Biomedical Engineering and Bioengineering Commons^™

Examining The Effects Of Quercetin On Phenotypic Characteristics Of Human Mesenchymal Stem Cells, Thomas M. Needy

Biomedical Engineering Undergraduate Honors Theses

Introduction A significant obstacle to mesenchymal stem cell (MSC) potency and therapeutic utility is in vitro senescence, an irreversible cessation of replication associated with age-related complications. Senolytic drugs, such as quercetin, may be helpful in selectively culling senescent cells while leaving non-senescent cells unaffected, thereby increasing potency of high-passage MSCs.

Methods The phenotypic, genotypic, and immunomodulatory effects of quercetin were assessed using in vitro models. Senescent cells, created through repeated subculturing of MSCs in vitro, and non-senescent cells were treated with 10 μM quercetin, differentiated into osteocytes, adipocytes, and chondrocytes, and analyzed to observe the effect of quercetin.

Results Quercetin …

Efficacy Of Mitophagy Inhibition As A Potentiating Agent For Conventional Chemotherapy, Morghan Relich, Shelby Bess

Biomedical Engineering Undergraduate Honors Theses

Cancer is a result of uncontrolled growth and reproduction of cells. Damaged or abnormal cells grow and multiply when they should not and in turn the cells continue to proliferate and metastasize. Malignant cells rely on functional mitochondria for proliferation, metastasis, and survival. These mitochondria maintain a functional mitochondrial network through a quality control mechanism called mitophagy. Mitophagy is a conserved intracellular process to maintain quality control and remove damaged mitochondria.

Previous research has been done to examine the effects of mitophagy in tumor cells, as well as the effects of mitophagy inhibition. One focus of current research has been …

Metabolic Responses Of Adipose-Derived Stem Cells In Collagen I Hydrogels, Caroline R. King

Biological Sciences Undergraduate Honors Theses

Peripheral nerve injury affects approximately 44 in 1 million people in the United States every year and can lead to incomplete nerve recovery and loss of motor and sensory function. A significant amount of energy is required for nerve injury repair. A lack of energy allocation to the injury site hinders repair. Current treatments include hollow nerve guidance conduits, decellularized nerve grafts, and autografts. However, they are limited by factors such as donor site morbidity and sustained immunosuppressive treatments. Using three-dimensional collagen I hydrogels laden with adipose-derived stem cells (ASCs) can assist in neural regeneration. Three-dimensional collagen scaffolds aim to …

Gene Mutation And Chemotherapy Response In Azoxymethane Induced Colorectal Tumors, Maya M. Vance

Biomedical Engineering Undergraduate Honors Theses

Colorectal cancer research is a field of increasing importance as disease prevalence continues to increase over time. In looking at the origin of the disease, a driver gene known as p53 is of particular interest for its role in the stimulation of the mutated Wnt pathway. Developing as a missense-type mutation, this gene that ordinarily functions as a tumor suppressor is investigated as a gene of interest for tumor development. In this study, a mouse model was used to examine the development of colorectal cancer with a total of n=34 samples, including n=9 tumors and n=25 colons. The concentration of …

Optimizing The Effects Of Yoda1 And Assessing The Effects Of Mrna Silencing Of Piezo1 Gene In Mesenchymal Stem Cells, Addison R. Mclaughlin

Biomedical Engineering Undergraduate Honors Theses

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that are capable of differentiating into various skeletal tissues, making them promising candidates for regenerative medicine. A critical factor influencing their differentiation potential is mechanosensitivity, the ability to respond to mechanical stimuli. The mechanosensitive calcium ion channel PIEZO1 has emerged as a key regulator in this process, particularly in osteogenic differentiation. This study investigated the role of PIEZO1 in MSC osteogenesis through pharmacological activation using YODA1 and gene silencing via siRNA. Human bone marrow-derived MSCs were cultured and induced for osteogenic differentiation under varying concentrations and durations of YODA1 treatment. Alizarin …

Fabrication And In Vitro Biocompatibility Assessment Of Composite-Coated Magnesium Materials, Bryce Williams

