3D-Printed Dual-Lineage Inductive Approach for Efficient Osteochondral Regeneration

Abstract

Osteochondral defect regeneration is challenging due to the mismatch between cartilage and subchondral bone. We developed a functionalized scaffold replicating the natural architecture, biochemical and biomechanical environment of both tissues to promote concurrent regeneration. Our bilayered, zone-specific scaffold combines tailored materials for each tissue type: gelatin methacryloyl (GelMA), modified hyaluronic acid, and umbilical cord-derived extracellular matrix (ECM) for the cartilage layer; GelMA, placenta-derived ECM, and nano amorphous calcium phosphate for the osseous layer. Using 3D digital light-processing printing, we constructed the scaffold with spatially distributed biochemical and biomechanical signaling. This approach created dual chondro-/osteogenic microenvironments facilitating bone marrow mesenchymal stem cell differentiation. In vivo studies demonstrated concurrent regeneration of cartilage and subchondral bone tissues with robust integration. This 3D-printed biomimetic scaffold, featuring dual-lineage inductive properties, shows promising potential for efficient osteochondral regeneration and addresses complex tissue engineering requirements.