Multifunctional Nanocomposite Hydrogels Based on ZIF-8 for Healing Bacteria-Infected Wounds

Abstract

Bacterial-infected wounds present a significant clinical challenge due to persistent bacterial infection, elevated reactive oxygen species (ROS) levels, and a complex inflammatory microenvironment, all of which impede the healing process. Vascular network damage further exacerbates these issues by disrupting the metabolic circulation, intensifying hypoxia, and promoting ROS accumulation. Conventional single-function wound dressings are inadequate to address the multifaceted biological requirements for effective wound healing. In this study, we designed a nanocomposite hydrogel (AM/AG-ZIF-8@Ba) composed of acrylamide (AM)/agarose (AG) and ZIF-8 nanoparticles loaded with baicalein (Ba) as an advanced wound dressing. The AM/AG-ZIF-8@Ba hydrogel demonstrated exceptional mechanical properties, superior moisture retention capabilities, and potent antibacterial activity. AM/AG-ZIF-8@Ba can release active substance Ba slowly for a long period of time under physiological environment, and the cumulative release ratio of Ba reaches 61.58% in 96 h, which is able to play the role of scavenging ROS continuously (scavenging ratio of 67.84 ± 1.42%). Concurrently, Zn²⁺, released by ZIF-8 degradation, has been shown to synergise with Ba, thereby promoting vascular regeneration and accelerating wound healing. In vivo experiments revealed that AM/AG-ZIF-8@Ba significantly accelerated wound healing, achieving a healing ratio of 92.57 ± 4.07% by day 14, which was significantly better than that of the control group (65.22 ± 4.67%). Histological analysis confirmed that AM/AG-ZIF-8@Ba effectively promoted neovascularization and collagen deposition while mitigating inflammatory responses (demonstrating a 63.78% reduction in pro-inflammatory cytokine IL-6 and a 99.97% increase in anti-inflammatory cytokine IL-10 compared to controls), highlighting the hydrogel’s regenerative potential. Therefore, AM/AG-ZIF-8@Ba, integrating antibacterial, antioxidant, and anti-inflammatory functions, represents a comprehensive and innovative solution for treating complex bacterial infection wounds, offering significant promise for advancing wound care and tissue regeneration.