Biomedical Engineering Undergraduate Honors Theses

This study provides a comparative assessment of the corrosion, morphology, and biological properties of four of the most promising coating methods for magnesium in biomedical applications, namely micro-arc oxidation (MAO), graphene oxide (GO)-containing MAO coating, MAO/sol-gel composite coating, and MAO/polycaprolactone (PCL) polymer dip coating approaches. Despite the abundance of research focused on these promising approaches, there is a notable lack of comparative studies evaluating their properties. To this end, the investigated composite coatings are ZK60+MAO, ZK60+MAO/GO, ZK60+MAO/Sol-gel, and ZK60+MAO/PCL composite coating. Several tests were used to assess various properties of the prepared groups such as in vitro corrosion characteristics, surface …

Insert Creation To Mimic Blood Vessels In Gel Phantoms, Courtney Bloom

Biomedical Engineering Undergraduate Honors Theses

Gel phantoms are commonly used in research settings due to their ability to mimic soft tissue. Creating these phantoms usually involves 3D printing an insert, embedding it in gel, and then washing the insert out. Polyvinyl alcohol (PVA) is typically used as the insert material, but it often swells and deforms the gel during the washout process. Aquapour, a water-soluble material, was investigated as a potential replacement for PVA. Unlike PVA, Aquapour comes in a powdered form that can be mixed with water to create a castable slurry. To create molds to cast Aquapour, SolidWorks was used to design two …

Personalized Model Of Cardiac Fibroblast Signaling Using Patient-Specific Data, Elizabeth A. Schuler

Chemical Engineering Undergraduate Honors Theses

Heart disease is the leading cause of death worldwide for both men and women, and cardiac fibroblasts are critical to heart form and function. Essential roles of cardiac fibroblasts include cell-cell communication, cell-cell signaling, and synthesizing and degrading the extracellular matrix (ECM), which controls structural support and tissue repair of the heart. Abnormal fibroblast signaling can lead to negative impacts, including fibrosis, impaired heart function, and inflammation. A computational model of cardiac fibroblast signaling on Netflux and MATLAB software was adapted and utilized to determine the effect of patient-specific levels of cytokines, hormones, growth factors, peptides, and membrane tension on …

Computationally Guided Liquid Crystal-Based Competitive Binding Sensing Platform For Optical Detection Of Spike Protein, Homa Ghaiedi, Shubham Pandey, Sophia Ezendu, Tibor Szilvasi, Karthik Nayani

Chemical Engineering Faculty Publications and Presentations

A liquid crystal (LC)-based sensing platform for the rapid optical detection of SARS-CoV-2 ' s spike protein's receptor binding domain (RBD) domain is introduced. This platform utilizes a thermotropic LC, hosted on metal-cation decorated substrates, onto which the spike protein can competitively bind. Density functional theory (DFT) calculations guide the experiments that reveal a homeotropic-to-planar transition in the LCs upon exposure to SARS-CoV-2 spike-decorated yeast, providing a basis for sensitive virus detection. The sensor's reversibility/specificity is confirmed through antibody-induced orientation recovery of the LCs initial orientation. Strikingly, the sensor can detect approximate to 2000 copies of the spike protein per …

Preclinical Development Of Genome Editing To Treat Duchenne Muscular Dystrophy By Exon Skipping, Made Harumi Padmaswari, Shilpi Agrawal, Christopher E. Nelson

Biomedical Engineering Faculty Publications and Presentations

Duchenne muscular dystrophy (DMD) is caused by loss-of-function mutations to the gene encoding dystrophin. Restoring the reading frame of dystrophin by removing internal out-of-frame exons may address symptoms of DMD. Therefore, the principle of exon skipping has been at the center stage in drug development for Duchenne muscular dystrophy (DMD) over the past two decades. Antisense oligonucleotides (AONs) have proven effective in modulating splicing sites for exon skipping, resulting in the FDA approval of several drugs using this technique in recent years. However, due to the temporary nature of AON, researchers are actively exploring genome editing as a potential long-term, …

In Vitro Investigation Of Macrophage Functional And Metabolic Modulation, Shelby Nicole Bess

