Bioinspired and absorbable self-gelling powder with anti-polyelectrolyte effect for effective hemostasis and tissue adhesion prevention of non-compressible wounds.

Abstract

Absorbable self-gelling hemostatic powders derived from natural polyelectrolytes (e.g. gelatin (Gel), starch, chitosan) have been explored for controlling non-compressible hemorrhage. However, their hemostatic efficacy is limited by the inherent polyelectrolyte effect, where salt ions in blood inhibit polymer chain hydration and extension, thereby weakening their rapid self-gelling and wet adhesion. Here, a bioinspired self-gelling powder (PGSB-Gel) based on Gel crosslinked by zwitterionic poly(glycidyl methacrylate-co-sulfobetaine methacrylate) (PGSB) is reported. Owing to the anti-polyelectrolyte effect and electrostatic interactions of zwitterionic poly-sulfobetaine (PSB) moieties, PGSB-Gel powder rapidly absorbs blood, simultaneously triggering its in situ transformation into a robust hydrogel within 6 s. The resulting hydrogel exhibits high adhesive strength (25 ± 2 kPa) and burst pressure (162 ± 9 mmHg) exceeding arterial pressure, ensuring reliable sealing of high-pressure wounds. Together with its bioinspired zwitterionic structure's affinity for blood cell membranes, the hydrogel enhances platelet and red blood cell capture, thus accelerating hemostasis. In multiple in vivo models of non-compressible wounds, PGSB-Gel reduced hemostasis time and blood loss by over 50% compared with commercial powders Celox™ and Bleedstop™, demonstrating superior hemostatic efficacy. Furthermore, this zwitterionic hydrogel serves as an antifouling physical barrier around wounds to prevent tissue adhesion. Overall, this study offers a transformative approach to polyelectrolyte-based hemostats for rapid hemostasis and improved recovery. STATEMENT OF SIGNIFICANCE: Absorbable self-gelling hemostatic powders derived from natural polyelectrolytes have been explored for controlling non-compressible hemorrhage. However, their hemostatic efficacy is limited by the inherent polyelectrolyte effect, where salt ions in blood inhibit polymer chain hydration and extension, thereby weakening their rapid self-gelling and adhesion. Herein, we present a bioinspired self-gelling powder based on natural gelatin crosslinked by a zwitterionic crosslinker. The powder rapidly absorbs blood and instantly self-gels in situ owing to the anti-polyelectrolyte effect and electrostatic interactions. The resulting hydrogel exhibits high adhesive strength, ensuring reliable wound sealing. Together with its zwitterionic structure's affinity for blood cell membranes, the hydrogel enhances blood cell capture, thus accelerating hemostasis. Furthermore, it serves as an antifouling physical barrier to prevent tissue adhesion.