Facile Formulation of a Resveratrol-Mediated Multibond Network Hydrogel with Efficient Sustainable Antibacterial, Reactive Oxygen Species Scavenging, Pro-Angiogenesis, and Immunomodulation Activities for Accelerating Infected Wound Healing

The management of chronic infected wounds remains a significant clinical challenge, largely due to the deficiency of optimal wound dressings with adequate mechanical strength, appropriate adhesiveness, and efficient sustainable antibacterial, reactive oxygen species (ROS) scavenging, pro-angiogenesis, and immunomodulation properties. To address such a dilemma, we employed a simple and facile strategy to utilize resveratrol (RSV) as a functional component to mediate hydrogel gelation in this study. The structure of this obtained hydrogel was supported by a multibond network, which not only endowed the resultant product with superior mechanical strength and moderate adhesiveness but also effectively prolonged the bioavailability of RSV. This strategy successfully integrated the entire system with sustainable antibacterial, ROS scavenging, pro-angiogenesis, and immunomodulation properties. Subsequent in vivo evidence has verified that this material was capable to accelerate the healing of chronic infected wounds. The underlying mechanism can be explained that this hydrogel is capable of propelling macrophage polarization from the M1 to M2 phenotype through modulating the PI3K/AKT signaling pathway to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling as well as maintaining the mitochondrial membrane potential level in the normal state under excessive inflammatory and oxidative stimulus. In summary, this multifunctional hydrogel wound dressing provides a feasible way to promote the bioavailability of RSV, which is conducive for preparing a promising candidate for chronic infected wound healing. What is more important, it is also beneficial to reveal the correlative mechanisms to establish advanced therapeutic platform for targeting other complex infection microenvironment.