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

Feng, Yajun; Zhang, Zixuan; Yan, Wenjing; Zhang, Zhuo; Li, Yang; Zhu, Chenhui; Fan, Daidi · Adv Mater · 2025

basic_science · Level V

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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<sub>2</sub>-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<sup>2+</sup> 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.

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