Statement of Purpose: Osteochondral defects (OCD) are common problems in orthopedics. The simultaneous regeneration of injured cartilage and subchondral bone is critical and a big challenge for the healing of osteochondral (OC) tissue. Our group recently developed high strength silk/silk-nano CaP (Silk/Silk-NanoCaP) scaffolds for OC regeneration. This study aimed to evaluate the in vivo biocompatiblity and OC repair performance of the bilayered scaffolds in rabbit model.