Date of Award

5-11-2025

Date Published

June 2025

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical and Chemical Engineering

Advisor(s)

Mary Beth Monroe

Keywords

fistula;hydrogel;PVA;scaffold;tissue engineering;wound healing

Abstract

Wound healing is a complex physiological process in reaction to tissue injury. Our bodies are generally capable of healing wounds on their own, unless the wound volume is too large and/or the normal physiological functions are interrupted due to disease. In these cases, the principles of wound healing can be applied in tissue engineering to develop new tissues that replace damaged tissue. Despite significant advances in research, key challenges in wound healing and tissue engineering remain unsolved, including chronic wound non-healing and complex, but scalable scaffold construction. Hydrogels are crosslinked polymers with three-dimensional networks that can hold excess amounts of fluid, and they can serve as scaffolds that mimic extracellular matrixes. This dissertation employs hydrogels to solve key problems in tissue engineering and wound healing applications. The first project concentrated on a major challenge in tissue engineering scaffolds: controlling scaffold degradation rates during healing while maintaining mechanical properties to support tissue formation. To address this problem, chitosan methacrylate was blended with poly(vinyl alcohol) (PVA) methacrylate (ChiPVAMA) using different photoinitiators to construct a photo-crosslinked hydrogel system. The ChiPVAMA platform displays fascinating properties for TE scaffolds, including degradability, tunability, suitability for cell encapsulation, and antimicrobial efficacy. This work provides a new hydrogel library for tissue engineering scaffolds and holds significant potential for applications in microfabrication and wound healing. In the second project, a novel hydrogel foam system was designed to treat chronic wounds (e.g., diabetic ulcers) with the ability to deliver mesenchymal stem cells (MSCs). MSCs, with their multifunctional differentiation capabilities, have been used to enhance wound closure but often suffer from limited engraftment. The PVA/Gelatin hydrogel scaffolds are rapidly fabricated using a cytocompatible gas blowing process to encapsulate MSCs within porous hydrogel foams. The porous structure within the resulting hydrogels allows nutrient and waster transfer to improve long-term MSC viability. By optimizing the thiol/methacrylate ratio of PVA combined with GelMA, a fully degradable platform that supports cell attachment was fabricated. These hybrid hydrogel foams, with encapsulated therapeutic cells, demonstrate strong potential for robust wound healing and serve as a promising platform for chronic wound dressings. In the third project, an advanced hydrogel system was developed with potential for treatment of fistula in Crohn’s disease (CD). A fistula is an abnormal tunnel connecting the gastrointestinal tract to the skin, causing abscesses, infections, and significant emotional distress for patients. Improved fistula plugs could reduce treatment invasiveness and improve long-term healing outcomes. Current plugs fail to address the pathophysiology of fistulas, which is hypothesized to contribute to high recurrence rates. To address this need, a hydrogel-based fistula plug was designed to target the underlying biological mechanisms of fistula formation, particularly the loss of the epithelial-mesenchymal transition (EMT) reversibility. Curcumin, a wound healing agent, was physically incorporated into a PVA/Gelatin hydrogel, and the effect of the system on the EMT was scrutinized. The results showed that curcumin effectively prevented the EMT while eliminating biofilm formation. This fully degradable and scalable system presents an excellent candidate for development of an injectable treatment for Crohn’s fistulas. These comprehensive works expand the scaffold library for tissue engineering and wound healing applications.

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Open Access

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Available for download on Thursday, June 18, 2026

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