Project Summary Approximately 10-25% of the population has degeneration of the temporomandibular joint (TMJ) condyle. Cartilage does not heal itself, and there are no mid-stage interventions to prevent condylar degeneration which can lead to life-threatening conditions such as changes to the airway. This proposal aims to improve translation of tissue engineering strategies for TMJ condylar regeneration toward human use in the clinic via characterization of the mandibular condyle of the Yucatan minipig, engineering neocartilage-bone implants with robust interfacial properties, and in vivo studies using neocartilage-bone implants to regenerate osteochondral defects of the TMJ condyle. Preliminary proteomics data show that spatial distributions of collagen types I and II can be achieved using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), indicators of fibrocartilage and hyaline articular cartilage, respectively. MALDI-IMS will serve as a powerful tool in a characterization of the Yucatan minipig mandibular condyle, including the spatial distributions of collagen types I, II, X, and XXVII. This characterization will provide gold standards for tissue-engineering approaches to treat condylar defects. Preliminary ex vivo experiments indicate a high feasibility of creating osteochondral defects on the TMJ condyle. Through these novel techniques, I will enhance tissue-engineering approaches for TMJ condyle regeneration in three specific aims. In Specific Aim 1, many techniques, including MALDI-IMS, will be used to characterize the TMJ condyle of the Yucatan minipig. This characterization will result in gold standard values for engineered tissues. In Specific Aim 2, a novel tissue-engineering technique involving seeding of mesenchymal stem cells into decellularized bone scaffolds, then combining with self-assembled neocartilage, will be interrogated. This will result in the formation of neocartilage-bone implants with robust interfacial properties for long term in vivo efficacy. Finally, in Specific Aim 3, neocartilage-bone implants will be used in a large animal study, where they will regenerate defects of the Yucatan minipig TMJ condyle. Successful completion of this proposal will enhance the translation of tissue engineering strategies for TMJ disorders toward the FDA paradigm of clinical trials and human use in the clinic.

Project Narrative Temporomandibular joint (TMJ) condyle degeneration affects approximately 50M Americans, and tissue- engineered implants have the potential to regenerate osteochondral defects on the TMJ condyle. This proposal will characterize the TMJ condyle of the Yucatan minipig, engineer neocartilage-bone implants with robust interfacial properties, and regenerate osteochondral defects of the TMJ condyle in a large minipig model. Successful completion of this proposal will enhance translation of neocartilage-bone implants toward human use by showing safety and efficacy in an in vivo model, modeled after FDA preclinical definitive animal studies.