Biomedical Engineering and Bioengineering Commons^™

Nature-Inspired Material Strategies Towards Functional Devices, Sayantan Pradhan

Theses and Dissertations

Naturally sourced, renewable biomaterials possess outstanding advantages for a multitude of biomedical applications owing to their biodegradability, biocompatibility, and excellent mechanical properties. Of interest in this dissertation are silk (protein) and chitin (polysaccharide) biopolymers for the fabrication of functional biodevices. One of the major challenges restricting these materials beyond their traditional usage as passive substrate materials is the ability to combine them with high-resolution fabrication techniques. Initial research work is directed towards the fabrication of micropatterned, flexible 2D substrates of silk fibroin and chitin using bench-top photolithographic techniques. Research is focused on imparting electrochemical properties to silk proteins using conducting …

Rheological Analysis Of The Mechanical Properties Of Murine Lungs Over The Lifespan, Olajumoke Olufunke Harrison

Theses and Dissertations

To study the effects of aging in murine lungs, we characterized C57Bl6j mice from neonatal to 24-month-old mice. Samples were divided into two groups: Young Mice (YM) and Middle Age/Old Age Mice (MOM). The YM group included the neonatal and 6-10week. The MOM group included 7- and 22–24-month-old mice. Rheological testing was performed using a TA Instruments DHR-2 Rheometer to collect the mechanics of each mice sample. Utilizing a 20-mm parallel plate fixture, a gap of 0.8-1.0-mm, and a temperature setting of 25C, we conducted a frequency sweep. Samples were the decellularized over a four-day process then lyophilized for mass …

Development Of A Single Use Device Intended To Wash Blood Clot Debris From A Stent Retriever In The Operating Room, Shane Diller

Theses and Dissertations

Ischemic stroke is a life-threatening condition that requires immediate surgical intervention to remove the blood clot that is lodged in the blood vessels of the brain. Mechanical thrombectomy, performed by an endovascular surgeon, involves inserting a stent retriever, which deploys distally and attempts to capture the clot when dragged backwards. A complication prevalent in 50% - 67% of cases is that the blood clot is only partially removed and clings to the mesh framework of the stent. The operating surgeon must either clean the debris from the stent retriever, to be reinserted or throw the stent retriever away and open …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Formulation And Validation Of Nanoparticle Controlled Delivery For Chemotherapeutic Drug Products, Shani L. Levit

Theses and Dissertations

Taxol, a formulation of paclitaxel (PTX), is one of the most widely used anticancer drugs, particularly for treating recurring ovarian carcinomas following surgery. Clinically, PTX is used in combination with other drugs such as lapatinib (LAP) to increase treatment efficacy. Delivering drug combinations with nanoparticles has the potential to improve chemotherapy outcomes. In this study, we use Flash NanoPrecipitation, a rapid, scalable process to encapsulate weakly hydrophobic drugs (logP in vitro. Encapsulating either PTX or LAP into nanoparticles increases drug potency. When PTX and LAP are co-loaded in the same nanoparticle, they have a synergistic effect that is greater than …

On-Demand Electrically Induced Decomposition Of Thin-Film Nitrocellulose Membranes For Wearable Or Implantable Biosensor Systems, Benjamin M. Horstmann

Theses and Dissertations

Implantable or subcutaneous biosensors used for continuous health monitoring have a limited functional lifetime requiring frequent replacement and therefore may be highly discomforting to the patient and become costly. One possible solution to this problem is use of biosensor arrays where each individual reserve sensor can be activated on-demand when the previous one becomes inoperative due to biofouling or enzyme degradation. Each reserve biosensor in the array is housed in an individual Polydimethylsiloxane (PDMS) well and is protected from exposure to bodily fluids such as interstitial fluid ( ISF) by a thin-film nitrocellulose membrane. Controlled activation is achieved by decomposing …

Quantification And Modeling Of Bladder Biomechanics Mechanisms Linking Spontaneous Rhythmic Contractions And Dynamic Elasticity To Detrusor Overactivity, Zachary E. Cullingsworth

Theses and Dissertations

Overactive bladder (OAB) is a chronic condition affecting approximately 20% of adults in the United States. Detrusor overactivity (DO) is the presence of non-voiding contractions in the detrusor (bladder) muscle during filling and is present in some individuals with OAB. DO is currently identified visually during a urodynamics (UD) study involving pressure catheters and filling and voiding of the bladder to evaluate function. UD provides limited subtyping of DO, and an incomplete understanding of mechanisms contributing to OAB.

Aim 1 of this study was to develop objective tools to quantify, subgroup and better understand …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

Extracellular Matrix Nanoparticles Effects On The Lung In Vivo, Brittaney E. Ritchie

Theses and Dissertations

Acute respiratory distress syndrome (ARDS) is a life-threatening condition that causes diffuse alveolar damage and a loss of the extracellular matrix (ECM). This leads to pulmonary edema and lung function deterioration. Our lab has created decellularized porcine lung, electrosprayed ECM nanoparticles that have been previously shown to have pro-regenerative capabilities in vitro.

