Chitosan/hyaluronic acid-based hydrophobic-covalent double-network hydrogel: phenylalanine-mediated erythrocyte anchoring for rapid hemostasis, anti-swelling, and antioxidation.

This study addresses critical limitations of conventional hemostatic materials-such as significant swelling and inadequate adhesion to wet tissues-by developing an injectable and photocurable hydrogel (OPP-HAMA). The hydrogel is constructed through a rational molecular design: phenylalanine is grafted onto an oxidized chitosan backbone via a Schiff base reaction, thereby introducing hydrophobic domains and active hemostatic sites. Subsequently, polyethylene glycol is conjugated to enhance structural flexibility, followed by crosslinking with methacrylated hyaluronic acid to form a stable dual-network architecture. This engineered structure enables excellent injectability and rapid photopolymerization within 30 s, facilitating the effective sealing of irregularly shaped wounds. The synergistic contribution of the positively charged chitosan moiety and hydrophobic interactions from phenylalanine promotes erythrocyte aggregation and platelet activation, enabling rapid hemostasis in clinically relevant models, including liver resection and cardiac puncture. The densely crosslinked network, reinforced by hydrophobic regions, exhibits outstanding anti-swelling properties (swelling ratio < 50%), thereby preventing tissue compression and maintaining robust adhesion under wet conditions (∼20 kPa). Moreover, the hydrogel demonstrates notable antioxidant and antibacterial activities, significantly accelerating wound repair in full-thickness skin injury models. This work presents a novel and integrated strategy for designing carbohydrate-based hydrogel adhesives with combined anti-swelling capabilities and highly efficient hemostatic performance.