AUTHORS : Takezawa T 2003 Biomaterials 2003 Jun ;24 (13):2267-2275 Natl Inst Agrobiol Sci, Lab Anim Cell Biol, Tsukuba, Ibaraki 3050901, Japan. Takezawa, T, Natl Inst Agrobiol Sci, Lab Anim Cell Biol, Ikenodai 2, Tsukuba, Ibaraki 3050901, Japan. Print A strategy for the development of tissue engineering scaffolds that regulate cell behavior The cellular scaffold represents an extracellular matrix (ECM) in vivo and a culture substratum in vitro, and provides microenvironmental signaling cues based upon the architecture and component for cells. This review article discusses the development of ideal cellular scaffolds for maintaining the activity of functional cells, for regulating cell behavior, and for reconstructing three-dimensional multicellular masses (3-DMMs). Four culture technologies devising the materials of cellular scaffolds developed by Author's group are also presented; the preparation of a multicellular spheroid utilizing a thermo-responsive polymer, the preparation of a three-dimensionally reconstructed multicellular mass (3-DRMM) with a medium circulating system utilizing cotton-gauze, a concept for organ engineering that can remodel an organ into a reconstructed organ by a continuous three-step perfusion to change the cellular scaffold, and a concept for cellomics study to culture cells on a substratum made of tissue/organ sections for histopathology (TOSHI-substratum) that conserve the microarchitecture and component of the original tissue in vivo. The former two tissue engineering technologies still lacked the method to design 3-DMMs with hierarchical tissue architectures based on cell lineages. To overcome this task, the latter two technologies that can convert tissue architecture in vivo into the three-dimensional culture mode in vitro were innovated. (C) 2003 Elsevier Science Ltd. All rights reserved.