Biomedical Engineering Reference
In-Depth Information
generation. In this chapter, we would like to describe the principles of “Cell Sheet Engineer‐
ing” and its application of clinical settings, featuring our recent translational research for pe‐
riodontal regeneration.
2. “Cell Sheet Engineering (CSE)”
The cell delivery for periodontal regeneration is usually performed with the combination
use of cells and scaffolds, although the location and the differentiation of transplanted is dif‐
ficult to control. In contrast to approaches that utilize scaffolds, we have developed an alter‐
native technology for cell transplantation using temperature responsive culture dishes,
which we call “Cell Sheet Engineering”.
2.1. Intelligent surface of
N
-isopropylacrylamide (PIPAAm) and fabrication of cell sheets
Poly(
N
-isopropylacrylamide) (PIPAAm) is a temperature responsive polymer that has been
widely utilized for novel biomedical applications. We have developed a PIPAAm-grafted
surface as a smart biointerface wherein cell attachment/detachment can be easily controlled
by simply changing the temperature (Okano et al., 1995; Yamada et al., 1990). This surface is
slightly hydrophobic under cell culture conditions of 37 °C, but readily becomes hydrated
and hydrophilic below its lower critical solution temperature (LCST) of 32 °C. Cells can ad‐
here, spread, and proliferate similarly to that on ungrafted tissue culture grade polystyrene
surfaces at 37 °C (Figure 1A), and cells detach from the surface by reducing temperature be‐
low LCST, making it possible to harvest the cells from the culture surfaces without the use
of proteolytic enzymes (Figure 1B).
A
B
Figure 1.
The principle of “Cell Sheet Engineering”.
A: Cells can attach and proliferate on grafted surface of the temperature responsive polymer
(poly (N-isopropylacrylamide: PIPAAm) at 37 °C, wherein PIPAAm is extensively dehy‐
drated and compact. B: At temperatures below 32 °C, cells with extracellular matrix proteins
spontaneously detach from the temperature responsive culture dishes, wherein PIPAAm is
fully hydrated with an extended-chain conformation. A simple temperature change can con‐
trol cell attachment/detachment without any damages. Modified and reprint from Iwata et
al., 2013.
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