Graduate Theses and Dissertations

Macrophages are a subset of immune cells with a variety of functions that are abundant in numerous tumor types such as colorectal and breast cancer. It has been suggested that macrophages may serve an important function as immune mediators in tumor behavior; however, macrophage activity is complex and remains not completely understood. The overall goal of this dissertation was to explore and exploit tumor-associated macrophage phagocytic function and the changes in their interactions with cancer cells in an in vitro mouse model and in 2D and 3D in vitro culture models. First, we wanted to better understand macrophage behavior under …

Using Deep Learning And Two-Photon Excitation Fluorescence Microscopy To Predict Breast Cancer Recurrence And Response To Chemotherapy, Nicholas Powell

Graduate Theses and Dissertations

Accurate prediction of breast cancer recurrence plays a critical role in guiding treatment decisions, particularly regarding the use of systemic therapy for patients. While genomic assays such as the Oncotype DX Recurrence Score offer valuable prognostic information, they are limited in accessibility and application. The work presented in this thesis explores an imaging-based approach for the prediction of breast cancer recurrence that combines multiphoton microscopy (MPM) with deep learning to classify individual breast cancer biopsy samples by risk of recurrence. Genomic differences in tumors with different recurrence potentials may translate to distinct optical and structural information that can be captured …

Quantifying Treatment Response To A Macrophage-Targeted Therapy In Combination With Immune Checkpoint Inhibitors After Exposure To Conventional Chemotherapy, Shelby N. Bess, Gaven K. Smart, Timothy J. Muldoon

Biomedical Engineering Faculty Publications and Presentations

Background: Conventional chemotherapeutic agents, such as 5-fluorouracil (5-FU), can exert anti-tumor effects through immunogenic cell death (ICD) induction. Researchers have found hallmarks that quantify ICD (such as the translocation of HMGB1 and calreticulin). Although chemotherapeutic agents can induce ICD, they increase the expression of immune checkpoints, limiting their effectiveness. Studies have emphasized the importance of investigating the heterogeneous responses of cells co-localized in a solid tumor (macrophages, tumor cells, etc.) to ICD induction. However, these studies were performed in vivo, which limits the collection of information on cell-cell interactions due to model complexity.

Methods: In this study, we used a …

Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Fibroblast growth factor 21 (FGF21) is an endocrine FGF that plays a vital role in regulating essential metabolic pathways. FGF21 increases glucose uptake by cells, promotes fatty acid oxidation, reduces blood glucose levels, and alleviates metabolic diseases. However, detailed studies on its stability and biophysical characteristics have not been reported. Herein, we present the overexpression, biophysical characterization, and metabolic activity of a soluble recombinant FGF21 (rFGF21). The far-UV circular dichroism spectra of rFGF21 show a negative trough at 215 nm, indicating that the protein’s backbone predominantly adopts a β sheet conformation. rFGF21 shows intrinsic tyrosine fluorescence at 305 nm. Thermal …

Pancreatic Cancer Extracellular Vesicles Stimulate Schwann Cell Activation And Perineural Invasion In Vitro Via Il-8/Ccl2, Emory Gregory, Isabel Powers, Azemat Jamshidi-Parsian, Robert J. Griffin, Younghye Song

Biomedical Engineering Faculty Publications and Presentations

Purpose Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related deaths, and perineural invasion (PNI), in which cancer cells infiltrate nerves, enables metastasis in most patients. PNI is largely attributed to Schwann cells (SC) that, when activated, accelerate cancer cell migration towards nerves. However, this cancer-associated reprogramming is generally under-appreciated. Additionally, tumor extracellular vesicle (EV) facilitation of cancer aggravation is well documented, but more investigation is required to better understand their role in PNI. Here, we assessed whether PDAC EVs mediate PNI via SC activation using tissue-engineered in vitro platforms and PANC-1 and HPNE human cell lines as models. …

In Vitro Comparative Study Of Composite Coatings For Magnesium-Based Bone Implants, Abdelrahman Amin, Bryce Williams, Thomas Mcgehee, Alyssandra Navarro, Vipul Patil, Mostafa Elsaadany, Hanna Ibrahim

