Temperature-Gating Titania Nanotubes Regulate Migration of Endothelial Cells

External stimuli-responsive biomaterials represent a type of promising candidates for addressing the complexity of biological systems. In this study, a platform based on the combination of temperature-sensitive polymers and a nanotube array was developed for loading sphingosine 1-phosphate (S1P) and regulating the migration of endothelial cells (ECs) at desired conditions. The localized release dosage of effectors could be controlled by the change of environmental temperature. At a culture temperature above the lower critical solution temperature, the polymer "gatekeeper" with a collapsed conformation allowed the release of S1P, which in turn enhanced the migration of ECs. The migration rate of single cells was significantly enhanced up to 58.5%, and the collective migration distance was also promoted to 25.1% at 24 h and 33.2% at 48 h. The cell morphology, focal adhesion, organization of cytoskeleton, and expression of genes and proteins related to migration were studied to unveil the intrinsic mechanisms. The cell mobility was regulated by the released S1P, which would bind with the S1PR1 receptor on the cell membrane and trigger the Rho GTPase pathway.