Biomedical Engineering and Bioengineering Commons^™

Injectable Immunomodulatory Strategies To Enhance Muscle Recovery Following Injury, Tai Huu Huynh

Graduate Theses and Dissertations

Although skeletal muscle displays an astonishing regenerative capacity, injuries or diseases that resulted in bedridden or chronic muscle wasting can overwhelm this intrinsic feature of skeletal muscle and lead to functional deficit (range of motion and/or strength) and overall reduction in quality of life. Microenvironmental cues within injured skeletal muscle dictate regenerative and repair process which are tightly coordinated interplay among resident cells, cells recruitment and immune response following an assault in the muscle extracellular matrix (ECM). The successful regeneration of functional tissues requires both appropriate modulation of the inflammatory response, and activation of a variety of cell populations. Biomaterials …

Bio-Methane Production From Anaerobic Co-Digestion Of Poultry Litter With Wheat Straw Improved By Process Optimization And Employment Of Advanced Techniques, Yuanhang Zhan

Graduate Theses and Dissertations

Anaerobic co-digestion (Co-AD) of poultry litter (PL) and wheat straw (WS) for sustainable waste management and simultaneously renewable bioenergy generation was improved by advanced technologies including micro-aeration (MA), biochar addition (BC), nanoparticles supplementation (NP) and their integrations. Response surface methodology (RSM) and artificial neural network (ANN) were used for the process modeling and optimization. First, a method by gradually increasing OLR was developed for the start-up of Co-AD of PL and WS in an anaerobic sequencing batch reactor (ASBR), with a continuous daily biogas production of (13.06 ± 0.21) L and methane content (MC) of (54.38 ± 0.53) % observed. …

Mitochondrial Transfer From Cancer-Associated Fibroblasts Increases Migration In Aggressive Breast Cancer, Kevin F. Gwolas, Sarah Libring, Emily Berestesky, Shayan Gholizadeh, Samantha C. Schwager, Andra R. Frost, Thomas R. Gaborski, Jian Zhang, Cynthia A. Reinhart-King

Biomedical Engineering Faculty Publications and Presentations

Cancer-associated fibroblasts (CAFs) have distinct roles within the tumor microenvironment, which can impact the mode and efficacy of tumor cell migration. CAFs are known to increase invasion of less-aggressive breast cancer cells through matrix remodeling and leader–follower dynamics. Here, we demonstrate that CAFs communicate with breast cancer cells through the formation of contact-dependent tunneling nanotubes (TNTs), which allow for the exchange of cargo between cell types. CAF mitochondria are an integral cargo component and are sufficient to increase the 3D migration of cancer cells. This cargo transfer results in an increase in mitochondrial ATP production in cancer cells, whereas it …

Co-Activation Of The Diaphragm And External Intercostal Muscles Through An Adaptive Closed-Loop Respiratory Pacing Controller, Rabeya Zinnat Adury, Ricardo Siu, Ranu Jung

Biomedical Engineering Faculty Publications and Presentations

Introduction: Respiratory pacing is a promising alternative to traditional mechanical ventilation that has been shown to significantly increase the survival and quality of life after the neural control of the respiratory system has been compromised. However, current pacing approaches to achieve adequate ventilation tend to target only the diaphragm without pacing external intercostal muscles that are also activated during normal inspiration. Furthermore, the pacing paradigms do not allow for intermittent sighing, which carries an important physiological role. We hypothesized that simultaneous activation of the diaphragm and external intercostal muscles would improve the efficiency of respiratory pacing compared to diaphragm stimulation …

Clinical Utility Of Mesenchymal Stem/Stromal Cells In Regenerative Medicine And Cellular Therapy, Vitali V. Maldonado, Neel H. Patel, Emma E. Smith, C. Lowry Barnes, Michael P. Gustafson, Raj R. Rao, Rebekah M. Samsonraj

