Engineered 3D Printing Bilayer Scaffold with Spatiotemporal Release of Drug for Synergistic Osteochondral Regeneration

Osteoarthritis (OA) is characterized by the disruption of chondro‐bone homeostasis, where progressive cartilage degeneration and aberrant bone remodeling exacerbate joint dysfunction. Restoring this imbalance remains a critical challenge in OA treatment. Here, a 3D‐printed bilayer scaffold with spatiotemporal release is presented, which integrates an alendronate sodium‐triphenylphosphine (ALN‐TPP)‐loaded polyacrylic acid/methacrylated flaxseed gum (PAA/FGMA) cartilage layer and an ALN‐TPP‐loaded PAA/vinyl‐modified montmorillonite (vinyl‐MMT) bone layer. Specifically, FGMA establishes a biomimetic microenvironment that supports the migration and proliferation of chondrocytes. vinyl‐MMT improves the mechanical strength of the scaffold, providing structural support for bone regeneration. Crucially, the differential degradation kinetics of the scaffolds orchestrate a temporal release of the ALN‐TPP. The faster‐degrading upper layer ensures rapid initial release of ALN‐TPP, which specifically targets dysfunctional mitochondrial metabolism characteristic of OA, reduces oxidative stress, and inhibits the expression of matrix‐degrading enzymes during the early critical phase. Simultaneously, the slower‐degrading lower layer provides a sustained release profile. ALN‐TPP promotes osteogenesis by stimulating osteoblast differentiation, which effectively reverses abnormal bone remodeling in osteoarthritis. In a rabbit model with osteochondral defects, the bilayer scaffold facilitates effective formation of hyaline‐like cartilage and achieves subchondral bone reconstruction. This work establishes a multifunctional therapeutic platform that can advance the repair of osteochondral defects.