AKIYAMA Yoshikatsu    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Switching of cell growth/detachment on heparin-functionalized thermoresponsive surface for rapid cell sheet fabrication and manipulation
Journal	Formal name：Biomaterials Abbreviation：Biomaterials ISSN code：01429612
Volume, Issue, Page	34(17),pp.4214-4222
Author and coauthor	Arisaka Yoshinori†, Kobayashi Jun, Yamato Masayuki, Akiyama Yoshikatsu, Okano Teruo*
Publication date	2013/06
Summary	Heparin-functionalized poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide) [P(IPAAm-co-CIPAAm)] grafted surface was designed for the switching of cell growth/detachment, achieved by the regulation of affinity binding between basic fibroblast growth factor (bFGF) and immobilized heparin through the temperature-dependent conformational change of grafted P(IPAAm-co-CIPAAm) chains. At 37 °C, bFGF-bound heparin-thermoresponsive surfaces were able to hold the two- to three-fold number of mouse fibroblast (NIH/3T3) cells than both bFGF-physisorbed surface and PIPAAm surface with soluble bFGF after a 3-day cultivation. Bound bFGF via heparin on shrunken grafted P(IPAAm-co-CIPAAm) chains at 37 °C was able to reinforce the formation and stabilization of bFGF-FGF receptor complex, although the activity of physisorbed bFGF on PIPAAm-grafted surfaces was decreased by non-specific and randomly oriented adsorption. At 20 °C, the cultured NIH/3T3 cell sheet with bFGF detached from heparin-functionalized thermoresponsive surface. The release of bFGF from the surfaces was induced by reducing the affinity binding between bFGF and immobilized-heparin due to increasing the mobility of the swollen grafted P(IPAAm-co-CIPAAm) chains. Therefore, heparin-functionalized thermoresponsive surface was able to enhance cell proliferation, and confluent cells detached themselves as a contiguous cell sheet due to switching cell growth by changing temperature. A cell culture system using this surface is useful for rapid cell sheet fabrication and manipulation.
DOI	10.1016/j.biomaterials.2013.02.056