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Stem Cell Proliferation and Differentiation through Capped Clay Nanotubes
Sonali Karnik, Darrell Robinson, David K. Mills, Louisiana Tech University
Invited Presentation, @016 Experimental Biology meetings, San Diego, CA April 2-6, 2016
Stem cells can be coaxed to grow into new bone or new cartilage better and faster when given
the right molecular cues. The challenge is inducing how and where stem cells grow and into the
right kind of cell in a three-dimension environment. Such a system requires a means to regulate
cell proliferation, cell-specific differentiation leading to bone-like or cartilage-like cells, tissue
specific matrix formation and functional tissues. Furthermore, depending on the target tissue,
control over the physical, chemical and mechanical influences is key to directing cell behavior in
three-dimensions, and, ultimately, as a method to grow tissues for regenerative medicine
applications. Hydrogels are hydrophilic three-dimensional networks of water-soluble polymers
whose composition, structure and material properties can be easily tuned. We designed a
hydrogel that provides control over local biomaterial properties and that permits guidance over
the process of development leading to extracellular matrix and tissue development. Our
hydrogel nanocomposite consisting of alginate or chitosan, growth factor (BMP-2, 4 or 6, VEGF)
doped halloysite nanotubes (HNTs) creates tunable cross-links that provide structure within the
gel. Results demonstrate that the addition of HNTs improved the material properties of the
nanocomposites and created a cell supportive environment. Pre-osteoblasts and mesenchymal
stem cells cultured with the nanocomposites differentiated into osteoblasts, proliferated and
then synthesized a type I collagen-rich matrix that was subsequent mineralized. Overall protein
synthesis increased in growth factor doped nanocomposites, as did synthesis of bone specific
proteins, osteocalcin, osteonectin, and osteopontin. While the focus in this study was on
osteoblast differentiation this approach may permit local control over behavior of varied cell
types and, ultimately, allow the engineering of complex tissues composed of multiple cell types
using a single stemcell source.
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