Nutrient Matrix-Supplying Hydrogel for <i>Chlorella vulgaris</i> Promotes Diabetic Wound Healing

Chronic wounds associated with diabetes mellitus exhibit delayed healing primarily due to hypoxia-induced impairment of angiogenesis and persistent inflammation. Recently, microalgae-based hydrogel dressings have emerged as promising candidates for managing diabetic chronic wounds. However, the survival and functional stability of microalgae within hydrogels remain poorly understood, as limited research has focused on developing matrices conducive to algal viability. In this study, we developed a novel hydrogel (HA-gel@CV) tailored to the survival environment of <i>Chlorella vulgaris</i> (CV) to enhance algal viability and accelerate diabetic wound healing. The hydrogel was synthesized through self-assembly using hyaluronic acid (HA) as the scaffold to load CV, sequentially incorporating ceramide, urea, <i>Portulaca oleracea</i> (PO) extract, and nicotinamide solution, with gelation shaped by peach gum polysaccharide (PGP). CV viability in HA-gel@CV was assessed over 5 days by quantifying cell density, total chlorophyll content, and oxygen production. Light and fluorescence microscopy, as well as macroscopic color analysis, confirmed that CV remained stable for more than 7 days and exhibited proliferation within the gel. In vitro studies demonstrated that HA-gel@CV enhanced cell proliferation, migration, and angiogenesis, while in vivo experiments showed reduced inflammation and improved vascular and tissue regeneration in diabetic wounds. In summary, HA-gel@CV represents a multifunctional hydrogel integrating oxygenation, anti-inflammatory, moisturizing, and reparative properties, demonstrating strong potential for treating diabetic chronic wounds.