Biomedical Engineering Faculty Publications and Presentations

Mesenchymal stem/stromal cells (MSCs) have been carefully examined to have tremendous potential in regenerative medicine. With their immunomodulatory and regenerative properties, MSCs have numerous applications within the clinical sector. MSCs have the properties of multilineage differentiation, paracrine signaling, and can be isolated from various tissues, which makes them a key candidate for applications in numerous organ systems. To accentuate the importance of MSC therapy for a range of clinical indications, this review highlights MSC-specific studies on the musculoskeletal, nervous, cardiovascular, and immune systems where most trials are reported. Furthermore, an updated list of the different types of MSCs used in …

Integrated Electrocoagulation, Ultrafiltration, Membrane Distillation, And Crystallization For Treating Produced Water, Mahmood Jebur, Yelyzaveta Bachynska, Xiaolei Hao, Sumith Ranil Wickramasinghe

Chemical Engineering Faculty Publications and Presentations

Produced water (PW) generated from hydraulic fracturing operations was treated using an integrated electrocoagulation, ultrafiltration, membrane distillation, and crystallization process (EC UF MDC). The aim was to determine the viability of this integrated process for maximizing water recovery. The results obtained here indicate that optimizing the various unit operations could lead to increased recovery of PW. Membrane fouling limits all membrane separation processes. A pretreatment step to suppress fouling is essential. Here, removal of total suspended solids (TSS) and total organic carbon (TOC) was achieved by electrocoagulation (EC) followed by ultrafiltration (UF). The hydrophobic membrane used in membrane distillation may …

Investigating The Effect Of Pancreatic Cancer Tumor-Derived Extracellular Vesicles On Schwann Cell Activation, Isabel Powers

Biomedical Engineering Undergraduate Honors Theses

Pancreatic cancer is one of the deadliest diseases because it is hard to identify in its early stages, has high chemoresistance, and early metastasis. Because of these traits, it is often associated with perineural invasion (PNI), where the cancer travels to the nervous system. Schwann cells (SC) are associated with both metastasis and PNI when activated. The purpose of this study was to determine if and how pancreatic tumor-derived extracellular vesicles (TEVs) can activate SC in PNI. This experiment was performed by embedding Schwann cells in a hydrogel to model the tumor microenvironment and treating them with isolated extracellular vesicles …

Investigating The Impact Of International Education On Cultural Understanding, Health Disparities And Collaboration Through Project-Based Learning, Breanna Kilgore

Biomedical Engineering Undergraduate Honors Theses

Global health is an interdisciplinary field emphasizing international health issues, causes, and solutions based on cultural and global understanding. We have all witnessed how crucial global health is with the global COVID-19 crisis that has affected everyone. To effectively work to solve global health issues, people from different backgrounds must work together to complete a common goal. Before problem solving begins, gaining a basic understanding of cultural differences and collaborating with different people is an essential skill to have. Previous studies have demonstrated the usefulness of study abroad experiences and international service-learning opportunities in promoting collaborations, cultural competency and personal …

Optimizing Three-Dimensional Bioengineered Co-Cultures For The Study Of Fibrotic Spinal Cord Injury, Sarah Aly

Biomedical Engineering Undergraduate Honors Theses

Spinal cord injuries (SCIs) have major physical implications on those affected^[1]. There are two main types of scarring that occur after injury; they are known as the glial and fibrotic scar. The injured site causes an altered micro-environment which transforms astrocytes from their normal to reactive state, thus inhibiting axonal regeneration. The effect of reactive astrocytes on fibrotic scarring is not fully understood due to limited study^[2,3]. Using Three-Dimensional (3D) bioengineered co-cultures of astrocytes and neuroblasts the pathological environment can be replicated and manipulated to further the study of fibrotic scarring. Temperature casted co-cultures were successfully …

Exploring The Effects Of Microarchitecture On Astrocyte Behavior And Vascular Remodeling In Spinal Cord Injury, Devin Gerber

