Cell sheet tissue engineering for scaffold-free three-dimensional (3D) tissue reconstruction.

Three-dimensional (3D) reconstruction of highly functional tissues is of great importance in advancing the clinical benefit of tissue engineering and regenerative medicine. In the last quarter century, many studies have found that by engineering a 3D microenvironment that resembles the in vivo tissue condition, cells exhibit behaviors and functions that reflect those of native tissue. Biomaterial scaffolds are a central technology for providing 3D microenvironments in vitro, and, in conjunction with diverse design and cell seeding advents, have produced highly functional and complex 3D tissues. Here, we describe a new approach to creating 3D cell-dense tissue-like constructs without a biomaterial scaffold. Cell sheet technology with cell sheet layering strategies generates highly cell dense, engineered tissue capable of direct crosstalk with the tissue-engraftment surface, in addition to paracrine-mediated signaling. In this chapter, we will introduce methods of reconstructing 3D tissue using cell sheet technology and the advantages of a scaffold-free design.