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Miller, Ryan C.; Lee, Jonghwi; Kim, Young Jun; Han, Hee‐Sun; Kong, Hyunjoon (, Advanced Functional Materials)Abstract 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 to reverse and prevent the propagation of senescence; however, their activity is short‐lived. Polymer‐stabilized crystallization of antioxidants has been shown to improve bioactivity, but the broad crystal size distribution (CSD) significantly increases the efficacy variation. Efforts are made to crystalize drugs in microdroplets to narrow the CSD, but the fraction of drops containing at least one crystal can be as low as 20%. To this end, this study demonstrates that in‐drop thermal cycling of hyaluronic acid‐modified antioxidant crystals, named microcrystal assembly for senescence control (MASC), can drive the fraction of microdrops containing crystals to >86% while achieving significantly narrower CSDs (13 ± 3 µm) than in bulk (35 ± 11 µm). Therefore, this approach considerably improves the practicality of CSD‐control in drops. In addition to exhibiting uniform release, MASC made with antioxidizing N‐acetylcysteine extends the release time by 40%. MASC further improves the restoration of reactive oxygen species homeostasis in MSCs, thus minimizing cellular senescence and preserving desired secretion activities. It is proposed that MASC is broadly useful to controlling senescence of a wide array of therapeutic cells during biomanufacturing.more » « less
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Kim, Byoung Soo; Kim, Min Ku; Cho, Younghak; Hamed, Eman E.; Gillette, Martha U.; Cha, Hyeongyun; Miljkovic, Nenad; Aakalu, Vinay K.; Kang, Kai; Son, Kyung-No; et al (, Science Advances)null (Ed.)“Living” cell sheets or bioelectronic chips have great potentials to improve the quality of diagnostics and therapies. However, handling these thin and delicate materials remains a grand challenge because the external force applied for gripping and releasing can easily deform or damage the materials. This study presents a soft manipulator that can manipulate and transport cell/tissue sheets and ultrathin wearable biosensing devices seamlessly by recapitulating how a cephalopod’s suction cup works. The soft manipulator consists of an ultrafast thermo-responsive, microchanneled hydrogel layer with tissue-like softness and an electric heater layer. The electric current to the manipulator drives microchannels of the gel to shrink/expand and results in a pressure change through the microchannels. The manipulator can lift/detach an object within 10 s and can be used repeatedly over 50 times. This soft manipulator would be highly useful for safe and reliable assembly and implantation of therapeutic cell/tissue sheets and biosensing devices.more » « less