Combating Inflammation and Promoting Anabolism in Osteoarthritic Cartilage Defect With an MMP13‐Sensing Dual‐Drug Scaffold

ABSTRACT Osteoarthritis (OA) is a widespread degenerative joint condition marked by progressive cartilage breakdown, and a chronic inflammatory microenvironment, where conventional therapies largely fail to halt disease progression. To address this unmet need, an intra‐articularly implantable, disease‐responsive scaffold was developed for combinatorial treatment to simultaneously combat inflammation and promote anabolism. The system is based on an MMP13‐sensing peptide‐modified type II collagen scaffold engineered for controlled release of celecoxib (CXB), an anti‐inflammatory agent, and fibroblast growth factor‐18 (FGF‐18), a pro‐anabolic growth factor. Comprehensive physicochemical characterization confirmed the scaffold's porous structure, successful conjugation of the responsive peptide, and MMP13‐dependent drug release. In vitro studies demonstrated excellent biocompatibility, potent anti‐inflammatory effects, and enhanced chondrogenic matrix production under IL‐1β stimulation. When evaluated the rat OA cartilage defect model, the dual‐drug scaffold significantly suppressed inflammation and subchondral bone damage, while promoting early matrix anabolism, and outperforming the control group. This MMP13‐sensing scaffold represents a precision medicine strategy for OA therapy, enabling intelligent, microenvironment‐driven drug delivery to disrupt the degenerative cycle and facilitate synergistic early‐stage anti‐inflammatory and anabolic effects.