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Updated: Mar 25, 2026

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Engineering Three-dimensional Epithelial Tissues Embedded within Extracellular Matrix
Published on: July 10, 2016
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Three-Dimensional Tissue Models Constructed by Cells with Nanometer- or Micrometer-Sized Films on the Surfaces
Chun-Yen Liu1, Michiya Matsusaki1, Mitsuru Akashi1,2
1Department of Applied Chemistry Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, 565-0871, Osaka, Japan.
Summary
Researchers developed novel methods to create artificial 3D tissues using hierarchical cell manipulation and extracellular matrix (ECM) coatings. These techniques enable precise control over cell density and organization for tissue engineering applications.
Area of Science:
- Tissue Engineering
- Biomaterials Science
- Cell Biology
Background:
- Living tissues exhibit complex hierarchical structures essential for function.
- EU regulations ban animal testing, increasing demand for artificial tissues.
- Tissue engineering faces challenges in replicating natural tissue complexity and function.
Purpose of the Study:
- To develop novel methods for fabricating artificial 3D tissues with controlled cellular organization.
- To engineer 3D constructs mimicking natural tissue structures for repair and transplantation.
- To create versatile tissue models for pharmaceutical research and development.
Main Methods:
- Developed a hierarchical cell manipulation technique using nanometer-sized fibronectin (FN) and gelatin (G) extracellular matrix (ECM) films.
- Utilized layer-by-layer coating methodology for uniform ECM film deposition on cell surfaces.
- Introduced collagen coating and multiple coating methods to create micrometer-sized ECM layers for controlled cell spacing.
Main Results:
- Successfully constructed 3D tissue constructs with high cell densities using FN/G coatings.
- Fabricated micro- to millimeter-sized 3D constructs with lower cell densities using collagen and multiple coating methods.
- Demonstrated precise control over cell distances and tissue properties at the single-cell level by varying ECM layer thickness.
Conclusions:
- The developed hierarchical cell manipulation techniques offer a versatile bottom-up approach for tissue engineering.
- Controlled ECM coating enables homogenous 3D tissue fabrication with defined cell types, locations, and properties.
- These advancements hold significant promise for achieving diverse goals in tissue engineering and regenerative medicine.

