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一种热交联方法,用于开发增强型弹性壳聚糖水凝胶,以用于控制严重出血的止血管理。

A thermal cross-linking approach to developing a reinforced elastic chitosan cryogel for hemostatic management of heavy bleeding.

机构信息

State Key Laboratory of Heavy Oil Processing, College of Chemistry and Chemical Engineering, China University of Petroleum (East China), 66 West Changjiang Road, Qingdao, Shandong 266580, China.

State Key Laboratory of Heavy Oil Processing, College of Chemistry and Chemical Engineering, China University of Petroleum (East China), 66 West Changjiang Road, Qingdao, Shandong 266580, China.

出版信息

Carbohydr Polym. 2024 Dec 1;345:122599. doi: 10.1016/j.carbpol.2024.122599. Epub 2024 Aug 9.

DOI:10.1016/j.carbpol.2024.122599
PMID:39227116
Abstract

Uncontrolled hemorrhage stands as the primary cause of potentially preventable deaths following traumatic injuries in both civilian and military populations. Addressing this critical medical need requires the development of a hemostatic material with rapid hemostatic performance and biosafety. This work describes the engineering of a chitosan-based cryogel construct using thermo-assisted cross-linking with α-ketoglutaric acid after freeze-drying. The resulting cryogel exhibited a highly interconnected macro-porous structure with low thermal conductivity, exceptional mechanical properties, and great fluid absorption capacity. Notably, assessments using rabbit whole blood in vitro, as well as rat liver volume defect and femoral artery injury models simulating severe bleeding, showed the remarkable hemostatic performance of the chitosan cryogel. Among the cryogel variants with different chitosan molecular weights, the 150 kDa one demonstrated superior hemostatic efficacy, reducing blood loss and hemostasis time by approximately 73 % and 63 % in the hepatic model, and by around 60 % and 68 %, in the femoral artery model. Additionally, comprehensive in vitro and in vivo evaluations underscored the good biocompatibility of the chitosan cryogel. Taken together, these results strongly indicate that the designed chitosan cryogel configuration holds significant potential as a safe and rapid hemostatic material for managing severe hemorrhage.

摘要

在民用和军事人群中,创伤后无法控制的出血是潜在可预防死亡的主要原因。为了应对这一关键的医疗需求,需要开发一种具有快速止血性能和生物安全性的止血材料。本工作描述了一种壳聚糖基水凝胶的工程设计,该水凝胶通过冷冻干燥后使用α-酮戊二酸进行热辅助交联。所得水凝胶具有高度互联的大孔结构、低导热系数、优异的机械性能和出色的流体吸收能力。值得注意的是,使用兔全血进行的体外评估,以及模拟严重出血的大鼠肝体积缺陷和股动脉损伤模型,均表明壳聚糖水凝胶具有出色的止血性能。在具有不同壳聚糖分子量的水凝胶变体中,分子量为 150 kDa 的水凝胶变体在肝模型中表现出更优的止血效果,可将失血量和止血时间分别减少约 73%和 63%,在股动脉模型中可减少约 60%和 68%。此外,全面的体外和体内评估强调了壳聚糖水凝胶良好的生物相容性。综上所述,这些结果强烈表明,设计的壳聚糖水凝胶结构具有作为安全快速止血材料用于严重出血管理的巨大潜力。

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