Modular alginate-based hydrogels embedding multilayer nanofibers: A synergistic strategy for hemostasis,...

Non-compressible hemorrhage remains a leading cause of trauma mortality, with ineffective management triggering infection, dysregulated inflammation, and multi-organ dysfunction. Herein, we report a multilayer nanofiber-reinforced alginate hydrogel (GT-F) combining rapid hemostasis, strong tissue adhesion, high mechanical resilience, and wound healing. The hydrogel matrix, composed of dopamine-modified methacrylate alginate (AMD) and gelatin methacryloyl (GelMA), was incorporated with tranexamic acid (TAX). The biomimetic multilayer nanofiber framework is constructed from hydrophobic polycaprolactone (PCL) and simultaneously encapsulates both the natural medicinal compound curcumin (Cur) and the quaternary ammonium antibacterial agent (HDEAB). Experimental results indicate that, within an optimal range, increasing AMD content enhances hydrogel crosslinking density, reducing pore size and equilibrium swelling. Compared to conventional GelMA hydrogel, compressive strength was nearly quadrupled, and tensile strength increased over threefold. In vitro and in vivo studies confirm that GT-F hydrogels exhibit excellent biocompatibility, degradability, rapid hemostasis (<30 s), and robust antimicrobial and antioxidant properties. In a rat liver puncture model, GT-F hydrogels markedly outperformed commercial gauze in hemostasis, reduced macrophage inflammatory infiltration, promoted proliferating cell nuclear antigen (PCNA) expression, accelerated wound repair, and exhibited anti-adhesion effects. Collectively, this study offers a promising hydrogel-based adhesive strategy for clinical management of non-compressible hemorrhage and tissue repair.