Regulation of Glucose Metabolism for Cell Energy Supply In Situ via High‐Energy Intermediate Fructose Hydrogels

Abstract The cellular functions, such as tissue‐rebuilding ability, can be directly affected by the metabolism of cells. Moreover, the glucose metabolism is one of the most important processes of the metabolism. However, glucose cannot be efficiently converted into energy in cells under ischemia hypoxia conditions. In this study, a high‐energy intermediate fructose hydrogel (HIFH) is developed by the dynamic coordination between sulfhydryl‐functionalized bovine serum albumin (BSA‐SH), the high‐energy intermediate in glucose metabolism (fructose‐1,6‐bisphosphate, FBP), and copper ion (Cu²⁺). This hydrogel system is injectable, self–healing, and biocompatible, which can intracellularly convert energy with high efficacy by regulating the glucose metabolism in situ. Additionally, the HIFH can greatly boost cell antioxidant capacity and increase adenosine triphosphate (ATP) in the ischemia anoxic milieu by roughly 1.3 times, improving cell survival, proliferation and physiological functions in vitro. Furthermore, the ischemic skin tissue model is established in rats. The HIFH can speed up the healing of damaged tissue by promoting angiogenesis, lowering reactive oxygen species (ROS), and eventually expanding the healing area of the damaged tissue by roughly 1.4 times in vivo. Therefore, the HIFH can provide an impressive perspective on efficient in situ cell energy supply of damaged tissue.