Biomedical Engineering Faculty Publications and Presentations

This study provides a comparative assessment of the corrosion, morphology, and biological properties of four of the most promising coating methods for magnesium in biomedical applications, namely micro-arc oxidation (MAO), graphene oxide (GO)-containing MAO coating, MAO/sol-gel composite coating, and MAO/polycaprolactone (PCL) polymer dip coating approaches. Despite the abundance of research focused on these promising coating approaches, there is a notable lack of comparative studies evaluating their properties. To this end, the investigated composite coatings are ZK60+MAO, ZK60+MAO/GO, ZK60+MAO/Sol-gel, and ZK60+MAO/PCL composite coating. Several tests were used to assess various properties of the prepared groups such as in vitro corrosion characteristics, …

Precision And Efficacy Of Rna-Guided Dna Integration In High-Expressing Muscle Loci, Made Harumi Padmaswari, Gabrielle Bulliard, Shilpi Agrawal, Mary S. Jia, Sabin Khadgi, Kevin A. Murach, Christopher E. Nelson

Biomedical Engineering Faculty Publications and Presentations

Gene replacement therapies primarily rely on adeno-associated virus (AAV) vectors for transgene expression. However, episomal expression can decline over time due to vector loss or epigenetic silencing. CRISPR-based integration methods offer promise for long-term transgene insertion. While the development of transgene integration methods has made substantial progress, identifying optimal insertion loci remains challenging. Skeletal muscle is a promising tissue for gene replacement owing to low invasiveness of intramuscular injections, relative proportion of body mass, the multinucleated nature of muscle, and the potential for reduced adverse effects. Leveraging endogenous promoters in skeletal muscle, we evaluated two highly expressing loci using homology-independent …

Multimodal Spectroscopy To Study Tumor Microenvironmental Changes In Vivo, April Mordi

Graduate Theses and Dissertations

Every year there are millions of new cancer diagnoses and deaths worldwide. While great strides have been made in technologies and drugs for cancer treatment, there is still a need to understand tumor response to therapy as many patients still endure treatment failure after completing their treatment regimen. Current clinical imaging techniques for detecting response to therapy are utilized weeks to months after the course of treatment, and present limitations to measuring response during treatment. Optical spectroscopy techniques can help meet this need to determine the response of tumors to treatment as it allows for near real-time in vivo characterization …

Synthesis And Process Optimization Of Cellulose Nanocrystals From Miscanthus X. Giganteus For Commercial Viability, Jaspreet Kaur

Graduate Theses and Dissertations

Cellulose nanocrystals (CNCs), derivatives of an abundant biopolymer, i.e., cellulose, are emerging as promising alternatives to petrochemical-based products due to their unique properties, including biodegradability, low toxicity, high strength, low density, large surface area and low coefficient of expansion. CNCs have diverse applications ranging from food packaging and textiles to drug delivery and medical implants, etc. Despite their potential, the widespread commercialization of CNCs faces significant hurdles owing to the high environmental burden and production costs. They are mainly driven by the commonly used source utilized for CNC synthesis i.e., wood and the intensive synthesis process i.e., requirement of …

Two-Photon Imaging For Characterizing Tumor Microenvironmental Changes In Non-Small Cell Lung Cancer Associated With Metastatic Recurrence, Paola Monterroso Diaz

Graduate Theses and Dissertations

Lung cancer remains the leading cause of cancer deaths, comprising nearly 25% of all cancer deaths (Sung et al., 2021a). The five-year survival rate of patients with non-small cell lung carcinoma (NSCLC) remains significantly low given that over half present with locally advanced or metastatic disease at time of diagnosis, and experience tumor recurrence following therapeutic intervention (Tamura et al., 2015; Uramoto & Tanaka, 2014). Current evaluation techniques to assess treatment response are lacking, given they are implemented several weeks after treatment completion and are solely based on anatomical changes in tumor size, forgoing other criteria such as functional or …

Investigation Of Neuro-Regenerative Therapeutic Potential Of Nerve Composite Matrix Hydrogels Embedded With Adipose-Derived Stem Cells, Inha Baek, Younghye Song

