Biomedical Engineering and Bioengineering Commons^™

Engineering The Development Of Neuromuscular Circuitry On-Chip, Inès Khiyara

Electronic Theses and Dissertations

Neuromuscular development happens in a complex interconnected network of biochemical pathways. This complicated embryonic development follows a strong, functional, and precise neuromuscular network that has interested both scientists and engineers who seek to better understand neuromuscular diseases. These disorders can be inherited or acquired, and their severity and mortality can vary. Researchers first studied the neuromuscular network from an organismal perspective, and more recently from an embryological, cellular, molecular, biochemical, and genetic perspective. From these studies, the fundamental principles of motor neuron pathfinding to muscles are widely understood, but the molecular drivers of specific nerve-muscle pairing remain unknown. Although in …

Development Of A Crosslinked Osteochondral Xenograft And A Collagen Stabilizing Intra-Articular Injection To Remediate Cartilage Focal Lesions To Prevent Osteoarthritis, Mark Lewis Mosher

Theses and Dissertations

Osteoarthritis is one of the most common causes of disability in adults in America. It is a progressive and degenerative disease where the articular cartilage is broken down and lost from the surfaces of bones causing chronic pain and swelling in the joints, and currently has no cure. The most commonly osteoarthritis starts from a focal lesion on the cartilage surface, which will expand on the surface and downwards through the thickness of the tissue. The current gold standard for correcting cartilage focal lesions is the osteochondral autograft/allograft transplantation (OAT), which replaces the defect with a fresh osteochondral graft. The …

In Vitro Bioreactor For Mechanical Control And Characterization Of Tissue Constructs, Samuel Coeyman

All Dissertations

Heart failure (HF) currently affects over 6 million Americans, 50% of whom die within 5 years of their initial diagnosis. A major contributor to the onset of HF is cardiac fibrosis in the myocardium, which arises when fibroblasts (FBs) are activated in response to heightened mechanical stress from overload conditions like hypertension. Activated FBs remodel the extracellular matrix (ECM) and secrete ECM proteins including collagen. FB remodeling has been studied in the past by applying forces and/or deformations to three-dimensional, cell-seeded gels and tissue constructs in vitro. Unfortunately, previous stretching platforms have traditionally not enabled mechanical property assessment to be …

Development Of A Tissue Engineered Cardiac Patch, Howard Herbert

All Dissertations

Cardiovascular Disease(CVD) is the leading cause of mortality in the developed world. CVD is most commonly manifested as atherosclerosis of the coronary arteries leading to Myocardial Infarction(MI). After MI, fibrosis of the ventricular wall leads to heart failure(HF), a pandemic affecting 26 million people globally. While therapies are continuously developed to combat HF, the treatment of choice, whole heart transplant, is limited by the availability of donor hearts. It is clear that there is a need to develop a long-term solution to combat HF and its enormous economic burden. Tissue Engineering and Regenerative Medicine holds promise as a possible solution …

Enhancing Human Schwann Cells Reparative Behavior Using Heparin/Collagen Layer-By-Layer Coatings, Luis Carlos Pinzon-Herrera

Graduate Theses and Dissertations

When a peripheral nerve injury (PNI) occurs, the gold standard for tissue regeneration is the use of autografts. However, due to the secondary effects produced by multiple surgeries involved in the removal and implantation of autografts for very small lesions, it is possible to replace them with the use of Nerve Guide Conduits (NGCs). However, NGCs are limited to short lesions (less than 1 cm). This limitation is caused by the absence of compounds in the extracellular matrix (ECM) that autografts can provide. Since much of the regenerative process takes place on the NGC surface, our work aims to modify …

Evaluation Of Cellulose Nanocrystal Inks And Their Structural Characteristics For 3d Bioprinting Of Customized Scaffolds, Patrick William Kuczwara

Graduate Theses and Dissertations

3D bioprinting of biological scaffolds requires control of the physicochemical properties of each unique structures. A promising material for control of properties is hydrogels, which can help create biomimetic scaffolds with controlled spatial arrangement of materials by integrating biological materials directly into layers during the bioprinting process. Nanocellulose offers a unique combination of properties including mechanical, biomimetic, and biocompatibility. These properties offer flexibility over the types, shapes, and applications of their printed hydrogel scaffolds, (i.e., tissue, drug, encapsulation). However, 3D bioprinting of nanocellulose-based hydrogels requires high loading percentages (i.e., >10 wt%) or chemical crosslinkers (i.e., bis(acyl)phosphane oxides (BAPO)). High solid …

