The fibrocartilage temporomandibular joint (TMJ) disc plays an essential role in normal joint function. In the majority of temporomandibular disorders, the disc is susceptible to degeneration and has little ability for self-repair. No alloplastic disc replacements have proven to be suitable for use, therefore tissue engineering is a promising approach that aims to develop a biologically functional disc replacement that could integrate with the joint and restore normal function. Porcine TMJ discs are a readily available scaffold material with an intrinsically similar morphology and characteristic extracellular matrix (ECM) alignment as the human TMJ disc that could be used as an ex vivo derived scaffold material. However, success of tissue engineering is limited by cellular integration and long term viability in dense scaffolds directed, in part, by diffusion limitations and alteration of the ECM. This work first validated the tissue engineering approach through characterization of chronically deformed TMJ discs, identifying key regional deviations in the intermediate and posterior zones of the disc due to disease. Then, focusing on the intermediate region of the disc, investigated how processing methods such as sterilization, decellularization, and laser micro-ablation to incorporate an artificial microporosity in the porcine TMJ disc, can be modulated to produce a scaffold that supports improved cell adhesion with minimal compromise to biomechanical integrity. With a mesenchymal stromal cell population, this scaffold was further shown to support extended cell growth, site-specific remodeling, and chondrogenesis in the presence of exogenous transforming growth factor-beta. Lastly, the feasibility of creating a scaffold that includes the entire disc and attachment tissue was investigated as a method to improve physiologic integration. A biomimetic whole disc culture system that could be used to investigate early cellular integration and remodeling was designed. The processing methods and culture paradigms developed herein can be used to produce a porcine derived TMJ disc biomaterial scaffold, including native attachment tissue, towards the purpose of generating a TMJ disc replacement.
|Advisor:||McFetridge, Peter S.|
|Commitee:||Allen, Kyle, McFetridge, Peter S., Schmidt, Christine, Vincent, Heather|
|School:||University of Florida|
|School Location:||United States -- Florida|
|Source:||DAI-B 80/07/(E), Dissertation Abstracts International|
|Keywords:||Decellularization, Fibrocartilage, Regenerative medicine, Temporomandiblar joint, Tissue eingineering|
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