open wounds account for about 50% of military injuries and 10% of non‐fatal traffic injuries. Scar tissue formation in these wounds may be reduced or prevented if treated with a combination of molecules whose release is tuned to the healing phases. The goal of this research was to develop flexible, layered drug delivery films for sequential, localized release of anti‐inflammatory, anti‐oxidant, and anti‐fibrotic molecules to soft tissue.

Films were composed of cellulose acetate phthalate (CAP) and Pluronic F‐127 (Pluronic). To impart flexibility, plasticizers, triethyl citrate (TEC) or tributyl citrate (TBC), were added. Mechanical analysis was performed on films as prepared …

Experimental-Computational Analysis Of Vigilance Dynamics For Applications In Sleep And Epilepsy, Farid Yaghouby

Theses and Dissertations--Biomedical Engineering

Epilepsy is a neurological disorder characterized by recurrent seizures. Sleep problems can cooccur with epilepsy, and adversely affect seizure diagnosis and treatment. In fact, the relationship between sleep and seizures in individuals with epilepsy is a complex one. Seizures disturb sleep and sleep deprivation aggravates seizures. Antiepileptic drugs may also impair sleep quality at the cost of controlling seizures. In general, particular vigilance states may inhibit or facilitate seizure generation, and changes in vigilance state can affect the predictability of seizures. A clear understanding of sleep-seizure interactions will therefore benefit epilepsy care providers and improve quality of life in patients. …

A Local, Sustained Delivery System For Zoledronic Acid And Rankl-Inhibitory Antibody As A Potential Treatment For Metastatic Bone Disease, Rohith Jayaram

Theses and Dissertations--Biomedical Engineering

Cancerous solid tumors can migrate and lead to metastatic bone disease. Drugs prescribed to reduce bone resorption from metastasis, such as zoledronic acid and the RANKL-inhibitory antibody Denosumab, cause side effects such as osteonecrosis of the jaw when delivered systemically. This project used two biocompatible materials, acrylic bone cement (PMMA) and poly(lactic-co-glycolic acid) (PLGA), to incorporate and sustain release of anti-resorptive agents. Results showed similar mechanical properties for acrylic bone cements loaded up to 6.6% drug by weight. Results showed sustained zoledronic acid release for 8 weeks from both systems, with PMMA releasing up to 22% of loaded drug and …

Diffuse Optical Measurements Of Head And Neck Tumor Hemodynamics For Early Prediction Of Chemo-Radiation Therapy Outcomes, Lixin Dong

Theses and Dissertations--Biomedical Engineering

Chemo-radiation therapy is a principal modality for the treatment of head and neck cancers, and its efficacy depends on the interaction of tumor oxygen with free radicals. In this study, we adopted a novel hybrid diffuse optical instrument combining a commercial frequency-domain tissue oximeter (Imagent) and a custom-made diffuse correlation spectroscopy (DCS) flowmeter, which allowed for simultaneous measurements of tumor blood flow and blood oxygenation. Using this hybrid instrument we continually measured tumor hemodynamic responses to chemo-radiation therapy over the treatment period of 7 weeks. We also explored monitoring dynamic tumor hemodynamic changes during radiation delivery. Blood flow data analysis …

The Effect Of Cholesterol On The Osteoblast Responsiveness To Hydrodynamic Pressure Stimulation, Kristen Lough

Theses and Dissertations--Biomedical Engineering

Hypercholesterolemia is a risk factor for osteoporosis but the underlying mechanism is unknown. Previous evidence suggests that osteoporosis results from an impaired regulation of osteoblasts by fluid pressure fluctuations in the bone matrix. Recently, our laboratory showed that enhanced cholesterol in the cell membrane, due to hypercholesterolemia, alters leukocyte mechanosensitivity. We predict a similar link between osteoblasts and hypercholesterolemia leading to osteoporosis. Specifically, we hypothesize that extracellular cholesterol modifies the osteoblast sensitivity to pressure. MC3T3-E1 cells were exposed to hydrodynamic pressures regimes (mean=40mmHg, amplitude=0-20mmHg, frequency=1Hz) for 1-12 hours. To assess the impact of membrane cholesterol enrichment, cells were pre-treated with …

Human Cardiovascular Responses To Simulated Partial Gravity And A Short Hypergravity Exposure, Qingguang Zhang

Theses and Dissertations--Biomedical Engineering

Orthostatic intolerance (OI), i.e., the inability to maintain stable arterial pressure during upright posture, is a major problem for astronauts after spaceflight. Therefore, one important goal of spaceflight-related research is the development of countermeasures to prevent post flight OI. Given the rarity and expense of spaceflight, countermeasure development requires ground-based simulations of partial gravity to induce appropriate orthostatic effects on the human body, and to test the efficacy of potential countermeasures.

To test the efficacy of upright lower body positive pressure (LBPP) as a model for simulating cardiovascular responses to lunar and Martian gravities on Earth, cardiovascular responses to upright …

Long Term Blood Oxygenation Membranes, Joseph V. Alexander

Theses and Dissertations--Biomedical Engineering

Hollow fiber membranes are widely used in blood oxygenators to remove carbon dioxide and add oxygen during cardiopulmonary bypass operations. These devices are now widely used off-label by physicians to perform extracorporeal blood oxygenation for patients with lung failure. Unfortunately, the hollow fiber membranes used in these devices fail prematurely due to blood plasma leakage and gas emboli formation.

This project formed ultrathin (~100nm) polymer coatings on polymer hollow fiber membranes. The coatings were intended to “block” existing pores on the exterior surfaces while permitting high gas fluxes. This coating is synthesized using surface imitated control radical polymerization.

The coating …