Nano-assisted dynamically assembled hydrogels with strong tissue adhesion and proactive immunomodulation for bone defect repair

The repair of tissue injuries, particularly irregular bone defects, continues to pose a significant challenge in the surgical field. Long-term enhancements in mechanical support, inflammation control, and osteogenic activity are essential for effective treatment of bone defects. Despite the development of numerous scaffold materials for bone regeneration, their limitations in shape adaptability, tissue adhesion, and immunomodulatory capabilities have restricted their applications in repairing irregular bone defects. Herein, we introduce a supramolecular assembly strategy for fabricating scaffolds based on polyphenols, polypeptides, and clay nanosheets (CNSs). This method synergistically integrates robust bio-adhesion, superior mechanical properties, and immunoregulatory functionality into a self-healing hydrogel system designed for treating irregular bone defects. The catechol and guanidinium groups within the hydrogel enable strong adhesion to bone tissue while exhibiting excellent antimicrobial and immunomodulatory activities. Furthermore, the incorporation of CNSs not only enhances the mechanical strength of the hydrogels but also significantly promotes the osteogenic differentiation of bone mesenchymal stem cells through the release of bioactive ions. In vivo studies demonstrated that the mechanically nano-enhanced, bio-adhesive, and immunomodulatory hydrogel effectively adapts to defects, adheres to bone tissue, positively regulates the inflammatory microenvironment, and ultimately accelerates the healing of bone defects, representing a promising and versatile strategy for the regeneration of bone and other tissue injuries. • A nanoclay co-assembled dynamic hydrogel based on antibacterial peptide and punicalagin was fabricated via cation-π strategy. • The polyphenol and cationic groups enabled synergistically nano-enhanced mechanical and adhesion properties of hydrogel. • The hydrogel exhibited excellent antioxidant, immunomodulatory and osteogenic activities. • The dynamically assembled hydrogel showed great potential for the treatment of irregular bone defects.