Effectively promoting skin wound healing remains a significant challenge in the medical field. Although stem cell-derived exosomes show potential in tissue regeneration, their local delivery and sustained release face challenges. To address these issues, we developed a collagen sponge based on type I and recombinant humanized type III collagen. Our study confirmed that exosomes were successfully loaded onto the sponge (sponge-Exo) and the sponge-Exo gradually released exosomes into the local milieu. The sponge-Exo played a crucial role in promoting the transition of macrophages from an inflammatory M1 phenotype to a regenerative M2 phenotype. Moreover, it enhanced the migration and proliferation of HDFs and promoted angiogenesis in HUVECs. Additionally, our findings revealed that the sponge-Exo accelerated wound healing by suppressing inflammatory response and stimulating angiogenesis in a rat full-thickness skin wounds model. Next generation sequencing (NGS) was used to explore the underlying mechanism of wound healing, and the results showed that the miRNAs (hsa-miR-21-5p and hsa-miR-29a-5p) associated with wound healing in exosomes were significantly up-regulated. These results highlight the remarkable effects of sponge-Exo on macrophage transformation, cell migration, proliferation and angiogenesis, which provide a potential prospect for the application in the field of skin wound healing.

中文翻译：

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使用负载外泌体的胶原蛋白海绵促进皮肤伤口愈合中的血管生成和抑制炎症反应


有效促进皮肤伤口愈合仍然是医学领域的重大挑战。尽管干细胞衍生的外泌体在组织再生中显示出潜力，但它们的局部递送和持续释放面临挑战。为了解决这些问题，我们开发了一种基于 I 型和重组人源化 III 型胶原蛋白的胶原蛋白海绵。我们的研究证实，外泌体成功加载到海绵上 （sponge-Exo），并且 sponge-Exo 逐渐将外泌体释放到局部环境中。sponge-Exo 在促进巨噬细胞从炎性 M1 表型转变为再生 M2 表型中起关键作用。此外，它增强了 HDFs 的迁移和增殖，促进了 HUVECs 中的血管生成。此外，我们的研究结果显示，海绵-Exo 通过抑制大鼠全层皮肤伤口模型中的炎症反应和刺激血管生成来加速伤口愈合。采用下一代测序 （NGS） 探索伤口愈合的潜在机制，结果显示外泌体中与伤口愈合相关的 miRNAs （hsa-miR-21-5p 和 hsa-miR-29a-5p） 显著上调。这些结果突出了 sponge-Exo 对巨噬细胞转化、细胞迁移、增殖和血管生成的显著影响，为在皮肤伤口愈合领域的应用提供了潜在的前景。