Engineering 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.

Leveraging Isocyanate Chemistry For Low Cost And Highly Functional Hydrogels, Henry Beaman

Dissertations - ALL

The development of novel biomaterials is an important step in providing higher quality products for wound healing, drug delivery, and tissue engineering. Progress is consistently being made in the development of new polymers, yet new polymer systems are often expensive and/or involve complex multistep synthesis methods. These limitations could hinder the translation and scalability of functionalized materials. To address the issues of complex synthesis and high cost, we have devised strategies for polymeric modification using isocyanate chemistry. Isocyanates are used in the manufacturing of polyurethanes. Isocyanates are highly reactive with common functional groups, such as amines, hydroxyls, and carboxylic acids. …

Characterization Of Thermal Gelation Properties In Bioresorbable Thermally Activated Hydrogel Polymers For Hernia Surgery Applications, Alexander Mayfield

All Theses

Hydrogel adhesives are a new class of materials with excellent biocompatibility, which makes them very attractive for biomaterial applications. It has been previously shown that Tetronic T1107, a four-arm poly (propylene oxide)-poly (ethylene oxide) (PPO-PEO) block copolymer, is useful as a chemical crosslinking thermo-responsive hydrogel for bioadhesive applications. The end groups of this polymer are modified with acrylate and N-hydroxysuccinimide (NHS) functional groups. The acrylate end group gives the polymer cohesive properties with long-range chemical crosslinking using dithiothreitol (DTT), while the NHS end group gives the polymer adhesive properties through bonding with amines found in organic tissue. It was found …

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 …

Mesenchymal Stromal Cell And Chondrocyte Mobility In 3d Bioprinted Hydrogel Constructs, Alesia Lokshina

Honors Undergraduate Theses

Osteoarthritis (OA) is a progressive cartilage degeneration disease with a complex pathologic mechanism. Although OA has devastating effects on patient quality of life and places a significant burden on the healthcare system, no disease-modifying drugs have been found, and surgical treatment options are often unsustainable. 3D bioprinting is a novel field within tissue engineering that focuses on developing biocompatible constructs that can be implanted to replace an organ or tissue. Such constructs have a great potential to become treatments for OA. Understanding cell mobility within hydrogels could play a vital role in advancing the development of biocompatible constructs. However, due …

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 …

Silk Hydrogels Incorporated With Melanin, Anne Lutz

Browse all Theses and Dissertations

Melanin is a naturally produced pigment found within the human body. Melanin is known for its ability to protect against Ultra Violet light, but also its ability to allow for mechanical protection. Making melanin a good addition to biomedical devices such as hydrogels. Silk hydrogels are weak in their load bearing capabilities but are known for their biocompatibility, biodegradability, and porosity. This makes the silk hydrogel a good material to incorporate melanin into in order to improve the mechanical properties. For the silk solution to form a solid, there must be a presence of both a catalyst and an oxidizer …

Development Of Novel Inks And Approaches For Printing Tissues And Organs, Shen Ji

Dissertations

Tissue engineering is a multidisciplinary field that investigates and develops new methods to repair, regenerate and replace damaged tissues and organs, or to develop biomaterial platforms as in vitro models. Tissue engineering approaches require the fabrication of scaffolds using biomaterials or fabrication of living tissues using cells. As the demands of customized, implantable tissue/organs are increasing and becoming more urgent, conventional scaffold fabrication approaches are difficult to meet the requirements, especially for complex large-scale tissue fabrication. In this regard, three-dimensional (3D) printing attracted more interest over the past decades due to its unrivaled ability to fabricate highly customized tissues or …

Bioadhesive Hydrogel Composite Cell Carrier For The Repair Of The Degenerated Intervertebral Disc, Thomas Richard Christiani

Theses and Dissertations

Lower back pain (LBP) affects the worldwide population and can be attributed to the degeneration of the intervertebral disc (IVD). The IVD is composed of a central nucleus pulposus (NP), a peripheral annulus fibrosus (AF), and adjacent cartilage endplates (CEPs). IVD degeneration is characterized by proteoglycan loss, tissue dehydration, and decreased hydrostatic pressure. In this work, the use of an injectable bioadhesive hydrogel composite for replacement of the degenerated NP was investigated.

