Coriander-Derived Exosome-Like Nanovesicles Laden Hydrogel with Antioxidant Property Accelerates Wound Healing

The oxidative balance and inflammatory responses play important roles in wound healing. Plant-derived exosome-like nanovesicles exhibit antioxidant or anti-inflammatory properties. However, their effects and underlying molecular mechanisms of action in wound healing remain unclear. Herein, coriander-derived exosome-like nanovesicles (CDENs) are isolated and characterized. It is found that the CDENs can be internalized by HaCaT cells and mouse skin tissue, promoting cell migration, scavenging reactive oxygen species (ROS) by increasing the expression of antioxidant enzymes, and effectively relieving inflammation. Furthermore, it designs a CDENs-based hydrogel with a sustained CDENs-release effect and excellent biocompatibility, and explored its potential for use in wound healing in vivo. During the different phases of wound healing, CDENs-hydrogel facilitated macrophage M2 polarization in the inflammation phase, promoted angiogenesis in the proliferation phase, and expedited collagen deposition in the remodeling phase. Mechanistically, through releasing CDENs, CDENs-hydrogel activated Nrf2 signaling pathway, which enhanced the antioxidant enzyme defense system and reduced the inflammatory response, ultimately accelerated wound healing process. This is the first report that CDENs-hydrogel holds great promise as a safe and effective alternative for clinical wound management.