In this study, the ECM nanoparticle effects on young murine lungs were tested in vivo. An ECM nanoparticle suspension, previously used for the in vitro studies, was aerosolized intratracheally into the lungs using a microsprayer. 24 hours later, the lung mechanics, bronchoalveolar lavage fluid, and histology …

Development Of A Torque-Based Device For The Quantification Of Arm Rigidity In Patients With Parkinson’S Disease, Georgina O. Miller

Theses and Dissertations

Parkinsonian rigidity is caused by the inability of the muscles to relax and extend properly, due to reduced dopamine levels and often begins on one side of the body before spreading contralaterally. The current standard for determining joint rigidity in a clinical setting is a test completed by the clinician based on the feel of the relaxed wrist and elbow joints as they are passively flexed and extended and a series of ordinal rating scales, the Movement Disorder Society’s – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Hoehn and Yahr Scale (H&Y), and Parkinson’s Disease Questionnaire-39 (PDQ-39). These methods are used …

The Effect Of Intermittent Theta Burst Stimulation On Biceps Corticomotor Excitability In Non-Impaired Individuals And Individuals With Tetraplegia, Blaize Majdic

Theses and Dissertations

Neuromodulation of the primary motor cortex (M1) in pair with physical therapy may be a promising method for improving motor outcomes after spinal cord injury (SCI). Increased excitability of the corticospinal motor pathways (i.e. corticomotor excitability) has shown to be associated with improved motor learning and skill acquisition. Intermittent theta burst stimulation (iTBS) is a form of non-invasive brain stimulation which can increase corticomotor excitability, as measured by an increase in the amplitude of motor evoked potentials (MEPs). However, the ability for iTBS to increase the corticomotor excitability of proximal muscles such as the biceps, and muscles affected by spinal …

Predicting Tgf-Β-Induced Epithelial-Mesenchymal Transition Using Data Assimilation, Mario J. Mendez, Matthew J. Hoffman, Elizabeth M. Cherry, Dr. Christopher Lemmon, Seth Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.

Age Dependent Regulation Of Cardiac Sodium Channel Gain Of Function, Madison Nowak, David Ryan King, Steven Poelzing, Seth Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.

Immunofluorescence Image Feature Analysis And Clustering Pipeline For Distinguishing Epithelial-Mesenchymal Transition, Shreyas Hirway, Nadiah Hassan, Dr. Christopher Lemmon, Dr. Seth Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.

Coupled Influence Of Heart Rate Variability And Subcellular Calcium Heterogeneity On Cardiac Electromechanical Dynamics, Vrishti M. Phadumdeo, Seth H. Weinberg Ph.D

Biology and Medicine Through Mathematics Conference

No abstract provided.

Designing Biomimetic Implant Surfaces To Promote Osseointegration Under Osteoporotic Conditions By Revitalizing Mechanisms Coupling Bone Resorption To Formation, Ethan M. Lotz

Theses and Dissertations

In cases of compromised bone remodeling like osteoporosis, insufficient osseointegration occurs and results in implant failure. Implant retention relies on proper secondary fixation, which is developed during bone remodeling. This process is disrupted in metastatic bone diseases like osteoporosis. Osteoporosis is characterized low bone mass and bone strength resulting from either accelerated osteoclast-mediated bone resorption or impaired osteoblast-mediated bone formation. These two processes are not independent phenomena. In fact, osteoporosis can be viewed as a breakdown of the cellular communication connecting bone resorption to bone formation. Because bone remodeling occurs at temporally generated specific anatomical sites and at different times, …

The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell

Theses and Dissertations

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition (EMT) …

Design And Testing Of An Agonist-Antagonist Position-Impedance Controlled Myoelectric Prosthesis, Christopher Aymonin

Theses and Dissertations

Intuitive prosthetic control is limited by the inability to easily convey intention and perceive physical requirements of the task. Rather than providing haptic feedback and allowing users to consciously control every component of manipulation, relegating some aspects of control to the device may simplify operation. This study focuses on the development and testing of a control scheme able to identify object stiffness and regulate impedance. The system includes an algorithm to detect the apparent stiffness of an object, a proportional nonlinear EMG control algorithm for interpreting a user’s desired grasp aperture, and an antagonistically acting impedance controller. Performance of a …

Development Of An Eye Movement Based Predictive Model For Discrimination Of Parkinson's Disease From Other Parkinsonisms And Controls, Mary Anisa Kannan

Theses and Dissertations

Purpose: Due to the neurological aspects of Parkinson’s Disease (PD) and the sensitivity of eye movements to neurological issues, eye tracking has the potential to be an objective biomarker with higher accuracy in diagnosis than current clinical standards. Currently when PD is diagnosed clinically, there is an accuracy of 74% when diagnosed by a general practitioner and 82% when diagnosed by a movement disorder specialist. This study was designed to: 1. Assess eye movements as a potential biomarker for Parkinson’s Disease. 2. Determine if eye movements can distinguish between Parkinson’s Disease and commonly confounded movement disorders with parkinsonian symptoms. 3. …

