title: Chitosan-Coated Diatom Silica as Hemostatic Agent for Hemorrhage Control.
abstract: Uncontrolled hemorrhage leads to high death risk both in military and civilian trauma. Current hemostatic agents still have various limitations and side effects. In this study, natural diatom silica obtained from diatomite and diatom culture was purified and developed for hemorrhage control. To improve the biocompatibility and hemostatic performance of diatom silica, a series of chitosan-coated diatom (CS-diatom) was developed. The composition of CS-diatom prepared was optimized by in vitro hemocompatibility and blood coagulation evaluation for that prepared with 0.5%, 1%, 3%, and 5% chitosan. The results demonstrated that the CS-diatom prepared with 1% chitosan exhibited favorable biocompatibility (hemolysis ratio < 5%, no cytotoxicity to MEFs), great fluid absorbility (24.39 ± 1.53 times the weight of liquid), and desirable hemostasis effect (351 ± 14.73 s at 5 mg/mL, 248 ± 32.42s at 10 mg/mL). Further blood coagulation mechanism study indicated that CS-diatom could provide an ideal interface to induce erythrocyte absorption and aggregation, along with activating the intrinsic coagulation pathway and thus accelerated blood coagulation. Benefitting from the multiple hemostatic performances, CS-diatom showed the shortest clotting time (98.34 ± 26.54 s) and lowest blood loss (0.31 ± 0.11 g) in rat-tail amputation model compare to diatomite and diatom as well as gauze and commercial QuikClot zeolite. The results evidenced that the CS-diatom was a safe and effective hemostatic agent and provided a new understanding of nonsynthetic mesoporous materials for hemorrhage control.
authors.affiliation: College of Marine Life Science, Ocean University of China , 5# Yushan Road, Qingdao 266003, Shandong Province, China.
authors.forename: Chao
authors.identifier: http://orcid.org/0000-0003-2327-1981
authors.initials: C
authors.lastname: Feng
authors.affiliation: College of Marine Life Science, Ocean University of China , 5# Yushan Road, Qingdao 266003, Shandong Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Qingdao First Sanatorium, Jinan Military Region , 27# West Hong Kong Road, Qingdao 266071, Shandong Province, China.
authors.forename: Guang Sheng
authors.initials: GS
authors.lastname: Wu
authors.affiliation: College of Marine Life Science, Ocean University of China , 5# Yushan Road, Qingdao 266003, Shandong Province, China.
authors.forename: Yu Zhi
authors.initials: YZ
authors.lastname: Mu
authors.affiliation: College of Marine Life Science, Ocean University of China , 5# Yushan Road, Qingdao 266003, Shandong Province, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Kong
authors.affiliation: Qingdao Municipal Hospital , 5# East Sea Road, Qingdao 266003, Shandong Province, China.
authors.forename: Chang Qing
authors.initials: CQ
authors.lastname: Jiang
authors.affiliation: College of Marine Life Science, Ocean University of China , 5# Yushan Road, Qingdao 266003, Shandong Province, China.
authors.forename: Xiao Jie
authors.initials: XJ
authors.lastname: Cheng
authors.affiliation: College of Marine Life Science, Ocean University of China , 5# Yushan Road, Qingdao 266003, Shandong Province, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Marine Life Science, Ocean University of China , 5# Yushan Road, Qingdao 266003, Shandong Province, China.
authors.forename: Xi Guang
authors.initials: XG
authors.lastname: Chen
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002460:Cell Line; D048271:Chitosan / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D017377:Diatoms / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005347:Fibroblasts / Q000187:drug effects; D006470:Hemorrhage / Q000188:drug therapy*; D006487:Hemostasis / Q000187:drug effects; D006490:Hemostatics / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry*; D051379:Mice; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D006490:Hemostatics; D012822:Silicon Dioxide; D048271:Chitosan
keywords: chitosan; diatom silica; hemorrhage control; hemostatic agent; porous silicon