Abstract

Multiphoton excited photochemistry is a powerful 3D fabrication tool that produces sub-micron feature sizes. Here we exploit the freeform nature of the process to create models of the extracellular matrix (ECM) of several tissues, where the design blueprint is derived directly from high resolution optical microscopy images (e.g. fluorescence and Second Harmonic Generation). To achieve this goal, we implemented a new form of instrument control, termed modulated raster scanning, where rapid laser shuttering (10 MHz) is used to directly map the greyscale image data to the resulting protein concentration in the fabricated scaffold. Fidelity in terms of area coverage and relative concentration relative to the image data is ~95%. We compare the results to an STL approach, and find the new scheme provides significantly improved performance. We suggest the method will enable a variety of cell-matrix studies in cancer biology and also provide insight into generating scaffolds for tissue engineering.

© 2013 Optical Society of America

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  20. X. Chen, M. A. Brewer, C. Zou, and P. J. Campagnola, “Adhesion and migration of ovarian cancer cells on crosslinked laminin fibers nanofabricated by multiphoton excited photochemistry,” Integr Biol (Camb) 1(7), 469–476 (2009).
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  26. C. E. Olson, M. J. Previte, and J. T. Fourkas, “Efficient and robust multiphoton data storage in molecular glasses and highly crosslinked polymers,” Nat. Mater. 1(4), 225–228 (2002).
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    [CrossRef] [PubMed]
  30. C. A. DeForest, B. D. Polizzotti, and K. S. Anseth, “Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments,” Nat. Mater. 8(8), 659–664 (2009).
    [CrossRef] [PubMed]
  31. R. G. Wylie, S. Ahsan, Y. Aizawa, K. L. Maxwell, C. M. Morshead, and M. S. Shoichet, “Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels,” Nat. Mater. 10(10), 799–806 (2011).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]
  35. S. Basu and P. J. Campagnola, “Properties of crosslinked protein matrices for tissue engineering applications synthesized by multiphoton excitation,” J. Biomed. Mater. Res. A 71(2), 359–368 (2004).
    [CrossRef] [PubMed]
  36. S. Basu, C. W. Wolgemuth, and P. J. Campagnola, “Measurement of Normal and Anomalous Diffusion of Dyes within Protein Structures Fabricated via Multiphoton Excited Cross-linking,” Biomacromolecules 5(6), 2347–2357 (2004).
    [CrossRef] [PubMed]
  37. C. Lorenz, I. C. Carlsen, T. M. Buzug, C. Fassnacht, and J. Weese, “A multi-scale line filter with automatic scale selection based on the Hessian matrix for medical image segmentation,” Lect. Notes Comput. Sci. 1252, 152–163 (1997).
    [CrossRef]
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2013 (1)

J. J. Rice, M. M. Martino, L. De Laporte, F. Tortelli, P. S. Briquez, and J. A. Hubbell, “Engineering the regenerative microenvironment with biomaterials,” Adv Healthc Mater 2(1), 57–71 (2013).
[CrossRef] [PubMed]

2012 (4)

C. A. DeForest and K. S. Anseth, “Advances in bioactive hydrogels to probe and direct cell fate,” Annu Rev Chem Biomol Eng 3(1), 421–444 (2012).
[CrossRef] [PubMed]

P. Lu, V. M. Weaver, and Z. Werb, “The extracellular matrix: a dynamic niche in cancer progression,” J. Cell Biol. 196(4), 395–406 (2012).
[CrossRef] [PubMed]

X. Chen, Y. D. Su, V. Ajeti, S. J. Chen, and P. J. Campagnola, “Cell adhesion on micro-structured fibronectin gradients fabricated by multiphoton excited photochemistry,” Cell Mol Bioeng 5(3), 307–319 (2012).
[CrossRef] [PubMed]

P. J. Su, Q. A. Tran, J. J. Fong, K. W. Eliceiri, B. M. Ogle, and P. J. Campagnola, “Mesenchymal Stem Cell Interactions with 3D ECM Modules Fabricated via Multiphoton Excited Photochemistry,” Biomacromolecules 13(9), 2917–2925 (2012).
[CrossRef] [PubMed]

2011 (4)

C. M. Soukoulis and M. Wegener, “Past achievements and future challenges in the development of three-dimensional photonic metamaterials,” Nat. Photonics 5, 523–530 (2011).

R. G. Wylie, S. Ahsan, Y. Aizawa, K. L. Maxwell, C. M. Morshead, and M. S. Shoichet, “Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels,” Nat. Mater. 10(10), 799–806 (2011).
[CrossRef] [PubMed]

P. Friedl and S. Alexander, “Cancer invasion and the microenvironment: plasticity and reciprocity,” Cell 147(5), 992–1009 (2011).
[CrossRef] [PubMed]

T. R. Cox and J. T. Erler, “Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer,” Dis. Model. Mech. 4(2), 165–178 (2011).
[CrossRef] [PubMed]

2010 (3)

D. Qin, Y. Xia, and G. M. Whitesides, “Soft lithography for micro- and nanoscale patterning,” Nat. Protoc. 5(3), 491–502 (2010).
[CrossRef] [PubMed]

J. J. Moon, J. E. Saik, R. A. Poché, J. E. Leslie-Barbick, S. H. Lee, A. A. Smith, M. E. Dickinson, and J. L. West, “Biomimetic hydrogels with pro-angiogenic properties,” Biomaterials 31(14), 3840–3847 (2010).
[CrossRef] [PubMed]

G. Kumi, C. O. Yanez, K. D. Belfield, and J. T. Fourkas, “High-speed multiphoton absorption polymerization: fabrication of microfluidic channels with arbitrary cross-sections and high aspect ratios,” Lab Chip 10(8), 1057–1060 (2010).
[CrossRef] [PubMed]

2009 (4)

C. A. DeForest, B. D. Polizzotti, and K. S. Anseth, “Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments,” Nat. Mater. 8(8), 659–664 (2009).
[CrossRef] [PubMed]

X. Chen, M. A. Brewer, C. Zou, and P. J. Campagnola, “Adhesion and migration of ovarian cancer cells on crosslinked laminin fibers nanofabricated by multiphoton excited photochemistry,” Integr Biol (Camb) 1(7), 469–476 (2009).
[CrossRef] [PubMed]

J. A. Santiago, R. Pogemiller, and B. M. Ogle, “Heterogeneous differentiation of human mesenchymal stem cells in response to extended culture in extracellular matrices,” Tissue Eng. Part A 15(12), 3911–3922 (2009).
[CrossRef] [PubMed]