Results indicate that the composite exhibits similar mechanical properties to the NP, adheres to AF tissue, and supports encapsulated mesenchymal stem cell (MSC) differentiation toward an NP-like phenotype …

Analysis Of Cellular Interactions Within A Collagen Hydrogel, Austin N. Worden

Theses and Dissertations

Evidence has arisen over the past several years that use of a three- dimensional (3D) culture system provides a distinct advantage over two- dimensional (2D) systems when cellular interactions are examined in a more natural environment. Changes in morphology, speed, and directionality of cells tested in both planar and 3D matrices have all demonstrated that using 3D system is advantageous. The changes to the cellular migration patterns were shown to be dependent on several variables within the surrounding substrate including cellular content, physical environment, and the matrix chemical milieu. We have taken advantage of using collagen hydrogels as a 3D …

Acoustofluidics And Soft Materials Interfaces For Biomedical Applications, Frank A. Fencl

Biomedical Engineering ETDs

This dissertation describes fabrication of devices and other tools for biomedical applications through the integration of acoustofluidic systems with bio separation assays, instrumentation components, and soft materials interfaces. For example, we engineer a new class of transparent acoustic flow chambers ideal for optical interrogation. We demonstrate efficacy of these devices by enhancing the signal for high throughput acoustic flow cytometry, capable of robust particle focusing across multiple parallel flowing streams. We also investigate an automated sampling system to determine the parameters of transient particle stream focusing in between sample boluses and air bubbles to model a high throughput, multi-sampling acoustic …

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 …

Modified Pamam Dendrimers In Tunable Drug-Delivery Systems: A Sustained-Release Dendrimer Hydrogel For Anti-Glaucoma Drugs And Surface-Engineered Macrophages As Nanoparticle Carriers For Targeted Anti-Cancer Therapy, Christopher A. Holden

Theses and Dissertations

Two specific drug-delivery applications were sought in this work using polyamidoamine (PAMAM) dendrimers. One drug-delivery system used a novel dendrimer hydrogel (DH) for sustained delivery of anti-glaucoma drugs. In this work, PAMAM G3.0 dendrimers were covalently bonded with poly(ethylene glycol) (PEG­₁₂₀₀₀) molecules which were subsequently acrylated, resulting in photocurable DH conjugates. For pharmacological studies, DH were loaded with a solution of intraocular pressure lowering drugs, brimonidine and timolol maleate, and were characterized for in vitro release and ex vivo transport and uptake. DH formulations were shown to increase the loading of drug molecules, increase transcorneal drug delivery, and …

3d Bioprinting Hydrogel For Tissue Engineering An Ascending Aortic Scaffold, Benjamin Stewart

Electronic Theses and Dissertations

The gold standard in 2016 for thoracic aortic grafts is Dacron^®, polyethylene terephthalate, due to the durability over time, the low immune response elicited and the propensity for endothelialization of the graft lumen over time. These synthetic grafts provide reliable materials that show remarkable long term patency. Despite the acceptable performance of Dacron^® grafts, it is noted that autographs still outperform other types of vascular grafts when available due to recognition of the host's cells and adaptive mechanical properties of a living graft. 3-D bioprinting patient-specific scaffolds for tissue engineering (TE) brings the benefits of non-degrading synthetic …

Design Of Robust Hydrogel Based On Mussel-Inspired Chemistry, Yuan Liu

Dissertations, Master's Theses and Master's Reports

The structure of catechol is found in mussel adhesive proteins and contributed to both wet-resistant adhesion and cohesive curing of these proteins. A synthetic nano-silicate, Laponite was incorporated into catechol-containing hydrogels and the hydrogel network-bound catechol formed strong reversible interfacial interaction with Laponite. The contribution of incorporated catechol-Laponite reversible interfacial interactions to the mechanics of hydrogels constructed by different strategies was studied. In the first strategy, Laponite and catechol were introduced into the double network hydrogel (DN) via the free radical co-polymerization of a catechol-containing monomer, backbone monomer, and crosslinker. The introduction of catechol-Laponite interactions significantly improved the compressive strength …

