摘要：The repair of osteochondral defects is one of the major clinical challenges in ***-established osteochondral tissue engineering methods have shown promising results for the early treatment of small ***,less success has been achieved for the regeneration of large defects,which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the *** this study,we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion *** developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite *** microstructure and mechanical properties of the scaffold were examined,and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle *** 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold,and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage,as demonstrated by hyaline-like cartilage *** histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control *** genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control *** findings showed the safety and efficacy of the cell-free“translation-ready”osteochondral scaffold,which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.