Temperature-responsive polymers are used as switching sequences to regulate interfacial phenomena and initiate unique biomedical and biotechnological applications. Special attention has been paid to poly(N-isopropylacrylamide) (PIPAAm), which exhibits a reversible temperature-dependent phase transition in aqueous solutions at the lower critical solution temperature (LCST) of 32 °C. Soluble and cross-linked PIPAAm undergo temperature-responsive dynamic volume changes, which are utilized for regulating on–off drug release and mimicking biological functions. However, no clinical studies on implantation of PIPAAm-based biomaterials have been reported. By contrast, PIPAAm-modified intelligent surfaces, which exhibit hydrophilic/hydrophobic alteration in response to temperature change, are readily adaptive to clinical applications because no PIPAAm molecules are eluted in the solution during the interaction with biological materials. The PIPAAm-immobilized surfaces achieve purifying bioactive molecules in aqueous media and recovering cell sheets to create three dimensional tissues for regeneration of damaged tissues only by changing temperature.