Biomedical Engineering Undergraduate Honors Theses

Spinal cord injury (SCI) is a common condition and is characterized by traumatic and progressive damage that results in limited neuron regeneration and thus a restricted recovery. In SCI, the vasculature is also severely damaged, which exacerbates inflammation at the injury site. Specifically, insufficient angiogenesis occurs at the site of injury due to the fibrotic pathological microenvironment1 . SCI also leads to the formation of a fluid-filled cavity and thus gliosis and fibrosis, forming a dense glial and fibrotic scar around the cavity. The microenvironment at the injury site plays a significant role in astrocyte behavior, promoting the transformation of …

A Comparison Of Optical Measurement Methods For The Growth Of S. Cerevisiae, Jackson Black

Chemical Engineering Undergraduate Honors Theses

Genetic engineering of living organisms provides the opportunity to express and harvest different proteins from cell surfaces. Yeast (S. cerevisiae) is one such organism and is capable of being grown on an industrial scale. Cellular concentration is an important parameter to monitor while fermentation processes are underway, in order to control the environment inside the growth medium and maximize yields. Spectrophotometry is a conventional method for measuring concentration, but is limited by a narrow absorbance range, and the need for on-site periodic sampling. A continuous method of measurement, as provided by Bug Labs BE2100 non-invasive biomass monitor, would …

Automated Segmentation Of Autofluorescence Lifetime Images Using A Convolutional Neural Network, Nicole Hooten

Biomedical Engineering Undergraduate Honors Theses

Chronic wounds affect nearly 1 out of every 50 people in the United States, decreasing quality of life and putting people with potential comorbidities at high risk for obtaining an infection. Wound healing progress in clinical settings is measured by tracking wound size and there are currently no non-invasive, quantitative measurement techniques. Previous studies have proposed nicotinamide adenine dinucleotide (NADH) autofluorescence lifetime (FLIM) imaging of the wound edge as a method to quantify the wound healing process by connecting the role of NADH in cellular metabolism to wound healing stage. However, evaluation of FLIM images is heavily subjective, as a …

Preparing Homogenous Composites Of Collagen And Cellulose Nanocrystals For Tissue Engineering Research, Zachary Stanley

Biological and Agricultural Engineering Undergraduate Honors Theses

Advancements in medicine and our understanding of stem cells have led to a greater emphasis on further developing research focused on tissue engineering. This research has led to the rise of both two-dimensional and three-dimensional scaffolds that can be utilized to repair bone, skin, vascular, and potentially even nervous tissue. One of the prominent compounds used in modern scaffolds is collagen-based hydrogels due to their low antigenicity and ability to provide structure to cells. There is potential to further improve upon this three-dimensional scaffold by incorporating cellulose nanocrystals (CNCs) into a composite hydrogel with collagen. The addition would increase the …

Correlation Of Intracellular Metabolites With Optical Metabolic Imaging In Polarized Macrophages As Indicators Of Metabolic Reprogramming, Abby Claire Denison, Shelby Bess

Biomedical Engineering Undergraduate Honors Theses

Macrophages are a type of immune cell that are characterized by their ability to differentiate into various active phenotypes based on environmental stimuli. They can generally be classified as one of two extremes: inflammatory/M1 or wound-healing/M2. Macrophage populations in vivo, however, are rarely homogenous, and since macrophages play vital roles in the immune response, particularly in the context of the tumor microenvironment (TME), it’s important to be able to investigate and understand heterogenous macrophage populations to develop more effective treatments. Recently, autofluorescence imaging such as multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) of metabolic cofactors NADH and FAD have …

Comprehensive Long- And Short- Read Sequencing Approaches To Screen The Mutational Landscape After Therapeutic Crispr-Editing For Duchenne Muscular Dystrophy, Mary Jia, Made Harumi Padmaswari, Landon Burcham, Shilpi Agrawal, Alexis Ivy, Abbey Bryan, Christopher E. Nelson

