Resveratrol-loaded engineered microcapsules with dual antimicrobial and ROS-scavenging for programmed wound healing

Hydrogel microparticles have been proved effective for the skin wound repair. Attempts in this area focus on how to enrich the structures and encapsulate bioactive substances to achieve the spatially controllable release for accelerated wound healing. Here, we propose a novel core-shell microcapsule delivery system with the spatial encapsulation and release of resveratrol (RSV) and chitosan (CS) to treat infected wounds. Such microcapsules (ALG-CS) were generated through microfluidic electrospray technology, with the inner core encapsulating RSV and outer layer covered with the imine bond-crosslinked CS hydrogel. The designed CS hydrogel coating can improve the stability of microcapsules and further prevent the premature leakage of RSV. The gradually degraded CS hydrogel layer in acidic environment accompanied with the subsequent release RSV contributed to the enhanced antibacterial properties of the microcapsules. In addition, the released RSV exhibited outstanding antioxidant capacities to protect cells from oxidative stress in vitro. Thus, by applying the obtained RSV-loaded ALG-CS microcapsules onto the S. aureus-infected wound beds, we have demonstrated that such microcapsules showed significant accelerated wound healing effects with alleviated oxidative stress, eliminated bacterial infection, down-regulated inflammatory response, and promoted collagen deposition and angiogenesis. These indicated that the microcapsule delivery systems are valuable for bacteria-infected wound therapy.