Biomaterials Commons^™

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) …

3-Dimensional Muscle Constructs: Using Hydrogels In Order To Model The Effects Of Exercise In Disease Conditions, Mark Mchargue

Theses and Dissertations--Biomedical Engineering

Currently, there is no standard in vitro model for studying the effects of mechanical stimulation on muscle in type II diabetes. Existing models primarily utilize electrical stimulation, which does not fully recapitulate the effects of exercise. In this thesis, we create a standardized in vitro model of murine muscle that can recapitulate the benefits seen in exercise when mechanically stimulated. Moreover, we show that a type II diabetes environment has similar effects on the muscle in vitro as well as in vivo.

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 …

Optimization Of A Novel Nipam-Based Thermoresponsive Copolymer For Intramuscular Injection As A Myoblast Delivery Vehicle To Combat Peripheral Artery Occlusive Disease, Quentin R. Klueter

Master's Theses

There is a need for a minimally invasive delivery method to enable cell therapies to combat peripheral artery occlusive disease (PAOD) in end stage patients. Myoblasts show promise as a cell mediated therapy but warrant an improved delivery method to increase cell retention in the region of interest because of their adherent nature, relative to previously used BM-MNC’s that are non-adherent. Contemporary issues with achieving successful cell therapies of vasculature can be mainly characterized by the lack of clinical translation from promising animal studies and absence of cell delivery scaffolding. Naturally, polymers have been widely experimented with as grafts to …

Development Of Cellulose-Based, Semi-Interpenetrating Network Hydrogels As Tissue-Adhesive, Thermoresponsive, Injectable Implants, Jesse Martin

Dissertations and Theses

Abstract Development of Cellulose-Based, Semi-Interpenetrating Network Hydrogels as Tissue-Adhesive, Thermoresponsive, Injectable Implants

Hydrogels are three-dimensional polymer networks with high water content and tunable mechanical properties, which have been widely investigated as replacements for soft tissues, such as the intervertebral disc (IVD). Various derivatives of the plant polysaccharide, cellulose, have been explored for use as injectable hydrogel implants. Methylcellulose (MC), which exhibits thermogelation at temperatures above 32°C, and relatively hydrophilic carboxymethyl-cellulose (CMC), are versatile cellulosic polymers that have shown promise as base materials for such applications. In prior work, functionalization with methacrylate groups allowed for the formation of stable, covalently crosslinked …

Injectable Gelatin-Silk Fibroin Composite Hydrogels For In Situ Cell Encapsulation, Ryann D. Boudreau

Honors Theses and Capstones

Hydrogels are widely used tools for tissue engineering and regenerative medicine. Characterized as biofunctional, water-based polymer matrices with tunable mechanical properties, hydrogels have promising but limited applications in biomedical engineering, due to poor and static matrix strength. Here we plan to rectify this issue by introducing a new hydrogel made from a composite of gelatin and silk fibroin crosslinked by microbial transglutaminase (mTG) instantly and beta sheet formation gradually, respectively. This interpenetrating network (IPN) shows enhanced mechanical stiffness and strength compared to gelatin hydrogels, and is capable of encapsulating human cells with high viability demonstrated by the encapsulation of human …

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 …

An Injectable Thermosensitive Biodegradable Hydrogel Embedded With Snap Containing Plla Microparticles For Sustained Nitric Oxide (No) Delivery For Wound Healing, Nikhil Mittal

Dissertations, Master's Theses and Master's Reports

After injury, wound healing is a complex sequential cascade of events essential for the proper recovery of the wound without the scar formation. Nitric oxide (NO) is a small, endogenous free-radical gas with antimicrobial, vasodilating and growth factor stimulating properties. NO has wide biomedical application especially in wound healing however, its usability is hindered due its administration problem as it is highly unstable.

In this work, poly (l-lactic acid) microparticles encapsulated with NO donor S-nitroso-N-acetyl-D-penicillamine (SNAP) were prepared using water-in-oil-water double emulsion solvent evaporation method for controlled delivery for NO at the specific site. The NO release from SNAP-PLLA microparticles …

Synthesis And Characterization Of Blue Light Poly(Β-Amino Ester)S, Nicholas John Kohrs

Theses and Dissertations--Biomedical Engineering

Volumetric muscle loss (VML) is a debilitating injury which results in full or partial loss of function. Current clinical options utilize tissue grafts and bracing to restore function. Tissue graft implantation oftentimes leads to serious complications, some of which end in graft rejection and thereby necessitate further surgeries and procedures. Polymeric scaffolds show promise as scaffolding systems due to their mechanical properties and overall degradation profiles. Scaffolds need appropriate mechanical properties, 10-60 kPa modulus, and overall degradation times, five days to two weeks, to initiate tissue regeneration. Poly(β-amino ester)s (PBAE), a class of synthetic polymers, act as a safe biocompatible …

Crafting Nanostructured Neural Interfaces With Hydrogel Particles, Emily Ann Morin

Doctoral Dissertations

Central nervous system neural device functionality hinges on effective communication with surrounding neurons. This depends on both the permissiveness of the device material to promote neuron integration and the ability of the device to avoid a chronic inflammatory response. Here, a facile approach has been developed exploring the multiple functionalities of hydrogel particles to provide cues to impart neural integration for such materials. Three distinct, yet interconnected tasks were undertaken: investigating hydrogel particle-modified substrate neuron integration and central nervous system inflammatory response, investigating guided hydrogel particle adsorption, and investigating hydrogel particles as local reservoirs for counteracting adverse effects from oxidative …

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 …

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 …

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 …

Poly(Vinyl Alcohol) Nanocomposite Hydrogels For Intervertebral Disc Prostheses, Elaine Wong

Electronic Thesis and Dissertation Repository

Spinal fusion is currently the gold standard for surgical intervention of intervertebral disc (IVD) diseases leading to neck and back pain failing conservative treatments. However, fusion removes motion between the vertebrae and can result in adjacent level degeneration. Total disc replacement (TDR) is an emerging treatment alternative that preserves motion, but materials found in clinically available devices bear little resemblance to the properties of the native IVD. Poly(vinyl alcohol) (PVA) hydrogels are biocompatible, have mechanical behaviour similar to natural tissues, and properties that can be tuned by varying polymer concentration and physical crosslinking through freeze-thaw cycling. Furthermore, their properties can …

Controlled Delivery Of Serp-1 Protein From Poly(Vinyl Alcohol) Hydrogel, Karen L. Kennedy

Electronic Thesis and Dissertation Repository

Poly(vinyl alcohol) (PVA) was selected and evaluated as a controlled drug delivery matrix for Serp-1, a potential new therapeutic with anti-inflammatory properties for control of restenosis. PVA hydrogels, containing a high water content, can be formed by physical crosslinking via a process involving freezing and thawing the material in multiple cycles. PVA, being a well known biomaterial, is suited for biomedical applications and the high water content and hydrophilicity provides a friendly environment for the delivery of large protein based drugs. Using bovine serum albumin (BSA) as a model protein, the controlled release properties of PVA were investigated. Release profiles …