Biomedical Engineering Undergraduate Honors Theses

Duchenne muscular dystrophy (DMD) is an X-linked muscle wasting disease caused by mutations in the Dmd gene resulting in non-functional dystrophin. Adeno-associated virus (AAV)-mediated delivery of classical CRISPR systems resulting in double-stranded breaks (DSBs) has yielded promise as a curative DMD therapeutic. However, the consequences of AAV-CRISPR require more thorough characterization. PCR-enriched short-read amplicon sequencing at cut sites is the most common method of sequencing CRISPR editing, but PCR bias results in unreliable quantification of on-target edits. We analyze orthogonal long- and short-read sequencing approaches to screen the outcomes of CRISPR technologies at the DNA and RNA-level for DMD. We …

A Wheelchair-Bed Transfer Device For Patients With Limited Mobility, Malachie Nichols

Biomedical Engineering Undergraduate Honors Theses

As the population ages, eldercare becomes more important than ever, yet many caregivers lack the resources they need to safely do their jobs. For those who take care of a disabled loved-one at home or work as home health aides, basic tasks can be frustrating and even dangerous. The high physical demands of moving and lifting patients make injuries common among home health care workers. Musculoskeletal injuries to the back, shoulders, wrists, and hands are especially common. The use of transfer devices such as Hoyer lifts, slide boards, and gait belts help to make moving patients easier and safer, but …

Study Of The Stability Of Heparin/Collagen Layer-By-Layer Coatings, Hector M. Apodaca Reyes

Chemical Engineering Undergraduate Honors Theses

Pairing heparin with collagen-based medical implants has opened a whole new area of research for enhancing the desired effect of current implants. In fact, heparin (HEP) and collagen (COL) layer-by-layer (LbL) coatings have shown impressive results in forming polyelectrolyte multilayers. It has been already seen on skin grafts, nerve guide conduits (NGCs), and drug delivery devices yielding promising results. Due to being a simple, cost-efficient, and versatile option to fabricate thin biomimetic films, this self-assembly technique is one of the most effective methods to immobilize extracellular matrix (collagen and heparin) onto medical devices and implants. Even though previous studies have …

Characterizing And Quantifying Shear-Induced Hemolysis In A Hollow Fiber Membrane System, Siddhi Bhat

Chemical Engineering Undergraduate Honors Theses

Clinical studies have shown that patients undergoing renal replacement therapy are more susceptible to developing hemolysis, or the rupturing of red blood cells. Rapid hemolysis can cause symptoms such as anorexia, vomiting, and even death in severe cases. The aim of this study is to identify how shear stress within a hollow fiber membrane impacts the level of hemolysis that occurs. This allows for the optimization of the ultrafiltration membranes that are typically used for hemofiltration treatments. The variables being studied are the radii of hollow fibers, number of fibers, and volumetric flow rate of blood being circulated. Here, we …

Comparing Firocoxib And Meloxicam In The Application Of Microneedle Patch For Transdermal Drug Delivery, Ruohan Li

Chemical Engineering Undergraduate Honors Theses

This thesis compares the performance of meloxicam and firocoxib in the aspects of its physical characteristic, chemical compositions, and in-vitro performances for transdermal pain management microneedle patches on farm animals. The microneedle patches are composed of polyvinyl alcohol (PVA), type I collagen (COL), and chitosan (CHI) as base material that carries NSAIDs to achieve therapeutic purposes. Scanning electron microscopy (SEM) was utilized to observe the morphological and physical characteristics of the microneedle patches. Both meloxicam and firocoxib microneedle patches were successfully prepared using the methodology, with organized microneedle distribution and sizing. And Fourier transform infrared spectroscopy (FTIR) confirmed the chemical …

Polymeric Biomaterials Approaches For Engineering The In Vitro Cellular Microenvironment For Mscs, Mahsa Letter-Mahsa Haseli

Graduate Theses and Dissertations

Cell therapy is a technology that relies on replacing diseased or dysfunctional cells with healthy functioning ones. One of the cells used for such advanced therapies are stem cells, owing to their ability to differentiate into specific cells required for repairing damaged or defective tissues or cells. The majority of cell-based products are intended to transiently persist in the patient, secreting factors which then allow the patient’s body to heal; in these products, the cells are subsequently eliminated from the body. Furthermore, unique manufacturing platforms, in addition to novel commercialization strategies, will be required to create a successful, sustainable cell …