S. Wang, C. Wong Po Foo, A. Warrier, M. M. Poo, S. C. Heilshorn, and X. Zhang, “Gradient lithography of engineered proteins to fabricate 2D and 3D cell culture microenvironments,” Biomed. Microdevices 11(5), 1127–1134 (2009).
[CrossRef] [PubMed]

2008 (1)

S. Maruo and J. T. Fourkas, “Recent progress in multiphoton microfabrication,” Laser Photon Rev 2(1-2), 100–111 (2008).
[CrossRef]

2006 (3)

H. B. Sun and S. Kawata, “Two-photon photopolymerization and 3D lithographic microfabrication,” Adv. Polym. Sci. 170, 169–273 (2006).
[CrossRef]

N. J. Sniadecki, R. A. Desai, S. A. Ruiz, and C. S. Chen, “Nanotechnology for cell-substrate interactions,” Ann. Biomed. Eng. 34(1), 59–74 (2006).
[CrossRef] [PubMed]

L. P. Cunningham, M. P. Veilleux, and P. J. Campagnola, “Freeform multiphoton excited microfabrication for biological applications using a rapid prototyping CAD-based approach,” Opt. Express 14(19), 8613–8621 (2006).
[CrossRef] [PubMed]

2005 (2)

S. Basu, L. P. Cunningham, G. D. Pins, K. A. Bush, R. Taboada, A. R. Howell, J. Wang, and P. J. Campagnola, “Multiphoton Excited Fabrication of Collagen Matrixes Cross-linked by a Modified Benzophenone Dimer: Bioactivity and Enzymatic Degradation,” Biomacromolecules 6(3), 1465–1474 (2005).
[CrossRef] [PubMed]

X. Jiang, D. A. Bruzewicz, A. P. Wong, M. Piel, and G. M. Whitesides, “Directing cell migration with asymmetric micropatterns,” Proc. Natl. Acad. Sci. U.S.A. 102(4), 975–978 (2005).
[CrossRef] [PubMed]

2004 (4)

J. L. Charest, L. E. Bryant, A. J. Garcia, and W. P. King, “Hot embossing for micropatterned cell substrates,” Biomaterials 25(19), 4767–4775 (2004).
[CrossRef] [PubMed]

S. Basu and P. J. Campagnola, “Properties of crosslinked protein matrices for tissue engineering applications synthesized by multiphoton excitation,” J. Biomed. Mater. Res. A 71(2), 359–368 (2004).
[CrossRef] [PubMed]

S. Basu, C. W. Wolgemuth, and P. J. Campagnola, “Measurement of Normal and Anomalous Diffusion of Dyes within Protein Structures Fabricated via Multiphoton Excited Cross-linking,” Biomacromolecules 5(6), 2347–2357 (2004).
[CrossRef] [PubMed]

B. Kaehr, R. Allen, D. J. Javier, J. Currie, and J. B. Shear, “Guiding neuronal development with in situ microfabrication,” Proc. Natl. Acad. Sci. U.S.A. 101(46), 16104–16108 (2004).
[CrossRef] [PubMed]

2003 (1)

M. Sridhar, S. Basu, V. L. Scranton, and P. J. Campagnola, “Construction of a laser scanning microscope for multiphoton excited optical fabrication,” Rev. Sci. Instrum. 74(7), 3474–3477 (2003).
[CrossRef]

2002 (4)

J. D. Pitts, A. R. Howell, R. Taboada, I. Banerjee, J. Wang, S. L. Goodman, and P. J. Campagnola, “New photoactivators for multiphoton excited three-dimensional submicron cross-linking of proteins: bovine serum albumin and type 1 collagen,” Photochem. Photobiol. 76(2), 135–144 (2002).
[CrossRef] [PubMed]

W. Zhou, S. M. Kuebler, K. L. Braun, T. Yu, J. K. Cammack, C. K. Ober, J. W. Perry, and S. R. Marder, “An Efficient Two-Photon-Generated Photoacid Applied to Positive-Tone 3D Microfabrication,” Science 296(5570), 1106–1109 (2002).
[CrossRef] [PubMed]

M. A. A. Neil, R. Juskaitis, M. J. Booth, T. Wilson, T. Tanaka, and S. Kawata, “Active Aberration Correction for the Writing of Three-Dimensional Optical Memory Devices,” Appl. Opt. 41(7), 1374–1379 (2002).
[CrossRef] [PubMed]

C. E. Olson, M. J. Previte, and J. T. Fourkas, “Efficient and robust multiphoton data storage in molecular glasses and highly crosslinked polymers,” Nat. Mater. 1(4), 225–228 (2002).
[CrossRef] [PubMed]

2000 (1)

J. D. Pitts, P. J. Campagnola, G. A. Epling, and S. L. Goodman, “Reaction efficiencies for sub-micron multi-photon freeform fabrications of proteins and polymers with applications in sustained release,” Macromolecules 33, 1514–1523 (2000).
[CrossRef]

1997 (1)

C. Lorenz, I. C. Carlsen, T. M. Buzug, C. Fassnacht, and J. Weese, “A multi-scale line filter with automatic scale selection based on the Hessian matrix for medical image segmentation,” Lect. Notes Comput. Sci. 1252, 152–163 (1997).
[CrossRef]

1991 (1)

L. A. Liotta and W. G. Stetler-Stevenson, “Tumor invasion and metastasis: an imbalance of positive and negative regulation,” Cancer Res. 51(18Suppl), 5054s–5059s (1991).
[PubMed]

1990 (1)

D. Balasubramanian, X. Du, and J. S. J. Zigler., “The reaction of singlet oxygen with proteins, with special reference to crystallins,” Photochem. Photobiol. 52(4), 761–768 (1990).
[CrossRef] [PubMed]

1986 (1)

D. F. Eaton, “Dye sensitized photopolymerization,” Adv Photochem 13, 427–487 (1986).
[CrossRef]

Ahsan, S.

R. G. Wylie, S. Ahsan, Y. Aizawa, K. L. Maxwell, C. M. Morshead, and M. S. Shoichet, “Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels,” Nat. Mater. 10(10), 799–806 (2011).
[CrossRef] [PubMed]

Aizawa, Y.

R. G. Wylie, S. Ahsan, Y. Aizawa, K. L. Maxwell, C. M. Morshead, and M. S. Shoichet, “Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels,” Nat. Mater. 10(10), 799–806 (2011).
[CrossRef] [PubMed]

Ajeti, V.

