Supramolecular hydrogels for sustained extracellular vesicle delivery

Abstract

AbstractExtracellular vesicles (EVs) have been explored as promising drug delivery platforms and cell-free therapies for a range of diseases. Despite their therapeutic potential, challenges persist in achieving sustained EV delivery. Here, we integrate EVs into a supramolecular and injectable hydrogel-based drug delivery system based on dodecyl- or octadecyl-modified hydroxypropyl methylcellulose (HPMC-C12 or -C18) that form non-covalent crosslinks with liposomes. Hydrogel mechanics and EV-release kinetics were tunable by varying liposome concentrations. Using mesenchymal stem cell-derived EVs (MSC-EVs), we confirm effective, hydrogel-mediated sustained EV delivery and uptake and a ~ 20% greater anti-inflammatory response in pathogenic vascular smooth muscle cells than bolus EV-only treatment. Graphical abstract