Fabricating Multifunctional Hemostatic Sponge For Hemorrhage Control And Healing Promotion Of Irregular Wound

Uncontrollable bleeding is the main cause of many trauma-associated deaths which usually occur in battlefields,medical emergency and operating rooms.The hemostatic sponges with good liquid absorbability and wound blocking capacity are widely used in daily life,operating rooms and battlefields.However,the traditional hemostatic sponges are inefficient for deep,irregular and noncompressible wounds with uncontrollable hemorrhage.Besides,wound healing encompasses a complex process of hemostasis,inflammation or migration,proliferation and tissue remodeling.After the sponges accomplish hemostasis,the residual materials may provide a favorable environment for the colonization of microorganisms,resulting in severe inflammatory response and delayed wound healing.As a result,it is important to fabricate multifunctional hemostatic sponges to control the noncompressible hemorrhage,prevent infection and accelerate wound healing.1.A dual-functional hemostatic sponge（TRAP-Sp）with a microporous structure and good mechanical properties for controlling massive and noncompressible hemorrhage was prepared by chemically immobilizing thrombin-receptor-agonist-peptide（TRAP）onto a starch/polyethylene glycol（PEG）sponge.The TRAP2-Sp1showed the best hemostatic performance among all samples in both rat artery uncontrollable hemorrhage and liver defect noncompressible hemorrhage models.When analyzing the hemostatic mechanism of TRAP-Sp,the high water absorption capacity of the sponge contributed to absorbing plasma,concentrating blood cells,and enhancing blood coagulation.After absorbing water,the shape-fixed TRAP-Sp with sufficient mechanical strength and high resilience can rapidly expand and apply pressure to the wound.TRAP immobilized on the sponge could activate the adhered platelets in an active pathway.Additionally,evaluation of cytotoxicity,hemolysis,and histology further highlighted the adequate biocompatibility of TRAP-Sp.2.A kind of starch-based macroporous sponges（KR-Sps）immobilized covalently with antimicrobial peptide KR12 using highly efficient thiol-ene photo click reaction were developed.The physical properties of these sponges could be fine-tuned by varying the ratio of modified starch/HS-PEG-SH and the polymer concentration.The in vitro and vivo results demonstrated that KR-Sps induced thrombosis,shortened clotting time and reduced the blood loss at bleeding site.Besides,KR12 immobilized sponge exhibited inherent antimicrobial properties against Gram（+）and（-）bacteria and methicillin-resistant Staphylococcus aureus（MRSA）,which could maintain at least5 days.3.A series of high fluid absorbent composite sponges with rapid expansion ability based on norbornene anhydride-modified polyvinyl alcohol（PVA）and gelatin were developed by foaming technique,chemical and physical crosslinking reaction,lyophilization.The prepared PVA@Gel-Sp₂ exhibited 3500%maximum water absorption ratio with a fast water absorption speed.Owing to the interconnected macroporous structure,good mechanical strength and high resilience,the compressed sponge could rapidly re-expand to more than 10 times volume in response to water and blood.Because of the synergistic effect of PVA-based sponge and gelatin,PVA@Gel-Sp₂ exhibited better hemostatic performance in vitro blood clotting tests,rat liver volume defect and femoral artery injury model.Besides,the full-thickness skin defect model had demonstrated that PVA@Gel-Sp₂could accelerate wound healing.In summary,the above porous sponges synthesized by foaming technology and photo crosslinking reaction possessed rapid shape recovery or expansion ability to fill the wound and block off the bleeding,which could be potentially applied in deep,irregular and noncompressible wounds with uncontrollable hemorrhage.The platelet-activated peptide was immobilized on the sponge to accelerate hemostasis in an active pathway;the antimicrobial peptide was immobilized to endow the sponge with antimicrobial property to prevent infection;the gelatin was incorporated into the sponge to provide natural cell adhesion motifs to accelerate wound healing.In this paper,based on porous sponge,a series of multifunctional expandable sponges were synthesized by chemical surface modification of peptide and integrating dual or multiple substrates together,which provided new strategies for fabricating hemostatic,antibacterial and wound healing dressings.