Biomaterials 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 …

De Novo Protein Binding To Zinc Oxide Through Biomineralization Pathways, Jean-Mark A. Francis

Theses and Dissertations

De novo proteins are structurally distinct from proteins found in nature and thus capable of having their amino acid sequence modified to accomplish tasks such as increasing protein-nanoparticle binding without unfolding or decomposing. Zinc Oxide nanoparticles are functionally distinct from their bulk counterparts and are widely used as semiconductors in a variety of fields such as medicine and agriculture. With demand for these nanoparticles increasing, environmentally sustainable methods of Zinc Oxide nanoparticle synthesis are being investigated as an eco-friendly alternative to currently utilized but environmentally hazardous chemical and physical techniques. This research investigates the binding characteristics between Zinc Oxide nanoparticles …

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 …

Insights Into The Characterization And Degradation Of Electrospun Polycaprolactone Scaffolds For Tissue Engineering Applications, Caleb B. Wells

Theses and Dissertations

Electrospun polymeric biodegradable scaffolds are essential in tissue engineering, particularly for Engineered Tissue Vascular Grafts (ETVGs), which promise advancements in treating coronary artery disease, peripheral arterial disease, congenital cardiovascular defects, and renal disease. These scaffolds present a solution to issues with autologous graft availability and durability. While large-diameter grafts in low-pressure environments have seen success, small-diameter grafts in high-flow scenarios remain challenging. Understanding polymeric scaffold degradation and behavior during incubation, especially under dynamic mechanical loading, is vital for clinical translation of small-caliber ETVGs.

This research focuses on characterizing the mechanical and microstructural properties of electrospun polycaprolactone (PCL) scaffolds and their …

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 …

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 …

A Highly Conductive, Flexible, And 3d-Printable Carbon Nanotube-Elastomer Ink For Additive Bio-Manufacturing, Andy Shar, Phillip Glass, Daeha Joung Ph.D.

Undergraduate Research Posters

The synthesis of a highly conductive, flexible, 3D-printable, and biocompatible ink has been of great interest in the field of bio-based additive manufacturing. Various applications include ultra-sensitive, microscale tactile sensors, patient-customizable scaffolds for cardiac and nerve tissue regeneration, and flexible electrocardiogram (ECG) electrodes. Here, a novel elastomeric carbon nanocomposite is presented consisting of amino-functionalized carbon nanotubes (CNT-NH₂) homogenously dispersed in a one-part room-temperature vulcanizing (RTV) silicone matrix. The use of acetone as a swelling solvent aids in electrical percolation through the elastomer matrix. CNT-NH₂ ratios can be tuned to fit various needs; higher tensile strength is favored …

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, …

Nature-Inspired Material Strategies Towards Functional Devices, Sayantan Pradhan

Theses and Dissertations

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

Applied Machine Learning In Extrusion-Based Bioprinting, Shuyu Tian

Theses and Dissertations

Optimization of extrusion-based bioprinting (EBB) parameters have been systematically conducted through experimentation. However, the process is time and resource-intensive and not easily translatable across different laboratories. A machine learning (ML) approach to EBB parameter optimization can accelerate this process for laboratories across the field through training using data collected from published literature. In this work, regression-based and classification-based ML models were investigated for their abilities to predict printing outcomes of cell viability and filament diameter for cell-containing alginate and gelatin composite hydrogels. Regression-based models were investigated for their ability to predict suitable extrusion pressure given desired cell viability when keeping …

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 …

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 …

Dendrimer-Based Therapeutic Delivery Vehicle For The Treatment Of Ocular Diseases, Remy C. Cooper

Theses and Dissertations

The treatment of ocular diseases poses a significant challenge to drug delivery design, due to the eye’s complex anatomy, with a semi-permeable blood-ocular barrier and associated immune privilege. To address some of the delivery challenges, polycationic dendrimers are explored as vehicle for the treatment of posterior chamber disease. Dendrimers are a class of polymeric nanoparticles that are highly branched, multivalent and monodisperse, whose three-dimensional globular architecture has given them the nickname of “synthetic proteins”. Dendrimers are synthesized by reacting monomers in a step-wise fashion to produce generationally and radially increasing structures, with core, interior and surface chains that are highly …

