Antibacterial hydrogel with pH-responsive microcarriers of slow-release VEGF for bacterial infected wounds repair

Abstract

Bacterial infection causes wound inflammation and makes angiogenesis difficult. It is urgent to develop effectively antibacterial and pro-vascularizing dressings for wound healing. The hydrogel is developed with pH-responsive drug-releasing microcarriers which were loaded with vascular endothelial growth factor (VEGF) that promotes angiogenesis and actively respond to wound pH for control and prolong VEGF release. The surfaces of the microcarriers were coated with polydopamine which can reduce the silver nanoparticles (AgNPs) in situ, and dynamically crosslink with the polyacrylamide, which forms a stable slow-release system with different release behavior for the VEGF and AgNPs. The hydrogel inhibited bacterial formation and accelerated wound healing. With the hydrogel dressing, 83.3% ± 4.29% of the wound heals at day 7, which is 40.9% ± 8.5% higher than the non-treatment group in defect infected model. The antibacterial properties of hydrogel down-regulate early inflammation-related cytokines, and the release of VEGF in the middle and late phases of wound healing in response to pH changes promotes angiogenesis and up-regulate the expression of angiogenesis-associated cytokine. The sequential release of antibacterial agents and pro-vascularizing agents in response to the change in wound microenvironmental cues facilitate temporally controlled therapy that suites the need of different wound healing phases. Collectively, the hydrogel loaded with multifunctional microcarriers that enable controlled release of AgNPs and VEGF is an effective system for treating infected wounds.