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用于凝血功能障碍穿透性伤口快速止血的液体激活自膨胀壳聚糖形状记忆冷冻凝胶

Liquid-Activated Self-Expanding Chitosan Shape Memory Cryogel for Rapid Hemostasis in Penetrating Wounds with Coagulation Disorders.

作者信息

Zhang Yuhui, Lang Yuanru, Zhang Jiakang, Fu Tao, Zhao Lin, Liu Qian, Chen Long, Zhang Peng, Zhang Yuntong, Fang Shuo, Lang Meidong

机构信息

Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China.

Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P. R. China.

出版信息

ACS Appl Bio Mater. 2025 Oct 20;8(10):9161-9179. doi: 10.1021/acsabm.5c01305. Epub 2025 Sep 25.

Abstract

Due to the complexity of anatomical structure, noncompressible hemorrhage in coagulation disorders often misses the ″golden window" of emergency treatment and becomes the key problem in trauma management. In this work, CS/ODX-G shape-memory cryogel with three-dimensional interoperable porous structure based on chitosan/oxidized dextran system was constructed by a strategy of synergistic cross-linking of dynamic Schiff base bonding and covalent bonding. The cryogel can be implanted minimally invasively with precompression technology. It swells rapidly in situ with blood triggering and utilizes elastic recoil properties to precisely conform to irregular wounds and create a dynamic mechanical compression effect. Additionally, synergistic effects of the capillary effect of multistage channels and surface amine protonation promote fibrin deposition, ultimately forming a multimode coordinated hemostatic mechanism of "morphology adaptation-mechanical compression-coagulation regulation". Meanwhile, cryogels exhibit broad-spectrum antimicrobial resistance and outstanding biocompatibility. In rat tail amputation, rat liver perforation, and normal/coagulopathic rabbit liver hemorrhage models, CS/ODX-G cryogel demonstrated excellent hemostatic efficacy and significant clinical advantages. Through multilevel structural design and coagulation pathway regulation, this work innovatively exploits cryogel that can adapt to the morphology of deep cavities and expedite the coagulation cascade, providing a hemostatic solution with rapid response and intelligent regulation for battlefield injuries (especially for patients with deep wounds and coagulopathies).

摘要

由于解剖结构的复杂性,凝血障碍中的不可压缩性出血常常错过紧急治疗的“黄金窗口”,成为创伤管理中的关键问题。在这项工作中,基于壳聚糖/氧化葡聚糖体系,通过动态席夫碱键和共价键协同交联的策略构建了具有三维互穿多孔结构的CS/ODX-G形状记忆冷冻凝胶。该冷冻凝胶可采用预压缩技术进行微创植入。它在血液触发下原位快速膨胀,并利用弹性回缩特性精确贴合不规则伤口,产生动态机械压迫效果。此外,多级通道的毛细作用和表面胺质子化的协同作用促进纤维蛋白沉积,最终形成“形态适应-机械压迫-凝血调节”的多模式协同止血机制。同时,冷冻凝胶具有广谱抗菌性和出色的生物相容性。在大鼠断尾、大鼠肝穿孔以及正常/凝血障碍兔肝出血模型中,CS/ODX-G冷冻凝胶展现出优异的止血效果和显著的临床优势。通过多级结构设计和凝血途径调控,这项工作创新性地开发出一种能够适应深部腔体形态并加速凝血级联反应的冷冻凝胶,为战场创伤(尤其是深部伤口和凝血障碍患者)提供了一种具有快速响应和智能调控功能的止血解决方案。

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