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具有多重止血功效的氧化葡聚糖交联多糖/蛋白/聚多巴胺复合冷冻胶,可用于非压迫性出血和伤口愈合。

Oxidized dextran crosslinked polysaccharide/protein/polydopamine composite cryogels with multiple hemostatic efficacies for noncompressible hemorrhage and wound healing.

机构信息

Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China; Biotech & Biomed Research Institute, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi 710069, China.

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, PR China.

出版信息

Int J Biol Macromol. 2022 Aug 31;215:675-690. doi: 10.1016/j.ijbiomac.2022.06.130. Epub 2022 Jun 29.

Abstract

Noncompressible hemorrhage caused by gunshots and sharp objects leads to higher trauma mortality, and cryogels have great potential in controlling noncompressible hemorrhage applications owing to their shape-memory properties. However, the use of non-toxic crosslinkers to prepare cryogels for noncompressible hemorrhage remains a challenge. In this study, a series of cryogels were prepared using oxidized dextran (ODex) as a biocompatible crosslinker, combined with the good hemostatic properties of chitosan (CS) and human-like collagen (HLC), and polydopamine nanoparticles (PDA-NPs) were also introduced to strengthen the shape recovery speed of the cryogels and further enhance their hemostatic performance. The CS/HLC/ODex/PDA-NPs (CHOP) cryogels presented a highly interconnected macroporous structure, powerful water/blood absorption capacity, robust mechanical performance, and rapid water/blood-triggered shape recovery. In vitro coagulation and coagulation mechanism tests showed that CHOP exhibited strong procoagulant ability, high adhesion to blood cells and fibrinogen, and the capacity to activate platelets and intrinsic pathways. In vivo hemostatic tests indicated that CHOP could effectively shorten the bleeding time and reduce the bleeding volume of liver incision bleeding and liver noncompressible hemorrhage. Meanwhile, CHOP exhibited good biocompatibility and biodegradability, and could promote wound healing. These results suggest that CHOP cryogels will be a promising hemostatic dressing.

摘要

由枪击和锐器造成的不可压缩性出血会导致更高的创伤死亡率,而由于其形状记忆特性,水凝胶在控制不可压缩性出血应用方面具有巨大的潜力。然而,使用无毒交联剂来制备用于不可压缩性出血的水凝胶仍然是一个挑战。在这项研究中,使用氧化葡聚糖 (ODex) 作为生物相容性交联剂,结合壳聚糖 (CS) 和类人胶原蛋白 (HLC) 的良好止血特性,制备了一系列水凝胶,并引入了聚多巴胺纳米粒子 (PDA-NPs) 以增强水凝胶的形状回复速度,并进一步提高其止血性能。CS/HLC/ODex/PDA-NPs (CHOP) 水凝胶呈现出高度互联的大孔结构、强大的水/血吸收能力、强大的机械性能和快速的水/血触发形状恢复。体外凝血和凝血机制测试表明,CHOP 表现出很强的促凝能力,对血细胞和纤维蛋白原具有高亲和力,并且能够激活血小板和内在途径。体内止血测试表明,CHOP 可以有效缩短出血时间,减少肝切开出血和肝不可压缩性出血的出血量。同时,CHOP 表现出良好的生物相容性和可生物降解性,并能促进伤口愈合。这些结果表明,CHOP 水凝胶将是一种有前途的止血敷料。

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