An Interleukin 4 Loaded Bi-phasic 3D Printed Scaffold Promotes Osteochondral Defect Regeneration

Multilayer scaffolds fabricated by 3D printing or other techniques have been applied to repair and regenerate osteochondral defects. However, it still remains a challenge of repairing and regenerating the articular cartilage and subchondral bone simultaneously. In this study, to enhance the repair efficacy of osteochondral defect, an interleukin-4 (IL4) incorporated bi-phasic scaffold was designed and fabricated by using digital light processing (DLP) and fused deposition modeling (FDM) printing techniques. The upper layer was the IL4 loaded radially-oriented gelatin methacrylate (GelMA) scaffold (GelMA-IL4) which was produced by DLP printing; its physical and biological properties were suitable for cartilage repair, and the IL4 reduced the negative effect of IL1β and M1 macrophages on chondrocytes in the inflammatory environment in vitro. The lower layer was the porous polycaprolactone and hydroxyapatite (PCL-HA) scaffold that was fabricated by FDM printing. It promoted osteogenic differentiation of cells. In the rabbit model with osteochondral defect, the IL4 loaded bi-phasic scaffold (bi-scaffold+IL4) showed an excellent performance in promoting the repair and regeneration of bone and significantly enhanced cartilage regeneration with more and healthier neo-cartilage tissue formation. Thus, the IL4 loaded bi-phasic scaffold has shown great potential to enhance regeneration of subchondral bone and cartilage and provides a promising strategy for repair of osteochondral defects.