Recent development of temperature-responsive surfaces and their application for cell sheet engineering.

Cell sheet engineering, which fabricates sheet-like tissues without biodegradable scaffolds, has been proposed as a novel approach for tissue engineering. Cells have been cultured and proliferate to confluence on a temperature-responsive cell culture surface at 37°C. By decreasing temperature to 20°C, an intact cell sheet can be harvested from the culture surface without enzymatic treatment. This new approach enables cells to keep their cell-cell junction, cell surface proteins and extracellular matrix. Therefore, recovered cell sheet can be easily not only transplanted to host tissue, but also constructed a three-dimensional (3D) tissue by layering cell sheets. Moreover, cell sheet manipulation technology and bioreactor have been combined with the cell sheet technology to fabricate a complex and functional 3D tissue in vitro. So far, cell sheet technology has been applied in regenerative medicine for several tissues, and a number of clinical studies have been performed. In this review, recent advances in the preparation of temperature-responsive cell culture surface, the fabrication of organ-like tissue and the clinical application of cell sheet engineering are summarized and discussed.