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2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1
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Xuetao Shi , * Song Chen , Jianhua Zhou , Haijun Yu , Lei Li , and Hongkai Wu *
1. Introduction
Human bone tissue is built in a hierarchical and exqui-
site way by assembling various cells (osteoblasts, osteoclasts
and osteocytes) of specifi c functions; the behaviors of these
well-organized cells in vivo, including the
proliferation, differentiation, apoptosis,
arrangement and protein secretion of
cells, are sophisticatedly managed.
[
1
,
2
]
In
healthy bone tissue, organized osteoblasts
produce a matrix of osteoid composed
mainly of mineralized collagenous fi bers
with self-organized longitudinal and trans-
versal orientations, which is considered to
be one of the vital factors responsible for
the anisotropic mechanical properties of
bone.
[
3–5
]
However, different from the cells
in a healthy human body, the cells in an
injured bone caused by tumor or other
bone-related diseases cannot perform self-
regulated behaviors properly such as the
specialized differentiation. In these cases,
tissue-engineering strategies that effec-
tively coordinate and direct cell behaviors
for bone tissue repair is crucial to address
the aforementioned issue.
Currently, there are two main
approaches for directing cell behaviors in
tissue engineering of bones, i.e., chem-
ical/biological signal cues and topograph-
ical cues. The chemical/biological signal
stimulation has been demonstrated to be
effective to regulate cell behaviors, espe-
cially to direct cell differentiation.
[
6–8
]
Human stem cells have
the potential to differentiate into diverse specialized cell types
and have excellent self-renewable property, and thus become
an overwhelmingly favorable choice for cell-based regenera-
tive therapies. However, implanting undifferentiated stem cells
into injured tissues might result in an adverse and undesired
outcome, for example, in the condition of cartilage regenera-
tion, bone spurs are formed instead.
[
9
]
Hence, the chemical/
biological signal stimulation has drawn ever-growing interest
in regulating stem cell differentiation towards a specialized cell
lineage. Numerous growth factors and chemical reagents have
been utilized to induce the specialized commitments of various
stem cells.
[
10
,
11
]
Besides growth factors that have effect on the
induction and promotion of osteogenic commitment of stem
cells, some chemical reagents such as dexamethasone (Dex),
ascorbic acid (ASC) and β -glycerophosphate (GP), the key oste-
ogenic factors in cell culture media for osteogenesis, have also
been loaded into scaffolds to induce cell differentiation due to
their longer active half-life and higher stability.
[
12–17
]
The supe-
riorities of these chemicals will prolong the interaction period
between stem cells and chemical molecules released from the
Directing Osteogenesis of Stem Cells with Drug-Laden,
Polymer-Microsphere-Based Micropatterns Generated
by Tefl on Microfl uidic Chips
Human bone tissue is built in a hierarchical way by assembling various cells
of specifi c functions; the behaviors of these cells in vivo are sophisticatedly
regulated. However, the cells in an injured bone caused by tumor or other
bone-related diseases cannot properly perform self-regulation behaviors, such
as specialized differentiation. To address this challenge, a simple one-step
strategy for patterning drug-laden poly(lactic- co -glycolic acid) (PLGA) micro-
spheres into grooves by Tefl on chips is developed to direct cellular alignment
and osteogenic commitment of adipose-derived stem cells (ADSCs) for bone
regeneration. A hydrophilic model protein and a hydrophobic model drug are
encapsulated into microsphere-based grooved micropatterns to investigate
the release of the molecules from the PLGA matrix. Both types of molecules
show a sustained release with a small initial burst during the fi rst couple of
days. Osteogenic differentiated factors are also encapsulated in the micropat-
terns and the effect of these factors on inducing the osteogenic differentia-
tion of ADSCs is studied. The ADSCs on the drug-laden micropatterns show
stronger osteogenic commitment in culture than those on fl at PLGA fi lm or
on drug-free grooved micropatterns cultured under the same conditions. The
results demonstrate that a combination of chemical and topographical cues is
more effective to direct the osteogenic commitment of stem cells than either
is alone. The microsphere-based groove micropatterns show potential for
stem cell research and bone regenerative therapies.
DOI: 10.1002/adfm.201200914
Dr. X. T. Shi , Dr. S. Chen , Dr. J. H. Zhou ,
Dr. H. J. Yu , Dr. L. Li , Prof. H. K. Wu
WPI-Advanced Institute for Materials Research
Tohoku University
Sendai 980-8578, Japan
E-mail: shi-xt@hotmail.com; chhkwu@ust.hk
Dr. J. H. Zhou , Prof. H. K. Wu
Department of Chemistry
Hong Kong University of Science and Technology
Hong Kong, China
Dr. L. Li
State Key Laboratory of Integrated Optoelectronics
Institute of Semiconductors
Chinese Academy of Sciences, Beijing, 100083, China
Adv. Funct. Mater. 2012,
DOI: 10.1002/adfm.201200914