Event Abstract Back to Event Development of biphasic scaffolds with distinct mechanical properties for the regeneration of osteochondral interface Zheng Zhang1, Jared Bushman1 and Joachim Kohn1 1 Rutgers, The State University of New Jersey, New Jersey Center for Biomaterials, United States Introduction: Osteochondral (OC) defects develop into osteoarthritis (OA), which affects 27 million Americans. Current surgical treatments and bioengineering approaches are non-restorative. The goal of this study is to regenerate OC interface using integrated, biphasic scaffolds composed of layers with distinct mechanical properties that support chondrogenic and osteogenic differentiations. Materials and Methods: Copolymers of poly(trimethylene carbonate) (PTMC), desaminotyrosyl tyrosine ethyl ester (DTE), and desaminotyrosyl tyrosine (DT) were prepared by triphosgene chemistry. Biphasic scaffolds composed of a flexible layer based on PTMC-DTE-DT overlaying a rigid layer with proven osteogenicity[1]-[3] were fabricated by sequentially pouring polymer slurries containing pre-sieved salt particles, followed by lyophilization and salt leaching. Results and Discussion: PTMC-DTE-DT copolymers are made of non-toxic monomers. PTMC is flexible and elastic[4],[5]; DTE provides stability and allows for cell attachment and proliferation; DT contains free carboxylic acid groups enabling functionalization and degradation. Copolymers with varying PTMC content showed E-modulus values ranging from 1 MPa (flexible) to 2 GPa (rigid). Interestingly, the copolymers with 80wt% of PTMC were highly stretchable (strain at break > 1000%) and elastic (permanent set < 5%, after 20 cycles to 50% strain). Copolymers with a high DT content swelled, degraded and dissolved within 1 wk, while copolymers with a high DTE content showed a slow degradation with mass loss < 5wt% at week 8. Selected copolymers supported attachment, proliferation, and chondrogenesis of human mesenchymal stem cells (hMSCs), and were biocompatible and biodegradable with good in vitro-in vivo correlations. Biphasic scaffolds with two well-integrated, yet distinct, regions designed to support the formation of bone and cartilage were fabricated (Figure 1). This study focuses on the rapid chondrogenesis of the cartilage layer. hMSCs were seeded to biphasic scaffolds from the cartilage-layer and cultured at chondrogenic conditions. As shown in Figure 2, the bone layer remained unchanged, while the cartilage layer swelled significantly. The bone layer displayed a very low Alcian Blue signal while the cartilage layer, especially the one with smaller pores, elicited a much stronger signal demonstrating relative abundance of glycosaminoglycans (GAGs) indicative of chondrogenic differentiation. The swelling in the chondrogenic layer may facilitate the integration of newly regenerated cartilage with the surrounding endogenous cartilage. The gel-like state is consistent with conditions (low modulus, high water content) that promote chondrogenic differentiation. Conclusions: Biphasic scaffolds with distinct mechanical properties were fabricated and used for bioengineering of OC. The low modulus, high elasticity and rapid swelling of the cartilage layer create biomimetic mechanical interface for OC regeneration. This work was supported in part by Award Number P41EB001046 from the National Institute of Biomedical Imaging and Bioengineering