Cell-materials interactions are deeply related to physicochemical nature of the surfaces. Poly(N-isopropylacrylamide) (PIPAAm) exhibits a transition from hydrophobic to hydrophilic across its lower-critical solution temperature (LCST) of 32oC.The surfaces on which PIPAAm is covalently grafted with the thickness of 15-20 nm achieve temperaturedependent cell adhesion/detachment control. When the temperature is reduced below 32oC, the surface becomes hydrophilic and swells, allowing cells to spontaneously detach from the surface without the need for enzymatic treatments. With this method, confluently cultured cells are harvested as tissue-like cell sheets with simply reducing temperature. In this review, we describe the clinical applications in regenerative medicine with cell sheet engineering using these intelligent ther morespoinsive surfaces.