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

Theses and Dissertations

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

The Role Of 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 …

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

Theses and Dissertations

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

Decellularized Matrices Effect On The Adaptive Immune Response, Kegan Sowers

Theses and Dissertations

Decellularized extracellular matrices have been a growing area of interest in the biomedical engineering fields of tissue engineering and regenerative medicine.As these materials move toward clinical applications, the immune response to these materials will be a driving force toward their success in clinical approaches. Fully digested decellularized matrix constructs derived from porcine liver, muscle and lung were created to test the adaptive immune response. Hydrogel characterization ensured that the materials had relatively similar stiffness levels to reduce variability, and in vitro studies were conducted. Each individual construct as well as a gelatin control were plated with a co-culture of macrophages …

Engineering Surface Properties To Modulate Inflammation And Stem Cell Recruitment Through Macrophage Activation, Kelly M. Hotchkiss

Theses and Dissertations

Biomaterials are becoming the most commonly used therapeutic method for treatment of lost or damaged tissue in the body. Metallic materials are chosen for high strength orthopaedic and dental applications. Titanium (Ti) implants are highly successful in young, healthy patients with the ability to fully integrate to surrounding tissue. However the main population requiring these corrective treatments will not be healthy or young, therefore further research into material modifications have been started to improve outcomes in compromised patients. The body’s immune system will generate a response to any implanted material, and control the final outcome. Among the first and most …

Nanomedicine Drug Delivery Across Mucous Membranes, Michael G. Lancina Iii

Theses and Dissertations

NANOMEDECINE DRUG DELIVERY ACROSS MUCOUS MEMBRANES

By Michael G. Lancina III

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth Univeristy, 2017.

Major Director: Dr. Hu Yang, Associate Professor, Chemical and Life Science Engineering

Control over the distribution of therapeutic compounds is a complex and somewhat overlooked field of pharmaceutical research. When swallowing a pill or receiving an injection, it is commonly assumed that drug will spread throughout the body in a more or less uniform concentration and find its way to wherever it is needed. In …

Modulating The Innate Immune Response To Electrospun Scaffolds And Polymer Degradative Byproducts, Daniel Abebayehu

Theses and Dissertations

Implanted biomaterials often induce inflammation that frequently leads to the foreign body response, fibrosis, and the failure of the implant. Thus, it is important to evaluate how cells interact with materials to promote a more regenerative response. It is critical to determine how to modulate the response of tissue resident innate immune cells, as they are among the first cells to interact with implanted materials. Among tissue resident innate immune cells are mast cells, which are inflammatory sentinels that degranulate and orchestrate the fate of other cell populations, such as monocytes/macrophages and lymphocytes. Mast cells have also been reported to …

Development Of An Electrospun And 3d Printed Cellular Delivery Device For Dermal Wound Healing, Ryan M. Clohessy

Theses and Dissertations

The goal of this research was to develop a system of individualized medicine that could be applied to dermal wounds serving as a wound dressing and synthetic extracellular matrix while delivering stem cells to the wound bed. First, fabrication parameters for electrospinning polymer fibers were determined. This involved evaluating fiber morphology with respect to polymer selection and solution concentration. Next, construct fabrication was examined to produce an integrated void space, or cargo area, suitable to maintain stem cells. In vitro studies to ensure stem cell viability and phenotype were conducted, and results supported the notion that cells could be administered …

Electrospraying Extracellular Matrix To Form Nanoparticles, Patrick Link

Theses and Dissertations

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of death worldwide. Alveolar wall destruction is a significant contributor to COPD. Inflammatory macrophages are a major source of the Extracellular Matrix (ECM) proteolysis. ECM breakdown causes air to get trapped in the alveoli, obstructing airflow. One step in curing COPD may be to convert inflammatory to pro-regenerative macrophages. Recently, decellularized ECM scaffolds have shown the ability to induce a pro-regenerative phenotype.

Yet these scaffolds are incapable for reaching the alveolar region of the lungs. To reach the alveolar region particles need a diameter of 1-5 μm or smaller than 300 …

Fabrication Of Flexible, Biofunctional Architectures From Silk Proteins, Ramendra K. Pal

Theses and Dissertations

Advances in the biomedical field require functional materials and processes that can lead to devices that are biocompatible, and biodegradable while maintaining high performance and mechanical conformability. In this context, a current shift in focus is towards natural polymers as not only the structural but also functional components of such devices. This poses material-specific functionalization and fabrication related questions in the design and fabrication of such systems. Silk protein biopolymers from the silkworm show tremendous promise in this regard due to intrinsic properties: mechanical performance, optical transparency, biocompatibility, biodegradability, processability, and the ability to entrap and stabilize biomolecules. The unique …

