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.