Tunable gelatin-based semi-IPN adhesive hydrogel for enhanced self-healing and hemostatic performance

Herein, we report semi-interpenetrating polymer network (semi-IPN) hydrogels composed of gelatin conjugated with oxidized caffeic acid and L-arginine (L-Arg), and various concentrations of acrylamide (6, 12, and 24 wt%). The resulting semi-IPN hydrogels (A-GelCA-A) provide covalent and dynamic reversible bonding, enabling tunable mechanical performances, self-healing ability, and biological activity. Among all formulations, A-GelCA-A hydrogel containing 12% acrylamide (A-GelCA-12 A), shows the optimized characteristics, including superior strength (4.9 ± 0.1 MPa), appropriate toughness (19.6 ± 2.2 kJ/m³), and viscoelastic stability. This hydrogel also exhibits self-healing ability and strong tissue adhesion (430 ± 20 kPa). Hemostatic evaluations reveal rapid clotting, minimal hemolysis (<5%), and reduced blood loss, attributed to the synergistic role of catechol and guanidinium groups. In vitro and in vivo studies also confirm that A-GelCA-A hydrogels are cytocompatible and could accelerate the wound healing process. These findings suggest that A-GelCA-12 A has the potential for use as a hemostatic adhesive for wound healing applications.