A Sprayable Hydrogel Based on Biomimetic Polypeptide‐Modified Lipid Nanoparticles for Treating Non‐Compressible Hemorrhaging

Non-compressible hemorrhaging is the main cause of death in modern warfare. A biomimetic peptide-modified lipid nanoparticle-based sprayable hydrogel is developed to mimic and amplify the blood coagulation process for effective hemostasis. A platelet adhesion peptide (PAP, sequence: GFOGER) and platelet crosslinking peptide (PCP, sequence: GGQQLK) are customized and conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N[methoxy (polyethylene glycol) 2000] acid (DSPE-PEG2000-COOH) via amido bonds to form DSPE-PEG-PAP and DSPE-PEG-PCP, respectively. These compounds are mixed with distearoyl-sn-glycero-3-phosphocholine, cholesterol, and distearoyl-sn-glycero-3-phospho-L-serine (DSPS) to construct the peptide-modified lipid nanoparticles via thin film rehydration. The nanoparticles are incorporated into a CaCl₂-sodium alginate sprayable hydrogel crosslinked via ionic bonds. The application of the hydrogel solution quickly gels and seals the wound. The PAP activates and adheres platelets, the DSPS and Ca²⁺ amplify prothrombin activation, and PCP strengthens the fibrin network. The hydrogel achieves rapid hemostasis within 30 s in a liver hemorrhage model. This sprayable hydrogel has significant potential for managing non-compressible hemorrhaging.