Multifunctional Hemostatic Hydrogels Based on Natural Ionic Polymers: Dual Crosslinking Strategy for Rapid Bleeding...

Uncontrolled hemorrhage remains a critical challenge in emergency and trauma scenarios, with limited options that combine rapid hemostasis, robust wet-tissue adhesion, and infection prevention in a single platform. Herein, this study reports a dual-crosslinked hydrogel system fabricated from natural ionic polymers-chitosan (CS), gelatin, and sodium alginate (SA)-incorporated with silver nanoparticles (AgNPs). The synergistic application of ionic crosslinking (Ca²⁺-mediated carboxyl coordination) and covalent crosslinking (genipin-mediated amino coupling) constructs a mechanically robust and cohesively stable network, overcoming the common trade-off between swelling capacity and mechanical strength in polysaccharide-based hydrogels. Systematic orthogonal optimization yielded a formulation (4% CS, 28.5% gelatin, 25% SA, 3 mg/mL AgNPs, and 0.1 mol/L Ca²⁺) that achieves a compressive strength of 2.71 MPa and an adhesion strength of 168.83 kPa. In a mouse liver injury model, both in situ and ex situ-applied hydrogels significantly shortened bleeding time and reduced blood loss by approximately 47 ± 2.5% and 49 ± 1.9%, respectively, demonstrating rapid and effective hemostasis. Moreover, an in vitro cell relative growth rate exceeding 85% was obtained from cultures with hydrogel leachate, confirming excellent antibacterial activity and biocompatibility. This study presents a multifunctional hydrogel with potent hemostatic performance and favorable biological properties for potential emergency care applications.