Molecular, Cellular, and Tissue Engineering Commons^™

Bioprinted Scaffolds For Investigating Fibroblast Alignment, Lillian Thro, Daeha Joung Ph.D.

Undergraduate Research Posters

Fibroblasts play a vital role in tissue repair, ECM remodeling, and maintaining structural integrity in human tissues. However, their behavior in engineered 3D microenvironments remains poorly understood. Traditional 2D cultures fail to capture the complex cell-cell and cell-matrix interactions that govern fibroblast alignment, migration, and proliferation in vivo. To address this gap, this project uses bioprinted scaffolds that mimic native ECM structures and provide a platform for studying fibroblast behavior in controlled microenvironments. The project focuses on varying scaffold channel properties—such as width, depth, and geometry—to investigate how physical cues influence fibroblast organization and collective migration. A biodegradable gelatin-based ECM …

The Bacteriostatic, Regenerative, And Immunomodulatory Properties Of Extracellular Matrix Particles For Lung Injury, Keera P. Rhoads

Theses and Dissertations

Acute respiratory distress syndrome (ARDS) is a prevalent, life-threatening lung condition, affecting nearly 200,000 Americans annually, with a 40% international mortality rate. There is no cure for ARDS, and current pharmacological treatments have limited effectiveness. Symptoms can be mitigated with mechanical ventilation, though this often leads to ventilator-induced lung injuries (VILI) and puts critically ill patients at risk of infections, including ventilator-associated pneumonia (VAP). A promising therapeutic is the extracellular matrix (ECM), a complex network of structural proteins and bioactive molecules that has been shown to have anti-inflammatory properties and prevent fibrosis. We aim to utilize the regenerative and immunomodulatory …

Modeling Synergistic Effects Of Integrin And Tgf-Β Signaling In Epithelial Mesenchymal Transition, Prerak Thakkar

Theses and Dissertations

The induction of Epithelial Mesenchymal Transition (EMT) is initiated by a

number of protiens and growth factors, one of which is the profibrotic cytokine Trans-

forming Growth Factor β (TGF-β). Within the extracellular matrix (ECM), TGF-β

is found in a latent, inactive form bound to proteins such as fibronectin (FN). For

TGF-β to contribute to EMT induction, it has to be extracted from the latent com-

plexes into a soluble form. This soluble, activated TGF-β can then bind to receptors

on the cell membrane, which causes the transduction of signals that begin EMT. Re-

search has shown that the release …

Characterization Of Nanoplastic-Induced Exacerbation Of Asthmatic Pathophysiology In A Murine In Vivo Model, Keith Li

Theses and Dissertations

As global plastic production increases, so does the environmental and biological presence of nanoplastics (NPs), raising growing concerns about their potential impact on human health. These particles have been detected in various organs, including the lungs, yet their role in respiratory inflammation remains largely unexplored. Emerging evidence suggests that NP exposure may influence immune responses in the lungs, particularly in individuals with preexisting conditions such as asthma. However, the specific ways in which these particles interact with allergen driven inflammation are still unclear.

In this study, a murine model of allergic airway inflammation was used to investigate how surface modified …

Modeling Synergistic Effects Of Integrin And Tgf-Beta Signaling In Epithelial Mesenchymal Transition, Prerak Thakkar

Biology and Medicine Through Mathematics Conference

No abstract provided.

Investigating The Regulation Of Epithelial-Mesenchymal Transition Through Fibronectin-Mediated Tgf-Β1 Mechanotransduction Using In Vitro Models Of Triple-Negative Breast Cancer, Michael M. Sofroniou

Theses and Dissertations

TGF-β1 is a potent regulator of epithelial-mesenchymal transtion (EMT), a cellular
transdifferentation process that promotes cellular motility and matrix remodeling, critical to tumorigenesis and metastasis. TGF-β1-induced EMT promotes the assembly of FN, which synergistically binds latent TGF-β1 to aid in its activation. The purpose of of this work is to further probe the effects of autocrine TGF-β1 signaling during EMT progression by utilizing CRISPR-Cas9 deletion of the TGFB1 gene in in vitro models of triple-negative breast cancer. The studies outlined in this work demonstrate that autocrine TGF-β1 maintains a baseline level of mesenchymal marker expression. It also functions to desensitize …

The Effects Of Various Nanoplastics On The Inflammatory Response In Primary Alveolar Epithelial Cells, Eunice J. Pak

Theses and Dissertations

As plastic pollution begins to multiply in the environment and the workplace, gradual degradation of these plastics creates an unseen threat to biological health: nanoplastics. These nanoplastics are common in day-to-day life, and have been found in various internal organs of the human body. The biological and health effects of these nanoplastics are still widely unknown, and only recently has research focused on the impacts of these particles on human health at the cellular level.