The Influence Of Pesticides On Us Corn Production Environmental Impact: A Comparative Life Cycle Assessment Of Dominant Production Practices, Kyle Marinoni Lawrence

Graduate Theses and Dissertations

In recent years there has been increasing interest in reducing agricultural environmental footprints in the United States, particularly for commodity crops like corn grain. Pest management is one aspect of agricultural production that is often identified as having potential for improvement with regard to environmental impact, but there is not a robust body of literature to identify the wide-scale influence of pesticides on yield and environmental impact. In this study, we hypothesized that the use of different classifications of pesticides has a significant impact on the overall environmental impact. To test this, agricultural models were created to represent the dominant …

Dpd Guided Insight On The Formation Process Of Polyethersulfone Membranes By Nonsolvent Induced Phase Separation And The Effects Of Additives, Eric Ledieu

Graduate Theses and Dissertations

Dissipative particle dynamics (DPD), a coarse grain simulation method, was applied to the membrane formation process of non-solvent induced phase separation (NIPS) to gain further insight on the mechanism of certain variables and how they affect the final morphology. NIPS involves two solutions, an organic polymer dissolved in an organic solvent colloquially called the dope and an aqueous coagulation bath, brought into contact with one another. The solvents then mix, causing the polymer to fall out of solution as an asymmetric membrane with a dense surface layer and a more open subsurface layer in response to the decreasing solubility. Polyethersulfone …

Effect Of Human Decellularized Skeletal Muscle On Recovery From Volumetric Muscle Loss Injury, Jacob Schluns

Graduate Theses and Dissertations

Volumetric muscle loss (VML) overwhelms muscle’s robust capacity for regeneration. A key event in the etiology of VML injury is the bulk loss of structural cues provided by the underlying extracellular matrix (ECM). While muscle is a highly structured tissue, with cell and ECM alignment in the direction of contractile force production, the impact of scaffold alignment on recovery remains unclear. Bulk human decellularized skeletal muscle (DSM) tissues were sectioned into 10 x 1-2 mm fibers. VML defects were repaired using multi-fiber implants consisting of approximately 8 fibers per defect arranged into two layers. Fibers were oriented 1) to the …

Automation Of Life Cycle Assessment, Jacob Hickman

Graduate Theses and Dissertations

An automation program, named Jacob LCA, was created to help perform life cycle assessment (LCA). The program uses a template file to perform controlled and consistently ordered actions with the LCA program, SimaPro, and effectively removes the need for manual user input. It can be set to run using data from one or more life cycle inventory (LCI) files, which allows for rapid iteration and testing of data. It also partially addresses some of the limitations of LCA by establishing a procedure through which temporal and spatial variations in data can be integrated into LCI files and then passed to …

Mitral Valve Imaging And Biomechanics: A Workflow Towards Computational Modeling And Validation, Sam Stephens

Graduate Theses and Dissertations

The mitral valve serves a critical role in healthy cardiac function by ensuring the unidirectional flow of oxygenated blood from the left atrium into the left ventricle. It experiences the highest pressures found within the heart and its closure is the result of a complex interaction of several different structures that, furthermore, are unique to each individual. Despite the valve’s vital role however, the specific function of these constituent structures is not fully understood. This, confounded by its asymmetric, personalized nature, make surgical interventions for the mitral valve far less effective than for its neighboring aortic valve. Efforts to overcome …

Development Of Medical Device For Volume Status Assessment Using Peripheral Venous Pressure, Audra Beneux