Engineer And Test A Biodegradable Microneedle Patch To Deliver Meloxicam For Managing Pain In Cattle, Katherine Alejandra Miranda Munoz

Graduate Theses and Dissertations

Microneedle patches are a promising source for transdermal diffusion of macromolecules and are designed to painlessly penetrate the skin. In this study, a biodegradable chitosan microneedle patch to deliver meloxicam for managing pain in cattle was tested. The potential of reuse of the polymeric solution to fabricate the patches, optimization of fabrication, morphological analysis of the microneedle patch and analysis of preservation of the chemical composition after sterilization were evaluated. In-vitro analysis consisted of studying in-vitro penetration mechanical properties, compression testing analysis of microneedle patch, and in-vitro drug release analysis. In-vivo studies were performed to analyze the dissolution capability of …

Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson

Electronic Theses and Dissertations

Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …

Investigating Spatial Heterogeneity In Myocardial Wound Environments To Improve Therapy, Michael Potter

All Dissertations

Heart failure is a broad pathology manifestation categorized by an inability of the heart to successfully pump blood throughout the vast vessel network of the body. Within the United States, heart failure is projected to increase by approximately 46% from 2012 to 2030. Modalities of heart failure are generally related to wall mechanics that are impacted following myocardial infarction events. Interplay exists between the wall mechanics, responding cell populations, and the spatial heterogeneities in the resultant scar. This interplay directs the myocardium towards heart failure modalities governed by overly stiff or compliant states. It is essential to elucidate details underlying …

Hypoxic Incubation Chamber, Simone Lisette Helfrich, Makenzie Nicole Jones

Biomedical Engineering: Graduate Reports and Projects

This paper describes the design, manufacturing, and testing of a novel controllable hypoxic incubator with fully functional oxygen gas control and temperature control in a humid environment. On the current market, a majority of the few hypoxic incubators use pre-mixed gas that does not offer precise control over gas concentration. The objective for this project was to create a chamber that allows the user to set the O2 concentration to varying set points of % O2 while maintaining the chamber at a constant body temperature, CO2 level, humidity, and sterility. To start the project, multiple concepts were developed for the …

Hypoxic Incubation Chamber, Simone Lisette Helfrich, Makenzie Nicole Jones

Master's Theses

This paper describes the design, manufacturing, and testing of a novel controllable hypoxic incubator with fully functional oxygen gas control and temperature control in a humid environment. On the current market, a majority of the few hypoxic incubators use pre-mixed gas that does not offer precise control over gas concentration. The objective for this project was to create a chamber that allows the user to set the O2 concentration to varying set points of % O2 while maintaining the chamber at a constant body temperature, CO2 level, humidity, and sterility. To start the project, multiple concepts were developed for the …

Conducting Polypyrrole Hydrogel Biomaterials For Drug Delivery And Cartilage Tissue Regeneration, Iryna Liubchak

Electronic Thesis and Dissertation Repository

Articular cartilage tissue has limited capacity for self-regeneration leading to challenges in the treatment of joint injuries and diseases such as osteoarthritis. The tissue engineering approach combines biomaterials, cells and bioactive molecules to provide a long-term and stable cartilage repair. In the following work, electroactive polymer polypyrrole~(PPy) was incorporated into the synthetic hydrogel to enhance the mechanical properties of the material for cartilage applications. PPy was loaded with drug compound and the \emph{on demand} drug release was demonstrated. The composite PPy hydrogel was 3D printed using stereolithography to create a porous tissue engineering scaffold. Biocompatibility and cell adhesion to the …

Cellular Bioenergetics: Experimental Evidence For Alcohol-Induced Adaptations, Liz Simon, Patricia E. Molina

School of Medicine Faculty Publications

At-risk alcohol use is associated with multisystemic effects and end-organ injury, and significantly contributes to global health burden. Several alcohol-mediated mechanisms have been identified, with bioenergetic maladaptation gaining credence as an underlying pathophysiological mechanism contributing to cellular injury. This evidence-based review focuses on the current knowledge of alcohol-induced bioenergetic adaptations in metabolically active tissues: liver, cardiac and skeletal muscle, pancreas, and brain. Alcohol metabolism itself significantly interferes with bioenergetic pathways in tissues, particularly the liver. Alcohol decreases states of respiration in the electron transport chain, and activity and expression of respiratory complexes, with a net effect to decrease ATP content. …

