Cell sheet technology and its applications in corneal tissue engineering

Abstract

Cell sheet technology (CST) is based on the use of poly (N-isopropylacrylamide, PNIPAAm), which can be exhibit reversible hydration and dehydration of its polymer chains in response to temperature changes across the lower critical solution temperature(LCST)of 32°C. By reducing the incubation temperature to 20°C, all cultured cells are harvested as intact sheets along with their deposited extracellular matrix (ECM) due to the conversion of the grafted PIPAAm from hydrophobic to hydrophilic, as ECM remains present on the basal surface of the cell sheets, they can maintain cell viability and function as well as directly transplanted to tissue beds or even layered to create three-dimensional (3D) tissue-like structures without any scaffolds or sutures. The temperature-sensitive surfaces' preparation approaches, density, thickness, membrane additive ingredients and so on, all affect cell adhesion and proliferation. It can maintain cell viability and improve function by accelerating cell sheet detachment through changing the membrane compositions, density as well as types of graft substrate. With CST, cultured autologous/allogeneic corneal seed cells in vitro used as transplant sources can overcome the problems of immunorejection of transplanted tissues as well as donor organ shortages. So far, the cell sheet of limbal epithelium and autologous oral mucosal epithelium obtained by the CST have been successfully used in clinical graft for ocular surface reconstruction. Finally, There is an overview of preparations of temperature-responsive surfaces, impacts of various factors that influenced cultured cells in vitro and clinical applications or clinically relevant animal experimentations of CST in corneal tissue engineering.