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Electrokinetic Transport in Cartilage
and Tissue-engineered Cartilage Scaffolds
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Funding: Morgan Tissue Engineering Initiative, Becton-Dickinson,
Cornell Center for Materials Research
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Cartilage is a compelling example of a biological tissue
in which coupled mechanical, physicochemical, and electrical stimuli
are thought to play a role in controlling cellular response to mechanical loading.
The physical properties of cartilage critical to its physiological function
are strongly influenced by the extracellular matrix generated by the cartilage
cells (chondrocytes). This extracellular matrix consists primarily of
collagen and proteoglycans, primary the large aggregating proteoglycan known as aggrecan.
Studies in animals, tissue explants, and engineered tissue scaffolds
have all shown that chondrocytes modify their extracellular matrix
in response to loading.
While this evidence compellingly correlates dynamic loading
with matrix synthesis, a complete mechanistic description has not
yet been developed, because the mechanisms that might explain these
results are numerous and difficult to isolate.
As is the case in engineered microsystems (which we use for
particle sorting,
interfacial characterization,
and
microscale pumps),
fluid flow and electric fields are intimately coupled in
biological tissues and engineered hydrogels because a fixed
charge typically exists in the solid phase and is balanced by a
mobile charge in the fluid. When the tissue deforms, the flow of
exuded liquid generates an electrical current and, it turn,
an electrical potential referred to as a streaming potential.
This phenomenon can be observed experimentally
by applying a compressive force F on a material sample and
observing the generated potential between electrodes
positioned at the top and bottom of the tissue.
Streaming potentials form both an effective diagnostic to
identify matrix properties and a potentially important
mechanotransductive mechanism. Streaming potential magnitudes can be
used as indicators of matrix health. Also, because
of their ubiquity, flow-induced electric fields may play a
role in the observed chondrocyte response to dynamic loading.
Because of the intimate coupling between flow and electric
field in native and tissue-engineered cartilage, it has
unfortunately been difficult to isolate the mechanotransductive
effect of streaming potential from the flow itself.
The use of engineered materials as scaffolds for cell
growth presents a unique opportunity to control the local
environment of cells and thus decouple the possible sources
for mechanotransductive response. In collaboration with
Larry Bonassar,
we are developing and testing biomaterials
to control mechanical, chemical, and electrical properties in tissue-engineered
scaffold to enable
more precise study of how individual physical stimuli regulate
cartilage cell behavior.
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Publications and Presentations on Electrokinetic Transport in Cartilage
and Tissue-engineered Cartilage Scaffolds
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Chandler EM,
Berglund CM,
Lee JS,
Polacheck WJ,
Gleghorn JP,
Kirby BJ,
Fischbach C
"Stiffness of Photocrosslinked Alginate Gels Regulates
Adipose Progenitor Cell Behavior, Biotechnology and Bioengineering 108:7;1683-1692, 2011.
doi
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Rouillard AD,
Berglund CM,
Lee JY,
Polacheck WJ,
Tsui YT,
Bonassar LJ,
Kirby BJ
"Methods for photocrosslinking alginate hydrogel scaffolds with
high cell viability,"
Tissue Engineering C, Vol 17(2), 2011.
doi
pdf
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Rouillard AD,
Tsui YT,
Polacheck WJ,
Lee JY,
Bonassar LJ,
Kirby BJ
"Control of the Electromechanical Properties of Alginate Hydrogels via
Ionic and Covalent Crosslinking and Microparticle Doping,"
Biomacromolecules, 11 (8), pp 2184–2189, 2010.
doi
pdf
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Rouillard AD,
Berglund CM,
Lee JY,
Polacheck WJ,
Tsui YT,
Bonassar LJ,
Kirby BJ
"Methods for photocrosslinking alginate hydrogel scaffolds with high cell viability,"
Orthopedic Research Society Meeting, New Orleans, LA, March 2010.
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Chandler EM,
Berglund CM,
Lee JS,
Kirby BJ,
Fischbach CF
"Photocrosslinked Alginate Gels for Analysis of
Stromal Cell Behavior in Tumors ",
Northeast Bioengineering Conference, Cambridge, MA, 3-5 Apr 2009.
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Rouillard AD,
Tsui Y,
Polacheck WJ,
Lee JY,
Bonassar LJ,
Kirby BJ
"Micropatterned hydrogel tissue scaffolds with controlled
electrokinetic properties for investigation of chondrocyte
mechanotransduction", MicroTAS 2007, Paris, France, October 2007.
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Rouillard AD,
Tsui Y,
Polacheck WJ,
Lee JY,
Bonassar LJ,
Kirby BJ
"Control of the electromechanical proterties of alginate
tissue scaffolds via ionic and covalent crosslinking
and microparticle doping", BMES 2007, Los Angeles, CA, September 2007.
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Rouillard AD,
Bonassar LJ,
Kirby BJ
"Control of electrokinetic properties of hydrogels for studies of mechanotransduction
in chondrocytes,"
BMES Annual Meeting Chicago, IL, Oct 2006.
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Rouillard AD,
Bonassar LJ,
Kirby BJ
"Studying cell mechanotransduction in chondrocytes via manipulation of electrokinetics in
alginate hydrogels,"
2nd New York Complex Matter Workshop Ithaca, NY, June 2006.
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Growth of fibroblasts grown on compliant (top) and stiff (bottom)
matrices show the importance of
matrix stiffness in lipogenic differentiation(see ref here).
We have collaborated with
Claudia Fischbach's lab to use our
photocrosslinked alginate matrices
(see refs
here
and
here
)
to study adipose progenitor cells.
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