Dopamine-functionalized bioinspired pre-chondrogenic hydrogel for cell-free cartilage regeneration

Articular cartilage has limited self-repair capacity due to the low metabolic activity and sparse distribution of chondrocytes. Although implantation of scaffolds that could induce the recruitment and chondrogenesis of endogenous bone marrow mesenchymal stem cells (BMSCs) provides a promising strategy for in-situ cartilage regeneration, establishing a culture environment suitable for the proliferation and oriented differentiation of BMSCs is challenging. Here, inspired by native cartilage architecture, we develop a biomimetic pre-chondrogenic hydrogel. Specifically, dopamine-functionalized chondroitin sulfate and hyaluronic acid are integrated into a self-assembled type I collagen network to mimic the cartilage-like extracellular matrix, while Kartogenin (KGN)-conjugated polydopamine nanoparticles are incorporated into the scaffold. In vitro and in vivo results demonstrated that the cartilage-mimicking microenvironment supports various cellular activities. The abundant dopamine in the hydrogel effectively attracts BMSCs and modulates oxidative stress. Meanwhile, the sustainable KGN release driven by the hydrolysis of covalent bonds promotes chondrogenic differentiation of recruited cells, thereby accelerating the repair of full-thickness cartilage defects. The synchronization effects of these two components achieved superior repair outcomes, providing support for the further application of cell-free advanced biomaterials scaffold in cartilage tissue engineering.