Design of Temperature-Responsive Polymer-Grafted Surfaces for Cell Sheet Preparation and Manipulation

This review focuses on the design of poly(N-isopropylacrylamide) (PIPAAm)-grafted surfaces for cell sheet preparation and manipulation, which are revolutionary tools for the creation of transplantable two-dimensional (2D) and engineered three-dimensional (3D) cellular tissues. Particularly, the thickness of grafted PIPPAm chains in the perpendicular direction is regulated to achieve temperature-dependent alteration of cell sheet preparation/harvesting. The 2D positioning of grafted PIPAAm in a direction parallel to the material surfaces facilitates spatially controlled micropatterns containing heterotypic cells. This review also describes the 2D manipulation of cell sheets and the creation of cell sheet-layered 3D tissue using the PIPAAm-grafted surface. With the aid of supporting materials such as membranes and gelatin hydrogels, cell sheets on PIPAAm-grafted surfaces can be manipulated and applied for transplantation in clinical settings and for the formation of 3D tissues in vitro. For the next generation of cell sheet-based tissue engineering, a challenging issue is the creation of large, thick tissues/organs such as cardiac and hepatic tissues/organs. The integration of various technologies including bioreactors and micropatterning is essential to achieve the creation of functional engineered 3D organs.