3D‐Printed In Situ Growth of Bilayer MOF Hydrogels for Accelerated Osteochondral Defect Repair

Abstract Repairing osteochondral (OC) defect presents a significant challenge due to the intricate structural requirements and the unpredictable differentiation pathways of bone marrow mesenchymal stem cells (BMSCs). To address this challenge, a novel biomimetic OC hydrogel scaffold is developed that features a structure of soft and hard components. This scaffold incorporates bilayer metal–organic frameworks (MOFs), specifically ZIF‐67 in the upper layer and ZIF‐8 in the lower layer, achieved through an in situ printing process. This configuration enables the spatial and temporal modulation of BMSC differentiation by controlling the release of Co 2 ⁺ and Zn 2 ⁺. The results demonstrate that the bilayer MOF hydrogels significantly outperform hydrogels that either lack MOFs or contain a single type of MOF in enhancing repair outcomes in rabbit models of knee OC defects. The improved regenerative efficacy is attributed to the distinct chondrogenic and osteogenic differentiation cues provided by the bilayer MOFs, effectively guiding BMSCs toward enhanced tissue regeneration. This customizable biomimetic OC hydrogel scaffold not only opens new avenues for innovative therapeutic strategies but also holds great promise for widespread clinical applications.