Integrating the old and new: smart thermoresponsive surfaces and 3D fabrication technologies for tissue engineering
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One promising direction of regenerative medicine is the development of cell sheet-based tissue-like constructs. The cell sheets preserve ECM and cell−cell junctions. This may greatly support cell adherence to damaged organ after transplantation. Furthermore, the cell sheets might be used as a building block to engineer large biological tissues with complex organizational architecture. This could be achieved by integrating cell sheets with three-dimensional biomaterial scaffolds. In this study, poly (N-isopropylacrylamide) films were used to produce cell sheets. The pNIPAm films were fabricated by a spin-coating technique. The spin-coating technique allows rapid fabrication of pNIPAm substrates with high reproducibility and uniformity. Because the method of polymer deposition can significantly impact the biological properties of pNIPAm films, the dynamics of cell behavior on spin-coated pNIPAm films of different thicknesses were first examined. Next, biological properties of harvested stromal and epithelial cell sheets after manipulation such as detachment from pNIPAm films, transfer, and re-attachment were assessed. The cell morphology, the pattern and speed of cell sheet recovery and total cell number in cell sheets were analyzed. In addition, the metabolic activity and cell viability of cell sheets before and after detachment and re-attachment were also examined. Next, an integrated-design approach was used to create three-dimensional constructs from cell sheets and three-dimensional natural (acellular pericardial matrix) or three-dimensional synthetic (two-photon polymerization-generated or surface selective laser sintered) scaffolds. These findings should promote further development of implantable tissues engineered from tissue-specific cell sheets and three-dimensional scaffolds.