Biomimetic Peptide Nanoparticles Participate In Natural Coagulation For Hemostasis And Wound Healing

Uncontrollable hemorrhage is a major challenge in surgical procedures and after major trauma.Without an effective hemostasis after injuries,excessive blood loss and even death might occur.In addition,the rapid wound healing cannot be ignored.Currently,various hemostatic agents have been designed in clinical practice.However,these hemostatic agents show limited efficacy in hemostasis and wound healing property,and are often non-biodegradable,or may induce immune response.Hence,there is an urgent need for advanced hemostatic materials with excellent hemostatic and wound healing efficacy.Peptides become the research direction of hemostatic materials because of the good biocompatibility and biosafety.Inspired by native coagulation process,herein,we designed and prepared a biomimetic self-assembled peptide network.This peptide network consists of two peptides,including the platelet mimicking peptide C₆KL and the fibrin mimicking peptide C₆KG.The C₆KL nanoparticles（NPs）can bind to the collagen at the wound site and transform into nanofibers.On the other hand,the C₆KG NPs can bind to GPIIb/IIIa receptors on the surface of activated platelets and transform into nanofibers.The in situ formed peptide network could interwind platelets,fibrin and red blood cells,forming embolism in the wound site and performing high efficacy in hemostatic and wound healing.Here,the C₆KL and C₆KG were prepared through standard solid-phase peptide synthesis techniques.transmission electron microscopy（TEM）,scanning electron microscopy（SEM）and confocal laser scanning microscopy（CLSM）experiments confirmed that C₆KL NPs could specifically adhere to collagen,then transformed into fibrous structures on the surface of collagen.On the other hand,C₆KG NPs specifically bound to GPIIb/IIIa receptors and fibrosis on the activated platelets and induce platelet aggregation.Then the platelet adhesion experiment indicated that the C₆KG NPs could induce the aggregation of activated platelets.The whole blood clotting experiment further showed that the blood clotting index in C₆KG group was lower than that of PBS group,indicting a faster clotting rate.The wound healing experiment validated that C₆KG NPs could promote the fibroblast cell migration,significantly improve the wound healing rate,and benefit to wound healing.Next,we embedded C₆KL and C₆KG NPs into CS/Alg solution to prepare C₆KL/C₆KG@CS/Alg solution.From the result of Rheometer spectra,the elasticity and viscosity of CS/Alg gel was improved by C₆KL/C₆KG peptides,which are beneficial to the adhesion of the hemostatic solution to the wound surface.Finally,C₆KL/C₆KG@CS/Alg solution was employed to treat three acute tissue injuries.Compared with blank group and CS/Alg group,the short bleeding time and small amount of blood loss in C₆KL/C₆KG@CS/Alg group validated the hemostatic efficacy.The injury livers were collected 14 d post-surgery,C₆KL/C₆KG@CS/Alg solution treated liver had remarkably smaller wound area,and the infiltration of liver cells was obvious.In summary,we designed a biomimetic self-assembled peptide network,to specifically target collagen and activated platelets at wound site by mimicking and participating in natural coagulation.The in situ constructible peptide network exhibited high hemostatic efficiency and accelerated wound healing ability.In addition,C₆KL and C₆KG showed excellent biocompatibility.Overall,the biomimetic self-assembled peptides C₆KL and C₆KG showed promising potential in disposing of massive hemorrhages as wound hemostatic drugs.