A multifunctional self-gelling hemostatic powder based on synergistic non-covalent interactions for rapid hemostasis and infected wound healing.

Abstract

Rapidly controlling severe hemorrhage, especially from non-compressible wounds or under challenging physiological conditions, remains a critical clinical challenge often unmet by current hemostatic materials that are limited by insufficient adhesion, mechanical robustness, or environmental stability. Herein, we address these limitations through rational molecular designing of a self-gelling hemostatic powder (P-pUMAA/QCS) based on synergistic non-covalent interactions. The cornerstone of our design strategy is the incorporation of urea-functionalized methacrylic acid (UMAA) as a powerful hydrogen bonding motif, which provides exceptional cohesive energy and interfacial adhesion critical for rapid hemostasis under demanding physiological conditions. This robust hydrogen bonding network synergizes with electrostatic interactions from quaternized chitosan (QCS), endowing the P-pUMAA/QCS with ultrafast in situ self-gelling (<15 s in blood, <3 s in acidic fluid) through rapid reconstruction of synergistic non-covalent interactions, strong wet-tissue adhesion (up to 76 kPa), and superior mechanical integrity capable of withstanding arterial pressure (>140 mmHg). Furthermore, the P-pUMAA/QCS demonstrates good biocompatibility, potent antibacterial activity, and rapid procoagulant effects. In vivo studies demonstrate rapid hemostasis in challenging models and accelerated infected wound healing through modulated inflammation and enhanced tissue regeneration. This multi-interaction approach yields a high-performance powder, offering a promising multifunctional platform for advanced hemorrhage control and wound management. STATEMENT OF SIGNIFICANCE: Uncontrolled bleeding is a leading cause of preventable death, yet current hemostatic materials often fail in challenging scenarios such as arterial or acidic gastric bleeds. Our study introduces a self-gelling hemostatic powder, designed at the molecular level, that harnesses synergistic non-covalent interactions between specially designed components. Our design incorporates urea-functionalized methacrylic acid, which provides powerful hydrogen bonding, working synergistically with electrostatic interactions from quaternized chitosan. This synergistic approach enables ultrafast in situ self-gelling, exceptional tissue adhesion, and mechanical integrity capable of withstanding arterial pressure. Beyond bleeding control, it exhibits antibacterial activity and accelerates healing. Animal studies demonstrate superior hemostatic performance across multiple bleeding models. This multi-interaction approach yields a high-performance powder, offering a promising multifunctional platform for advanced hemorrhage control and wound management.