An Injectable Dual-Layer Hydrogel Integrating Adhesive and Bioactive Functions for Cartilage Regeneration.

Abstract

Minimally invasive cartilage repair demands injectable hydrogels that can adhere strongly within fluid-filled joint environments, sustain mechanical integrity under physiological loading, and deliver bioactive cues to direct chondrogenesis. Here, a two-step bioadhesive hydrogel platform that unites interfacial chemistry with biological functionality for effective articular cartilage regeneration is reported. An aldehyde-functionalized hyaluronic acid (Ald-HAMA) primer forms rapid Schiff-base linkages with amine-rich cartilage surfaces, establishing a stable adhesive interface. A secondary photo-cross-linkable hydrogel composed of methacryloyl-modified gelatin (GelMA), hyaluronic acid (HAMA), and platelet lysate (PLMA) overlays this priming layer, generating a cohesive, bioactive composite upon UV exposure. The dual-layer system achieves ultrafast gelation (≤60 s, G' = 7.31 kPa), robust compressive strength (53.3 kPa), and high interfacial adhesion (136 kPa) under aqueous conditions. Incorporation of PLMA enables sustained release of endogenous growth factors, significantly enhancing glycosaminoglycan deposition and collagen type-II expression relative to the clinical standard Chondro-Gide. Ex-vivo cartilage defect models further demonstrate strong interfacial integration and neotissue formation. This modular, injectable adhesive hydrogel has potential to integrate with existing arthroscopic workflows, offering a clinically translatable strategy that bridges mechanical stability, bioadhesion, and biochemical signaling for next-generation cartilage regeneration therapies.