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一种基于负载白藜芦醇的离子液体/甲基丙烯酰化明胶水凝胶的多功能敷料,用于促进糖尿病伤口愈合。

A multi-purpose dressing based on resveratrol-loaded ionic liquids/gelatin methacryloyl hydrogel for enhancing diabetic wound healing.

作者信息

Xu Shaochen, Jiang Chao, Yu Tao, Chen Kai

机构信息

Department of Bone and Joint and Sports Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, China.

Department of Orthopedic Surgery, Tongji Hospital, Tongji University School of Medicine, China.

出版信息

Int J Biol Macromol. 2024 Dec;283(Pt 2):136773. doi: 10.1016/j.ijbiomac.2024.136773. Epub 2024 Oct 21.

Abstract

Diabetic wound (DW) is a multifaceted challenge, characterized by persistent bacterial infections and compromised angiogenesis. To address these issues and enhance DW healing, we developed a novel strategy using a photo-crosslinked hydrogel system composed of ionic liquids (ILs) and gelatin methacryloyl (GelMA) loaded with resveratrol (Res). The ILs/GelMA hydrogel was fabricated via a simple photo-crosslinking process, resulting in desirable mechanical properties, biocompatibility, and controlled release kinetics. Res was incorporated into the hydrogel matrix (ILs/GelMA@Res) to ensure sustained release, facilitating angiogenesis and accelerating wound healing. In vitro studies demonstrated that the ILs/GelMA@Res hydrogel exhibited potent antibacterial activity against Staphylococcus aureus and Escherichia coli, inhibiting bacterial growth and biofilm formation. Furthermore, the sustained release of Res from the hydrogel promoted angiogenesis by activating the PI3K/AKT signaling pathways associated with VEGF and FGF, enhancing endothelial cell proliferation, migration, and tube formation. In a DW mice model, the ILs/GelMA@Res hydrogel demonstrated accelerated wound closure, reduced inflammation, and robust neovascularization. This multifunctional hydrogel-based delivery system holds considerable potential for clinical translation, offering a safe and effective treatment modality for diabetic patients with chronic wounds.

摘要

糖尿病伤口(DW)是一个多方面的挑战,其特征是持续的细菌感染和受损的血管生成。为了解决这些问题并促进DW愈合,我们开发了一种新策略,使用由负载白藜芦醇(Res)的离子液体(ILs)和甲基丙烯酰化明胶(GelMA)组成的光交联水凝胶系统。ILs/GelMA水凝胶通过简单的光交联过程制备,具有理想的机械性能、生物相容性和可控的释放动力学。将Res掺入水凝胶基质(ILs/GelMA@Res)以确保持续释放,促进血管生成并加速伤口愈合。体外研究表明,ILs/GelMA@Res水凝胶对金黄色葡萄球菌和大肠杆菌具有强大的抗菌活性,可抑制细菌生长和生物膜形成。此外,水凝胶中Res的持续释放通过激活与血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(FGF)相关的磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)信号通路促进血管生成,增强内皮细胞增殖、迁移和管腔形成。在DW小鼠模型中,ILs/GelMA@Res水凝胶显示出加速伤口闭合、减轻炎症和强大的新生血管形成。这种基于多功能水凝胶的递送系统在临床转化方面具有巨大潜力,为患有慢性伤口的糖尿病患者提供了一种安全有效的治疗方式。

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