Labeling Melanoma Cells With Black Microspheres For Improved Sensitivity In Detection Via Photoacoustic Flow Cytometry, Tori Kocsis

Electronic Theses and Dissertations

Melanoma is an aggressive form of skin cancer known for developing into metastatic disease. Current clinical diagnostics, including medical imaging and tissue biopsy, provide a poor prognosis since the cancer is in the late stages of disease progression. In recent years, photoacoustic flow cytometry has allowed for the detection of circulating melanoma cells within patient blood samples in vitro. Although this method exploits the naturally-produced melanin within the cells, it has only successfully detected highly-pigmented melanoma cell lines. Since various forms of melanoma exist, each with varying melanin concentrations, this research aims to provide a novel method for detecting lightly-pigmented …

Mitral Valve Tissue Engineering - A Dynamic Model For Investigating The Mechanism Of Valvular Pathology, Collin Owens

All Dissertations

Heart valve disease affects an average of 2.5% of the population in the United States. The mitral valve (MV) is the most complex of the heart’s four valves and is most associated with the disease by exhibiting altered extracellular matrix (ECM) which translates into stenosis or regurgitation. These diseases are typically degenerative in nature and can be accelerated by risk factors such as diabetes and hypertension. With diabetes and hypertension affecting 425 million and 1.39 billion people worldwide, further investigation into these risk factors is warranted. This study aims to develop and test an in vitro model of MV disease. …

A 3d Tissue Engineering Model To Study Mitral Valve Annulus Calcification Under Diabetic Conditions, Erin James

All Theses

The most complex heart valve is the mitral valve (MV). Many pathologies can affect the MV, including stenosis, regurgitation, prolapse, and mitral annulus calcification (MAC). MAC is chronic degeneration of the annulus, which is the fibrous, saddle-shaped “ring” that can contract and relax with the myocardium. The prevalence of MAC is around 15% but increases in patients with other cardiovascular diseases and risk factors. It is also thought to increase in patients with type 2 diabetes, but MAC has not been properly characterized within this population because of confounding factors such as cardiac disease and kidney disease. The goal of …

Engineering Of Ideal Systems For The Study And Direction Of Stem Cell Asymmetrical Division And Fate Determination, Martina Zamponi

Biomedical Engineering Theses & Dissertations

The cellular microenvironment varies significantly across tissues, and it is constituted by both resident cells and the macromolecules they are exposed to. Cues that the cells receive from the microenvironment, as well as the signaling transmitted to it, affect their physiology and behavior. This notion is valid in the context of stem cells, which are susceptible to biochemical and biomechanical signaling exchanged with the microenvironment, and which plays a fundamental role in establishing fate determination and cell differentiation events. The definition of the molecular mechanisms that drive stem cell asymmetrical division, and how these are modulated by microenvironmental signaling, is …

Optimizing Crispr/Cas9-Mediated Knockdown Of Angptl3 In Liver Cell Lines And Mouse Hepatocytes, Meredith Reeves

All Theses

Familial hypercholesterolemia (FH) is a genetic condition characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) that leads to an increased risk of developing cardiac disease early in life (Shah et al., 2020). Current treatments such as statins and PCSK9 inhibitors have helped lower LDL-C levels, however they require repeated administration every 4-6 weeks to remain effective (Raal et al., 2018). Angiopoietin-like 3 (ANGPTL3) is an inhibitor of plasma lipid metabolism that has become a promising molecular target for the treatment of FH. Individuals with non-functional copies of ANGPTL3 demonstrate low levels of plasma LDL-C and triglycerides, indicating a protective …

Functional Requirements For A Samd14-Capping Protein Complex In Stress Erythropoiesis, Suhita Ray, Linda Chee, Yichao Zhou, Meg A. Schaefer, Michael J. Naldrett, Sophie Alvarez, Nicholas T. Woods, Kyle J. Hewitt

