Injectable decellularized extracellular matrix hydrogel with cell-adaptable supramolecular network enhances cartilage regeneration by regulating inflammation and facilitating chondrogenesis

Abstract

Osteoarthritis, characterized by progressive loss of cartilage, affects millions of people worldwide and clinically lacks effective treatments. Herein, we present an injectable, biodegradable supramolecular decellularized extracellular matrix (dECM) hydrogel, which can be injected into the joints and provide biomimetic microenvironments to drive cartilage regeneration. Benefiting from the cell-adaptable dynamic network and cartilage-specific compositions, the supramolecular dECM hydrogel not only enhances cell proliferation and migration, but also facilitates chondrogenesis. Furthermore, compared with the conventional dECM hydrogels, the supramolecular dECM hydrogel is instrumental in regulating inflammation, which consequently leads to a marked suppression of genes linked to cell death and cartilage degradation. In vivo analysis confirms that stem cells, when delivered via the supramolecular dECM hydrogel, remain viable for up to three months within the restored cartilage. The regenerated tissue exhibits hyaline-cartilage structure, good mechanical properties, and cartilage-specific extracellular matrix deposition that align closely with those of native cartilage. We envision that this supramolecular dECM hydrogel could serve as a valuable platform for cartilage regeneration and could strongly facilitate the clinical translation of dECM-based materials for tissue regeneration.