Graduate Theses and Dissertations

The severe side effects of acute dehydration and blood loss may be prevented if assessed and treated quickly. As amplifier technology has improved, small peripheral venous pressure (PVP) signals collected using a transducer on an intravenous catheter can be analyzed to monitor patient volume status. This thesis details the development of an embedded system prototype that quickly and accurately assesses volume status using PVP analysis. The volume prediction algorithm classified 10 seconds of PVP data as “dehydrated” or “resuscitated”. The hardware design consisted of four primary areas: analog signal conditioning, processing, user interaction, and power. After data collection, the signal …

Transcriptome Profiling Of A Synergistic Volumetric Muscle Loss Repair Strategy, Kevin Roberts, John Taehwan Kim, Jacob Schluns, Grady Dunlap, Jamie Hestekin, Jeffery Wolchok

Biomedical Engineering Faculty Publications and Presentations

Volumetric muscle loss overwhelms skeletal muscle’s ordinarily capable regenerative machinery, resulting in severe functional deficits that have defied clinical repair strategies. In this manuscript we pair the early in vivo functional response induced by differing volumetric muscle loss tissue engineering repair strategies that are broadly representative of those explored by the field (scaffold alone, cells alone, or scaffold + cells) to the transcriptomic response induced by each intervention. We demonstrate that an implant strategy comprising allogeneic decellularized skeletal muscle scaffolds seeded with autologous minced muscle cellular paste (scaffold + cells) mediates a pattern of increased expression for several genes known …

A Biochemical Necroptosis Model Explains Cell-Type-Specific Responses To Cell Death Cues, Geena V. Ildefonso, Marie Oliver Metzig, Alexander Hoffmann, Leonard A. Harris, Carlos F. Lopez

Biomedical Engineering Faculty Publications and Presentations

Necroptosis is a form of regulated cell death associated with degenerative disorders, autoimmune and inflammatory diseases, and cancer. To better understand the biochemical mechanisms regulating necroptosis, we constructed a detailed computational model of tumor necrosis factor-induced necroptosis based on known molecular interactions from the literature. Intracellular protein levels, used as model inputs, were quantified using label-free mass spectrometry, and the model was calibrated using Bayesian parameter inference to experimental protein time course data from a well-established necroptosis-executing cell line. The calibrated model reproduced the dynamics of phosphorylated mixed lineage kinase domain-like protein, an established necroptosis reporter. A subsequent dynamical systems …

Early Introduction Of 3d Modeling Modules Promotes The Development Of Simulation Skills In Downstream Biomedical Engineering Curricula, Mary S. Jia, Raj R. Rao, Mostafa Elsaadany

Biomedical Engineering Faculty Publications and Presentations

Background

Recent advancements in additive manufacturing have made 3D design a desirable skill in combating the historically slow development of biomedical products. Due to the broad applicability of additive manufacturing to biomedical engineering, 3D design and 3D printing are attractive educational tools for biomedical engineering students. However, due to the multidisciplinary nature of biomedical engineering, finding a suitable spot in the curriculum to teach students basic and application-based skills for 3D manufacturing is difficult. Furthermore, prior training in fundamental 3D design skills may be needed to support the use of application-based supplementary content.

Results

We designed a SolidWorks Simulations toolkit …

Local Il-10 Delivery Modulates The Immune Response And Enhances Repair Of Volumetric Muscle Loss Muscle Injury, Tai Huynh, Cassandra Reed, Zain Blackwell, Peyton Phelps, Luis Carlos Pinzon-Herrera, Jorge Almodovar, David A. Zaharoff, Jeffery Wolchok

Biomedical Engineering Faculty Publications and Presentations

This study was designed to test the hypothesis that in addition to repairing the architectural and cellular cues via regenerative medicine, the delivery of immune cues (immunotherapy) may be needed to enhance regeneration following volumetric muscle loss (VML) injury. We identified IL-10 signaling as a promising immunotherapeutic target. To explore the impact of targeting IL-10 signaling, tibialis anterior (TA) VML injuries were created and then treated in rats using autologous minced muscle (MM). Animals received either recombinant rat IL-10 or phosphate buffered saline (PBS) controls injections at the site of VML repair beginning 7 days post injury (DPI) and continuing …