YAMATO Masayuki    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Simultaneous enhancement of cell proliferation and thermally induced harvest efficiency based on temperature-responsive cationic copolymer-grafted microcarriers
Journal	Formal name：Biomacromolecules Abbreviation：Biomacromolecules ISSN code：15257797/15264602
Volume, Issue, Page	13(6),pp.1765-1773
Author and coauthor	Tamura Atsushi†, Nishi Masanori, Kobayashi Jun, Nagase Kenichi, Yajima Hirofumi, Yamato Masayuki, Okano Teruo*
Publication date	2012/06
Summary	The development of large-scale suspension cell cultures using microcarriers has long been a focus of attention in the fields of pharmacy and biotechnology. Previously, we developed cell-detachable microcarriers based on temperatureresponsive poly(N-isopropylacrylamide) (PIPAAm)-grafted beads, on which adhering cells can be noninvasively harvested by only reducing the temperature without the need for proteolytic enzyme treatment. In this study, to improve the cell harvest efficiency from bead surfaces while maintaining cell adhesion and proliferation properties, we prepared temperatureresponsive cationic copolymer-grafted beads bearing a copolymer brush consisting of IPAAm, positively charged quaternary amine monomer (3-acrylamidopropyl trimethylammonium chloride; APTAC), and hydrophobic monomer (N-tert-butylacrylamide; tBAAm). The incorporation of positively charged APTAC into the grafted copolymer brush facilitated bead dispersibility in a cell culture system containing Chinese hamster ovary (CHO-K1) cells and consequently allowed for enhanced cell proliferation in the system compared to that of unmodified CMPS and conventional PIPAAm homopolymer-grafted beads. Additionally, P(IPAAm-co-APTAC-co-tBAAm) terpolymer-grafted beads exhibited the most rapid and efficient cell detachment behavior after the temperature was reduced to 20 °C, presumably because the highly hydrated APTAC promoted the overall hydration of the P(IPAAm-co-APTAC-co-tBAAm) chains. Therefore, P(IPAAm-co-APTAC-co-tBAAm) terpolymer-grafted microcarriers are effective in facilitating both cell proliferation and thermally induced cell detachment in a suspension culture system.
DOI	10.1021/bm300256e