Three-Dimensional Tissue Models Constructed by Cells with Nanometer- or Micrometer-Sized Films on the Surfaces

Chun Yen Liu, Michiya Matsusaki, Mitsuru Akashi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Living tissues or organ modules consist of different types of highly organized cells and extracellular matrices (ECMs) in a hierarchical manner, such as the multilayered structure of blood vessels and the radial structures of hepatic lobules. Due to animal examinations being banned in the EU since 2013 and a shortage in the demand for tissue repair or organ transplantation, the creation of artificial 3D tissues possessing specific structures and functions similar to natural tissues are key challenges in tissue engineering. To date, we have developed a simple but unique bottom-up approach, a hierarchical cell manipulation technique, with a nanometer-sized ECM matrix consisting of fibronectin (FN) and gelatin (G) on cell surfaces. About 10 nm thick FN/G ECM films on cell surfaces were coated successfully by using layer-by-layer coating methodology. Various 3D constructs with higher cell density with different types of cells were successfully constructed. In addition to the construction of tissues with higher cell densities, other tissues, such as cartilage or skin tissues, with different cell densities are also important tissue models for tissue engineering and pharmaceutical industries. Thus, we recently developed other methodologies, the collagen coating method and multiple coating method, to fabricate micrometer-sized level ECM layers on cell surfaces. Various micro- or millimeter-sized 3D constructs with lower cell densities were constructed successfully. By using these two methods, cell distances in 2D or 3D views can be controlled by different thicknesses of ECM layers on cell surfaces at the single-cell level. Both FN/G and the collagen coating method resulted in homogenous 3D tissues with a controlled layer numbers, cell type, cell location, and properties; these will be promising to achieve different goals in tissue engineering.

Original languageEnglish
Pages (from-to)783-796
Number of pages14
JournalChemical Record
Issue number2
Publication statusPublished - 2016 Apr 1

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Biochemistry
  • General Chemical Engineering
  • Materials Chemistry


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