X. Chen, Y. D. Su, V. Ajeti, S. J. Chen, and P. J. Campagnola, “Cell adhesion on micro-structured fibronectin gradients fabricated by multiphoton excited photochemistry,” Cell Mol Bioeng 5(3), 307–319 (2012).
[CrossRef] [PubMed]

Alexander, S.

P. Friedl and S. Alexander, “Cancer invasion and the microenvironment: plasticity and reciprocity,” Cell 147(5), 992–1009 (2011).
[CrossRef] [PubMed]

Allen, R.

B. Kaehr, R. Allen, D. J. Javier, J. Currie, and J. B. Shear, “Guiding neuronal development with in situ microfabrication,” Proc. Natl. Acad. Sci. U.S.A. 101(46), 16104–16108 (2004).
[CrossRef] [PubMed]

Anseth, K. S.

C. A. DeForest and K. S. Anseth, “Advances in bioactive hydrogels to probe and direct cell fate,” Annu Rev Chem Biomol Eng 3(1), 421–444 (2012).
[CrossRef] [PubMed]

C. A. DeForest, B. D. Polizzotti, and K. S. Anseth, “Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments,” Nat. Mater. 8(8), 659–664 (2009).
[CrossRef] [PubMed]

Balasubramanian, D.

D. Balasubramanian, X. Du, and J. S. J. Zigler., “The reaction of singlet oxygen with proteins, with special reference to crystallins,” Photochem. Photobiol. 52(4), 761–768 (1990).
[CrossRef] [PubMed]

Banerjee, I.

J. D. Pitts, A. R. Howell, R. Taboada, I. Banerjee, J. Wang, S. L. Goodman, and P. J. Campagnola, “New photoactivators for multiphoton excited three-dimensional submicron cross-linking of proteins: bovine serum albumin and type 1 collagen,” Photochem. Photobiol. 76(2), 135–144 (2002).
[CrossRef] [PubMed]

Basu, S.

S. Basu, L. P. Cunningham, G. D. Pins, K. A. Bush, R. Taboada, A. R. Howell, J. Wang, and P. J. Campagnola, “Multiphoton Excited Fabrication of Collagen Matrixes Cross-linked by a Modified Benzophenone Dimer: Bioactivity and Enzymatic Degradation,” Biomacromolecules 6(3), 1465–1474 (2005).
[CrossRef] [PubMed]

S. Basu and P. J. Campagnola, “Properties of crosslinked protein matrices for tissue engineering applications synthesized by multiphoton excitation,” J. Biomed. Mater. Res. A 71(2), 359–368 (2004).
[CrossRef] [PubMed]

S. Basu, C. W. Wolgemuth, and P. J. Campagnola, “Measurement of Normal and Anomalous Diffusion of Dyes within Protein Structures Fabricated via Multiphoton Excited Cross-linking,” Biomacromolecules 5(6), 2347–2357 (2004).
[CrossRef] [PubMed]

M. Sridhar, S. Basu, V. L. Scranton, and P. J. Campagnola, “Construction of a laser scanning microscope for multiphoton excited optical fabrication,” Rev. Sci. Instrum. 74(7), 3474–3477 (2003).
[CrossRef]

Belfield, K. D.

G. Kumi, C. O. Yanez, K. D. Belfield, and J. T. Fourkas, “High-speed multiphoton absorption polymerization: fabrication of microfluidic channels with arbitrary cross-sections and high aspect ratios,” Lab Chip 10(8), 1057–1060 (2010).
[CrossRef] [PubMed]

Booth, M. J.

Braun, K. L.

W. Zhou, S. M. Kuebler, K. L. Braun, T. Yu, J. K. Cammack, C. K. Ober, J. W. Perry, and S. R. Marder, “An Efficient Two-Photon-Generated Photoacid Applied to Positive-Tone 3D Microfabrication,” Science 296(5570), 1106–1109 (2002).
[CrossRef] [PubMed]

Brewer, M. A.

X. Chen, M. A. Brewer, C. Zou, and P. J. Campagnola, “Adhesion and migration of ovarian cancer cells on crosslinked laminin fibers nanofabricated by multiphoton excited photochemistry,” Integr Biol (Camb) 1(7), 469–476 (2009).
[CrossRef] [PubMed]

Briquez, P. S.

J. J. Rice, M. M. Martino, L. De Laporte, F. Tortelli, P. S. Briquez, and J. A. Hubbell, “Engineering the regenerative microenvironment with biomaterials,” Adv Healthc Mater 2(1), 57–71 (2013).
[CrossRef] [PubMed]

Bruzewicz, D. A.

X. Jiang, D. A. Bruzewicz, A. P. Wong, M. Piel, and G. M. Whitesides, “Directing cell migration with asymmetric micropatterns,” Proc. Natl. Acad. Sci. U.S.A. 102(4), 975–978 (2005).
[CrossRef] [PubMed]

Bryant, L. E.

J. L. Charest, L. E. Bryant, A. J. Garcia, and W. P. King, “Hot embossing for micropatterned cell substrates,” Biomaterials 25(19), 4767–4775 (2004).
[CrossRef] [PubMed]

Bush, K. A.

S. Basu, L. P. Cunningham, G. D. Pins, K. A. Bush, R. Taboada, A. R. Howell, J. Wang, and P. J. Campagnola, “Multiphoton Excited Fabrication of Collagen Matrixes Cross-linked by a Modified Benzophenone Dimer: Bioactivity and Enzymatic Degradation,” Biomacromolecules 6(3), 1465–1474 (2005).
[CrossRef] [PubMed]

Buzug, T. M.

C. Lorenz, I. C. Carlsen, T. M. Buzug, C. Fassnacht, and J. Weese, “A multi-scale line filter with automatic scale selection based on the Hessian matrix for medical image segmentation,” Lect. Notes Comput. Sci. 1252, 152–163 (1997).
[CrossRef]

Cammack, J. K.

W. Zhou, S. M. Kuebler, K. L. Braun, T. Yu, J. K. Cammack, C. K. Ober, J. W. Perry, and S. R. Marder, “An Efficient Two-Photon-Generated Photoacid Applied to Positive-Tone 3D Microfabrication,” Science 296(5570), 1106–1109 (2002).
[CrossRef] [PubMed]

Campagnola, P. J.

