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Updated: Jan 30, 2026

Tissue Engineering: Construction of a Multicellular 3D Scaffold for the Delivery of Layered Cell Sheets
Published on: October 3, 2014
Cell sheet tissue engineering: Cell sheet preparation, harvesting/manipulation, and transplantation
Jun Kobayashi1, Akihiko Kikuchi2, Takao Aoyagi3
1Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, TWIns, 8-1 Kawadacho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Cell sheet tissue engineering utilizes temperature-responsive surfaces for preparing and harvesting cell sheets with extracellular matrices. This technology facilitates the creation of 2D and 3D tissues for clinical transplantation, with ongoing research focusing on larger tissue constructs and vascularization.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- Cell sheet tissue engineering enables the creation of transplantable 2D and 3D tissues and organs.
- Key aspects include material surface effects, interfacial cell sheet properties, and manipulation techniques.
Purpose of the Study:
- To review the preparation, harvesting, manipulation, and transplantation of cell sheets in tissue engineering.
- To highlight the role of temperature-responsive polymers in cell sheet technology.
- To discuss challenges and future directions for creating larger 3D tissues and organs.
Main Methods:
- Utilizing temperature-responsive cell culture surfaces, specifically poly(N-isopropylacrylamide) (PIPAAm)-grafted tissue culture polystyrene (TCPS).
- Harvesting contiguous cell sheets with extracellular matrices (ECMs) by temperature reduction.
- Employing cell sheet manipulators for the formation of 3D tissues.
Main Results:
- PIPAAm-immobilized TCPS allows cell sheet harvesting without disrupting ECMs, cell-cell junctions, or membrane proteins.
- Ligand-immobilized and porous hydrophilic PIPAAm-grafted surfaces enhance cell sheet preparation and harvesting efficiency.
- Cell sheet manipulation facilitates the assembly of 3D tissues.
Conclusions:
- Cell sheet technology, particularly with PIPAAm-modified surfaces, is a viable method for generating transplantable tissues.
- Clinical applications are established in seven settings, including cardiac, corneal, and cartilage repair.
- Future advancements require efficient production of differentiated cells from induced pluripotent stem (iPS) cells and improved vascularization strategies for large-scale tissue engineering.
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