In this thesis, poly(methyl methacrylate) and three forms of polystyrene (carboxyl-modified, amine-modified, and neutral surface charge) have been tested on submerged primary C57BL/6 mouse alveolar …

The Sexually Dimorphic Role Of Connexin 43 In Bone Remodeling And Disuse-Induced Bone Loss, Gabriel A. Hoppock

Theses and Dissertations

Bone loss is frequently experienced by individuals undergoing long-term disuse, such as prolonged bedrest, immobilization due to paralysis or injury, and conditions such as spaceflight. Under normal physiological conditions, bone remodeling is balanced by bone-forming osteoblasts and bone-resorbing osteoclasts, and the activity of osteoblasts and osteoclasts is orchestrated by osteocytes. Osteocytes are the most abundant cell type found in bone and ample evidence suggests they are bone’s main mechanosensory cell type. Therefore, understanding osteocyte biology and responses to mechanical signals, or lack thereof during unloading, may lead to new therapeutic targets to combat bone loss during disuse. Previous data has …

The Regulation Of Laryngeal Cancer Cell Phenotype And Proliferation By 24r,25-Dihydroxyvitamin D3 Is Correlated With Erα Isoform Expression, Cydney Dennis

Theses and Dissertations

Laryngeal cancer is the most common type of head and neck cancer and is associated with poor prognosis due to common delayed diagnoses. The sex disparities associated with laryngeal cancer are constantly growing, as the risk of malignancy in males is continually increasing compared to women. Due to the high chance of late-stage diagnosis requiring aggressive treatments, there is a high demand for less aggressive treatment options and early-stage diagnostic markers. The apparent sex disposition of the larynx, the correlation between sex hormones, and the risk of malignancy in aging men suggest that estrogen may play a role in laryngeal …

Muscle-Nerve Signaling And Its Role In Myogenesis, Synaptogenesis, And Regeneration, James T. Redden

Theses and Dissertations

Despite only comprising 0.1% of the myofiber surface area, a healthy motor endplate is densely packed with acetylcholine receptors (AChRs) responsible for mediating activity between the connected motor neuron and skeletal muscle via the neurotransmitter, acetylcholine. Loss of the endplate, known as fragmentation, is caused by car crashes, deep lacerations, and other traumatic injuries to the innervating nerve or direct injuries to the limb muscle(s) with intramuscular denervation as a common comorbidity. In both cases, endplate fragmentation begins within a week of injury proceeding muscle atrophy causing decreased mobility, paralysis, and quality of life. Endplate fragmentation of intact muscle fibers …

T Cell Polarization Regulates The Inflammatory Response And Tissue Regeneration At The Peri-Implant Interface, Derek Avery

Theses and Dissertations

Unresolved healing and localized chronic inflammation are common occurrences after biomaterial implantation, resulting in unfavorable clinical outcomes such as implant failure or fibrous encapsulation. T cells are adaptive immune cells found in lymph nodes, thymus, spleen, bone marrow, and around biomaterials, significantly impacting the degree of inflammation and wound healing. T cells are vital for inflammatory cytokine production and modulation of innate immune cells, including neutrophils and macrophages. T cells can be differentiated into two primary subsets, CD4⁺ and CD8⁺ T cells, playing distinctive roles in various pathologies and disease states. While T cells have been characterized well …

Modeling Epithelial-Mesenchymal Transition In A 3d Multicellular Model Of Tgf-Β1 Signaling, Kristin Kim, Chris Lemmon

Biology and Medicine Through Mathematics Conference

No abstract provided.

Finite Element Analysis Of 3d-Printed Pcl Scaffolds, Ireolu K. Orenuga, Joao Soares, Phillip D. Glass, Daeha Joung Ph.D.