X. Chen, Y. D. Su, V. Ajeti, S. J. Chen, and P. J. Campagnola, “Cell adhesion on micro-structured fibronectin gradients fabricated by multiphoton excited photochemistry,” Cell Mol Bioeng 5(3), 307–319 (2012).
[CrossRef] [PubMed]

P. J. Su, Q. A. Tran, J. J. Fong, K. W. Eliceiri, B. M. Ogle, and P. J. Campagnola, “Mesenchymal Stem Cell Interactions with 3D ECM Modules Fabricated via Multiphoton Excited Photochemistry,” Biomacromolecules 13(9), 2917–2925 (2012).
[CrossRef] [PubMed]

X. Chen, M. A. Brewer, C. Zou, and P. J. Campagnola, “Adhesion and migration of ovarian cancer cells on crosslinked laminin fibers nanofabricated by multiphoton excited photochemistry,” Integr Biol (Camb) 1(7), 469–476 (2009).
[CrossRef] [PubMed]

L. P. Cunningham, M. P. Veilleux, and P. J. Campagnola, “Freeform multiphoton excited microfabrication for biological applications using a rapid prototyping CAD-based approach,” Opt. Express 14(19), 8613–8621 (2006).
[CrossRef] [PubMed]

S. Basu, L. P. Cunningham, G. D. Pins, K. A. Bush, R. Taboada, A. R. Howell, J. Wang, and P. J. Campagnola, “Multiphoton Excited Fabrication of Collagen Matrixes Cross-linked by a Modified Benzophenone Dimer: Bioactivity and Enzymatic Degradation,” Biomacromolecules 6(3), 1465–1474 (2005).
[CrossRef] [PubMed]

S. Basu, C. W. Wolgemuth, and P. J. Campagnola, “Measurement of Normal and Anomalous Diffusion of Dyes within Protein Structures Fabricated via Multiphoton Excited Cross-linking,” Biomacromolecules 5(6), 2347–2357 (2004).
[CrossRef] [PubMed]

S. Basu and P. J. Campagnola, “Properties of crosslinked protein matrices for tissue engineering applications synthesized by multiphoton excitation,” J. Biomed. Mater. Res. A 71(2), 359–368 (2004).
[CrossRef] [PubMed]

M. Sridhar, S. Basu, V. L. Scranton, and P. J. Campagnola, “Construction of a laser scanning microscope for multiphoton excited optical fabrication,” Rev. Sci. Instrum. 74(7), 3474–3477 (2003).
[CrossRef]

J. D. Pitts, A. R. Howell, R. Taboada, I. Banerjee, J. Wang, S. L. Goodman, and P. J. Campagnola, “New photoactivators for multiphoton excited three-dimensional submicron cross-linking of proteins: bovine serum albumin and type 1 collagen,” Photochem. Photobiol. 76(2), 135–144 (2002).
[CrossRef] [PubMed]

J. D. Pitts, P. J. Campagnola, G. A. Epling, and S. L. Goodman, “Reaction efficiencies for sub-micron multi-photon freeform fabrications of proteins and polymers with applications in sustained release,” Macromolecules 33, 1514–1523 (2000).
[CrossRef]

Carlsen, I. C.

C. Lorenz, I. C. Carlsen, T. M. Buzug, C. Fassnacht, and J. Weese, “A multi-scale line filter with automatic scale selection based on the Hessian matrix for medical image segmentation,” Lect. Notes Comput. Sci. 1252, 152–163 (1997).
[CrossRef]

Charest, J. L.

J. L. Charest, L. E. Bryant, A. J. Garcia, and W. P. King, “Hot embossing for micropatterned cell substrates,” Biomaterials 25(19), 4767–4775 (2004).
[CrossRef] [PubMed]

Chen, C. S.

N. J. Sniadecki, R. A. Desai, S. A. Ruiz, and C. S. Chen, “Nanotechnology for cell-substrate interactions,” Ann. Biomed. Eng. 34(1), 59–74 (2006).
[CrossRef] [PubMed]

Chen, S. J.

X. Chen, Y. D. Su, V. Ajeti, S. J. Chen, and P. J. Campagnola, “Cell adhesion on micro-structured fibronectin gradients fabricated by multiphoton excited photochemistry,” Cell Mol Bioeng 5(3), 307–319 (2012).
[CrossRef] [PubMed]

Chen, X.

X. Chen, Y. D. Su, V. Ajeti, S. J. Chen, and P. J. Campagnola, “Cell adhesion on micro-structured fibronectin gradients fabricated by multiphoton excited photochemistry,” Cell Mol Bioeng 5(3), 307–319 (2012).
[CrossRef] [PubMed]

X. Chen, M. A. Brewer, C. Zou, and P. J. Campagnola, “Adhesion and migration of ovarian cancer cells on crosslinked laminin fibers nanofabricated by multiphoton excited photochemistry,” Integr Biol (Camb) 1(7), 469–476 (2009).
[CrossRef] [PubMed]

Cox, T. R.

T. R. Cox and J. T. Erler, “Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer,” Dis. Model. Mech. 4(2), 165–178 (2011).
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Cunningham, L. P.

L. P. Cunningham, M. P. Veilleux, and P. J. Campagnola, “Freeform multiphoton excited microfabrication for biological applications using a rapid prototyping CAD-based approach,” Opt. Express 14(19), 8613–8621 (2006).
[CrossRef] [PubMed]

S. Basu, L. P. Cunningham, G. D. Pins, K. A. Bush, R. Taboada, A. R. Howell, J. Wang, and P. J. Campagnola, “Multiphoton Excited Fabrication of Collagen Matrixes Cross-linked by a Modified Benzophenone Dimer: Bioactivity and Enzymatic Degradation,” Biomacromolecules 6(3), 1465–1474 (2005).
[CrossRef] [PubMed]

Currie, J.

B. Kaehr, R. Allen, D. J. Javier, J. Currie, and J. B. Shear, “Guiding neuronal development with in situ microfabrication,” Proc. Natl. Acad. Sci. U.S.A. 101(46), 16104–16108 (2004).
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J. J. Rice, M. M. Martino, L. De Laporte, F. Tortelli, P. S. Briquez, and J. A. Hubbell, “Engineering the regenerative microenvironment with biomaterials,” Adv Healthc Mater 2(1), 57–71 (2013).
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C. A. DeForest and K. S. Anseth, “Advances in bioactive hydrogels to probe and direct cell fate,” Annu Rev Chem Biomol Eng 3(1), 421–444 (2012).
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C. A. DeForest, B. D. Polizzotti, and K. S. Anseth, “Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments,” Nat. Mater. 8(8), 659–664 (2009).
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Desai, R. A.

