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 …

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 …

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 …

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 …

Characterization Of Swelling Ratio And Water Content Of Hydrogels For Cartilage Engineering Applications, Emily E. Gill, Renay S.-C. Su, Julie C. Liu

The Summer Undergraduate Research Fellowship (SURF) Symposium

Due to the high prevalence of arthritis and cartilage-related injuries, tissue engineers are studying ways to grow cartilage tissue replacements. Resilin, an elastomeric protein found in insect cuticles, is known for its extraordinary resilience and elasticity. In previous studies, recombinant resilin-based hydrogels, or cross-linked protein networks, exhibited potential for use in cartilage tissue scaffolds. Our lab successfully developed resilin-based proteins with a sequence based on the mosquito gene and showed that resilin-based hydrogels possess mechanical properties of the same order of magnitude as native articular cartilage. In addition, these mechanical properties can be controlled by changing the protein concentration. To …

Adhesive Elastomeric Proteins, Haefa Mansour, Julie Liu

The Summer Undergraduate Research Fellowship (SURF) Symposium

Sutures and staples commonly used to close surgical wounds tend to be much stiffer than the surrounding tissue, often resulting in external tissue damage. Surgical adhesives provide a promising alternative to these sutures and staples. Ideal surgical adhesives are biocompatible, able to set well and remain sticky in moist conditions, possess strong adhesive and cohesive properties, and exhibit mechanical properties that mimic those of the surrounding tissue. Unfortunately, the adhesives available today are unable to satisfactorily meet all of these criteria. We are utilizing protein engineering techniques to design, create, and test a new surgical adhesive that combines the adhesive …