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新型 GA-CSNPs 载胶原纤维纳米复合支架的体内外对糖尿病创面愈合的影响。

In vitro and in vivo effect of novel GA-CSNPs loaded col-fibrin nanocomposite scaffold on diabetic wound healing.

机构信息

Biochemistry and Biotechnology Laboratory, Central Leather Research Institute, Council of Scientific and Industrial Research (CSIR), Chennai, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.

出版信息

J Biomed Mater Res B Appl Biomater. 2023 May;111(5):1074-1088. doi: 10.1002/jbm.b.35215. Epub 2022 Dec 30.

DOI:10.1002/jbm.b.35215
PMID:36583262
Abstract

A non-healing wound is a common problem associated with diabetes mellitus. Chronic inflammation, challenging re-epithelization, unusual growth factors, and impaired angiogenesis are the multifactorial events that contribute to impaired wounds. Hence, in the present work, an innovative GA-CSNPs nanocomposite scaffold has been fabricated by integrating Gallic acid (GA) loaded chitosan nanoparticles (GA-CSNPs) into a genipin crosslinked collagen-fibrin (Col-fibrin) scaffold as wound dressing material. The in vitro RT-PCR study carried out using NIH/3T3 mouse fibroblast cells showed that treatment with GA-CSNPs nanocomposite scaffold aids in an upsurge in the expression of Col-I, III, and VEGF, which further supports the synthesis of extracellular matrix, increases neovascularization and development of the established vascular system. In vivo wound contraction study results revealed that diabetic wounds treated with GA-CSNPs nanocomposite scaffold show a faster rate of wound closure (p < .001), histopathology results showed accelerated fibroblast cell migration, reduction of the inflammatory cells, enhanced collagen along with hexosamine synthesis. In addition, immunohistochemistry results showed increased vascularization, a significant decrease in macrophage recruitment, and reduced expression of MMP-9 compared to the Col-fibrin scaffold and Control groups. Overall data suggest that the fabricated GA-CSNPs nanocomposite porous 3-D scaffold can be a hopeful therapeutic choice for diabetic wound management.

摘要

不愈合的伤口是与糖尿病相关的常见问题。慢性炎症、挑战性的再上皮化、异常的生长因子和受损的血管生成是导致伤口愈合受损的多因素事件。因此,在本工作中,通过将负载没食子酸(GA)的壳聚糖纳米颗粒(GA-CSNPs)整合到京尼平交联的胶原-纤维蛋白(Col-fibrin)支架中,制备了一种创新的 GA-CSNPs 纳米复合材料支架作为伤口敷料材料。使用 NIH/3T3 小鼠成纤维细胞进行的体外 RT-PCR 研究表明,GA-CSNPs 纳米复合材料支架的处理有助于 Col-I、III 和 VEGF 的表达增加,这进一步支持细胞外基质的合成,增加新生血管形成和已建立的血管系统的发育。体内伤口收缩研究结果表明,用 GA-CSNPs 纳米复合材料支架治疗的糖尿病伤口具有更快的伤口闭合速度(p<.001),组织病理学结果显示成纤维细胞迁移加速,炎症细胞减少,胶原和己糖胺的合成增加。此外,免疫组织化学结果表明与 Col-fibrin 支架和对照组相比,血管生成增加,巨噬细胞募集减少,MMP-9 表达降低。总体数据表明,所制备的 GA-CSNPs 纳米复合材料多孔 3-D 支架可能是糖尿病伤口管理的有希望的治疗选择。

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