It remains a clinical challenge for cutaneous wound healing and skin regeneration. Endothelial cells participate in the formation of blood vessels and play an important role in the whole process of wound healing. Recent studies suggested that exosomes contribute to the intercellular communication through paracrine pathways, and sustained release of exosomes from hydrogel-based materials provide a promising strategy for curing wound defects. In this study, we isolated exosomes derived from human umbilical vein endothelial cells (HUVECs) and found that HUVECs derived exosomes (HUVECs-Exos) could promote the proliferation and migration activities of keratinocytes and fibroblasts, which are two important effector cells for skin regeneration. Then we developed gelatin methacryloyl (GelMA) hydrogel as the wound dressing to incorporate HUVECs-Exos and applied it to the full-thickness cutaneous wounds. It demonstrated that GelMA scaffold could not only repair the wound defect, but also achieve sustained release of exosomes. The in vivo results showed accelerated re-epithelialization, promotion of collagen maturity and improvement of angiogenesis. Collectively, our findings suggested that HUVECs-Exos could accelerate wound healing and GelMA mediated controlled release of HUVECs-Exos might offer a new method for repairing cutaneous wound defects.

中文翻译：

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GelMA与HUVEC衍生的外泌体的持续释放相结合，可促进皮肤伤口愈合并促进皮肤再生。

它仍然是皮肤伤口愈合和皮肤再生的临床挑战。内皮细胞参与血管的形成，并在伤口愈合的整个过程中发挥重要作用。最近的研究表明，外泌体通过旁分泌途径促进细胞间通讯，并且从水凝胶基材料中持续释放外泌体为治愈伤口缺陷提供了一种有希望的策略。在这项研究中，我们分离了来自人脐静脉内皮细胞（HUVEC）的外泌体，发现HUVEC衍生的外泌体（HUVECs-Exos）可以促进角质形成细胞和成纤维细胞的增殖和迁移活性，这是皮肤再生的两个重要效应细胞。然后，我们开发了明胶甲基丙烯酰（GelMA）水凝胶作为伤口敷料，将HUVECs-Exos纳入其中，并将其应用于全层皮肤伤口。这表明，GelMA支架不仅可以修复伤口缺损，而且可以实现外泌体的持续释放。体内结果显示加速了上皮再生，促进了胶原蛋白的成熟并改善了血管生成。总的来说，我们的发现表明HUVECs-Exos可以促进伤口愈合，而GelMA介导的HUVECs-Exos的控释可能为修复皮肤伤口缺损提供了一种新方法。促进胶原蛋白成熟和改善血管生成。总的来说，我们的发现表明HUVECs-Exos可以促进伤口愈合，而GelMA介导的HUVECs-Exos的控释可能为修复皮肤伤口缺损提供了一种新方法。促进胶原蛋白成熟和改善血管生成。总的来说，我们的发现表明HUVECs-Exos可以加速伤口愈合，而GelMA介导的HUVECs-Exos的控制释放可能为修复皮肤伤口缺损提供了一种新方法。