Alpha-ketoglutarate supramolecular network accelerates diabetic wound healing through exudates management and neovascularization

Abstract

Healing of chronic wounds such as diabetic foot ulcers is a critical clinical challenge due to the failure management of excess exudates, persistent inflammatory responses, and vascular microcirculatory disturbances by most traditional wound dressings. To promote the wound healing under diabetic pathological environment, a supramolecular network, polyethyleneimine/polyacrylic acid/alpha-ketoglutarate (PEI/PAA/αKG) with bioactive and metabolic αKG was developed herein for exudates management and vascular microcirculatory reconstruction. Once deposited onto the wound area, the PEI/PAA/αKG supramolecular powder would quickly adsorb the exudates and in-situ gel to form a robust protective barrier for sustainably managing the wound exudates during the healing process. Owing to the reversible H-bonding and electrostatic interactions in the network, bioactive αKG monomer could responsively dissociate from the supramolecular network in a pH-dependent manner to promote the chronic diabetic wound healing. The collagen deposition, soft tissue regeneration, and neovascularization of the healing wound were all obviously enhanced under the mediation of PEI/PAA/αKG supramolecular hydrogel. It was further confirmed that the outstanding effect of PEI/PAA/αKG on angiogenesis under diabetic condition results from the function of αKG on cellular oxidative stress regulation. The present method of materializing therapeutic molecules provides a potential strategy to solve the problem of metabolic molecules in biomedical application.