Plant-inspired visible-light-driven bioenergetic hydrogels for chronic wound healing

Abstract

Chronic bioenergetic imbalances and inflammation caused by hyperglycemia are obstacles that delay diabetic wound healing. However, it is difficult to directly deliver energy and metabolites to regulate intracellular energy metabolism using biomaterials. Herein, we propose a light-driven bioenergetic and oxygen-releasing hydrogel (PTKM@HG) that integrates the thylakoid membrane-encapsulated polyphenol nanoparticles (PTKM NPs) to regulate the energy metabolism and inflammatory response in diabetic wounds. Upon red light irradiation, the PTKM NPs exhibited oxygen generation and H 2 O 2 deletion capacity through a photosynthetic effect to restore hypoxia-induced mitochondrial dysfunction. Meanwhile, the PTKM NPs could produce exogenous ATP and NADPH to enhance mitochondrial function and facilitate cellular anabolism by regulating the leucine-activated mTOR signaling pathway. Furthermore, the PTKM NPs inherited antioxidative and anti-inflammatory ability from polyphenol. Finally, the red light irradiated PTKM@HG hydrogel augmented the survival and migration of cells keratinocytes, and then accelerated angiogenesis and re-epithelialization of diabetic wounds. In short, this study provides possibilities for effectively treating diseases by delivering key metabolites and energy based on such a light-driven bioenergetic hydrogel. The prominent photosynthetic features of PTKM NPs endowed the hydrogel with the ability to regulate hyperglycemia-induced oxidative stress, hypoxia, inflammation, and metabolic disorders via sunlight-driven supplementation of exogenous energy and metabolites for diabetic wound healing. • It is critical to resolve chronic bioenergetic imbalance and inflammation for diabetic wound healing. • A light-driven bioenergetic hydrogel was constructed based on thylakoid membrane-encapsulated polyphenol nanoparticles. • The hydrogel not only continuously releases O 2 , but also yields exogenous NADPH and ATP through photosynthetic effect. • The hydrogel can alleviate hyperglycemia-induced oxidative stress, hypoxia, inflammation, and metabolic disorders.