Cartilage Decellularized Extracellular Matrix-Based Hydrogel with Enhanced Tissue Adhesion and Promoted Chondrogenesis for Cartilage Tissue Engineering

Articular cartilage defects caused by trauma or osteoarthritis remain a significant challenge in clinical practice due to their poor self-healing capacity. Current clinical approaches are generally limited by their complex procedures or certain postoperation complications. Therefore, it is crucial to develop an effective strategy for one-step cartilage repair with long-term functional cartilage regeneration. This study reports the creation of an injectable hydrogel composed of cartilage decellularized extracellular matrix (CdECM) and hyaluronic acid methacrylate (HAMA). In the presence of photoinitiator ruthenium (Ru)/sodium persulfate (SPS), visible light (450 nm) not only triggered the polymerization of CdECM and HAMA to form stable hydrogel in 1 min but also facilitated the tyrosine cross-links between biotissue and CdECM without any further moiety grafting, which cannot be achieved by routinely used photoinitiators and provides the hybrid hydrogel with bioadhesive properties. This dual-network hybrid hydrogel demonstrated robust adhesion strength to cartilage and significantly enhanced mechanical performance in comparison to that of CdECM or HAMA alone. Further in vitro culture demonstrated the promotive effect of hybrid hydrogel on encapsulated porcine bone marrow mesenchymal stem cells toward chondrogenic differentiation after 21 days of incubation compared with HAMA. Through in vivo subcutaneous implantation in a mouse model for two and 4 weeks, we further illustrated that the hybrid hydrogel has improved biocompatibility in comparison to HAMA alone. Thus, the presented hydrogel is a promising biomaterial for cartilage regeneration through minimally invasive arthroscopic injection in clinical practice.