Chapter 29 - Intelligent Surfaces for Cell-Sheet Engineering

Abstract

This chapter introduces the intelligent surface of polymer, N-isopropylacrylamide (PIPAAm), and the practical applications of cell-sheet engineering for regenerative medicine. PIPAAm is a nanoscale material, which is not toxic for cells. This surface is slightly hydrophobic under cell culture conditions at 37°C but readily becomes hydrated and hydrophilic below its lower critical solution temperature (LCST), 32°C. Thus, the attachment and detachment of cells on the culture surface can be controlled by simple temperature change. Cell sheets fabricated with the intelligent surface can be applied in order to fabricate thick tissues because cell sheets connect with each other in a short time. Neonatal rat cardiomyocyte sheets are fabricated to enhance the function of cardiac tissue and their characteristics are examined. When four sheets are layered, engineered constructs are macroscopically observed to pulse spontaneously. When they are transplanted into subcutaneous heart tissue-like structures, neovascularization within contractile tissues is observed. Chondrocyte sheets applied to cartilage regeneration are prepared with the cell-sheet technique using temperature-responsive culture dishes. Layered chondrocyte sheets are able to maintain the phenotype of cartilage and can be attached to the sites of cartilage damage, which acts as a barrier to prevent a loss of proteoglycan from these sites and to protect them from catabolic factors in the joint. Chondrocyte sheets with a consistent cartilaginous phenotype and adhesive properties are confirmed and may lead to a new strategy for cartilage regeneration. Hepatic tissue sheets transplanted into the subcutaneous space results in efficient engraftment to the surrounding cells, with the formation of two-dimensional hepatic tissues that stably persist for longer than 200 days.