Targeting extracellular vesicle delivery to the lungs by microgel encapsulation

Extracellular vesicles (EVs) secreted by stem and progenitor cells have significant potential as cell-free ‘cellular’ therapeutics. Yet, small EVs (<200 nm) are rapidly cleared after systemic administration, mainly the liver, presenting challenges targeting to a specific organ or tissue. Microencapsulation using natural nano-porous hydrogels (microgels) has been shown enhance engraftment increase survival of transplanted cells. We sought encapsulate within microgels target their delivery lung virtue size-based retention pulmonary microcirculation. Mesenchymal stromal cell (MSC) derived were labelled with lipophilic dye (DiR) encapsulated agarose-gelatin microgels. Endothelial bone marrow macrophages able take up in vitro, but less efficiently than uptake free EVs. Following intrajugular microgel selectively retained lungs for 72h, while liver. Furthermore, microgel-loaded demonstrated greater cells, particular CD45+ immune assessed flow cytometry compared may be novel tool enhancing targeted future therapeutic applications.