A Chitosan‐Dextran Hydrogel Based on a Site‐Isolated Grafting Strategy for Long‐Term Wet Tissue Adhesion and Wound Healing

To address the poor wet adhesion and limited functionality of existing hydrogel dressings, this study develops a PCMC-DODS dual-network hydrogel based on chitosan and dextran via a mussel-inspired, site-isolated grafting strategy. Protocatechuic aldehyde and dopamine are separately conjugated onto two distinct polysaccharide backbones; the steric hindrance of the chains suppresses polyphenol self-polymerization, while Schiff base and hydrogen bonds form a dynamic crosslinking network. The hydrogel gels within 30 s, is injectable and self-healing, and achieves a lap shear strength of 50.2 kPa on porcine skin after 24 h, significantly outperforming a commercial fibrin sealant. It exhibits ∼90% DPPH radical scavenging, clear antibacterial inhibition zones against E. coli and S. aureus, and good biocompatibility. In a rat tail amputation model, it reduces blood loss by ≈76.9% versus control and matches the hemostatic efficacy of the clinical fibrin sealant. In a full-thickness skin defect model, it scavenges reactive oxygen species, alleviates inflammation, and accelerates healing, leaving only 9.8% residual wound area by day 9. This work provides a practical spatial-isolation strategy for robust wet adhesion in natural bio-based hydrogels, highlighting the clinical potential of PCMC-DODS as a multifunctional tissue adhesive and wound dressing.