N. J. Sniadecki, R. A. Desai, S. A. Ruiz, and C. S. Chen, “Nanotechnology for cell-substrate interactions,” Ann. Biomed. Eng. 34(1), 59–74 (2006).
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Dickinson, M. E.

J. J. Moon, J. E. Saik, R. A. Poché, J. E. Leslie-Barbick, S. H. Lee, A. A. Smith, M. E. Dickinson, and J. L. West, “Biomimetic hydrogels with pro-angiogenic properties,” Biomaterials 31(14), 3840–3847 (2010).
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D. Balasubramanian, X. Du, and J. S. J. Zigler., “The reaction of singlet oxygen with proteins, with special reference to crystallins,” Photochem. Photobiol. 52(4), 761–768 (1990).
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P. J. Su, Q. A. Tran, J. J. Fong, K. W. Eliceiri, B. M. Ogle, and P. J. Campagnola, “Mesenchymal Stem Cell Interactions with 3D ECM Modules Fabricated via Multiphoton Excited Photochemistry,” Biomacromolecules 13(9), 2917–2925 (2012).
[CrossRef] [PubMed]

Epling, G. A.

J. D. Pitts, P. J. Campagnola, G. A. Epling, and S. L. Goodman, “Reaction efficiencies for sub-micron multi-photon freeform fabrications of proteins and polymers with applications in sustained release,” Macromolecules 33, 1514–1523 (2000).
[CrossRef]

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T. R. Cox and J. T. Erler, “Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer,” Dis. Model. Mech. 4(2), 165–178 (2011).
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C. Lorenz, I. C. Carlsen, T. M. Buzug, C. Fassnacht, and J. Weese, “A multi-scale line filter with automatic scale selection based on the Hessian matrix for medical image segmentation,” Lect. Notes Comput. Sci. 1252, 152–163 (1997).
[CrossRef]

Fong, J. J.

P. J. Su, Q. A. Tran, J. J. Fong, K. W. Eliceiri, B. M. Ogle, and P. J. Campagnola, “Mesenchymal Stem Cell Interactions with 3D ECM Modules Fabricated via Multiphoton Excited Photochemistry,” Biomacromolecules 13(9), 2917–2925 (2012).
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Fourkas, J. T.

G. Kumi, C. O. Yanez, K. D. Belfield, and J. T. Fourkas, “High-speed multiphoton absorption polymerization: fabrication of microfluidic channels with arbitrary cross-sections and high aspect ratios,” Lab Chip 10(8), 1057–1060 (2010).
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S. Maruo and J. T. Fourkas, “Recent progress in multiphoton microfabrication,” Laser Photon Rev 2(1-2), 100–111 (2008).
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J. L. Charest, L. E. Bryant, A. J. Garcia, and W. P. King, “Hot embossing for micropatterned cell substrates,” Biomaterials 25(19), 4767–4775 (2004).
[CrossRef] [PubMed]

Goodman, S. L.

J. D. Pitts, A. R. Howell, R. Taboada, I. Banerjee, J. Wang, S. L. Goodman, and P. J. Campagnola, “New photoactivators for multiphoton excited three-dimensional submicron cross-linking of proteins: bovine serum albumin and type 1 collagen,” Photochem. Photobiol. 76(2), 135–144 (2002).
[CrossRef] [PubMed]

J. D. Pitts, P. J. Campagnola, G. A. Epling, and S. L. Goodman, “Reaction efficiencies for sub-micron multi-photon freeform fabrications of proteins and polymers with applications in sustained release,” Macromolecules 33, 1514–1523 (2000).
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S. Wang, C. Wong Po Foo, A. Warrier, M. M. Poo, S. C. Heilshorn, and X. Zhang, “Gradient lithography of engineered proteins to fabricate 2D and 3D cell culture microenvironments,” Biomed. Microdevices 11(5), 1127–1134 (2009).
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Howell, A. R.

S. Basu, L. P. Cunningham, G. D. Pins, K. A. Bush, R. Taboada, A. R. Howell, J. Wang, and P. J. Campagnola, “Multiphoton Excited Fabrication of Collagen Matrixes Cross-linked by a Modified Benzophenone Dimer: Bioactivity and Enzymatic Degradation,” Biomacromolecules 6(3), 1465–1474 (2005).
[CrossRef] [PubMed]

J. D. Pitts, A. R. Howell, R. Taboada, I. Banerjee, J. Wang, S. L. Goodman, and P. J. Campagnola, “New photoactivators for multiphoton excited three-dimensional submicron cross-linking of proteins: bovine serum albumin and type 1 collagen,” Photochem. Photobiol. 76(2), 135–144 (2002).
[CrossRef] [PubMed]

Hubbell, J. A.

J. J. Rice, M. M. Martino, L. De Laporte, F. Tortelli, P. S. Briquez, and J. A. Hubbell, “Engineering the regenerative microenvironment with biomaterials,” Adv Healthc Mater 2(1), 57–71 (2013).
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B. Kaehr, R. Allen, D. J. Javier, J. Currie, and J. B. Shear, “Guiding neuronal development with in situ microfabrication,” Proc. Natl. Acad. Sci. U.S.A. 101(46), 16104–16108 (2004).
[CrossRef] [PubMed]

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X. Jiang, D. A. Bruzewicz, A. P. Wong, M. Piel, and G. M. Whitesides, “Directing cell migration with asymmetric micropatterns,” Proc. Natl. Acad. Sci. U.S.A. 102(4), 975–978 (2005).
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Juskaitis, R.

Kaehr, B.

B. Kaehr, R. Allen, D. J. Javier, J. Currie, and J. B. Shear, “Guiding neuronal development with in situ microfabrication,” Proc. Natl. Acad. Sci. U.S.A. 101(46), 16104–16108 (2004).
[CrossRef] [PubMed]

Kawata, S.

King, W. P.

J. L. Charest, L. E. Bryant, A. J. Garcia, and W. P. King, “Hot embossing for micropatterned cell substrates,” Biomaterials 25(19), 4767–4775 (2004).
[CrossRef] [PubMed]

Kuebler, S. M.

W. Zhou, S. M. Kuebler, K. L. Braun, T. Yu, J. K. Cammack, C. K. Ober, J. W. Perry, and S. R. Marder, “An Efficient Two-Photon-Generated Photoacid Applied to Positive-Tone 3D Microfabrication,” Science 296(5570), 1106–1109 (2002).
[CrossRef] [PubMed]

Kumi, G.

