Biomedical Engineering and Bioengineering Commons^™

Development Of A Cell-Based Regenerative Strategy To Modulate Angiogenesis And Inflammation In Ischemic Muscle, Fiona E. Serack

Electronic Thesis and Dissertation Repository

The delivery of human adipose-derived stromal cells (hASCs) to ischemic tissues represents a promising strategy to promote vascular regeneration for patients with critical limb ischemia (CLI). This thesis focused on the evaluation of hydrogels to enhance the retention and pro-angiogenic capacity of hASCs following delivery in vivo. Additionally, priming strategies to augment the paracrine function of hASCs were developed and assessed.

Recognizing the importance of endogenous macrophages in the pro-regenerative function of hASCs, delivery using a previously-developed hydrogel system, composed of peptide-functionalized methacrylated glycol chitosan (MGC-RGD) and a copolymer of poly(ethylene glycol) and poly(trimethylene carbonate) (PEG(PTMC-A)₂), was …

Conducting Polypyrrole Hydrogel Biomaterials For Drug Delivery And Cartilage Tissue Regeneration, Iryna Liubchak

Electronic Thesis and Dissertation Repository

Articular cartilage tissue has limited capacity for self-regeneration leading to challenges in the treatment of joint injuries and diseases such as osteoarthritis. The tissue engineering approach combines biomaterials, cells and bioactive molecules to provide a long-term and stable cartilage repair. In the following work, electroactive polymer polypyrrole~(PPy) was incorporated into the synthetic hydrogel to enhance the mechanical properties of the material for cartilage applications. PPy was loaded with drug compound and the \emph{on demand} drug release was demonstrated. The composite PPy hydrogel was 3D printed using stereolithography to create a porous tissue engineering scaffold. Biocompatibility and cell adhesion to the …

Development Of The Cell-Free Protein Biomanufacturing Platform For The Therapeutic Human Protein Production And The Topical Delivery Applications Using The Nanosized Hydrogel System, Jeehye Kim

LSU Doctoral Dissertations

Proteins are highly structural polymers, performing an enormous range of roles within organisms. Unlike synthetic polymers, proteins have a significant hierarchical ordering that can be disrupted by many environmental factors, which limits the scale-up manufacturing capability as well as the utilization of proteins as therapeutic agents. In this study, the Cell-Free Protein Synthesis (CFPS) system was developed to enhance the production capacity and applications of the therapeutic proteins. The CFPS is an advanced biosynthetic and genetic-engineered system. It enables the efficient production of proteins when the conventional cell-based protein synthesis systems cannot be applied, and when sophisticated control is required …

Complementary Techniques To Study The Behavior Of Water And The Effect On Diffusion And Degradation In Hydrogels, Paige Rockwell

Master’s Theses

Hydrogels exhibit biocompatibility in a range of biomedical applications, including drug delivery. This thesis aims to develop complementary techniques to measure the diffusion and degradation behaviors within an injectable, hydrolytically degradable hydrogel, formed via the covalent crosslinking of ethoxylated trimethylolpropane tri-3- mercaptopropionate (ETTMP) and poly(ethylene glycol) diacrylate (PEGDA), to determine its suitability as a drug delivery matrix. The characterization of water as either free, within the network openings of the hydrogel, or bound, tightly associated with the polymer chains, was determined using differential scanning calorimetry (DSC). The mobility of each type of water within the hydrogels was determined via nuclear …

Design Of Cell-Instructive Biomaterial Scaffolds For Intervertebral Disc Regeneration, Nadia Sharma

Electronic Thesis and Dissertation Repository

Biomaterials-based therapies targeting the nucleus pulposus (NP) have the potential to promote regeneration and restore mechanical function to the intervertebral disc. This study developed composite hydrogels incorporating decellularized NP (DNP) and assessed its effects on viability, retention and differentiation of U-CH1 cells, an NP progenitor-like cell line. A minimal protocol was developed to decellularize bovine NP that reduced nuclear content while preserving key extracellular matrix components predicted to be favourable for bioactivity. The resulting DNP demonstrated cell-instructive effects, supporting U-CH1 viability and retention within the hydrogels, and promoted the differentiation of the progenitor-like cells towards an NP-like phenotype. These studies …

Tissue Equivalent Gellan Gum Gel Materials For Clinical Mri And Radiation Dosimetry, Pawel Brzozowski

Electronic Thesis and Dissertation Repository

Hydrogels contain high amount of water allowing their use as surrogates to human tissues with specific properties that can be tuned by additives. Gellan gum is a gel-forming material of interest and is a replacement for other common gelling agent with limited use as a tissue phantom. Therefore, this thesis examines the application of gellan gum gels as a novel magnetic resonance imaging (MRI) phantom with a design of experiments model to obtain tunable properties. The analysis was extended to include mechanical and electrical properties with a separate design of experiment. Gels doped with synthesized superparamagnetic iron oxide nanoparticles (SPIONs) …

Design Of Tissue-Specific Cellular Microenvironments For Adipose-Derived Stromal Cell Culture And Delivery, Arthi Shridhar

