Diabetic wound healing breakthrough: theaflavin-3, 3’-digallate nanoparticles@hydrogel activates the TGF-β1/SMAD3 pathway

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-03-19 DOI:10.1016/j.phymed.2025.156617

Xu Dong , Jianyin Miao , Ling Wu , Ziyu Kong , Zenghui Liu , Diyi Jia , Qingqing Zhai , Dan Zhang , Yan Xu

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引用次数: 0

Abstract

Background

Diabetes patients face an elevated wound infection susceptibility and delayed healing processes. Currently, no existing literature has reported on the effect and mechanism of theaflavin-3, 3’-digallate nanoparticles (TFDG NPS) and TFDG NPS@hydrogels on diabetic wounds.

Purpose

Given that the treatment options for diabetic wound are limited, the aim of this study is to develop an innovative therapeutic approach to address diabetic wounds.

Methods

The TFDG NPS were prepared using ionic cross-linking, and they were then characterized. The biocompatibility of the TFDG NPS and TFDG NPS@hydrogel was assessed using a Cell Counting Kit-8 (CCK-8) assay and live/dead staining on HK-2 cells in vitro. Diabetic ICR mice were induced through intraperitoneal injection of streptozocin (STZ). They were then subjected to the creation of two full-thickness wounds on their dorsal areas. The effect and mechanism of the TFDG NPS and TFDG NPS@hydrogel on wound healing in diabetic mice were evaluated using a histological analysis, a western blot analysis, and molecular docking.

Results

The optimal TFDG NPS proportion was found to be TFDG:Gelatin (Gel):Chitosan (CS) = 2:1:1. Images photographed using a transmission electron microscope (TEM) revealed that the TFDG NPS appeared spherical, with a diameter of approximately 140 ± 20 nm. The favorable bio-compatibility of the TFDG NPS and TFDG NPS@hydrogel was confirmed using cell experiments. Animal studies demonstrated that both the TFDG NPS and TFDG NPS@hydrogel enhanced collagen fiber accumulation and new blood vessel density, reduced F4/80 infiltration, and upregulated the expression levels of TGF-β1, SMAD3, Collagen I, and α-SMA. The potential mechanism may involve activation of the TGF-β1/SMAD3 pathway, stimulating the secretion of Collagen I and α-SMA, and thereby facilitating wound closure in diabetic mice. The molecular docking results confirmed a high affinity between TFDG and TGF-β1/SMAD3.

Conclusion

TFDG NPS and TFDG NPS@hydrogel promoted wound closure in diabetic mice through the TFG-β1/SMAD3 pathway, thus exhibiting promising therapeutic potential for diabetic wound treatment.

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糖尿病创面愈合突破：茶黄素- 3,3 ' -二化物nanoparticles@hydrogel激活TGF-β1/SMAD3通路

背景糖尿病患者伤口易感染，愈合过程延迟。目前，还没有文献报道黄素-3, 3'-二镓酸盐纳米颗粒（TFDG NPS）和 TFDG NPS@ 水凝胶对糖尿病伤口的作用和机制。目的鉴于糖尿病伤口的治疗方案有限，本研究旨在开发一种创新的治疗方法来解决糖尿病伤口问题。方法采用离子交联法制备 TFDG NPS，然后对其进行表征。采用细胞计数试剂盒-8（CCK-8）检测法和体外 HK-2 细胞活/死染色法评估了 TFDG NPS 和 TFDG NPS@hydrogel 的生物相容性。通过腹腔注射链脲佐菌素（STZ）诱导糖尿病 ICR 小鼠。然后在小鼠背侧造成两个全厚伤口。结果发现 TFDG NPS 的最佳比例为 TFDG:Gelatin (Gel):Chitosan (CS) = 2:1:1。使用透射电子显微镜（TEM）拍摄的图像显示，TFDG NPS 呈球形，直径约为 140 ± 20 nm。细胞实验证实了 TFDG NPS 和 TFDG NPS@hydrogel 具有良好的生物相容性。动物实验表明，TFDG NPS 和 TFDG NPS@hydrogel 都能增强胶原纤维的积累和新生血管的密度，减少 F4/80 的浸润，并上调 TGF-β1、SMAD3、胶原 I 和 α-SMA 的表达水平。其潜在机制可能是激活了 TGF-β1/SMAD3 通路，刺激了胶原 I 和 α-SMA 的分泌，从而促进了糖尿病小鼠伤口的闭合。结论TFDG NPS和TFDG NPS@水凝胶通过TFG-β1/SMAD3通路促进糖尿病小鼠伤口闭合，因此在糖尿病伤口治疗方面具有良好的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.