Integrated and Bifunctional Bilayer 3D Printing Scaffold for Osteochondral Defect Repair

Abstract Bioinspired scaffolds with two distinct regions resembling stratified anatomical architecture provide potential strategies for osteochondral defect repair and are studied in preclinical animals. However, delamination of the two layers often causes tissue disjunction between the regenerated cartilage and subchondral bone, leading to few commercially available clinical applications. This study develops an integrated poly(ε‐caprolactone) (PCL)‐based scaffold for repairing osteochondral defects. An extracellular matrix (ECM)‐incorporated 3D printing composite scaffold (ECM/PCL) coated with ECM hydrogel (E‐co‐E/PCL) is fabricated as the upper layer, and magnesium oxide nanoparticles coated with polydopamine (MgO@PDA)‐incorporated composite scaffold (MD/PCL) is fabricated using 3D printing as the bottom layer. The physicochemical and mechanical properties of the bilayer scaffold meet the requirements in designing and fabricating the osteochondral scaffold, especially a strong interface possessed between the two layers. By in vitro study, the integrated scaffold stimulates proliferation, chondrogenic differentiation, and osteogenic differentiation of human bone mesenchymal stem cells. Moreover, the integrated bilayer scaffold exhibits well repair ability to facilitate simultaneous regeneration of cartilage and subchondral bone after implanting into the osteochondral defect in rats. In addition, cartilage “tidemarks” completely regenerated after 12 weeks of implantation of the bilayer scaffold, which indicates no tissue disjunctions formed between the regenerated cartilage and subchondral bone.