Abstract
In the past two decades, as a novel approach for tissue engineering, cell sheet engineering has been proposed by our laboratory. Poly(N-isopropylacrylamide) (PIPAAm), which is a well-known temperature-responsive polymer, has been grafted on tissue culture polystyrene (TCPS) surfaces through an electron beam irradiated polymerization. At 37 °C, where the PIPAAm modified surface is hydrophobic, cells can adhere, spread on the surface and grow to confluence. By decreasing temperature to 20 °C, since the surface turns to hydrophilic, cells can detach themselves from the surface spontaneously and form an intact cell sheet with extracellular matrix. For obtaining a temperature-induced cell attachment and detachment, it is necessary to immobilize an ultra thin PIPAAm layer on the TCPS surfaces. This review focuses on the characteristics of PIAPAm modified surfaces exhibiting these intelligent properties. In addition, PIPAAm modified surfaces giving a rapid cell-sheet recovery has been further developed on the basis of the characteristic of the PIPAAm surface. The designs of temperature-responsive polymer layer have provided an enormous potential to fabricate clinically applicable regenerative medicine.
Highlights
There are many synthetic polymers with molecular structures sensitive to environmental changes, such as pH [1], electric field [2], chemical species [3], and temperature [4]
No significant difference in the expressions of cell phenotypic markers between cells cultured on PIPAAm-tissue culture polystyrene (TCPS) and commercially available TCPS has been observed
Cells have been reported to be unable to adhere on bulk PIAAm hydrogel even at 37 °C. These results suggest a possible mechanism that cells are unable to adhere onto the surface of PIPAAm-TCPS with a thick PIPAAm layer, where dehydrated PIPAAm chains at the outermost region of thicker PIPAAm layer still retain a slight higher mobility—like a free gel
Summary
There are many synthetic polymers with molecular structures sensitive to environmental changes, such as pH [1], electric field [2], chemical species [3], and temperature [4]. PIPAAm-modified silica and analytic molecules, the retention times of hydrophobic molecules have been found to increase with increasing temperature without any change in the eluent [7,8,9] In this review, another PIPAAm major application developed as an innovative approach for regenerative medicine by our laboratory has been summarized [10,11,12,13,14,15,16]. PIPAAm has been grafted on a substrate, which can exhibit a reversible cell adhesion to, and detachment from, the polymer-modified surface in response to temperature. (b) At 20 °C, cells detach from hydrated PIPAAm layer, and form an intact cell sheet
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