Mussel-Inspired Tissue-Adhesive Hydrogel Based on the Polydopamine–Chondroitin Sulfate Complex for Growth-Factor-Free Cartilage Regeneration

Glycosaminoglycan-based hydrogels are widely used for cartilage repair because glycosaminoglycans are the main component of the cartilage extracellular matrix and can maintain chondrocyte functions. However, most of the glycosaminoglycan-based hydrogels are negatively charged and cell-repellant, and they cannot host cells or favor tissue regeneration. Inspired by mussel chemistry, we designed a polydopamine-chondroitin sulfate-polyacrylamide (PDA-CS-PAM) hydrogel with tissue adhesiveness and super mechanical properties for growth-factor-free cartilage regeneration. Thanks to the abundant reactive catechol groups on the PDA, a cartilage-specific PDA-CS complex was formed by the self-assembly of PDA and CS, and then the PDA-CS complex was homogenously incorporated into an elastic hydrogel network. This catechol-group-enriched PDA-CS complex endowed the hydrogel with good cell affinity and tissue adhesiveness to facilitate cell adhesion and tissue integration. Compared with bare CS, the PDA-CS complex in the hydrogel was more effective in exerting its functions on adhered cells to upregulate chondrogenic differentiation. Because of the synergistic effects of noncovalent interactions caused by the PDA-CS complex and covalently cross-linked PAM network, the hydrogel exhibited super resilience and toughness, meeting the mechanical requirement of cartilage repair. Collectively, this tissue-adhesive and tough PDA-CS-PAM hydrogel with good cell affinity creates a growth-factor-free and biomimetic microenvironment for chondrocyte growth and cartilage regeneration and sheds light on the development of growth-factor-free biomaterials for cartilage repair.