Nebraska Center for Biotechnology: Faculty and Staff Publications

Acute anemia induces rapid expansion of erythroid precursors and accelerated differentiation to replenish erythrocytes. Paracrine signals—involving cooperation between stem cell factor (SCF)/Kit signaling and other signaling inputs—are required for the increased erythroid precursor activity in anemia. Our prior work revealed that the sterile alpha motif (SAM) domain 14 (Samd14) gene increases the regenerative capacity of the erythroid system in a mouse genetic model and promotes stress-dependent Kit signaling. However, the mechanism underlying Samd14’s role in stress erythropoiesis is unknown. We identified a protein-protein interaction between Samd14 and the α- and β-heterodimers of the F-actin capping protein (CP) complex. Knockdown of …

Development Of In Vitro Bone Organoid Models For The Recapitulation Of Bone Complexity, Yongkuk Park

Doctoral Dissertations

Osteoporosis is the most common skeletal disorder that thins and weakens the bones, yet the detailed mechanisms remain poorly understood and limited therapeutic options are available. This can be attributed to the lack of relevant experimental models that can recapitulate the bone complexity and bone remodeling. Mouse models have identified many critical genes and molecules regulating bone metabolism but are limited to studying detailed cellular and molecular processes due to anatomical inaccessibility and restricted ability to manipulate bone structure. Considerable efforts have been made to generate physiologically relevant models by using synthetic and biomaterial-based 3D scaffolds. However, there are no …

The Influence Of Flow Mechanotransduction On Endothelial Cells In The Lymphatic Valve Sinus, Joshua Daniel Hall

Doctoral Dissertations

Fluid flow in the cardiovascular and lymphatic systems influences the phenotype of endothelial cells that line the interior to the vessel via mechanotransduction. Geometric features in a vessel such as curvature, bifurcation, and valves promote heterogeneous fluid flow profiles, inducing a heterogeneous endothelial phenotype within a vessel region. Certain flow conditions are associated with vascular dysfunction, and diseases such as atherosclerosis preferentially develop in areas of flow disturbance. Lymphatic vessels are highly analogous to blood vessels, although lymphatic flow characteristics and its effect on lymphatic endothelial cells (LECs) via mechanotransduction have been comparatively less examined. The most significant geometric features …

A Novel Electroconductive Nanofibrous Scaffold For Bone Regeneration, Mitchell Kenter

Medical Engineering Theses

The goal of this study was to develop a biodegradable and conductive scaffold to mimic the piezoelectric properties of bone and the architecture of the extracellular matrix. Poly(3,4- ethylenedioxythiophene) (PEDOT) is a conductive polymer of great interest in tissue engineering due to excellent electrical stability and biocompatibility. To enhance its conductivity, dopants such as dimethyl sulfoxide (DMSO) can be added. Engineered graphene oxide (GO) can also be introduced as oxidant to enhance conductivity and mechanical properties. PEDOT nanocomposites were synthesized by oxidative polymerization of 3, 4-Etylenedioxythiophene monomer (EDOT) in the presence of GO, DMSO, ferric chloride and various solvents. The …

Investigating The Effect Of Dissolved Oxygen-Assisted Corneal Cross-Linking (Cxl) On Porcine Corneas, Julianni Dar

Electronic Theses and Dissertations

Corneal cross-linking is a clinical procedure that is known to stop the progression of keratoconus, an eye disease that affects the cornea’s structure, ultimately leading to vision loss in its advanced stages. The typical treatment plan includes riboflavin and UV-A exposure in the hope to increase the mechanical properties of the cornea. There are two types of CXL pathways, with Type-II CXL requiring oxygen. Naturally, the dissolved oxygen is limited in the cornea; therefore, limiting the effect of Type-II CXL. This study proposes to improve the Type-II CXL contribution by integrating dissolved oxygen during the standard CXL treatment used in …

A Microfluidic Assay For Single Cell Bacterial Adhesion Studies Under Shear Stress, Amanda Trusiak

Electronic Theses and Dissertations

The study of bacterial adhesion to host cells is important in understanding bacterial pathogenesis and developing new therapeutic approaches. Here, we studied bacterial adhesion under shear stress using a novel microfluidic method. Specifically, the adhesion of a uropathogenic E. coli strain (FimHOn, ATCC 700928/CFT073) to mannose-modified substrates was studied under flow conditions. The FimHOn E. coli strain expresses FimH which is a mannose-specific adhesin found on the fimbriae that binds to glycoproteins on the epithelium. We developed a microfluidic method that mimics bacterial adhesion to urothelial cells. First, the microfluidic channels were modified by sequentially adsorbing BSA-mannose and BSA onto …