Biomedical Engineering Faculty Publications and Presentations

Traumatic spinal cord injury (SCI) induces permanent sensorimotor deficit below the site of injury. There is various research conducted to provide effective therapy, however, SCI is still considered incurable due to the complex nature of the injury site. Recently, our lab developed a combinatorial therapeutic for SCI repair comprising human adipose-derived stem cell (hASC)-embedded nerve composite hydrogels using different ratios of decellularized sciatic nerve (dSN) and spinal cord (dSC) matrices. This study investigated angiogenic and neurotrophic effects of the combinatorial therapeutic in vitro. Compression testing was performed to analyze mechanical properties of the composite hydrogels and showed no significant difference …

Noncontact Diffuse Reflectance Spectroscopy Of Synovial Fluid Samples For Rapid Identification Of Infections, Erin E. Drewke, Robert L. Brand, Caroline G. Geels, Hanna K. Jensen, Kevin Wong, Jarret D. Sanders, Narasimhan Rajaram

Biomedical Engineering Faculty Publications and Presentations

Severe joint infections, such as septic arthritis, require rapid diagnostic testing of the synovial fluid aspirated from joints level so that a surgical team can be assembled quickly. We present a diffuse reflectance spectroscopy (DRS) system for noncontact determination of infection. Using a light-tight syringe holder and fiber optic probe, diffusely reflected light from 475 to 655 nm was acquired from 18 patient samples through the wall of a syringe in a noncontact and sterile manner. We determined the reflectance ratios at two different wavelengths—R ₄₉₀/R ₆₀₀ and R ₅₈₀/R ₆₀₀ and found statistically significant …

Assessing The Effects Of Dasatinib On Mesenchymal Stem/Stromal Cells, David P. Heinrichs, Vitali Maldonado, I Kade Karisma Gita Ardana, Ryan M. Porter, Rebekah M. Samsonraj

Biomedical Engineering Faculty Publications and Presentations

Introduction

Progressive aging, or senescence, of mesenchymal stem/stromal cells (MSCs) is a major obstacle faced when trying to culture potent stem cells for use in therapy. Senescent cells are irreversibly nondividing cells that cease performing critical functional effects. Elimination of senescent cells using biochemical means, such as the use of senolytic drugs like dasatinib, may be useful in retaining the viable and proliferating populations of the cells.

Methods

An in vitro approach was used to investigate the effect of dasatinib on phenotypic, genotypic, and immunomodulatory functionality of osteogenic and adipogenic differentiated MSCs. Replicative senescence was achieved through multiple sub-culturing in …

Simultaneous Modulation Of Pulse Charge And Burst Period Elicits Two Differentiable Referred Sensations, T. R. Benigni, A. E. Pena, S. S. Kuntaegowdanahalli, J. J. Abbas, R. Jung

Biomedical Engineering Faculty Publications and Presentations

Objective. To investigate the feasibility of delivering multidimensional feedback using a single channel of peripheral nerve stimulation by complementing intensity percepts with flutter frequency percepts controlled by burst period modulation. Approach. Two dimensions of a distally referred sensation were provided simultaneously: intensity was conveyed by the modulation of the pulse charge rate inside short discrete periods of stimulation referred to as bursts and frequency was conveyed by the modulation of the period between bursts. For this approach to be feasible, intensity percepts must be perceived independently of frequency percepts. Two experiments investigated these interactions. A series of two alternative forced …

Development Of Tissue-Engineered Model Of Fibrotic Scarring After Spinal Cord Injury To Study Astrocyte Activation And Neurite Outgrowth In Vitro, Nikolas Ala-Kokko, Inha Baek, Younghye Song

Biomedical Engineering Faculty Publications and Presentations

Traumatic spinal cord injuries (SCI) are debilitating injuries affecting twenty-seven million people worldwide and cause functional impairments. Despite decades of research and medical advancements, current treatment options for SCI remain limited, in part due to the complex pathophysiology of spinal cord lesions including cellular transformation and extracellular matrix (ECM) remodeling. Recent studies have increased focus on fibrotic scarring after SCI, and yet much remains unclear about the impact of fibrotic scarring on SCI lesion progression. Here, using collagen and decellularized spinal cord-based composite hydrogels, a three-dimensional (3D) cell culture model mimicking the fibrous core of spinal cord lesions was implemented …

