Enhanced therapeutic effects of mesenchymal stem cell-derived extracellular vesicles within chitosan hydrogel in the treatment of diabetic foot ulcers

IF 4.2 3区医学 Q2 ENGINEERING, BIOMEDICAL

Journal of Materials Science: Materials in Medicine Pub Date : 2023-08-28 DOI:10.1007/s10856-023-06746-y

Shuangshuang Yang, Siyu Chen, Chengpeng Zhang, Jing Han, Chunyuan Lin, Xiaohui Zhao, Huizhen Guo, Yi Tan

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Abstract

Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have emerged as promising candidates for cell-free therapy in various diseases, including chronic cutaneous wounds. However, the lack of standardized protocols for EVs’ preparation and identification poses a significant challenge to their clinical application. Thus, the objective was to develop a safe and efficient method for the large-scale production of hUCMSC-derived EVs while establishing a comprehensive identification protocol encompassing morphology, particle size distribution, protein expression, and purity. This study observed that most of the EVs acquired through the protocol exhibited either a cup-shaped or round-shaped structure, with a median diameter of ~73.25?nm. The proportions of EVs positive for CD9, CD63, and CD81 were 37.5%, 38.6%, and 19.8%, respectively. To enhance their therapeutic potential in wound treatment, EVs were incorporated into chitosan hydrogel, forming chitosan hydrogel-EVs (CS-EVs). Furthermore, it was demonstrated that CS-EVs exhibited continuous release of EVs into the surrounding environment and, importantly, that the released EVs were internalized by human umbilical vein endothelial cells (HUVECs), resulting in significant enhancement of cell migration and angiogenesis. Additionally, in a rat model of diabetic foot ulcers, CS-EVs demonstrated a robust therapeutic effect in promoting wound healing. Following a 15-day treatment period, the group treated with CS-EVs demonstrated an impressive 93.3% wound closure ability, accompanied by a high degree of re-epithelialization. In contrast, the control group exhibited only a 71.5% reduction in wound size. In summary, this study offers solutions for the purification, characterization, and application of EVs in clinical wound treatment. These results not only offer fresh perspectives on the involvement of hUCMSC-derived EVs in wound healing but also introduce a non-invasive approach for applying EVs that holds practical significance in skin repair.

Graphical Abstract

Abstract Image

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壳聚糖水凝胶增强间充质干细胞来源的细胞外囊泡治疗糖尿病足溃疡的疗效

来源于人脐带间充质干细胞(hUCMSCs)的细胞外囊泡(EVs)已成为各种疾病(包括慢性皮肤伤口)无细胞治疗的有希望的候选者。然而，电动汽车的制备和鉴定缺乏标准化的方案，这对其临床应用构成了重大挑战。因此，我们的目标是开发一种安全有效的方法来大规模生产humcc衍生的电动汽车，同时建立一个全面的鉴定方案，包括形态、粒度分布、蛋白质表达和纯度。研究发现，通过该方案获得的大多数ev呈杯状或圆形结构，中位直径约为73.25 nm。CD9、CD63和CD81的阳性率分别为37.5%、38.6%和19.8%。为了提高ev在创面治疗中的应用潜力，我们将其掺入壳聚糖水凝胶中，形成壳聚糖水凝胶- ev (cs - ev)。此外，研究表明，cs - ev能够将ev持续释放到周围环境中，重要的是，释放的ev被人脐静脉内皮细胞(HUVECs)内化，从而显著增强细胞迁移和血管生成。此外，在糖尿病足溃疡大鼠模型中，cs - ev在促进伤口愈合方面表现出强大的治疗作用。经过15天的治疗期，cs - ev治疗组显示出令人印象深刻的93.3%的伤口愈合能力，并伴有高度的再上皮化。相比之下，对照组的伤口大小仅减少了71.5%。综上所述，本研究为ev的纯化、表征和在临床伤口治疗中的应用提供了解决方案。这些结果不仅为humcc衍生的ev参与伤口愈合提供了新的视角，而且为ev在皮肤修复中具有实际意义的应用提供了一种非侵入性方法。图形抽象

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来源期刊

Journal of Materials Science: Materials in Medicine 工程技术-材料科学：生物材料

CiteScore

8.00

自引率

0.00%

发文量

审稿时长

3.5 months

期刊介绍： The Journal of Materials Science: Materials in Medicine publishes refereed papers providing significant progress in the application of biomaterials and tissue engineering constructs as medical or dental implants, prostheses and devices. Coverage spans a wide range of topics from basic science to clinical applications, around the theme of materials in medicine and dentistry. The central element is the development of synthetic and natural materials used in orthopaedic, maxillofacial, cardiovascular, neurological, ophthalmic and dental applications. Special biomedical topics include biomaterial synthesis and characterisation, biocompatibility studies, nanomedicine, tissue engineering constructs and cell substrates, regenerative medicine, computer modelling and other advanced experimental methodologies.