An Antibiotic-Free Multifunctional Quercetin-Loaded Mesoporous Bioactive Glass Platform for Healing Infected Diabetic Wounds

Abstract

Treating infected diabetic wounds remains a significant clinical challenge due to persistent inflammation, bacterial infections, and impaired early tissue regeneration. A quercetin-loaded mesoporous bioactive glass (MBG@Que) system was developed to achieve synergistic antibacterial and regenerative effects. In vitro research demonstrated that MBG@Que accelerated the repair of infected diabetic wounds through various mechanisms, including approximately 90% antibacterial activity, induction of M2 macrophage polarization (50.4% CD206-positive cells), a tube formation rate of 87.8%, early nerve regeneration, and extracellular matrix remodeling. In vivo studies further confirmed that MBG@Que effectively expedited wound healing, achieving approximately 99% wound closure by day 10 while promoting re-epithelialization, collagen deposition, early vascular regeneration, and early neural regeneration (mean fluorescence intensity of NF200 was approximately threefold higher in the MBG@Que group) and reducing inflammatory infiltration in infected diabetic rats. Transcriptomic analysis indicated that MBG@Que exerts multi-pathway regulatory effects on the wound microenvironment, including immune response, PI3K–Akt signaling, and AGE–RAGE signaling pathways. Overall, this study establishes a multifunctional biomaterial platform that integrates antibacterial activity, immunomodulation, and neurovascular early regeneration into a single antibiotic-free scaffold, providing a novel strategy for the treatment of infected diabetic wounds.