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Overview
Tissue Engineering Basics
Nanotechnology Methods
Design Examples
Nanomaterials
Nanodevices
Nature Nanotechnology, January 2011
• Motivation: repair of damaged tissues and organs
• Used to think that the matrix simply defined tissue boundaries
• The key is in the ECM
Tissue
Engineering
Basics
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.
Extracellular Matrix
• Protein fibres (collagen, elastin)• Adhesive protein (laminin,
fibronectin)• Polysaccharides (hyaluronic acid,
heparan sulphate)• Cell adhesion (integrin, cadherin)
Tissue
Engineering
Basics
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.
Extracellular Matrix• The key is in the ECM– Topography– Mechanical Properties– Growth Factor Concentration– ECM Molecules
• The ECM promotes a unique microenvironment that fosters tissue organization
Tissue
Engineering
Basics
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.
Tissue
Engineering
Basics
Extracellular Matrix• The key is in the ECM– Topography– Mechanical Properties– Growth Factor Concentration– ECM Molecules
• The ECM promotes a unique microenvironment that fosters tissue organization
control the ECM -> control the tissue
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.
Tissue
Engineering
Basics
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.
Nan
otec
hnol
ogy
Met
hods Electrospinning
• Simple• Usually at upper-range of
natural 50-500 nm fiber diameter
Self Assembly• Smaller fibers and pore
sizes• Can include functional
motifs – mechanical and instructive matrix support
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.
Nan
otec
hnol
ogy
Met
hods Electrospinning
• Polymer solution charged and fed into electric field
• Carrier solution evaporates and fibrils are deposited on substrate
• http://www.youtube.com/watch?v=E1zuQEYGMJ0
Barnes, C.P. et al. Nanofiber technology: Designing the next generation of tissue engineering scaffolds. Adv. Drug. Deliv. Rev. 2007
Nan
otec
hnol
ogy
Met
hods Self-assembly
Zhang, S. Fabrication of novel biomaterials through molecular self-assembly. Nature Biotechnol. 2003.
Nan
otec
hnol
ogy
Met
hods Self-assembly:
Ionic Self-complementary peptide
• Peptide of 16 AA• Alternating polar/nonpolar• Form stable β-strands and β-sheets• Form nanofibers by hydrophobicity• Matrices with high H2O content
Zhang, S. Fabrication of novel biomaterials through molecular self-assembly. Nature Biotechnol. 2003.
Nan
otec
hnol
ogy
Met
hods Self-assembly:
Surfactant-type peptide
• Charged head group and nonpolar tail• Form nanotubes and nanovesicles• Form interconnected network• Similar to carbon nanotube behavior
Zhang, S. Fabrication of novel biomaterials through molecular self-assembly. Nature Biotechnol. 2003.
Nan
otec
hnol
ogy
Met
hods Self-assembly:
Surface nanocoating peptide
• Three regions:– Anchor– Linker– Functional Head
• Can be used in inkjet printer
Zhang, S. Fabrication of novel biomaterials through molecular self-assembly. Nature Biotechnol. 2003.
Nan
otec
hnol
ogy
Met
hods Self-assembly:
Molecular switch peptide
• Strong dipoles• Conformation changes from α<->β• Could be coupled with metal
nanocrystals
Zhang, S. Fabrication of novel biomaterials through molecular self-assembly. Nature Biotechnol. 2003.
Nan
otec
hnol
ogy
Met
hods Non-fibrous ECM components
• Adhesion proteins• Growth factors• Topography
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.
Nan
otec
hnol
ogy
Met
hods Adhesion Proteins
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Re’em, T. The effect of immobilized RGD peptide in macroporous alginate scaffolds on TGFbeta1-induced
chondrogenesis of human mesenchymal stem cells. Biomaterials. 2010.
