Simultaneous Enhancement
of Cell Proliferation and
Thermally Induced Harvest Efficiency Based on Temperature-Responsive
Cationic Copolymer-Grafted Microcarriers
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Abstract
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 temperature-responsive
poly(<i>N</i>-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
temperature-responsive cationic copolymer-grafted beads bearing a
copolymer brush consisting of IPAAm, positively charged quaternary
amine monomer (3-acrylamidopropyl trimethylammonium chloride; APTAC),
and hydrophobic monomer (<i>N</i>-<i>tert</i>-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-<i>co</i>-APTAC-<i>co</i>-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-<i>co</i>-APTAC-<i>co</i>-tBAAm) chains. Therefore, P(IPAAm-<i>co</i>-APTAC-<i>co</i>-tBAAm) terpolymer-grafted microcarriers are effective
in facilitating both cell proliferation and thermally induced cell
detachment in a suspension culture system