3D Printed Silk Fibroin‐Gelatin Construct Targeting BMP Signaling for Articular Cartilage Regeneration Within a Full‐Thickness Cartilage Defect in a Surgically Induced Osteoarthritic Rat Knee Joint

ABSTRACT Regenerating articular cartilage within osteoarthritis (OA)‐affected joints remains a long‐standing challenge. This study introduces a novel chemically modified silk‐based biomaterial to modulate key signaling pathways involved in OA and cartilage repair. The designed biomaterial concurrently inhibits the bone morphogenetic protein (BMP) signaling, aberrantly activated during OA, and inherently facilitates Wnt/β‐catenin signaling, a crucial factor for chondrogenesis and cartilage homeostasis. The dual modulation was achieved by covalently conjugating the potent BMP inhibitor LDN‐193189 to the Silk Fibroin–Gelatin (SF‐G) bioink. The chemically decorated SF‐G construct served as a biomimetic delivery platform and a mechanically robust support, ideally suited for regenerating load‐bearing articular cartilage. The functionalized material was implanted into a critical‐sized cartilage defect in the rat femoral trochlear groove, which had been previously subjected to OA by anterior cruciate ligament transection. The results confirmed successful neocartilage regeneration, evidenced by dense Safranin O staining and expression of cartilage‐specific collagen. The absence of hypertrophic markers, fibrocartilage, and inflammation indicates the authenticity of hyaline cartilage formation in a severe OA microenvironment. Overall, the LDN‐193189‐conjugated SF‐G construct overcame the challenges of maintaining phenotypic stability in articular cartilage of OA joints, representing a promising regenerative approach for restoring lost cartilage.