A Computational Assessment Of Lisfranc Injuries And Their Surgical Repairs, Michael Perez

Theses and Dissertations

While Lisfranc injuries in the mid foot are less common than other ankle and mid foot injuries, they pose challenges in both properly identifying them and treating them. When Lisfranc injuries are ligamentous and do not include obvious fractures, they are very challenging for clinicians to identify unless weight bearing radiographs are used. The result is that 20%-40% of Lisfranc injuries are missed in the initial evaluation. Even when injuries are correctly identified the outcomes of surgical procedures remain poor. Existing literature has compared the different surgical procedures but has not had a standard approach or procedures across studies. This …

Assessment Of Access Methods For Mobile Maps For Individuals Who Are Blind Or Visually Impaired, David Parker

Theses and Dissertations

When people go to a mall, museums, or other such locations they tend to rely on maps to find their way around. However, for people who are blind or visually impaired (BVI) maps are not easily accessible and they depend on other means, such as a guide, to get around. Research has only just begun to investigate providing maps for people who are BVI on touch screen devices. Many different types of feedback have been used: audio (sound), tactile (touch), audio-tactile, and multitouch. Some research has been conducted on the benefit of using multiple fingers (multitouch) and has found conflicting …

Cell Type And Substrate Dependence Of Fibronectin Properties And Mechanotransduction, Navpreet S. Saini

Theses and Dissertations

Fibronectin is an important protein that is able to bind to other fibronectin molecules and to cell surface receptors. In doing so, the interactions fibronectin can perform is important for the processes of cell migration and tissue formation. Understanding the properties of fibronectin and fibril assembly is useful for areas such as wound healing, where fibronectin molecules are assembled to protect the tissue and to perform other tasks. Because of these reasons, it is important to understand how fibronectin is assembled and how its properties affect the fibril assembly, which in return affects the way the cell matrix operates. Previously …

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D₃ levels have better prognoses than patients with low serum vitamin D_3. However, double-blind clinical trials on the efficacy of vitamin D₃ supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D₃ supplements who had ‘estrogen receptor positive’ …

Mechanochemical Regulation Of Epithelial Tissue Remodeling: A Multiscale Computational Model Of The Epithelial-Mesenchymal Transition Program, Lewis Scott

Theses and Dissertations

Epithelial-mesenchymal transition (EMT) regulates the cellular processes of migration, growth, and proliferation - as well as the collective cellular process of tissue remodeling - in response to mechanical and chemical stimuli in the cellular microenvironment. Cells of the epithelium form cell-cell junctions with adjacent cells to function as a barrier between the body and its environment. By distributing localized stress throughout the tissue, this mechanical coupling between cells maintains tensional homeostasis in epithelial tissue structures and provides positional information for regulating cellular processes. Whereas in vitro and in vivo models fail to capture the complex interconnectedness of EMT-associated signaling networks, …

Engineering The Alveolar Gas Exchange Barrier With Extracellular Matrix Coatings For Bioengineered Lungs, Bethany M. Young

Theses and Dissertations

Lower respiratory diseases are currently the third leading cause of death worldwide. For many end-stage patients with these diseases, there is no cure and a shortage of donor organs available for transplant. A promising solution is to design regenerative scaffolds or complete bioengineered lungs, using decellularized lung tissues as a template for regeneration. Recent advances in the field have made significant strides towards developing a transplantable lung. However, the current technology has not produced a functional lung for in vivo transplant due to immature gas exchange barriers. The mechanisms driving alveolar barrier maturation and role that extracellular matrix (ECM) plays …

The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link

Theses and Dissertations

Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …

Regulation Of Cellular Patterning Through The Extracellular Matrix, Lewis Scott, Lauren Griggs, Vani Narayanan, Daniel Conway Phd, Seth H. Weinberg Phd, Christopher Lemmon Phd

Biology and Medicine Through Mathematics Conference

No abstract provided.

Intercellular Sodium Nanodomain Signaling Regulates Repolarization In Cardiac Tissue, Madison Nowak, Seth Weinberg Ph.D.

Biology and Medicine Through Mathematics Conference

No abstract provided.

Chemotherapeutic Drug Cytotoxicity Measurement With A 3d Biomimetic Microfluidic Device And Computational Fluid Dynamics Model, Maryam Moarefian, Caroline Jones, Luke Achenie, Danesh Tafti

Biology and Medicine Through Mathematics Conference

No abstract provided.

Investigating Smoke Exposure And Chronic Obstructive Pulmonary Disease (Copd) With A Calibrated Agent Based Model (Abm) Of In Vitro Fibroblast Wound Healing., J Alex Ratti, Angela Reynolds, Rebecca L. Heise

Biology and Medicine Through Mathematics Conference

No abstract provided.