Wang YING, Jie LUO, Chuanhao ZHENG, et al. Preparation of self-assembling peptide-based hydrogels and its application in traumatic hemorrhage of hepatic parenchymal[J]. Journal of Army Medical University, 2024, 46(11): 1206-1213.
DOI:
Wang YING, Jie LUO, Chuanhao ZHENG, et al. Preparation of self-assembling peptide-based hydrogels and its application in traumatic hemorrhage of hepatic parenchymal[J]. Journal of Army Medical University, 2024, 46(11): 1206-1213. DOI: 10.16016/j.2097-0927.202402062.
Preparation of self-assembling peptide-based hydrogels and its application in traumatic hemorrhage of hepatic parenchymal
To prepare FLIVIGSII peptide (FI peptide) and investigate its physicochemical properties and hemostatic effect
in vivo
and
in vitro
.
Methods
2
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
2
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 rang
e 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
2
The FI peptide exhibits a rapid and efficient hemostatic effect
indicating a promising clinical application in the hemostasia of hepatic parenchymal traumatic hemorrhage.
关键词
Keywords
references
ALGHAMDI T, VIEBAHN C, JUSTINGER C, et al . Arterial blood supply of liver segment Ⅳ and its possible surgical consequences[J ] . Am J Transplant, 2017, 17(4): 1064-1070. DOI: 10.1111/ajt.14089.
XIANG C G, DU Y Y, MENG G F, et al . Long-term functional maintenance of primary human hepatocytes in vitro [J ] . Science, 2019, 364(6438): 399-402. DOI: 10.1126/science.aau7307..
GUO B L, DONG R N, LIANG Y P, et al . Haemostatic materials for wound healing applications[J ] . Nat Rev Chem, 2021, 5(11): 773-791. DOI: 10.1038/s41570-021-00323-z.
REN H, ZHANG Z, CHENG X L, et al . Injectable, self-healing hydrogel adhesives with firm tissue adhesion and on-demand biodegradation for sutureless wound closure[J ] . Sci Adv, 2023, 9(33): eadh4327. DOI: 10.1126/sciadv.adh4327.
CROSS A J, CONNOR S J. Hemostasis and thrombosis in major liver resection[J]. Semin Thromb Hemost, 2015, 41(1): 99-107. DOI: 10.1055/s-0034-1398385.
YUK H, WU J J, SARRAFIAN T L, et al . Rapid and coagulation-independent haemostatic sealing by a paste inspired by barnacle glue[J ] . Nat Biomed Eng, 2021, 5(10): 1131-1142. DOI: 10.1038/s41551-021-00769-y.
ZHAO W B, SUN W T, WANG W J, et al . Robust and wet adhesive self-gelling powders for rapid hemostasis and efficient wound healing[J ] . ACS Appl Mater Interfaces, 2024, 16(6): 6756-6771. DOI: 10.1021/acsami.3c14944.
LIU C K, LIU C, LIU Z Y, et al . Injectable thermogelling bioadhesive chitosan-based hydrogels for efficient hemostasis[J ] . Int J Biol Macromol, 2023, 224: 1091-1100. DOI: 10.1016/j.ijbiomac.2022.10.194.
CHEN Z M, ZHANG K, FAN J Q, et al . In situ construction of ligand nano-network to integrin αvβ3 for angiogenesis inhibition[J ] . Chin Chem Lett, 2020, 31(12): 3107-3112. DOI: 10.1016/j.cclet.2020.04.006..
LI M M, ZHAO X R, DAI J F, et al . Peptide therapeutics and assemblies for cancer immunotherapy[J ] . Sci China Mater, 2019, 62(11): 1759-1781. DOI: 10.1007/s40843-019-9451-7.
GUAN T, LI J Y, CHEN C Y, et al . Self-assembling peptide-based hydrogels for wound tissue repair[J ] . Adv Sci, 2022, 9(10): e2104165. DOI: 10.1002/advs.202104165.
SUN W Z, GREGORY D A, ZHAO X B. Designed peptide amphiphiles as scaffolds for tissue engineering[J]. Adv Colloid Interface Sci, 2023, 314: 102866. DOI: 10.1016/j.cis.2023.102866.
HE H J, LIU S, WU D F, et al . Enzymatically formed peptide assemblies sequestrate proteins and relocate inhibitors to selectively kill cancer cells[J ] . Angew Chem Int Ed, 2020, 59(38): 16445-16450. DOI: 10.1002/anie.202006290.
ZENG X Z, AN H W, WANG H. Chemical reactions trigger peptide self-assembly in vivo for tumor therapy[J ] . ChemMedChem, 2021, 16(16): 2452-2458.DOI: 10.1002/cmdc.202100254.
WEI S D, CHEN F P, GENG Z, et al . Self-assembling RATEA16 peptide nanofiber designed for rapid hemostasis[J ] . J Mater Chem B, 2020, 8(9): 18 97-1905. DOI: 10.1039/c9tb02590a.
SUBRAMANIAM S, KANDIAH K, CHEDGY F, et al . A novel self-assembling peptide for hemostasis during endoscopic submucosal dissection: a randomized controlled trial[J ] . Endoscopy, 2021, 53(1): 27-35. DOI: 10.1055/a-1198-0558.
HAO R R, PENG X T, ZHANG Y, et al . Rapid hemostasis resulting from the synergism of self-assembling short peptide and O -carboxymethyl chitosan[J ] . ACS Appl Mater Interfaces, 2020, 12(50): 55574-55583. DOI: 10.1021/acsami.0c15480..
JIA Z G, WHITAKER S K, TOMICH J M, et al . Organization and structure of branched amphipathic oligopeptide bilayers[J ] . Langmuir, 2016, 32(38): 9883-9891. DOI: 10.1021/acs.langmuir.6b02421.
BARROS S M, WHITAKER S K, SUKTHANKAR P, et al . A review of solute encapsulating nanoparticles used as delivery systems with emphasis on branched amphipathic peptide capsules[J ] . Arch Biochem Biophys, 2016, 596: 22-42. DOI: 10.1016/j.abb.2016.02.027.
BARROS S M, AVILA L A, WHITAKER S K, et al . Branched amphipathic peptide capsules: different ratios of the two constituent peptides direct distinct bilayer structures, sizes, and DNA transfection efficiency[J ] . Langmuir, 2017, 33(28): 7096-7104. DOI: 10.1021/acs.langmuir.7b00912.
ZHAO X, LUO J L, HUANG Y, et al . Injectable antiswelling and high-strength bioactive hydrogels with a wet adhesion and rapid gelling process to promote sutureless wound closure and scar-free repair of infectious wounds[J ] . ACS Nano, 2023, 17(21): 22015-22034. DOI: 10.1021/acsnano.3c08625.