Scaffold-free tissue engineering using cell sheet technology

Abstract

Cell sheet technology is a tissue engineering methodology requiring no scaffolds. Confluent cultured cells can be harvested as an intact cell sheet using a temperature-responsive polymer, poly(N-isoproplyacrylamide) (PIPAAm), grafted cell culture surface, offering noninvasive control of cell attachment and detachment only by changing the temperature across 32 °C, without any protease treatments. Avoiding protease treatment preserves complete cell–cell junctions, cell surface proteins, and the extracellular matrix in the cell sheet. Therefore, functional three-dimensional (3D) tissue can be easily fabricated by layering cell sheets without the use of scaffolds. Cell sheet technology has been applied in regenerative medicine for several tissues, and a number of clinical trials have already started. In addition, to fabricate more complex and functional 3D tissue, cell micro-patterning technology can be combined with cell sheet technology, and this interdisciplinary technology could produce interesting results. In this review, recent advances in temperature-responsive culture surfaces, cell sheet and cell micro-patterning technologies are summarized and discussed. In addition, the application of these technologies to regenerative medicine and the re-construction of various tissues including heterogeneous tissues are also discussed.