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

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.