The most severe cases of TMJ disorders consist of mandibular condyle degeneration. Unfortunately, no regenerative options exists 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. A condylar defect will be treated with novel multilayer scaffold implant designed to promote site-specific tissue regeneration. We have strong pilot in-vivo data showing that our scaffolds components regenerate fibrous and cartilage tissue in our novel goat model, and bone in a segmental defect model. We will implant the scaffolds in a mediolateral grove-shaped condylar defect. We 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, we will study the properties of a multilayer scaffold design in-vitro. We will characterize the permeability and release of TGFβs from the scaffold. Second, we will assess the functional healing of condylar defects treated with the multilayer scaffolds. We will assess mechanical properties, regenerate tissue composition, and condylar architecture formation using terminal assays at 1, 3 and 6 months post-surgery. Third, we will study the regeneration potential of three cell subpopulations found on the condyle. Successful completion of this proposal is the critical step to provide a regenerative therapy to treat TMJ mandibular cartilage degeneration, and a basis for successful osteochondral tissue regeneration in other sites.

This proposal develops an acellular therapy for the in vivo regeneration of the mandibular condyle cartilage of the temporomandibular joint using a novel multi-layer scaffold design and biomaterials. The novel scaffold design will be used to recapitulate the native tissue architecture. Furthermore, we have developed a novel clinically relevant injury model for the TMJ in goats, which is used in the proposed studies.