Undergraduate Research Posters

Finite Element Analysis of 3D-printed PCL Scaffolds for Synergizing Cellular Micro-Environment and Mechanical Stimuli to Enhance Engineered Tissue Growth in Vitro

Ireolu Orenuga,1 Phillip Glass,2 Daeha Joung,2 Joao S. Soares1

1. Department of Mechanical and Nuclear Engineering, College of Engineering, Virginia Commonwealth University
2. Department of Physics, College of Humanities & Sciences, Virginia Commonwealth University

Introduction: Tissue engineering aims to create viable and functional engineered tissues via biodegradable scaffolds and autologous cells. Scaffolds play an essential part in organizing the architecture of developing tissues and aid in the proper function of implants acutely by serving as mechanical support and long-term by …

The Wound Healing And Antibacterial Properties Of Mesenchymal Stromal Cell Extracellular Matrix Nanoparticles, Emily N. Wandling

Theses and Dissertations

Treatments for acute respiratory distress syndrome (ARDS) are still unavailable and the prevalence of the disease has only increased due to the Covid-19 pandemic. Mechanical ventilation regiments are still utilized to support declining lung function, but they also contribute to lung damage and increase the risk of bacterial infection. The anti-inflammatory and pro-regenerative abilities of mesenchymal stromal cells (MSCs) have shown to be a promising therapy for ARDS. We propose to utilize the regenerative effects of MSC secretome and the extracellular matrix (ECM) into a nanoparticle. Our mouse MSC (MMSC) ECM nanoparticles were characterized using size, zeta-potential, and mass spectrometry …

Investigating Tgf-Β1 And Fibronectin Signaling In Low Oxygen Environments, Caitlin E. Williams

Theses and Dissertations

Breast cancer is the second leading cause of death in women, second to lung cancer. It’s one of the most well-known cancers, with almost 300,000 new cases estimated to be diagnosed in 2023. Breast cancer often begins in ductal epithelial cells, and these cells will typically undergo a cellular transformation process known as epithelial-mesenchymal transition (EMT) in early stages. Breast cancer becomes deadly when it reaches a metastatic stage. As a part of the metastatic process, transformed cells will conduct remodeling of the extracellular matrix (ECM) to allow for migration of an otherwise non-migratory cell type.

As dense tumors form, …

Exploring Cell Differentiation Vs. Localization In Engineered Ligament-To-Bone Entheses, Saagar N. Sheth, Michael E. Brown, Jennifer L. Puetzer

Undergraduate Research Posters

The anterior cruciate ligament (ACL) connects to bone via structurally complex insertions known as entheses that translate load from elastic ligament and stiff bone via gradients in organization, composition, and cell phenotype [1]. These gradients are not recreated in graft repair or engineered replacements, yielding limited repair options and high failure rates [2]. Previously, we developed a culture system that uses a tensile-compressive interface to guide ligament fibroblasts to develop early postnatal-like entheses by 6 weeks [3]; however, cells used were isolated from the entirety of the neonatal bovine ACL from bone to bone and likely contained multiple cell phenotypes …

Novel Microfabricated Systems To Elucidate The Role Of Anisotropic Stiffness In The Tumor Microenvironment, Jiten Narang

Theses and Dissertations

Cancer is the second leading cause of death in women and late stage (metastatic) cancers have abysmal survival rates compared to early stage regional cases (27% vs 86%). As a tumor grows, the surrounding extracellular matrix (ECM) is reorganized into a dense, collagen rich matrix. The new matrix of aligned collagen fibers provides unique mechanical cues such as anisotropic stiffness and contact guidance. Matrix turnover also constricts local vasculature and restricts delivery of key nutrients and signaling molecules to malignant cells to outside the tumor creating a chemotactic gradient from outside to inside. In this work, we developed a novel …

Dna Condensation State Regulates Nuclear Lamina Strain And Cellular Adaptation To Physiological Forces, Brooke E. Danielsson

Theses and Dissertations

The nucleus is the largest and stiffest organelle and is exposed to mechanical forces transmitted through the cytoskeleton from outside the cell, as well as from forces generation within the cell. In recent years, the nucleus has been proposed to act as a cellular mechanosensor, with changes to nuclear shape and architecture playing an important role in how the cell responds to physiological forces. Aberrant forms of the nuclear envelope protein lamin A/C, as well as epigenetic modifications to chromatin, has been shown to modify nuclear stiffness and viscosity, therefore effecting nuclear mechanics and mechanotransduction. Altered nuclear mechanics is associated …

Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko

Theses and Dissertations

Respiratory distress syndrome (RDS) is characterized by shortness of breath and low oxygen levels. RDS affects the neonatal and adult populations. In the neonatal population, RDS can be classified as NRDS (Neonatal respiratory distress syndrome), while in adults, it is known as ARDS (acute respiratory distress syndrome). This dissertation examines a therapeutic approach to NRDS and a mechanistic approach to ARDS with in vivo and in vitro models of lung injury. NRDS is characterized by a deficiency or lack of surfactant. Surfactant is an essential compound composed of phospholipids and proteins to prevent the lungs from collapsing. There are several …

