An Injectable and Photocrosslinkable Hydrogel Based on Recombinant Human Collagen Type XVII Promotes Osteochondral Regeneration by Activating the TGF β/SMAD Signaling Pathway.

The management of articular cartilage defects remains a major clinical challenge owing to the tissue's limited intrinsic regenerative capacity. Conventional collagen-based hydrogels often fail to achieve functional repair due to a mismatch between their biological functions and mechanical properties. Here, for the first time, we apply recombinant human collagen type XVII (rhCOL17) to cartilage repair by engineering an injectable and photocrosslinkable hydrogel based on rhCOL17. A systematic screening identified the 15% methacrylated rhCOL17 (CMA) formulation as possessing optimal mechanical properties and biocompatibility, featuring a suitable 3-dimensional porous structure, moderate swelling, slow degradation, and rapid in situ photocrosslinking capability. In vitro experiments demonstrated that the CMA hydrogel is noncytotoxic and notably promotes the proliferation, migration, and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and chondrocytes, as evidenced by the up-regulation of SOX9, COL2, and ACAN. In vivo, using a rat knee joint full-thickness cartilage defect model, the BMSCs-laden 15% CMA composite hydrogel (BMSCs@CMA) achieved superior osteochondral integrated repair, with the regenerated tissue closely resembling native cartilage in macroscopic morphology, subchondral bone mineralization, histological structure, and collagen type II deposition. Mechanistically, transcriptome sequencing, molecular docking, and molecular dynamics simulations collectively demonstrate that rhCOL17 directly binds to transforming growth factor-β1 (TGF-β1) with high affinity and stable interaction, subsequently activating the TGF-β/SMAD signaling pathway to orchestrate BMSCs chondrogenesis. In conclusion, this study establishes the pivotal role of collagen type XVII in cartilage regeneration, presenting a promising, minimally invasive strategy with mechanical adaptability and active inductive functionality for functional cartilage defect repair, and expands the cross-tissue application prospects of rhCOL17.