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

Abstract 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 CaCl 2 ‐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 Ca 2+ 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.