Expansion of Stem Cells by Nanotissue Engineering - Stem-Cell Nanoengineering - page 236

Table 14.1 ( Continued )

Category Nanomaterial Stem cell Significance/result(s) Reference(s)

Natural
polymers

Collagen MSC MSCs successfully cultured [52]

Silk/PEO MSC PEO was added to improve

processability; Improved adhesion and
proliferation

[53, 54]

Other
modifications

PCLnano-fiber/
PLLA nano-fiber

ESC-MSC Cells infiltrated into the scaffold rather

than migration along the surface;
Enhanced proliferation

[60]

P(LLA-CL) SMC Enhanced proliferation [55]

Starch/PCL MSC Example of blending with natural

materials; combination of micro- and
nanofibers
Better morphology and cell growth

[61]

P(EOT-BT) MSC Microfibers with nanopores are

successful for cell adhesion and
proliferation

[59]

MSC, mesenchymal stem cell; PCL, poly( ε -caprolactone); CSC, carcinoma stem cell; ESC, embryonic stem
cell; SSC, somatic stem cell; NSC, neural stem cell; TCPS, tissue culture polystyrene; TSC, tendon stem
cell; PLGA, poly( d , l - lactide-co-glycolide); HSC, hematopoietic stem cell, PES, polyethersulfone; hASC,
human adipose stem cell; PEO, poly(ethylene oxide); P(LLA-CL), poly ( l -lactic-co- ε -caprolactone); SMC,
smooth muscle cell; P(EOT-BT), poly(ethylene oxide terephthalate)-poly(butylene terephthalate).

and hydrophobicity. Intensive attempts have been made at fabricating PCL fibers for tissue
engineering based on mesenchymal stem cells (MSCs) [19, 21-23], ESCs [24], somatic stem cells
(SSCs) [25] and neural stem cells (NSCs) [26].
In 2003, Yushimoto et al . explored PCL nanofiber matrices for expanding MSCs. Penetration
of cells and abundant ECM were observed in the cell-fiber constructs after 1 week. Scanning
electron microscopy (SEM) images showed that the surfaces of the constructs were covered
with several layers of cells by the fourth week [21]. Ruckh et al . further quantified cell growth
along with live cell imaging. After a short-term (7 days) culture of MSCs in PCL nanofibers,
live cell fluorescence staining and MTT assay showed significantly higher proliferation of
MSCs on nanofibers than two-dimensional control surfaces. The SEM analysis also sup-
ported the fluorescence microscopy results that the MSCs preferentially adhere, spread, and
colonize on nanofiber matrices compared to two-dimensional surfaces [19].
The physical parameters of PCL nanofibers, such as diameter of the fibers and morphology
of the fiber surface, can influence cell attachment and growth. This has been confirmed by a
study using mouse ESCs (P19) and mouse MSCs. Matrices with a thickness of 0.6 mm were
found to provide a better substrate for cell proliferation rather than scaffolds with a thickness
of 0.1 mm, possibly due to more dimensional stability [22]. To demonstrate that nanofiber
surface modification affects stem-cell behavior, the surface of the PCL nanofibers was modi-
fied by He + irradiation, which led to a slight smooth surface and different nanoscale surface
chemical structures. The results showed that early attachment, further proliferation as well as
osteoblastic markers, were higher for MSC on He + irradiated PCL [23].
One of the drawbacks of nanofiber matrices is their small pore size, which results in poor
cell infiltration and migration. To capitalize on the properties of microfibers (i.e., pores large
enough for cell migration) and nanofibers (i.e., physical mimicking of native ECM), multi-
layered matrices can be fabricated to increase the pore size for cell migration. Mesenchymal
stem cells were attached well on both single and bi-layered matrices but were more spread