Protonated-chitosan sponge with procoagulation activity for hemostasis in coagulopathy  

作　　者：Zhenhua Huang Dong Zhang Laiqiang Tong Fan Gao Shaozan Zhang Xinqing Wang Yina Xie Fangping Chen Changsheng Liu 

机构地区：[1]Engineering Research Center for Biomedical Materials of Ministry of Education,East China University of Science and Technology,Shanghai,200237,PR China [2]Key Laboratory for Ultrafine Materials of Ministry of Education,School of Materials Science and Engineering,East China University of Science and Technology,Shanghai,200237,PR China

出　　处：《Bioactive Materials》2024年第11期174-192,共19页生物活性材料（英文）

基　　金：National Natural Science Foundation of China(No.32171342;51772100);National Key Research and Development Program of China(2022YFB3804300).

摘　　要：Hemostatic materials are essential for managing acute bleeding in medical settings.Chitosan(CS)shows promise in hemostasis but its underlying mechanism remains incompletely understood.We unexpectedly discovered that certain protonated-chitosan(PCS)rapidly assembled plasma proteins to form protein membrane(PM)upon contact with platelet-poor plasma(PPP).We hypothesized that the novel observation was intricately related to the procoagulant effect of chitosan.Herein,the study aimed to elucidate the conditions necessary and mechanism for PM formation,identify the proteins within the PM and PCS's procoagulant action at the molecule levels.We confirmed that the amount of–NH3+groups(>4.9 mmol/g)on PCS molecules played a crucial role in promoting coagulation.The–NH3+group interacted with blood's multiple active components to exert hemostatic effects:assembling plasma proteins including coagulation factors such as FII,FV,FX,activating blood cells and promoting the secretion of coagulation-related substances(FV,ADP,etc)by platelets.Notably,the hemostatic mechanism can be extended to protonated-chitosan derivatives like quaternized,alkylated,and catechol-chitosan.In the blood clotting index(BCI)experiment,compared to other groups,PCS95 achieved the lowest BCI value(∼6%)within 30 s.Protonated-chitosan exhibited excellent biocompatibility and antibacterial properties,with PCS95 demonstrating inhibition effectiveness of over 95%against Escherichia coli(E.coil)and Staphylococcus aureus(S.aureus).Moreover,PCS performed enhanced hemostatic effectiveness over chitosan-based commercially agents(Celox™and ChitoGauze®XR)in diverse bleeding models.In particular,PCS95 reduced bleeding time by 70%in rabbit models of coagulopathy.Overall,this study investigated the coagulation mechanism of materials at the molecular level,paving the way for innovative approaches in designing new hemostatic materials.

关 键 词：SPONGE INCOMPLETE sized 

分 类 号：O62[理学—有机化学]