Hypoxia, excessive reactive oxygen species (ROS), and an impaired inflammatory microenvironment are key barriers to diabetic wound healing, collectively hindering cell migration, proliferation, and neovascularization, ultimately leading to failure in the healing process. Therefore, developing an effective therapeutic strategy capable of simultaneously addressing these challenges remains a critical clinical need. In this study, we developed CeS-Gel, an advanced hydrogel dressing integrating live microalgae and CeO₂ nanoparticles within a dual-crosslinked silk hydrogel network. By harnessing photosynthesis, CeS-Gel provided a continuous and reliable oxygen supply, significantly enhancing cell migration and proliferation. Additionally, CeS-Gel exhibited potent ROS-scavenging properties, effectively mitigating oxidative stress-induced cellular damage while directly promoting M2 macrophage polarization, thereby modulating the inflammatory response. In vivo experiments demonstrated that CeS-Gel markedly accelerated wound healing in diabetic mice, achieving a 93.2 % wound closure rate. Furthermore, CeS-Gel effectively alleviated hypoxia, promoted neovascularization, and exhibited anti-inflammatory and immunoregulatory effects. This living microalgae-silk gel represents a promising approach for improving chronic diabetic wound healing with great potential for clinical application.

Keywords: Diabetic wound healing; Dual-cross-linked silk hydrogel; Immunoregulatory; Photosynthetic oxygenation; ROS-scavenging.

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缺氧、过量的活性氧（ROS）和受损的炎症微环境是糖尿病伤口愈合的关键障碍，这些因素共同阻碍了细胞迁移、增殖和新生血管形成，最终导致愈合过程失败。因此，开发一种能够同时应对这些挑战的有效治疗策略仍然是临床上迫切需要的。在这项研究中，我们开发了一种名为CeS-Gel的先进水凝胶敷料，它在双交联丝素水凝胶网络内整合了活微藻和CeO₂纳米粒子。通过利用光合作用，CeS-Gel提供了连续可靠的氧气供应，显著增强了细胞迁移和增殖。此外，CeS-Gel表现出强大的ROS清除性能，有效地减轻了氧化应激引起的细胞损伤，并直接促进了M2巨噬细胞极化，从而调节炎症反应。体内实验表明，CeS-Gel显著加速了糖尿病小鼠的伤口愈合，实现了93.2%的伤口闭合率。此外，CeS-Gel有效缓解了缺氧、促进新生血管生成，并表现出抗炎和免疫调节作用。这种活微藻-丝素凝胶代表了一种改善慢性糖尿病伤口愈合且具有巨大临床应用潜力的方法。

关键词：糖尿病伤口愈合；双交联丝素水凝胶；免疫调节；光合作用供氧；ROS清除。