Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Investigation Of Mechanical Regulation On Stat3 Activity And Mmp Production, Jaxson R. Libby

Honors Theses and Capstones

Transcription factor, STAT3, is inappropriately expressed in cancer cells, and has contrasting activation in 2D versus 3D microenvironments. 2D plates are often used for drug screening and do not always recapitulate in vivo responses. To combat inaccurate 2D drug studies, a 3D hydrogel was created to support the growth of cancer cells into a tumor-like environment. The hydrogel consists of a biocompatible dextran homopolysaccharide, cell adhesion RGD sequences, and crosslinker MMP labile peptides. A pH dependent reaction couples the RGD sequences to dextran then the polymers are crosslinked into a gel. Crosslinking is accomplished using terminal cysteine peptide sequences, allowing …

Synthesis Of Thiol-Acrylate Hydrogels For 3d Cell Culture And Microfluidic Applications, Anowar Hossain Khan

LSU Doctoral Dissertations

Globally cell culture is an $18.98 billion industry as of 2020, with an 11.6 percent annual growth rate. Drug discovery has an estimated worth of $69.8 billion in 2020 and is predicted to grow to $110.4 billion by 2025. Three-dimensional (3D) cell culture of cancer cells is one of the rapidly growing felids since it better recapitulates in vivo conditions compared to two-dimensional (2D) models. However, it is challenging to grow 3D tumor spheroids outside the body, and some of the existing technology can generate these spheroids outside the human body but poorly mimic in vivo tumor models. Therefore, there …

Therapeutic Injectable Iron-Chelating Hydrogels, Debbie Campbell-Rance

Theses and Dissertations

ABSTRACT

Therapeutic Injectable Iron-Chelating Hydrogels for Improved Central Nervous System Regeneration

By

Debbie S. Campbell-Rance

A dissertation submitted in partial fulfillment of the requirements of the degree of Doctor of Philosophy at Virginia Commonwealth University 2021.

Director: Xuejun Wen, M.D., Ph.D., AIMBE Fellow, Alice T. and William H. Goodwin Jr. Endowed Chair Professor in Regenerative Medicine, Institute for Engineering and Medicine, Department of Chemical and Life Science Engineering

Severe traumatic brain and spinal cord injuries are major global public health and socioeconomic problems in terms of mortality and morbidity. Currently there are two main lines of treatment under development for …

Structure-Property Relationships Of Polymer Films And Hydrogels To Control Bacterial Adhesion, Kristopher W. Kolewe

Doctoral Dissertations

The emergence and spread of antibiotic resistance across microbial species necessitates the need for alternative approaches to mitigate the risk of infection without relying on commercial antibiotics. Biofilm-related infections are a class of notoriously difficult to treat healthcare-associated infections that frequently develop on the surface of implanted medical devices. As biofilm formation is a surface-associated phenomenon, understanding how the intrinsic properties of materials affect bacterial adhesion enables the development of structure-property relationships that can guide the future design of infection-resistant materials. Despite lacking visual, auditory, and olfactory perception, bacteria still manage to sense and attach to surfaces. Previously, it has …

Vitreous Gel Physics, Svetlana Morozova

Doctoral Dissertations

The transparent vitreous, which fills the posterior cavity of the eye, is incredibly engineered. The charged polyelectrolyte hyaluronic acid (HA) network swells to maintain the pressure in the eye, while stiff collagen type II bundles help absorb any external mechanical shock. Our investigations have contributed to a few key developments related to the physical properties of the vitreous: (1) The stiff collagen network that supports the soft gel network is self-assembled from single triple-helix collagen proteins. Electrostatic interactions drive this assembly, such that the size and concentration are optimized at physiological salt concentrations. The width of the assemblies remarkably changes …

Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen

Doctoral Dissertations

The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment. A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has a mechanical …

Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick

Doctoral Dissertations

The goal of this dissertation was to parse the roles of physical, mechanical and chemical cues in the phenotype plasticity of smooth muscle cells (SMCs) in atherosclerosis. We first developed and characterized a novel synthetic hydrogel with desirable traits for studying mechanotransduction in vitro. This hydrogel, PEG-PC, is a co-polymer of poly(ethylene glycol) and phosphorylcholine with an incredible range of Young’s moduli (~1 kPa - 9 MPa) that enables reproduction of nearly any tissue stiffness, exceptional optical and anti-fouling properties, and support for covalent attachment of extracellular matrix (ECM) proteins. To our knowledge, this combination of mechanical range, low …

Brown Adipogenesis Of Mouse Embryonic Stem Cells In Alginate Microstrands, Andrea Mannarino Unser

Legacy Theses & Dissertations (2009 - 2024)

The ability of brown adipocytes (fat cells) to dissipate energy as heat shows great promise for the treatment of obesity and other metabolic disorders. Employing pluripotent stem cells, with an emphasis on directed differentiation, may overcome many issues currently associated with primary fat cell cultures. However, brown adipocytes are difficult to transplant in vivo due to the instability of fat, in terms of necrosis and neovascularization, once injected. Thus, 3D cell culture systems that have the potential to mimic adipogenic microenvironments are needed, not only to advance brown fat implantation, but also to better understand the role of brown adipocytes …

Three-Dimensional Hydrogel Cell Culture Systems For Modeling Neural Tissue, John P. Frampton

Legacy Theses & Dissertations (2009 - 2024)

Two-dimensional (2-D) neural cell culture systems have served as physiological models for understanding the cellular and molecular events that underlie responses to physical and chemical stimuli, control sensory and motor function, and lead to the development of neurological diseases. However, the development of three-dimensional (3-D) cell culture systems will be essential for the advancement of experimental research in a variety of fields including tissue engineering, chemical transport and delivery, cell growth, and cell-cell communication. In 3-D cell culture, cells are provided with an environment similar to tissue, in which they are surrounded on all sides by other cells, structural molecules …