Controlled release of mesenchymal stem cell-derived nanovesicles through glucose- and reactive oxygen species-responsive hydrogels accelerates diabetic wound healing

IF 10.5 1区医学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of Controlled Release Pub Date : 2024-11-07 DOI:10.1016/j.jconrel.2024.11.003

Fangzhou Du , Shumang Zhang , Shikai Li , Shaocong Zhou , Dongao Zeng , Jingzhong Zhang , Shuang Yu

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Abstract

Wound healing is often impaired in patients with diabetes. Mesenchymal stem cells (MSCs) and MSCs-derived nanovesicles (MNVs) hold promise as therapeutic agents for managing diabetic wounds. However, efficient delivery and controlled release of MNVs within these wounds are essential for maximizing therapeutic effectiveness. In this study, we developed a dual-responsive hydrogel designed to respond to elevated levels of glucose and reactive oxygen species. This hydrogel combines polyvinyl alcohol with phenylboronic acid-grafted chitosan, referred to as PBA-CP, while MNVs were produced by shearing MSCs through membranes with varying pore sizes. The composite PBA-CP/MNVs hydrogel significantly accelerated wound healing in a diabetic wound model by promoting epithelialization, dermal reconstruction, hair follicle formation, and angiogenesis. MNVs were readily taken up by keratinocytes, fibroblasts, and endothelial cells, stimulating their proliferation and migration. Altogether, the chitosan-based PBA-CP/MNVs composite hydrogel presents a promising therapeutic strategy for diabetic wound treatment.

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通过葡萄糖和活性氧响应水凝胶控制间充质干细胞衍生纳米颗粒的释放，加速糖尿病伤口愈合。

糖尿病患者的伤口愈合通常会受到影响。间充质干细胞（MSCs）和间充质干细胞衍生的纳米颗粒（MNVs）有望成为治疗糖尿病伤口的药物。然而，要最大限度地提高治疗效果，必须在这些伤口内高效输送和控制 MNVs 的释放。在这项研究中，我们开发了一种双重响应水凝胶，旨在对升高的葡萄糖和活性氧水平做出反应。这种水凝胶结合了聚乙烯醇和苯硼酸接枝壳聚糖（称为 PBA-CP），而 MNV 则是通过剪切具有不同孔径的膜产生的。PBA-CP/MNVs复合水凝胶通过促进上皮化、真皮重建、毛囊形成和血管生成，显著加快了糖尿病伤口模型的伤口愈合。MNV 很容易被角质形成细胞、成纤维细胞和内皮细胞吸收，刺激它们的增殖和迁移。总之，基于壳聚糖的 PBA-CP/MNVs 复合水凝胶为糖尿病伤口治疗提供了一种前景广阔的治疗策略。

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来源期刊

Journal of Controlled Release 医学-化学综合

CiteScore

18.50

自引率

5.60%

发文量

700

审稿时长

39 days

期刊介绍： The Journal of Controlled Release (JCR) proudly serves as the Official Journal of the Controlled Release Society and the Japan Society of Drug Delivery System. Dedicated to the broad field of delivery science and technology, JCR publishes high-quality research articles covering drug delivery systems and all facets of formulations. This includes the physicochemical and biological properties of drugs, design and characterization of dosage forms, release mechanisms, in vivo testing, and formulation research and development across pharmaceutical, diagnostic, agricultural, environmental, cosmetic, and food industries. Priority is given to manuscripts that contribute to the fundamental understanding of principles or demonstrate the advantages of novel technologies in terms of safety and efficacy over current clinical standards. JCR strives to be a leading platform for advancements in delivery science and technology.