Skin-Inspired and Self-Regulated Hydrophobic Hydrogel for Diabetic Wound Therapy

Diabetic wounds are refractory and recurrent diseases that necessitate the development of multifunctional dressings. Inspired by the structure and function of the skin, we herein delicately design a novel swollen hydrophobic hydrogel (QL@MAB) composed of hydrophobic methyl acrylate (MA) and (3-acrylamidophenyl)boronic acid (AAPBA) network and co-loaded with antioxidant quercetin (Q) and antibiotic levofloxacin (L) for efficient diabetic wound therapy. The hydrophobic MA segments undergo phase separation to form a dense "epidermis", ensuring prolonged drug diffusion, long-term water retention, and high water content. Meanwhile, the AAPBA segments generate glucose-labile "sweat pores" via borate ester bonds with the polyphenol drug Q. Upon encountering the hyperglycemic wound microenvironment, the "sweat pores" are dilated due to the cleavage of the borate ester bonds and exposure of the diffusion channel, facilitating drug release for accelerated wound healing. In the infected diabetic rats, QL@MAB achieves rapid wound debridement and re-epithelization while promoting angiogenesis, hair follicle regeneration, and extracellular matrix remodeling. Taken together, this study not only represents a multipronged dressing for effective interventions of diabetic wounds but also contributes to the rational design of smart hydrogels tailored for biomedical applications.