In‐Drop Thermal Cycling of Microcrystal Assembly for Senescence Control (MASC) with Minimal Variation in Efficacy

The secretome from mesenchymal stem cells (MSCs) have recently gained attention for new therapeutics. However, clinical application requires in vitro cell manufacturing to attain enough cells. Unfortunately, this process often drives MSCs into a senescent state that drastically changes cellular secretion activities. Antioxidants are used reverse and prevent the propagation of senescence; however, their activity is short-lived. Polymer-stabilized crystallization antioxidants has been shown improve bioactivity, but broad crystal size distribution (CSD) significantly increases efficacy variation. Efforts made crystalize drugs microdroplets narrow CSD, fraction drops containing at least one can be as low 20%. To end, study demonstrates in-drop thermal cycling hyaluronic acid-modified antioxidant crystals, named microcrystal assembly senescence control (MASC), drive microdrops crystals >86% while achieving narrower CSDs (13 ± 3 µm) than bulk (35 11 µm). Therefore, approach considerably improves practicality CSD-control drops. In addition exhibiting uniform release, MASC with antioxidizing N-acetylcysteine extends release time by 40%. further restoration reactive oxygen species homeostasis MSCs, thus minimizing preserving desired It proposed broadly useful controlling wide array therapeutic during biomanufacturing.