Wound healing is an obvious clinical concern that can be hindered by inadequate angiogenesis, inflammation, and chronic hypoxia. While exosomes derived from adipose tissue-derived stem cells have shown promise in accelerating healing by carrying therapeutic growth factors and microRNAs, intracellular cargo delivery is compromised in hypoxic tissues due to activated hypoxia-induced endocytic recycling. To address this challenge, we have developed a strategy to coat oxygen nanobubbles with exosomes and incorporate them into a polyvinyl alcohol/gelatin hybrid hydrogel. This approach not only alleviates wound hypoxia but also offers an efficient means of delivering exosome-coated nanoparticles in hypoxic conditions. The self-healing properties of the hydrogel, along with its component, gelatin, aids in hemostasis, while its crosslinking bonds facilitate hydrogen peroxide decomposition, to ameliorate wound inflammation. Here, we show the potential of this multifunctional hydrogel for enhanced healing, promoting angiogenesis, facilitating exosome delivery, mitigating hypoxia, and inhibiting inflammation in a male rat full-thickness wound model.

伤口愈合是一个明显的临床问题，可能会因血管生成不足、炎症和慢性缺氧而受到阻碍。虽然源自脂肪组织干细胞的外泌体已显示出通过携带治疗性生长因子和 microRNA 来加速愈合的前景，但由于激活的缺氧诱导的内吞再循环，细胞内货物输送在缺氧组织中受到损害。为了应对这一挑战，我们开发了一种策略，用外泌体包裹氧纳米气泡，并将其纳入聚乙烯醇/明胶混合水凝胶中。这种方法不仅可以缓解伤口缺氧，而且还提供了一种在缺氧条件下递送外泌体包被纳米颗粒的有效方法。水凝胶的自愈特性及其成分明胶有助于止血，而其交联键则促进过氧化氢分解，从而减轻伤口炎症。在这里，我们展示了这种多功能水凝胶在雄性大鼠全层伤口模型中增强愈合、促进血管生成、促进外泌体递送、减轻缺氧和抑制炎症的潜力。