Stem Cell-Derived Nanovesicles Embedded in Dual-Layered Hydrogel for Programmed ROS Regulation and Comprehensive Tissue Regeneration in Burn Wound Healing.

Burn wounds often bring high risks of delayed healing process and even death. Reactive oxygen species (ROS) play a crucial role in burn wound repair. However, the dynamic process in wound healing requires both the generation of ROS to inhibit bacteria and the subsequent reduction of ROS levels to initiate and promote tissue regeneration, which calls for a more intelligent ROS regulation dressing system. Hence, a dual-layered hydrogel (Dual-Gel) tailored to the process of burn wound repair is designed: the inner layer hydrogel (Gel 2) first responds to bacterial hyaluronidase (Hyal) to deliver aggregation-induced emission photosensitizer functionalized adipose-derived stem cell nanovesicles, which generate ROS upon light irradiation to eliminate bacteria; then the outer layer hydrogel (Gel 1) continuously starts a long-lasting consumption of excess ROS at the wound site to accelerate tissue regeneration. Simultaneously, the stem cell nanovesicles trapped in the burns wound also provide nutrients and mobilize neighboring tissues to thoroughly assist in inflammation regulation, cell proliferation, migration, and angiogenesis. In summary, this study develops an intelligent treatment approach on burn wounds by programmatically regulating ROS and facilitating comprehensive wound tissue repair.