Designing A Self-Regulating And Portable Heating Device For A Microfluidic Based Biosensor, Riya Mahajan

Discovery Undergraduate Interdisciplinary Research Internship

Paper-based biosensors are powerful microfluidic analytical devices that are potentially useful for a wide range of applications, ranging from medical diagnostics to agricultural and environmental monitoring. Molecular diagnostics have limitations because they need to send samples back to a centralized laboratory, which increases the cost and turnaround time of the test. This project aims to create a simple-to-use, low-cost, and portable heating system that would facilitate the creation of a field-deployable paper-based analytical device that can incubate the sample at elevated temperatures for conducting isothermal molecular assays. Our design aims to miniaturize a commercial water bath and will be fabricated …

Interactions Between Soft Nanoparticles And Mammalian Cells, Mitchell Raith

Doctoral Dissertations

Nanoparticles have been of interest to the pharmaceutical industry since the 1980s. The first FDA approved nanoparticle-based therapies included liposomal anesthesia agents. Since then, the amount of FDA-approved nanoparticle therapies remains low. This is because nanoparticle-patient interactions can be very complex and are not well understood. Complicating factors also include increasing obesity rates among the patient population and many small animal pre-clinical trials are completed with healthy, lean animals. The biochemical differences between lean and obese patients prevents early studies from accurately predicting nanoparticle clinical behaviors. Many nanoparticles fail in trails. In this thesis, I aimed to uncover how nanoparticles …

Characterization Of Fundamental Parameters That Modulate Acoustofluidic-Mediated Molecular Delivery To Cells., Connor Sterling Centner

Electronic Theses and Dissertations

Cell-based therapies represent the latest biotechnological revolution in medicine, but significant limitations exist in non-viral intracellular delivery techniques during manufacturing of cell therapies. To address these limitations, a novel acoustofluidic device was developed to deliver ultrasound waves into a flow chamber for rapid molecular delivery to human cells. Our acoustofluidic device delivers biomolecules by inducing expansion and collapse of exogenous gas-filled microbubbles (“cavitation”), which enhances molecular delivery to nearby cells. Experimental studies were conducted to characterize key parameters that influence acoustofluidic-mediated molecular delivery to human cells. A clinical ultrasound transducer was generally utilized with varying cationic microbubble concentrations. Intracellular delivery …

Erythrocyte Deformability In Response To Glucose Using Liquid Crystals, Jayden Goff

Biomedical Engineering Undergraduate Honors Theses

The worldwide prevalence of diabetes mellitus is rapidly increasing with about 9.3% of the adult population living with the disease. People with diabetes have trouble regulating their blood glucose levels which typically leads to hyperglycemia. Under normal physiological conditions, erythrocytes can undergo deformations in response to shear stress when passing through capillaries with a smaller diameter. Poorly managed hyperglycemia can lead to the glycosylation of erythrocyte membrane proteins and hemoglobin. This glycosylation leads to increased rigidity of the cells along with decreased deformability in response to mechanical stress; therefore, these cells have a higher susceptibility of getting stuck in the …

The Influence Of Mmp14 On Angiogenesis In Chemotherapy-Treated Tumors, Abdussaboor Muhammad

Biomedical Engineering Undergraduate Honors Theses

Colorectal cancer is the third most common cancer in the world, and it is the fourth most common cause of cancer related death (1). There have been many significant advancements regarding the treatment of cancer which aim to shrink the size of tumors in patients. However, there is still more that needs to be understood about the many different factors that play a role in colorectal cancer development.

Angiogenesis is the process of forming new blood vessels from existing ones and it requires breaking down and remodeling of the extracellular matrix (ECM) in order to allow endothelial cells to migrate …

Design Of A Four Channel Pulsatile Perfusion Bioreactor For Ex-Vivo Study Of Vascular Grafts, Thomas M. Fair

All Theses

Cardiovascular diseases are the leading cause of death in the United States. Atherosclerosis in peripheral arteries is a major contributing factor. Autologous saphenous vein grafts are the most common bypass grafts for treating peripheral artery diseases. A quarter of these grafts fail within a year, and around half have failed within 10 years of the initial surgery. Graft failure is attributed to the development of intimal hyperplasia indicated by the migration and proliferation of vascular smooth muscle cells, fibroblasts, and the deposition of extracellular proteins.

Increases in flow, pressure, the pulse frequency, and the differential of pressure that model an …