Extracellular vesicles (EVs) are nanometer-sized vesicles carrying bioactive molecules secreted from various cell types. Due to their unique properties (e.g., low immunogenicity, signaling modulation, tissue repair), EVs has a plethora of applications such as cancer, cardiovascular, and neurodegeneration.

• However, there are clinical challenges - difficult large-scale production, inconsistent yield and purification, limited targeting specificity, delivery barriers & poor biodistribution, etc.

• The objectives of this study are to (i) develop hydrogel-based implantable bioreactor with actuator, (ii) apply mechanical stimuli to enhance EV secretion & transport, and (iii) optimize NK-cell-derived EVs (NK-EVs) for melanoma therapy

• We hypothesized that mechanical stimuli enhance EV secretion of natural killer (NK) cells.