Investigation Of Polymeric Composites For Controlled Drug Release, Hsi-Wei Yeh

Theses and Dissertations

The Electrospray (ES) technique is a promising particle generation method for drug delivery due to its capabilities of producing monodisperse PLGA composite particles with unique configurations and high drug encapsulation efficiency. In the dissertation work, the coaxial dual capillary ES was used to generate drug-loaded core-shell PLGA particles to study the effects of particle filling materials, drug loading locations and particle shell thicknesses on the resultant in vitro release behaviors of the hydrophilic and/ or hydrophobic model drugs. Through release profile characterization of drug-loaded PLGA particles (particle size: 400 nm and 1 μm), it was confirmed that the co-encapsulation of …

Development And Characterization Of Lung Derived Extracellular Matrix Hydrogels, Robert A. Pouliot

Theses and Dissertations

Chronic obstructive pulmonary disease (COPD) including emphysema is a devastating condition, increasing in prevalence in the US and worldwide. There remains no cure for COPD, rather only symptomatic treatments. Due to unique challenges of the lung, translation of therapies for acute lung injury to target chronic lung diseases like COPD has not been successful. We have been investigating lung derived extracellular matrix (ECM) hydrogels as a novel approach for delivery of cellular therapies to the pulmonary system.

During the course of this work we have developed and characterized a lug derived ECM hydrogel that exhibits “injectability,” allowing cells or dugs …

An Injectable Stem Cell Delivery System For Treatment Of Musculoskeletal Defects, Shirae Leslie

Theses and Dissertations

The goal of this research was to develop a system of injectable hydrogels to deliver stem cells to musculoskeletal defects, thereby allowing cells to remain at the treatment site and secrete soluble factors that will facilitate tissue regeneration. First, production parameters for encapsulating cells in microbeads were determined. This involved investigating the effects of osmolytes on alginate microbead properties, and the effects of alginate microbead cell density, alginate microbead density, and effects of osteogenic media on microencapsulated cells. Although cells remained viable in the microbeads, alginate does not readily degrade in vivo for six months. Therefore, a method to incorporate …

Characterization Of Fibrin Matrix Incorporated Electrospun Polycaprolactone Scaffold, Cho Yi Wong

Theses and Dissertations

Specific objective: Guided tissue regeneration (GTR) aims to regenerate the lost attachment apparatus caused by periodontal disease through the use of a barrier membrane. For the GTR procedures to be successful, barrier membranes are required to be present at the surgical site for an extended period of time (weeks to months). Synthetic membranes have the advantage of prolonged presence in a wound site; however, they do not actively contribute to wound healing. Biologic membranes are recognized by the host tissue and participate in wound healing but have the disadvantage of early resorption. Therefore, the goal of this study is …

Characterization Of Poly(Dimethylsiloxane) Blends And Fabrication Of Soft Micropillar Arrays For Force Detection, Thomas J. Petet Jr

Theses and Dissertations

Diseases involving fibrosis cause tens of thousands of deaths per year in the US alone. These diseases are characterized by a large amount of extracellular matrix, causing stiff abnormal tissues that may not function correctly. To take steps towards curing these diseases, a fundamental understanding of how cells interact with their substrate and how mechanical forces alter signaling pathways is vital. Studying the mechanobiology of cells and the interaction between a cell and its extracellular matrix can help explain the mechanisms behind stem cell differentiation, cell migration, and metastasis. Due to the correlation between force, extracellular matrix assembly, and substrate …

Effects Of Antidepressants On Human Mesenchymal Stem Cell Differentiation On Clinically Relevant Titanium Surfaces, Nancy B. Ayad

Theses and Dissertations

Selective Serotonin Reuptake Inhibitors (SSRIs) are the most frequently prescribed class of drugs worldwide and are implemented in the treatment of depression and other psychiatric disorders. SSRIs relieve depressive symptoms by modulating levels of the neurotransmitter serotonin in the brain. SSRIs block the function of the serotonin transporter, thereby increasing concentrations of extracellular serotonin. However, serotonin levels in the neurons of the brain only account for 5% while the remaining 95% is present outside the brain. Serotonin receptors and transporter are located on bone resident cells (mesenchymal stem cells (MSCs)), osteoblasts and osteoclasts, and serotonergic activity is believed to affect …