Towards The Systematic Evaluation Of Variable Modes Of Mechanical Conditioning On The Compositional, Microstructural And Mechanical Properties Of Engineered Tissue Vascular Grafts., Sarah Saunders

Theses and Dissertations

Coronary artery bypass surgery (CABG) remains one of the most common cardiac surgical procedures performed worldwide, frequently involving multiple bypasses, and commonly employing the patient’s internal mammary artery, radial artery, or saphenous vein. CABG is often not possible because native vessels were already employed in previous interventions or are diseased themselves. Synthetic vascular grafts are currently integral tools of vascular surgery and have had relative success in large-caliber applications providing substantial benefit to aortic or iliac grafting; however, small diameter (< 6 mm) arterial grafts have not yet translated into clinical effectiveness due to thrombosis and anastomotic intimal hyperplasia. ETVGs present an exciting potential alternative in vascular grafting by offering a blood vessel substitute that could exhibit all the functional characteristics of native vasculature. In addition to relieving supply limitations associated with coronary artery bypass surgery ETVGs are especially ideal for pediatric patients with congenital heart disease who require grafts that grow as they do, eliminating the need for reoccurring invasive surgeries.

Though the role of biomechanics in regulating cellular behavior promoting non-thrombogenicity, vasoactivity, and ECM synthesis and maintenance is well …

Effect Of Viscoelasticity On Cellular Morphology And Activity, Thomas J. Petet Jr

Theses and Dissertations

It has been well established that there is a link between substrate stiffness and cellular activities such as proliferation, migration, and differentiation. Less characterized is the link between the time-dependent viscosity of a substrate with those cellular activities. To explore this, PDMS substrates were created with predictably tunable stiffness and viscosity parameters. A simulated model was also developed in parallel to explore the potential effects of viscosity in a computationally predictive way. It was found that the inclusion of viscosity caused a major paradigm shift to a non-zero substrate equilibrium that was sensitive to increases in the substrate stiffness. Finally, …

Regulation Of Osseous Healing By Macrophage-Derived Wnt Ligands, Jefferson Overlin Abaricia

Theses and Dissertations

Osseous healing is regulated by various classes of cells and signaling mechanisms. Of these, Wnt signaling has long been known to be critically important in directing the differentiation of mesenchymal stem cells (MSCs) into osteoblasts during bone healing. However, the source of these Wnt ligands is not known. Recently, a body of literature has arisen finding both beneficial and detrimental effects of macrophage-derived Wnt ligands on the regeneration of other tissues (liver, kidney, heart, and intestine), often by regulating inflammatory activation and stem cell behavior. As macrophages have been well-characterized as orchestrators of healing, their use of Wnt signaling to …

Therapeutic Modalities For Preventing Osteoarthritis Following Trauma To The Knee, Kayla M. Scott

Theses and Dissertations

Over 32.5 million adults in the United States and 300 million worldwide have osteoarthritis (OA). To date, there are no disease-modifying therapeutics, only strategies to slow OA progression through pain management, regenerative medicine approaches, and ultimately joint replacement.

On a microscale, a phenotypic shift of the normally quiescent articular chondrocytes leads to aberrant expression of pro-inflammatory and catabolic pathways, which are hypothesized to contribute to OA progression. Of note, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and WNT/β-catenin signaling are key players disrupting cartilage homeostasis and driving inflammatory pathway activation. These pathways become dysregulated and form a positive feedback loop, increasing …

A Mechanism Behind The Mechanotransduction Of Surface Characteristics In Osteoblasts, Otto J. Juhl Iv

Theses and Dissertations

Biomaterials for use in bone regeneration and healing range from metal and metal alloy implants to hydrogel-based solutions. These materials can be optimized to increase bone healing and integration by improving the mechanical and biological properties. Regardless of the material itself, the cell-substrate interaction is key to the success of the biomaterial once implanted. Substrate surface characteristics such as roughness, wettability, and particle density are well-known contributors to a substrate’s overall osteogenic potential, and therefore the substrate's overall success. Unfortunately, it is still unknown how these substrate surface characteristics are transduced into intracellular signals by cells, preventing specific tailoring of …

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 …

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 …

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.

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, …

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 …

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 …