Development Of Orthogonally Crosslinked Thiol-Ene Hydrogels For Encapsulation Of Pancreatic Beta-Cells, Han Shih

Open Access Dissertations

Type I diabetes mellitus (T1DM) is an autoimmune disease caused by auto-reactive T-cell-mediated destruction of insulin-producing β-cells. Effective encapsulation strategies can protect the transplanted islets from direct attack by host immune cells while maintaining insulin secretion. To achieve this goal, I have developed a hydrogel conformal coating using a visible light-mediated interfacial thiol-ene photopolymerization. Unlike conventional chain-growth visible light polymerizations, no additional cytotoxic co-initiator or co-monomer was required in thiol-ene gelation scheme for rapid gelation. More importantly, islets coated with thiol-ene gel maintained their viability and function in vitro. In addition to microencapsulate β-cells, the second objective of my …

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 …

Fabrication And Characterization Of An Extracellular Matrix Hydrogel For Aortic Valve Applications, Brady Culbreth

All Theses

With an estimated 5 million people suffering from valve disease in the United, valve disease is currently the leading cause of cardiovascular disease. Each year, between 80,000 and 85,000 aortic valve replacements are performed in order to treat the stenotic heart valves. Despite this being a worldwide epidemic, the current valve replacement options that are on the market have distinct limitations. Furthermore, a viable alternative does not exist for the patients that are not candidates for the current treatment methods. Our proposed solution to this epidemic is to create a highly viable injectable scaffold that would allow for the minimally …

Design And Production Of A Hydrogel Forming Polypeptide: Engaging High School Students In Protein Design, James K. Deyling

ETD Archive

Bioinks are a class of hydrogel that have the potential to be the ink used in the creation of printed organs, connective tissue, and other important structures within the body. One class of material that may be a suitable bioink hydrogel is elastin-like polypeptides (ELPs), which are synthetic biopolymers inspired by the naturally existing connective tissue elastin. ELPs consist of a repeat pentapeptide sequence (GXGVP)n, where X is any of the 20 naturally existing amino acids other than proline. These biomolecules are capable of exhibiting environmental responsiveness when exposed to certain stimulus such as salt concentration, temperature, and pH, depending …

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 …

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 …

Synthesis And Characterization Of Clickable Dendrimer Hydrogels For Ocular Drug Delivery, Jingfei Tian

Theses and Dissertations

Topical medication is a standard treatment for glaucoma. However, frequent dosing makes the therapy inconvenient and patient unfriendly. There is a great need to develop new topical formulations that provide long lasting noninvasive drug release. In this thesis, novel clickable dendrimer hydrogels for anti-glaucoma drug delivery were synthesized and characterized. Polyamidoamine (PAMAM) dendrimers have been widely applied for drug delivery. The physical characteristics they possess include monodispersity, water solubility, encapsulation ability, and a large number of surface groups. Polycationic PAMAM dendrimer G3 was surface modified with alkyne-PEG5-acid and then reacted with polyethylene glycol bisazide (PEG-BA, 1100 gmol-1) through click chemistry …

Engineering Beta-Cell Spheroids For Type 1 Diabetes Treatment, Xiaoyan Liu

All Dissertations

Diabetes mellitus, the third most common disease in the world, is a chronic metabolic disorder caused by a failure of insulin production and/or an inability to respond to insulin. Specifically, type 1 diabetes is a disorder characterized by targeted autoimmune-directed destruction of a patient's beta-cell population within the pancreatic islets of Langerhans. The current primary treatment for type 1 diabetes is daily multiple insulin injections. However, this treatment cannot provide sustained physiological release, and the insulin amount is not finely tuned to glycemia. Pancreatic transplants or islet transplants would be the preferred treatment method but the lack of donor tissue …