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Electrokinetic Transport in Cartilage and Tissue-engineered Cartilage Scaffolds
Funding: Morgan Tissue Engineering Initiative, Becton-Dickinson, Cornell Center for Materials Research
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.

Archival Publications

PDF version of AUTHORS: TITLE

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

PDF version of Chandler, Berglund, Lee, Polacheck, Gleghorn, Fischbach: Stiffness of Photocrosslinked Alginate Gels Regulates
Adipose Progenitor Cell Behavior

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 pdf

PDF version of Rouillard, Tsui, Polacheck, Lee, Bonassar, Kirby: 
Control of the Electromechanical Properties of
Alginate Hydrogels via Ionic and Covalent
Cross-Linking and Microparticle Doping

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

Presentations and Other Publications
24-27 Oct 2012

Santana SM , Fischbach C , Kirby BJ
"Immunocapture of Circulating Tumor Cells in Tissue-Engineered GEDI Microdevices", BMES 2012, Atlanta, Georgia.

6-9 Mar 2010

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.

3-5 Apr 2009

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.

5 Mar 2009

Berglund CM, Lee JY, Yang W, Lee JS, Chandler EM, Fischbach CF, Kirby BJ
"Synthesis and Characterization of Photocrosslinked Alginate Hydrogels", Bioengineering Expo, Ithaca, NY.

5 Mar 2009

Lee JY, Berglund CM, Yang W, Gleghorn JP, Bonassar LJ, Kirby BJ
"Biological Characterization of Chondrocytes Seeded in Photocrosslinked Alginate Tissue Scaffolds", Bioengineering Expo, Ithaca, NY.

30 Jan 2009

Kirby BJ
"Geometric micro- and mesopatterning for control of cell transport and microenvironemnt in microdevices and tissue-engineered scaffolds", Carnegie-Mellon Mechanical Engineering Seminar Series, Pittsburgh, PA.

27 Oct 2008

Kirby BJ
"Geometric patterning to control cell growth, capture, and transport", NBTC Annual Symposium, Ithaca, NY.

4 Mar 2008

Kirby BJ
"Micropatterning in injection-molded microdevices and engineered tissue scaffolds: the role of electrokinetic coupling", University of Illinois Mechancal Science and Engineering Department, Urbana, IL

7-11 Oct 2007

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.

1 Oct 2007
PDF version of Chandler, Berglund, Lee, Polacheck, Gleghorn, Fischbach: Stiffness of Photocrosslinked Alginate Gels Regulates
Adipose Progenitor Cell Behavior

Chandler EM, Cossell CM, Polacheck WJ, Lee JY, Kirby BJ, Fischbach C
"Effect of Substrate Stiffness on Heterotypic Cellular Interactions in Breast Cancer, Nanobiotechnology Symposium, Cornell University, Ithaca, NY. doi pdf

26-29 Sep 2007

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

10 May 2007

Kirby BJ
"Electromechanical coupling in microfabricated and tissue-engineered systems", University of Toronto Analytical Chemistry Seminar Series, Toronto, Canada.

24 Apr 2007

Kirby BJ
"Electromechanical coupling in microfabricated and tissue-engineered systems", Lafayette Bioengineering and Biomedicine Symposium, Easton, PA.

26 Feb 2007

Kirby BJ
"Design and control of micro/nanoscale fluid systems via polymer synthesis and geometric patterning", Biological and Environmental Engineering Seminar Series, Cornell University, Ithaca, NY.

25 Jan 2007

Kirby BJ
"Design and control of micro/nanoscale fluid systems via polymer synthesis and geometric patterning", Textiles and Apparel Seminar Series, Cornell University, Ithaca, NY.

Oct 2006

Rouillard AD, Bonassar LJ, Kirby BJ
"Control of electrokinetic properties of hydrogels for studies of mechanotransduction in chondrocytes," BMES Annual Meeting Chicago, IL.

Jun 2006

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.

Stress-strain curve of tissue-engineered scaffolds used for seeding chondrocytes. We are designing biomaterials with controlled material properties so as to enable studies of mechanotransduction in chondrocytes during physiological loading.

Growth of fibroblasts grown on functionalized (top) and RGD-functionalized (bottom) matrices show the importance of adhesion in fibroblast growth (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.
6mm disks of tissue-engineered cartilage produced by culturing bovine articular chondrocytes in a photocrosslinked alginate matrix. We are interested in the electrokinetic properties of these matrices and the effects of these properties on tissue development.