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多功能氧化葡聚糖交联烷基化壳聚糖/载药及银掺杂介孔生物活性玻璃冷冻凝胶用于不可压缩伤口的止血

Multifunctional Oxidized Dextran Cross-Linked Alkylated Chitosan/Drug-Loaded and Silver-Doped Mesoporous Bioactive Glass Cryogel for Hemostasis of Noncompressible Wounds.

作者信息

Lei Dong, Zhao Jing, Zhu Chenhui, Jiang Min, Ma Pei, Mi Yu, Fan Daidi

机构信息

Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi'an 710069, China.

Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an 710069, China.

出版信息

Gels. 2023 Jun 1;9(6):455. doi: 10.3390/gels9060455.

Abstract

Noncompressible wounds resulting from accidents and gunshots are typically associated with excessive bleeding, slow wound healing, and bacterial infection. Shape-memory cryogel presents great potential in controlling the hemorrhaging of noncompressible wounds. In this research, a shape-memory cryogel was prepared using a Schiff base reaction between alkylated chitosan (AC) and oxidized dextran (ODex) and then incorporated with a drug-laden and silver-doped mesoporous bioactive glass (MBG). Hydrophobic alkyl chains enhanced the hemostatic and antimicrobial efficiency of the chitosan, forming blood clots in the anticoagulated condition, and expanding the application scenarios of chitosan-based hemostats. The silver-doped MBG activated the endogenous coagulation pathway by releasing Ca and prevented infection through the release of Ag. In addition, the proangiogenic desferrioxamine (DFO) in the mesopores of the MBG was released gradually to promote wound healing. We demonstrated that AC/ODex/Ag-MBG DFO(AOM) cryogels exhibited excellent blood absorption capability, facilitating rapid shape recovery. It provided a higher hemostatic capacity in normal and heparin-treated rat-liver perforation-wound models than gelatin sponges and gauze. The AOM gels simultaneously promoted infiltration, angiogenesis, and tissue integration of liver parenchymal cells. Furthermore, the composite cryogel exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli. Thus, AOM gels show great promise for clinical translation in treating lethal, noncompressible bleeding and the promotion of wound healing.

摘要

由事故和枪伤导致的不可压缩性伤口通常伴随着出血过多、伤口愈合缓慢以及细菌感染。形状记忆冷冻凝胶在控制不可压缩性伤口出血方面具有巨大潜力。在本研究中,通过烷基化壳聚糖(AC)与氧化葡聚糖(ODex)之间的席夫碱反应制备了一种形状记忆冷冻凝胶,然后将其与载药且掺杂银的介孔生物活性玻璃(MBG)复合。疏水性烷基链提高了壳聚糖的止血和抗菌效率,在抗凝条件下形成血凝块,并扩展了基于壳聚糖的止血剂的应用场景。掺杂银的MBG通过释放Ca激活内源性凝血途径,并通过释放Ag预防感染。此外,MBG介孔中的促血管生成去铁胺(DFO)逐渐释放以促进伤口愈合。我们证明了AC/ODex/Ag-MBG DFO(AOM)冷冻凝胶表现出优异的血液吸收能力,有助于快速形状恢复。在正常和肝素处理的大鼠肝穿孔伤口模型中,它比明胶海绵和纱布具有更高的止血能力。AOM凝胶同时促进了肝实质细胞的浸润、血管生成和组织整合。此外,复合冷冻凝胶对金黄色葡萄球菌和大肠杆菌具有抗菌活性。因此,AOM凝胶在治疗致命性、不可压缩性出血以及促进伤口愈合的临床转化方面显示出巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a09/10297613/c8757c2aca65/gels-09-00455-sch001.jpg

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