Abstract
Three-dimensional (3D) bioprinting has been extensively explored for tissue repair and regeneration, while the insufficient nutrient and oxygen availability in the printed constructs, as well as the lack of adaptive dimensions and shapes, compromises the overall therapeutic efficacy and limits their further application. Herein, inspired by the natural symbiotic relationship between salamanders and algae, we present novel living photosynthetic scaffolds by using an in situ microfluidic-assisted 3D bioprinting strategy for adapting irregular-shaped wounds and promoting their healing. As the oxygenic photosynthesis unicellular microalga (Chlorella pyrenoidosa) was incorporated during 3D printing, the generated scaffolds could produce sustainable oxygen under light illumination, which facilitated the cell proliferation, migration, and differentiation even in hypoxic conditions. Thus, when the living microalgae-laden scaffolds were directly printed into diabetic wounds, they could significantly accelerate the chronic wound closure by alleviating local hypoxia, increasing angiogenesis, and promoting extracellular matrix (ECM) synthesis. These results indicate that the in situ bioprinting of living photosynthetic microalgae offers an effective autotrophic biosystem for promoting wound healing, suggesting a promising therapeutic strategy for diverse tissue engineering applications.