Electronic Thesis and Dissertation Repository

The development of in vitro cell culture models that investigate tissue-specific effects of the extracellular matrix (ECM) on stem/progenitor cell lineage-commitment can contribute towards the design of improved cell delivery strategies. This thesis developed processing methods that conserved ECM bioactivity to generate well-characterized 2- and 3-D culture platforms that facilitated the evaluation of ECM composition on the adipogenic and osteogenic differentiation of human adipose-derived stromal cells (ASCs). Initial work compared α-amylase and pepsin digestion as methods to fabricate ECM coatings. The effects of enzyme processing and ECM composition were explored using human decellularized adipose tissue (DAT) and bovine tendon collagen …

Development Of In Situ Forming Hydrogels For Intra-Articular Drug Delivery, Andy Prince

Electronic Thesis and Dissertation Repository

Hydrogels are 3-dimensional crosslinked polymer networks that can absorb significant amounts of water. The physical properties associated with hydrogels affords them resemblance to biological tissues making them good candidates for biomedical applications. Many pharmaceuticals, specifically non-steroidal anti-inflammatory drugs (NSAIDs), have poor aqueous solubility, which limits their bioavailability and efficacy. People suffering from chronic osteoarthritis (OA) are required to frequently take large doses to mitigate pain, which can lead to serious side effects. Hydrogels are good strategies to deliver NSAIDs via articular injection because they can form solid gels in situ. This thesis describes the synthesis, formulation, mechanical testing, in …

Designing Synthetic Environments To Control Valvular Interstital Cells In Vitro, Kent E. Coombs

Biomedical Sciences ETDs

Aortic valve disease (AVD) is a large contributor to health costs in the United States affecting 2.8% of the population greater than 75 years old. With a growing elderly population due to medical advances, AVD will continue to rise in prevalence over time. Current treatments for AVD are insufficient due to a lack of preventative therapies and the bioprosthetic valves used for surgical replacement have major limitations. Tissue engineered heart valves (TEHVs) present an ideal solution to current AVD needs because of their biocompatibility, capability to integrate with the host’s tissue, and ability to utilize the natural repair mechanisms of …

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 …

Degradability Of Poly(Ethylene) Based Microgels And Methods Of Improving High Polydispersity Index, Abrar Alniemi

Williams Honors College, Honors Research Projects

In order to improve upon the utilization of poly(ethylene glycol) (PEG) microgel-based scaffolds in drug delivery applications, this work explores the use of degradable and non-degradable PEG for tunable scaffolds. Previously, issues concerning the required uniformity in microgel size and low polydispersity index have been encountered. As such, methods of refining polymer synthesis, microgel fabrication, and microgel size separation were explored. Overall, no solution has been found to correct the issue for the microgels were still observed to have high polydispersity index regardless of varied troubleshooting alterations.

Tissue-Guided Engineering Of Polyethylene Glycol Hydrogels, Lauren Jansen

Doctoral Dissertations

Polyethylene glycol (PEG) hydrogels are tunable cell culture platforms that recapitulate tissue geometry, water content, and bulk modulus. Despite these benefits, PEG hydrogels elicit an acute immune response, limiting their use in regenerative medicine, and they critically underrepresent the cell-instructive proteins found in the extracellular matrix (ECM). Here, I developed a new class of tissue-specific PEG-based materials and provided biocompatible strategies to improve the user handling and cell viability post-encapsulation when using these hydrogels. I also demonstrated that decreasing the protein fouling to PEG does not decrease the foreign body response to implanted hydrogels, a common misconception in the field. …

Developing Afm Techniques For Testing Peg Hydrogels, Hannah L. Cebull, Jessica Stukel, Rebecca Willits

Williams Honors College, Honors Research Projects

Many instruments are used to find elastic properties of biological samples using methods such as tensile and bending tests, but using the atomic force microscope (AFM) is considered a non-destructive method because it can provide repeated local stiffness information without damaging the sample. It additionally allows the sample to be tested in an aqueous environment, which is optimal for soft materials such as hydrogels. The nanoindentation is performed via cantilever, measuring the deflection of the cantilever during the contact of the sample using a laser. Compared to hard samples, testing soft materials can present more challenges when working with the …

Bioactive Poly(Beta-Amino Ester) Biomaterials For Treatment Of Infection And Oxidative Stress, Andrew L. Lakes

Theses and Dissertations--Chemical and Materials Engineering

Polymers have deep roots as drug delivery tools, and are widely used in clinical to private settings. Currently, however, numerous traditional therapies exist which may be improved through use of polymeric biomaterials. Through our work with infectious and oxidative stress disease prevention and treatment, we aimed to develop application driven, enhanced therapies utilizing new classes of polymers synthesized in-house. Applying biodegradable poly(β-amino ester) (PBAE) polymers, covalent-addition of bioactive substrates to these PBAEs avoided certain pitfalls of free-loaded and non-degradable drug delivery systems. Further, through variation of polymer ingredients and conditions, we were able to tune degradation rates, release profiles, cellular …

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 …