G. Kumi, C. O. Yanez, K. D. Belfield, and J. T. Fourkas, “High-speed multiphoton absorption polymerization: fabrication of microfluidic channels with arbitrary cross-sections and high aspect ratios,” Lab Chip 10(8), 1057–1060 (2010).
[CrossRef] [PubMed]

Lee, S. H.

J. J. Moon, J. E. Saik, R. A. Poché, J. E. Leslie-Barbick, S. H. Lee, A. A. Smith, M. E. Dickinson, and J. L. West, “Biomimetic hydrogels with pro-angiogenic properties,” Biomaterials 31(14), 3840–3847 (2010).
[CrossRef] [PubMed]

Leslie-Barbick, J. E.

J. J. Moon, J. E. Saik, R. A. Poché, J. E. Leslie-Barbick, S. H. Lee, A. A. Smith, M. E. Dickinson, and J. L. West, “Biomimetic hydrogels with pro-angiogenic properties,” Biomaterials 31(14), 3840–3847 (2010).
[CrossRef] [PubMed]

Liotta, L. A.

L. A. Liotta and W. G. Stetler-Stevenson, “Tumor invasion and metastasis: an imbalance of positive and negative regulation,” Cancer Res. 51(18Suppl), 5054s–5059s (1991).
[PubMed]

Lorenz, C.

C. Lorenz, I. C. Carlsen, T. M. Buzug, C. Fassnacht, and J. Weese, “A multi-scale line filter with automatic scale selection based on the Hessian matrix for medical image segmentation,” Lect. Notes Comput. Sci. 1252, 152–163 (1997).
[CrossRef]

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P. Lu, V. M. Weaver, and Z. Werb, “The extracellular matrix: a dynamic niche in cancer progression,” J. Cell Biol. 196(4), 395–406 (2012).
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Marder, S. R.

W. Zhou, S. M. Kuebler, K. L. Braun, T. Yu, J. K. Cammack, C. K. Ober, J. W. Perry, and S. R. Marder, “An Efficient Two-Photon-Generated Photoacid Applied to Positive-Tone 3D Microfabrication,” Science 296(5570), 1106–1109 (2002).
[CrossRef] [PubMed]

Martino, M. M.

J. J. Rice, M. M. Martino, L. De Laporte, F. Tortelli, P. S. Briquez, and J. A. Hubbell, “Engineering the regenerative microenvironment with biomaterials,” Adv Healthc Mater 2(1), 57–71 (2013).
[CrossRef] [PubMed]

Maruo, S.

S. Maruo and J. T. Fourkas, “Recent progress in multiphoton microfabrication,” Laser Photon Rev 2(1-2), 100–111 (2008).
[CrossRef]

Maxwell, K. L.

R. G. Wylie, S. Ahsan, Y. Aizawa, K. L. Maxwell, C. M. Morshead, and M. S. Shoichet, “Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels,” Nat. Mater. 10(10), 799–806 (2011).
[CrossRef] [PubMed]

Moon, J. J.

J. J. Moon, J. E. Saik, R. A. Poché, J. E. Leslie-Barbick, S. H. Lee, A. A. Smith, M. E. Dickinson, and J. L. West, “Biomimetic hydrogels with pro-angiogenic properties,” Biomaterials 31(14), 3840–3847 (2010).
[CrossRef] [PubMed]

Morshead, C. M.

R. G. Wylie, S. Ahsan, Y. Aizawa, K. L. Maxwell, C. M. Morshead, and M. S. Shoichet, “Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels,” Nat. Mater. 10(10), 799–806 (2011).
[CrossRef] [PubMed]

Neil, M. A. A.

Ober, C. K.

W. Zhou, S. M. Kuebler, K. L. Braun, T. Yu, J. K. Cammack, C. K. Ober, J. W. Perry, and S. R. Marder, “An Efficient Two-Photon-Generated Photoacid Applied to Positive-Tone 3D Microfabrication,” Science 296(5570), 1106–1109 (2002).
[CrossRef] [PubMed]

Ogle, B. M.

P. J. Su, Q. A. Tran, J. J. Fong, K. W. Eliceiri, B. M. Ogle, and P. J. Campagnola, “Mesenchymal Stem Cell Interactions with 3D ECM Modules Fabricated via Multiphoton Excited Photochemistry,” Biomacromolecules 13(9), 2917–2925 (2012).
[CrossRef] [PubMed]

J. A. Santiago, R. Pogemiller, and B. M. Ogle, “Heterogeneous differentiation of human mesenchymal stem cells in response to extended culture in extracellular matrices,” Tissue Eng. Part A 15(12), 3911–3922 (2009).
[CrossRef] [PubMed]

Olson, C. E.

C. E. Olson, M. J. Previte, and J. T. Fourkas, “Efficient and robust multiphoton data storage in molecular glasses and highly crosslinked polymers,” Nat. Mater. 1(4), 225–228 (2002).
[CrossRef] [PubMed]

Perry, J. W.

W. Zhou, S. M. Kuebler, K. L. Braun, T. Yu, J. K. Cammack, C. K. Ober, J. W. Perry, and S. R. Marder, “An Efficient Two-Photon-Generated Photoacid Applied to Positive-Tone 3D Microfabrication,” Science 296(5570), 1106–1109 (2002).
[CrossRef] [PubMed]

Piel, M.

X. Jiang, D. A. Bruzewicz, A. P. Wong, M. Piel, and G. M. Whitesides, “Directing cell migration with asymmetric micropatterns,” Proc. Natl. Acad. Sci. U.S.A. 102(4), 975–978 (2005).
[CrossRef] [PubMed]

Pins, G. D.

S. Basu, L. P. Cunningham, G. D. Pins, K. A. Bush, R. Taboada, A. R. Howell, J. Wang, and P. J. Campagnola, “Multiphoton Excited Fabrication of Collagen Matrixes Cross-linked by a Modified Benzophenone Dimer: Bioactivity and Enzymatic Degradation,” Biomacromolecules 6(3), 1465–1474 (2005).
[CrossRef] [PubMed]

Pitts, J. D.

J. D. Pitts, A. R. Howell, R. Taboada, I. Banerjee, J. Wang, S. L. Goodman, and P. J. Campagnola, “New photoactivators for multiphoton excited three-dimensional submicron cross-linking of proteins: bovine serum albumin and type 1 collagen,” Photochem. Photobiol. 76(2), 135–144 (2002).
[CrossRef] [PubMed]

J. D. Pitts, P. J. Campagnola, G. A. Epling, and S. L. Goodman, “Reaction efficiencies for sub-micron multi-photon freeform fabrications of proteins and polymers with applications in sustained release,” Macromolecules 33, 1514–1523 (2000).
[CrossRef]

Poché, R. A.