Tissue Engineered Models Of Environmental And Metabolism-Driven Cancer-Nerve Crosstalk, Emory Gregory

Graduate Theses and Dissertations

Purpose: Within the last 30 years, cancer-nerve interactions have garnered attention for causing patient pain, increasing the risk of recurrence, and decreasing patient prognosis. There are 2 key forms cancer-nerve crosstalk takes: perineural invasion (PNI), in which cancer cells infiltrate nerves as a route for metastasis, and tumor innervation (TI), in which neurites penetrate solid tumors to promote tumor progression. Present in vitro models of cancer-nerve crosstalk primarily include Matrigel® mouse matrix and collagen I hydrogels; whereas collagen I hydrogels neglect tumor extracellular matrix (ECM) complexity, Matrigel® is controversial for its batch-to-batch inconsistencies and inclusion of experiment-altering growth factors. Decellularized …

Development Of A High-Throughput Screening Platform To Profile Gene Delivery And Transcriptional Control In Macrophages, Alexis Ivy

Graduate Theses and Dissertations

Macrophages are an important cell type in the body responsible for orchestrating the inflammatory response and return to homeostasis. Macrophages are often implicated in a multitude of disease pathologies including delayed wound healing, excessive fibrosis, autoimmune disease, and immunosuppression within the tumor microenvironment. Although macrophages have been targeted for therapeutic applications, success in utilizing them has remained elusive due to their relative ease of phenotype switching between inflammatory and anti-inflammatory. The challenge that remains is developing clinically relevant delivery vehicles that can target macrophages without causing a phenotypic switch counter-productive to the desired response. This is especially important when targeting …

Feasibility Study For The Application Of A Solar Powered Absorption Chilling System For Cooling Poultry Houses In Northwest Arkansas, Matthew James Kelly

Graduate Theses and Dissertations

This paper investigates the economic feasibility of utilizing a solar-powered absorption chiller to provide cooling for poultry houses in northwest Arkansas. An existing thermodynamic model of a poultry house was modified to account for cooling. A simulation was performed using actual weather data from Fayetteville, Arkansas for 26 flocks of broilers at four cooling capacities for the 2020, 2021, and 2022 calendar years. Based on the simulation, the savings from reduced electricity use for ventilation and the cost of the required absorption chiller and solar thermal array for an 8-house farm were calculated. While providing cooling was found to reduce …

Optimization Of And Mechanistic Insights Into Photocatalytic And Non-Thermal Plasma Degradation Of Organic Pollutants For Sustainable Wastewater Treatment, Yiting Xiao

Graduate Theses and Dissertations

Water pollution by organic pollutants poses a significant environmental threat, necessitating the development of advanced treatment technologies to ensure sustainable and efficient remediation. This dissertation explored innovative approaches to enhance the degradation of organic pollutants through the integration of photocatalytic and plasma-assisted systems, with a focus on optimizing these processes using methodologies ranging from response surface methodology (RSM) to advanced machine learning techniques. The first part of the dissertation investigated the degradation of organic pollutants in flocculated liquid digestate using photocatalytic titanate nanofibers (TNFs) synthesized via a hydrothermal method. This study represents the first application of TNFs, with a bandgap …

Cellular Energy Cycle Mediates An Advection-Like Forward Cell Flow To Support Collective Invasion, Jian Zhang, Jenna Mosier, Yusheng Wu, Logan Waddle, Paul V. Taufelele, Wenjun Wang, Heng Sun, Cynthia A. Reinhart-King

Biomedical Engineering Faculty Publications and Presentations

Collective cell migration is a model for nonequilibrium biological dynamics, which is important for morphogenesis, pattern formation, and cancer metastasis. The current understanding of cellular collective dynamics is based primarily on cells moving within a 2D epithelial monolayer. However, solid tumors often invade surrounding tissues in the form of a stream-like 3D structure, and how biophysical cues are integrated at the cellular level to give rise to this collective streaming remains unclear. Here, it is shown that cell cycle-mediated bioenergetics drive a forward advective flow of cells and energy to the front to support 3D collective invasion. The cell division …