Multifunctional ultrafast hydrogel for arthroscopic surgery: An enzymatically cross-linked, nanosilicate-reinforced system promotes dual cartilage and subchondral bone regeneration

Background: Arthroscopic repair of osteochondral (OC) defects using injectable hydrogels remains highly challenging due to the high-pressure, water-filled environment of the joint during arthroscopic surgery. Conventional hydrogels exhibit slow gelation kinetics, prolonged setting times, poor adhesion to wet tissues, and insufficient mechanical strength, rendering them prone to washout throughout the procedure. Methods: To address these limitations, we incorporated a small amount of transglutaminase (TG) and synthetic lithium silicate nanoplatelets (SN) into a gelatin-oxidized starch (GelS) precursor and evaluated the regenerative performance of the resulting hydrogel under simulated arthroscopic conditions. In vivo, the hydrogels were implanted into osteochondral defects in rats to assess their repair efficacy. Results: The GelS-TG-SN hydrogel demonstrated ultrafast enzymatic gelation, robust underwater adhesion, and significantly enhanced mechanical strength. It was cytocompatible, displayed anti-inflammatory activity, and supported context-dependent dual-lineage differentiation of Synovial-derived stem cells (SDSCs) chondrogenesis in a cartilage-like niche and PI3K-Akt-mediated osteogenesis in a vascular-like niche. Following 8-week implantation, it enabled coordinated regeneration of cartilage and subchondral bone, recapitulating native osteochondral architecture. Conclusion: The GelS-TG-SN nanocomposite hydrogel offers a compelling strategy for effective osteochondral regeneration in arthroscopic surgical environments. The Translational Potential of this Article: This hydrogel platform offers an elegant and clinically accessible solution for arthroscopic osteochondral repair. Its ultrafast gelation-achieved in under one minute-combined with resilient adhesion under constant irrigation enables seamless intraoperative application without auxiliary instrumentation. By capitalizing on the body's intrinsic osteochondral gradient, a single injection orchestrates synchronized regeneration of cartilage and subchondral bone. Such integration of procedural simplicity with inherent regenerative bioactivity underscores its promise as a genuinely "one-step" therapy ready for clinical translation.