J. J. Moon, J. E. Saik, R. A. Poché, J. E. Leslie-Barbick, S. H. Lee, A. A. Smith, M. E. Dickinson, and J. L. West, “Biomimetic hydrogels with pro-angiogenic properties,” Biomaterials 31(14), 3840–3847 (2010).
[CrossRef] [PubMed]

Pogemiller, R.

J. A. Santiago, R. Pogemiller, and B. M. Ogle, “Heterogeneous differentiation of human mesenchymal stem cells in response to extended culture in extracellular matrices,” Tissue Eng. Part A 15(12), 3911–3922 (2009).
[CrossRef] [PubMed]

Polizzotti, B. D.

C. A. DeForest, B. D. Polizzotti, and K. S. Anseth, “Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments,” Nat. Mater. 8(8), 659–664 (2009).
[CrossRef] [PubMed]

Poo, M. M.

S. Wang, C. Wong Po Foo, A. Warrier, M. M. Poo, S. C. Heilshorn, and X. Zhang, “Gradient lithography of engineered proteins to fabricate 2D and 3D cell culture microenvironments,” Biomed. Microdevices 11(5), 1127–1134 (2009).
[CrossRef] [PubMed]

Previte, M. J.

C. E. Olson, M. J. Previte, and J. T. Fourkas, “Efficient and robust multiphoton data storage in molecular glasses and highly crosslinked polymers,” Nat. Mater. 1(4), 225–228 (2002).
[CrossRef] [PubMed]

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D. Qin, Y. Xia, and G. M. Whitesides, “Soft lithography for micro- and nanoscale patterning,” Nat. Protoc. 5(3), 491–502 (2010).
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Rice, J. J.

J. J. Rice, M. M. Martino, L. De Laporte, F. Tortelli, P. S. Briquez, and J. A. Hubbell, “Engineering the regenerative microenvironment with biomaterials,” Adv Healthc Mater 2(1), 57–71 (2013).
[CrossRef] [PubMed]

Ruiz, S. A.

N. J. Sniadecki, R. A. Desai, S. A. Ruiz, and C. S. Chen, “Nanotechnology for cell-substrate interactions,” Ann. Biomed. Eng. 34(1), 59–74 (2006).
[CrossRef] [PubMed]

Saik, J. E.

J. J. Moon, J. E. Saik, R. A. Poché, J. E. Leslie-Barbick, S. H. Lee, A. A. Smith, M. E. Dickinson, and J. L. West, “Biomimetic hydrogels with pro-angiogenic properties,” Biomaterials 31(14), 3840–3847 (2010).
[CrossRef] [PubMed]

Santiago, J. A.

J. A. Santiago, R. Pogemiller, and B. M. Ogle, “Heterogeneous differentiation of human mesenchymal stem cells in response to extended culture in extracellular matrices,” Tissue Eng. Part A 15(12), 3911–3922 (2009).
[CrossRef] [PubMed]

Scranton, V. L.

M. Sridhar, S. Basu, V. L. Scranton, and P. J. Campagnola, “Construction of a laser scanning microscope for multiphoton excited optical fabrication,” Rev. Sci. Instrum. 74(7), 3474–3477 (2003).
[CrossRef]

Shear, J. B.

B. Kaehr, R. Allen, D. J. Javier, J. Currie, and J. B. Shear, “Guiding neuronal development with in situ microfabrication,” Proc. Natl. Acad. Sci. U.S.A. 101(46), 16104–16108 (2004).
[CrossRef] [PubMed]

Shoichet, M. S.

R. G. Wylie, S. Ahsan, Y. Aizawa, K. L. Maxwell, C. M. Morshead, and M. S. Shoichet, “Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels,” Nat. Mater. 10(10), 799–806 (2011).
[CrossRef] [PubMed]

Smith, A. A.

J. J. Moon, J. E. Saik, R. A. Poché, J. E. Leslie-Barbick, S. H. Lee, A. A. Smith, M. E. Dickinson, and J. L. West, “Biomimetic hydrogels with pro-angiogenic properties,” Biomaterials 31(14), 3840–3847 (2010).
[CrossRef] [PubMed]

Sniadecki, N. J.

N. J. Sniadecki, R. A. Desai, S. A. Ruiz, and C. S. Chen, “Nanotechnology for cell-substrate interactions,” Ann. Biomed. Eng. 34(1), 59–74 (2006).
[CrossRef] [PubMed]

Soukoulis, C. M.

C. M. Soukoulis and M. Wegener, “Past achievements and future challenges in the development of three-dimensional photonic metamaterials,” Nat. Photonics 5, 523–530 (2011).

Sridhar, M.

M. Sridhar, S. Basu, V. L. Scranton, and P. J. Campagnola, “Construction of a laser scanning microscope for multiphoton excited optical fabrication,” Rev. Sci. Instrum. 74(7), 3474–3477 (2003).
[CrossRef]

Stetler-Stevenson, W. G.

L. A. Liotta and W. G. Stetler-Stevenson, “Tumor invasion and metastasis: an imbalance of positive and negative regulation,” Cancer Res. 51(18Suppl), 5054s–5059s (1991).
[PubMed]

Su, P. J.

P. J. Su, Q. A. Tran, J. J. Fong, K. W. Eliceiri, B. M. Ogle, and P. J. Campagnola, “Mesenchymal Stem Cell Interactions with 3D ECM Modules Fabricated via Multiphoton Excited Photochemistry,” Biomacromolecules 13(9), 2917–2925 (2012).
[CrossRef] [PubMed]

Su, Y. D.

X. Chen, Y. D. Su, V. Ajeti, S. J. Chen, and P. J. Campagnola, “Cell adhesion on micro-structured fibronectin gradients fabricated by multiphoton excited photochemistry,” Cell Mol Bioeng 5(3), 307–319 (2012).
[CrossRef] [PubMed]

Sun, H. B.

H. B. Sun and S. Kawata, “Two-photon photopolymerization and 3D lithographic microfabrication,” Adv. Polym. Sci. 170, 169–273 (2006).
[CrossRef]

Taboada, R.

