Exosomes are 30-200 nm-sized extracellular vesicles that are increasingly recognized as potential drug delivery vehicles. However, the rapid clearance of exogenous exosomes from the blood post-injection limits their therapeutic potential. Here, we report bioactive exosome-tethered PEO-based hydrogels for the localized delivery of therapeutic exosomes. Using cholesterol-modified DNA tethers, the lipid membrane of exosomes was functionalized with initiators to graft polymers in the presence of additional initiators and crosslinker using photoinduced Atom Transfer Radical Polymerization (ATRP). This strategy of tethering exosomes within the hydrogel network allowed their controlled release over one month, much longer than physically entrapped exosomes. The release profile can also be tuned by varying the crosslinking density of the polymer network. The use of photocleavable tethers demonstrated on-demand release of exosomes. The therapeutic potential of the hydrogels was confirmed through the delivery of a growth factor, bone morphogenetic protein 2, to promote osteogenic differentiation in C2C12 and MC3T3 cells. Thus, ATRP-based exosome-tethered hydrogels represent a tunable platform with improved efficacy and extended-release profile.

Controlled release of exosomes using ATRP-based hydrogels

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ACS Fall 2022

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