Preparation of self-assembling peptide-based hydrogels and its application in traumatic hemorrhage of hepatic parenchymal

Abstract

Objective To prepare FLIVIGSII peptide (FI peptide) and investigate its physicochemical properties and hemostatic effect in vivo and in vitro. Methods The self-assembling peptide-based hydrogels were prepared by the FI peptide mixed with water. After gross observation for the hydrogel state of the FI peptide, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used for its microstructure, and dynamic light scattering (DLS) was performed for its size. The hemostatic effect of FI peptide after being mixed with blood samples treated with 3.8% sodium citrate was observed, and the microstructure of the blood clot was observed with SEM. CCK-8 assay and hemolysis assay were performed to verify its biocompatibility. After a rat model of hepatic parenchymal perforation and hemorrhage was established, 15 female SD rats (6~8 weeks old, weighing 150 g) were randomly divided into control group, FI peptide group and fibrin sealant group. The hemostatic effect of FI peptide and prognosis was observed and analyzed after treatment in each group, and the hemostatic mechanism was also investigated. Results FI peptides were successfully prepared, and it could rapidly self-assemble into a nanofiber network hydrogel in water, and further cause formation of blood clots. SEM showed that FI peptides self-assembled to form fibrous hydrogels after mixing with water. TEM results verified that the FI peptide formed into nanofibers in a diameter of 13.70±2.31 nm after gelatinization in water, and DLS results verified that the FI peptide formed polydisperse and multi-size nanofibers in water (in a range of 148.2~208.0 nm or 575.0~807.0 nm). The fibrous hydrogel formed by the FI peptide mixed with the blood could envelop the red blood cells, thus form a physical hemostatic barrier to achieve blood clotting in seconds. FI peptide hydrogel had no cytotoxicity to normal hepatocytes (L-O2 cells) and did not cause hemolysis of red blood cells. In in vivo experiment, FI peptide quickly formed nanofiber hydrogel when in contact with blood, thus formed physical hemostasis barrier to achieve hemostasis within a few seconds (hemostasis time < 5 s). Conclusion The FI peptide exhibits a rapid and efficient hemostatic effect, indicating a promising clinical application in the hemostasia of hepatic parenchymal traumatic hemorrhage.

Keywords

• peptide
• self-assembly
• hydrogel
• hemostasis
• liver
• hepatic parenchymal hemorrhage