Paintable Bioactive Extracellular Vesicle Ink for Wound Healing

Thetreatment of cutaneous wounds involving complex biologicalprocesses has become a significant public health concern worldwide.Here, we developed an efficient extracellular vesicle (EV) ink toregulate the inflammatory microenvironment and promote vascular regenerationfor wound healing. The technology, termed portable bioactive ink fortissue healing (PAINT), leverages bioactive M2 macrophage-derivedEVs (EVM2) and a sodium alginate precursor, forming a biocompatibleEV-Gel within 3 min after mixing, enabling it to be smeared on woundsin situ to meet diverse morphologies. The bioactive EVM2 reprogram macrophage polarization and promote the proliferationand migration of endothelial cells, thereby effectively regulatinginflammation and enhancing angiogenesis in wounds. Through integrationwith a 3D printing pen, the platform enables EV-Gel to be appliedto wound sites having arbitrary shapes and sizes with geometric matchesfor tissue repairment. When evaluated using a mouse wound model, PAINTtechnology accelerates cutaneous wound healing by promoting the angiogenesisof endothelial cells and the polarization of macrophages to M2 phenotypein vivo, demonstrating the high potential of bioactive EV ink as aportable biomedical platform for healthcare.