Synergistic intercellular junction and anti-inflammation wound healing therapy via bioengineered hybrid nanovesicles

Impaired skin wound healing with excessive inflammation affects millions of patients globally. The resulting chronic pain can severely impact the quality of life for people afflicted by the condition. However, the treatment of skin wounds faces enormous challenges due to complex wound microenvironments. Here, we report the design of bioengineered hybrid nanovesicles (BHNVs) that enable advanced wound healing by concurrently providing effective intercellular junction and inflammation relief. The surface of hybrid nanovesicles is modified by trans-membrane DNA functional structures with a zipper part at the outside and a DNAzyme signal output part at the inside. Asiaticoside, an active ingredient from herbal medicines, and signal recognition DNA complex are encapsulated into the nanovesicles. From both outside and inside, these components of the hybrid nanovesicles work synergistically to address wound healing from both extra- and intracellular perspectives. Upon vesicle-cell fusion, the zipper part at the outside can facilitate cell-cell junction, and the DNAzyme signal output part at the inside can hinder while monitoring inflammatory responses. The released Asiaticoside can improve cell proliferation, enhance angiogenesis, accelerate cell migration/adhesion, and promote wound healing with the combination effect of anti-oxidation and anti-ulceration. Together, BHNVs are shown to successfully accelerate wound healing and prevent inflammation. Favorable therapeutic outcomes are achieved both in vitro and in vivo, indicating a robust modality for local wound management with enhanced therapeutic effects.