Matrix modified with adhesion proteins
Unmodified scaffold
Spreading and attaching to matrix
Only cell-cell adhesion
Nan
otec
hnol
ogy
Met
hods Growth Factors
• bFGF – Basic Fibroblast Growth Factor• Promotes angiogenesis
Freeman, I. The effect of sulfation of alginate hydrogels on the specific binding and controlled release of heparin-binding proteins. Biomaterials. 2008.
bFGF bound to scaffold
bFGF adsorbed to scaffold
bFGF absent
Nan
otec
hnol
ogy
Met
hods Growth Factors
• bFGF – Basic Fibroblast Growth Factor• Promotes angiogenesis
Freeman, I. The effect of sulfation of alginate hydrogels on the specific binding and controlled release of heparin-binding proteins. Biomaterials. 2008.
bFGF bound to scaffold
bFGF adsorbed to scaffold
bFGF absent
Nan
otec
hnol
ogy
Met
hods Topography
• Endothelial Cells
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Teixeira, AI. Epithelial contact guidance on well-defined micro- and nanostructured substrates. J. Cell. Sci. 2003.
Flat topography
Grooved topography
Cardiomyocytes
• ECM forces cardiomyocytes to couple mechanically
• Nanogrooved surface can force cell alignment in same way
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Kim, DH. Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs. PNAS. 2010.
Epithelial Cells
• Epithelial cells are polarized and adhere to other cells
• Nanofibres modified with surface molecules can promote these effects
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Feng, ZQ. The effect of nanofibrous galactosylated chitosan scaffolds on the formation of rat primary hepatocyte aggregates and the maintenance of liver
function. Biomaterials. 2009.
Bone
• Osteoblasts influenced by bone matrix
• Nanostructures used to enhance osteogenesis
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Roohani-Esfahani, SI. The influence hydoxyapatite nanoparticle shape and size on the properties of biphasic calcium phosphate scaffolds coarted with
hydroxyapatite-PCL composites. Biomaterials. 2010.
Nan
omat
eria
lsCarbon Nanotubes
• CNT sponges increase conductivity of matrix
• Also use to increase tensile strength
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Wang, S. F., Shen, L., Zhang, W. D. & Tong, Y. J. Preparation and mechanical properties of chitosan/carbon nanotubes composites. Biomacromolecules. 2005
Gui, X. et al. Soft, highly conductive nanotube sponges and composites with controlled compressibility.ACS Nano. 2010.
Nan
omat
eria
lsNanotitanate Wires
• Specially fabricated wires to promote cell-matrix adhesion
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Wu, S. L. et al. A biomimetic hierarchical scaffold: natural growth of nanotitanates on three-dimensional microporous Ti-based metals. Nano Lett. 2008
Nan
omat
eria
lsNanospheres
• Control the release of growth factors
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Zhang, SF. Nanoparticulate systems for growth factor delivery. Pharm. 2009.
Nan
omat
eria
lsGold Nanowires
• Control wire with electrophoresis and dielectrophoresis
• Control localization of biomolecules
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Fan, D. Subcellular-resolution delivery of a cytokine through precisely manipulated nanowires. Nature Nanotechnology. 2010.
Nan
omat
eria
lsPhage, magnetic iron oxide and gold nanoparticles
• Manipulate geometry of cell mass with 3D structure
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Souza, G. Three-dimensional tissue culture based on magnetic cell levitation. Nature Nanotechnology. 2010.
Nan
odev
ices
Electrical Recording
• Penetrates cell membrane, measure intracellular signals
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Tian, B. Three dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science. 2010.
Nan
odev
ices
Biosensors
• Optical biosensor – photoluminescence differs by presence of drug or reactive species
Dvir, Tal, et al. Nanotechnological strategies for engineering complex tissues. Nature Nanotechnology. 2011.Heller, DA. Multimodal optical sensing and analyte specificity using single-walled carbon nanotubes. Nature Nanotech. 2009.
Summary
Tissue Engineering Basics
Nanotechnology Methods
Design Examples
Nanomaterials
Nanodevices
Nature Nanotechnology, January 2011