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负载山奈酚的原位电纺敷料通过降低基质金属蛋白酶9促进糖尿病溃疡愈合

In-Situ Electrospinning Dressings Loaded with Kaempferol for Reducing MMP9 to Promote Diabetic Ulcer Healing.

作者信息

Li Jianwen, Meng Hongqi, Guo Wenlai, Zhou Lubin, Wu Siyu, Gao Guanghui, Liu Quanzhe, You Di, Qu Wenrui

机构信息

Gastroenteric Medicine and Digestive Endoscopy Center, the Second Hospital of Jilin University, Changchun, 130041, People's Republic of China.

Joint International Research Laboratory of Ageing Active Strategy and Bionic Health in Northeast Asia of Ministry of Education, Changchun, 130041, People's Republic of China.

出版信息

Int J Nanomedicine. 2025 Jan 28;20:1101-1117. doi: 10.2147/IJN.S501370. eCollection 2025.

Abstract

BACKGROUND

Diabetic foot ulcers (DFUs) are often associated with persistent inflammatory response, impaired macrophage polarization, and slow vascular regeneration. Existing treatments cannot be adapted to wounds and do not achieve the desired therapeutic effects. The high porosity of biomaterials induces more M2 macrophages, while the natural compound kaempferol inhibits the expression of matrix metalloproteinase 9 (MMP9) and thus inhibits the associated inflammatory and immunological responses.

METHODS

portable electrospinning dressings (PEDs) were prepared from the spinning solution using a portable electrospinning device. The material properties of PEDs were examined by scanning electron microscope, contact angle tester and WVTR-C3. Then, the in vitro biocompatibility of the dressings was evaluated using NIH3T3 cells. The in vivo wound healing efficacy of the dressings was analyzed in the diabetic wound model rats. Histological and immunofluorescence staining were performed to determine the status of epithelization, collagen deposition, MMP9 expression, macrophage polarization, inflammation response and angiogenesis.

RESULTS

Material science experiments have shown that the dressing has optimal fiber micromorphology and good water vapor transport properties (WVTR: 4.88 kg m 24h); in vivo, diabetic wound experiments have shown that the high porosity and pharmacological effects of PED4 can mutually promote the rapid healing of diabetic wounds (healed 95.9% on day 15), facilitate the transformation of macrophages from M1-type to M2-type and regulate the expression of MMP9.

CONCLUSION

Portable electrospinning dressings equipped with kaempferol not only better fit irregular wounds, but also promote wound healing through MMP9 and macrophage polarization. Thus, PEDs show great promise for advancing research of personalized diabetic wound healing.

摘要

背景

糖尿病足溃疡(DFUs)常伴有持续的炎症反应、巨噬细胞极化受损和血管再生缓慢。现有的治疗方法无法适应伤口,达不到预期的治疗效果。生物材料的高孔隙率可诱导更多的M2巨噬细胞,而天然化合物山奈酚可抑制基质金属蛋白酶9(MMP9)的表达,从而抑制相关的炎症和免疫反应。

方法

使用便携式静电纺丝装置从纺丝溶液制备便携式静电纺丝敷料(PEDs)。通过扫描电子显微镜、接触角测试仪和WVTR-C3检测PEDs的材料性能。然后,使用NIH3T3细胞评估敷料的体外生物相容性。在糖尿病伤口模型大鼠中分析敷料的体内伤口愈合效果。进行组织学和免疫荧光染色以确定上皮化、胶原沉积、MMP9表达、巨噬细胞极化、炎症反应和血管生成的状态。

结果

材料科学实验表明,该敷料具有最佳的纤维微观形态和良好的水汽传输性能(WVTR:4.88 kg m² 24h);在体内,糖尿病伤口实验表明,PED4的高孔隙率和药理作用可相互促进糖尿病伤口的快速愈合(第15天愈合率为95.9%),促进巨噬细胞从M1型向M2型转变并调节MMP9的表达。

结论

配备山奈酚的便携式静电纺丝敷料不仅能更好地贴合不规则伤口,还能通过MMP9和巨噬细胞极化促进伤口愈合。因此,PEDs在推进个性化糖尿病伤口愈合研究方面显示出巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df95/11786600/06ec0728b089/IJN-20-1101-g0001.jpg

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