Thermoresponsive polymers and their biomedical application in tissue engineering - a review.

Thermoresponsive polymers hold great potential in the biomedical field, since they enable the fabrication of cell sheets, in situ drug delivery and 3D-printing under physiological conditions. In this review we provide an overview of several thermoresponsive polymers and their application, with focus on poly(N-isopropylacrylamide)-surfaces for cell sheet engineering. Basic knowledge of important processes like protein adsorption on surfaces and cell adhesion is provided. For different thermoresponsive polymers, namely PNIPAm, Pluronics, elastin-like polypeptides (ELP) and poly(N-vinylcaprolactam) (PNVCL), synthesis and basic chemical and physical properties have been described and the mechanism of their thermoresponsive behavior highlighted. Fabrication methods of thermoresponsive surfaces have been discussed, focusing on PNIPAm, and describing several methods in detail. The latter part of this review is dedicated to the application of the thermoresponsive polymers and with regard to cell sheet engineering, the process of temperature-dependent cell sheet detachment is explained. We provide insight into several applications of PNIPAm surfaces in cell sheet engineering. For Pluronics, ELP and PNVCL we show their application in the field of drug delivery and tissue engineering. We conclude, that research of thermoresponsive polymers has made big progress in recent years, especially for PNIPAm since the 1990s. However, manifold research possibilities, e.g. in surface fabrication and 3D-printing and further translational applications are conceivable in near future.