Injectable dual-cross-linked microalgae-silk gel ameliorates diabetic wound healing by promoting oxygenation and ROS...

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.