Osteochondral Tissue Engineering for the TMJ Condyle Using a Novel Gradient Scaffold

Abstract

The articulation of the temporomandibular joint (TMJ), or the jaw joint, is one of the most complex and least studied joints of the musculoskeletal system. Painful disorders of the TMJ, known as temporomandibular disorders (TMDs), have considerable prevalence with over 10 million patients in the United States alone, which may severely interfere with everyday activities like chewing, yawning, talking, and laughing. Within the TMJ, the inferior joint space, which includes the mandibular condyle, typically sustains the greatest damage in TMDs. The objective of this thesis was to characterize the condylar cartilage biomechanics, and to explore novel routes to fabricate integrated gradient-based osteochondral constructs. Pioneering efforts were made toward understanding structure-function correlations for the condylar cartilage. A greater stiffness of the condylar cartilage in the anteroposterior direction than in the mediolateral direction under tension was observed, corresponding to the never before seen anteroposterior organization of collagen fibers. A positive correlation between the thickness and stiffness of the cartilage under compression suggested that their regional variations may be related phenomena caused in response to cartilage loading patterns. Beyond these vital biomechanical characterization efforts, novel microsphere-based gradient scaffolds were developed to address functional osteochondral tissue regeneration. Novel microsphere sintering routes, using ethanol as an anti-solvent or sub-critical CO2 for melting point depression, were established to construct microsphere-based scaffolds. A technique to create opposing macroscopic gradients of encapsulated growth factors using poly(D,L-lactide-co-glycolic acid) microspheres was developed, and in vitro studies with human umbilical cord stem cells provided promising results for osteochondral tissue regeneration. By encapsulating nanoparticles in the microspheres, a proof-of-concept was provided for creating functional scaffolds with a gradient in stiffness. This thesis lays down the foundation for a combined growth factor-stiffness gradient approach that could lead to a translational-level regenerative solution to osteochondral tissue regeneration with extended applications in other areas, including tissue engineering of heterogeneous/interfacial tissues.