PROJECT SUMMARY The most severe cases of TMJ disorders consist of mandibular condyle degeneration. Unfortunately, no regenerative options exist, and current treatments do not restore full function. The articulating tissue of the condyle is a fibrocartilage that consists of an intricate interface between fibrous, cartilaginous, and boney tissue that is essential for normal function and that is lost in severe TMJ disorders. The objective of this study is to regenerate fibrocartilage-bone interface of the mandibular condyle in skeletally mature goats using a comprehensive tissue engineering approach. I hypothesize that a multilayer scaffold will allow for site-specific fibrous-cartilage-bone regeneration of the mandibular condyle cartilage when compared to a homogenous sponge scaffold and untreated control defects. First, I will study the properties of a multilayer scaffold design in-vitro. I will characterize the permeability and release of TGFβs from the scaffold. Second, I will study the regeneration potential of three cell subpopulations found on the condyle. Third, I will implant our scaffold in mandibular condyle defects of goats and assess their potential for functional regeneration. This proposal highlights the contributions that the PI will make throughout the duration of the training, which will primarily focus on the completion of scaffold fabrication and characterization, as well as the study of the regenerative potential of TMJ cells subpopulations in vitro and of our bilayer scaffold in vivo. Successful completion of this proposal is the critical step to providing a regenerative therapy to treat TMJ mandibular cartilage degeneration and a basis for successful osteochondral tissue regeneration in other sites.