Novel regenerable cell culture system using signal responsive membrane substrate

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In recent years, bio-reactors and bio-artificial organs utilizing cellular functions have been developed, although there are still unsolved problems such as that they cannot be used for a long time period. One of the substantial differences between synthetic materials and biomaterials is their ability to self-repair. When some cells die on the artificial material, inflammatory substances are released from the dead cells and damage adjacent living cells, leading to the expansion of the inflammation. In this study, we developed a rapid regenerable cell culture system. Namely, the material can selectively recognize local cell death and subsequently remove the dead cells actively from the material surface, so that the resulting vacant spaces can be regenerated voluntarily and quickly by the growth of surrounding cells. Cells are detached from N-isopropylacrylamide (NIPAM) grafted surface by temperature decreasing below 32℃, because NIPAM changes its properties. In this study, a crown is used as a sensor that recognizes signals from dead cells, and NIPAM is used as an actuator. A designed polymer is a copolymer of NIPAM and Benzo-18-Crown-6-acrylamide (BCAm) with a pendant crown ether receptor. When the crown ether captures specific ion, the LCST shifts to higher temperature, because guest-host complex makes the polymer chain more hydrophilic. Therefore, when the cells die, the polymer surface recognizes potassium ion released from the dead cells, NIPAM hydrates, and selectively detach the dead cells. This study is a pioneering approach that recognizes cell signals and which works in living systems in the novel field of tissue engineering.