1. Introduction
Scald or burn injuries deep into the dermis always face obstacles during the recovery process due to both decline in repair function and persistent infection,[1-3] which can result in chronic wound healing and pose a risk of sepsis.[4] Various tissue engineered materials with beneficial healing ingredients have been developed for serve scald or burn wound healing,[5] however, always can’t realize mass production.[6] Stem cells can be expanded in vitro , and exhibit high activity in enhancing metabolism, regulating immunity, and promoting skin reconstruction.[7]But cell transplantation on wound is facing low survival rates, and potential safety risks on tumor cells and organ, which obstruct its clinical promotion.[8-10] While, extracellular vesicles (EVs) of stem cells not only retain their effective cytokines, but also exhibit greater safety, stability, tissue penetration, and delivery capacity.[11-13] Besides, facile nanovesicle extrusion technology from cell membranes has also been reported to replicate characteristics of EVs, making cells-derived nanovesicles a hopeful candidate for precision treatment.[14-17] However, the anti-infectious ability of nanovesicles still needs to be enhanced.
The bacteria present in the necrotic tissue invade deeply, producing toxins and other metabolites, and resulting in persistent inflammation.[18] Deep injuries that cover larger surface area (over 15% of the total adult body surface) carry a higher risk of cytokines diffusing throughout the body, which can lead to systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), sepsis, and even death.[19] Besides, antibiotic resistance can easily occur due to the use of systemic antibiotics for the treatment of localized infections.[20] Photodynamic therapy without leading to drug resistance has attracted considerable attention in the field of antibiotics.[21,22] Tang et al have reported a series of aggregation-induced emission (AIE) photosensitizers that hold potential applications in bioimaging and photodynamic therapy. The aggregates of AIEgens in aqueous condition demonstrate not only high luminescence efficiencies but also efficient reactive oxygen species (ROS) generation, photostability and bacterial targeting ability.[23,24] Thus, it might be feasible to enhance the anti-infectious property of nanovesicles through AIEgens encapsulation.
For long-term wound treatment processes, continuous delivery of nanovesicles is also crucial. The commonly used injection method would result in rapid metabolism and degradation of nanovesicles on wounds, shortening their effective time.[25] To achieve sustained and effective concentration, a controllable release carrier that can protect the nanovesicles and form a reservoir on the wound is urgently needed. Based on the wet healing theory, hydrogel wound dressing can protect the wound from exposure to infections, absorb excess exudate, and promote the dissolution and exfoliation of deep necrotic tissue.[26,27] However, the preparation of controllable release hydrogels commonly requires UV light, heating or catalyst for gelation, which might harm the beneficial biological components of nanovesicles.[28] Temperature sensitive hydrogel PF-127 have been utilized for in situ gelation on wounds without affecting the functions of nanovesicles,[29] but it is more suitable for a constant temperature internal environment rather than on the surface of the skin.