S. Basu, L. P. Cunningham, G. D. Pins, K. A. Bush, R. Taboada, A. R. Howell, J. Wang, and P. J. Campagnola, “Multiphoton Excited Fabrication of Collagen Matrixes Cross-linked by a Modified Benzophenone Dimer: Bioactivity and Enzymatic Degradation,” Biomacromolecules 6(3), 1465–1474 (2005).
[CrossRef] [PubMed]

J. D. Pitts, A. R. Howell, R. Taboada, I. Banerjee, J. Wang, S. L. Goodman, and P. J. Campagnola, “New photoactivators for multiphoton excited three-dimensional submicron cross-linking of proteins: bovine serum albumin and type 1 collagen,” Photochem. Photobiol. 76(2), 135–144 (2002).
[CrossRef] [PubMed]

Tanaka, T.

Tortelli, F.

J. J. Rice, M. M. Martino, L. De Laporte, F. Tortelli, P. S. Briquez, and J. A. Hubbell, “Engineering the regenerative microenvironment with biomaterials,” Adv Healthc Mater 2(1), 57–71 (2013).
[CrossRef] [PubMed]

Tran, Q. A.

P. J. Su, Q. A. Tran, J. J. Fong, K. W. Eliceiri, B. M. Ogle, and P. J. Campagnola, “Mesenchymal Stem Cell Interactions with 3D ECM Modules Fabricated via Multiphoton Excited Photochemistry,” Biomacromolecules 13(9), 2917–2925 (2012).
[CrossRef] [PubMed]

Veilleux, M. P.

Wang, J.

S. Basu, L. P. Cunningham, G. D. Pins, K. A. Bush, R. Taboada, A. R. Howell, J. Wang, and P. J. Campagnola, “Multiphoton Excited Fabrication of Collagen Matrixes Cross-linked by a Modified Benzophenone Dimer: Bioactivity and Enzymatic Degradation,” Biomacromolecules 6(3), 1465–1474 (2005).
[CrossRef] [PubMed]

J. D. Pitts, A. R. Howell, R. Taboada, I. Banerjee, J. Wang, S. L. Goodman, and P. J. Campagnola, “New photoactivators for multiphoton excited three-dimensional submicron cross-linking of proteins: bovine serum albumin and type 1 collagen,” Photochem. Photobiol. 76(2), 135–144 (2002).
[CrossRef] [PubMed]

Wang, S.

S. Wang, C. Wong Po Foo, A. Warrier, M. M. Poo, S. C. Heilshorn, and X. Zhang, “Gradient lithography of engineered proteins to fabricate 2D and 3D cell culture microenvironments,” Biomed. Microdevices 11(5), 1127–1134 (2009).
[CrossRef] [PubMed]

Warrier, A.

S. Wang, C. Wong Po Foo, A. Warrier, M. M. Poo, S. C. Heilshorn, and X. Zhang, “Gradient lithography of engineered proteins to fabricate 2D and 3D cell culture microenvironments,” Biomed. Microdevices 11(5), 1127–1134 (2009).
[CrossRef] [PubMed]

Weaver, V. M.

P. Lu, V. M. Weaver, and Z. Werb, “The extracellular matrix: a dynamic niche in cancer progression,” J. Cell Biol. 196(4), 395–406 (2012).
[CrossRef] [PubMed]

Weese, J.

C. Lorenz, I. C. Carlsen, T. M. Buzug, C. Fassnacht, and J. Weese, “A multi-scale line filter with automatic scale selection based on the Hessian matrix for medical image segmentation,” Lect. Notes Comput. Sci. 1252, 152–163 (1997).
[CrossRef]

Wegener, M.

C. M. Soukoulis and M. Wegener, “Past achievements and future challenges in the development of three-dimensional photonic metamaterials,” Nat. Photonics 5, 523–530 (2011).

Werb, Z.

P. Lu, V. M. Weaver, and Z. Werb, “The extracellular matrix: a dynamic niche in cancer progression,” J. Cell Biol. 196(4), 395–406 (2012).
[CrossRef] [PubMed]

West, J. L.

J. J. Moon, J. E. Saik, R. A. Poché, J. E. Leslie-Barbick, S. H. Lee, A. A. Smith, M. E. Dickinson, and J. L. West, “Biomimetic hydrogels with pro-angiogenic properties,” Biomaterials 31(14), 3840–3847 (2010).
[CrossRef] [PubMed]

Whitesides, G. M.

D. Qin, Y. Xia, and G. M. Whitesides, “Soft lithography for micro- and nanoscale patterning,” Nat. Protoc. 5(3), 491–502 (2010).
[CrossRef] [PubMed]

X. Jiang, D. A. Bruzewicz, A. P. Wong, M. Piel, and G. M. Whitesides, “Directing cell migration with asymmetric micropatterns,” Proc. Natl. Acad. Sci. U.S.A. 102(4), 975–978 (2005).
[CrossRef] [PubMed]

Wilson, T.

Wolgemuth, C. W.

S. Basu, C. W. Wolgemuth, and P. J. Campagnola, “Measurement of Normal and Anomalous Diffusion of Dyes within Protein Structures Fabricated via Multiphoton Excited Cross-linking,” Biomacromolecules 5(6), 2347–2357 (2004).
[CrossRef] [PubMed]

Wong, A. P.

X. Jiang, D. A. Bruzewicz, A. P. Wong, M. Piel, and G. M. Whitesides, “Directing cell migration with asymmetric micropatterns,” Proc. Natl. Acad. Sci. U.S.A. 102(4), 975–978 (2005).
[CrossRef] [PubMed]

Wong Po Foo, C.

S. Wang, C. Wong Po Foo, A. Warrier, M. M. Poo, S. C. Heilshorn, and X. Zhang, “Gradient lithography of engineered proteins to fabricate 2D and 3D cell culture microenvironments,” Biomed. Microdevices 11(5), 1127–1134 (2009).
[CrossRef] [PubMed]

Wylie, R. G.

R. G. Wylie, S. Ahsan, Y. Aizawa, K. L. Maxwell, C. M. Morshead, and M. S. Shoichet, “Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels,” Nat. Mater. 10(10), 799–806 (2011).
[CrossRef] [PubMed]

Xia, Y.

D. Qin, Y. Xia, and G. M. Whitesides, “Soft lithography for micro- and nanoscale patterning,” Nat. Protoc. 5(3), 491–502 (2010).
[CrossRef] [PubMed]

Yanez, C. O.

G. Kumi, C. O. Yanez, K. D. Belfield, and J. T. Fourkas, “High-speed multiphoton absorption polymerization: fabrication of microfluidic channels with arbitrary cross-sections and high aspect ratios,” Lab Chip 10(8), 1057–1060 (2010).
[CrossRef] [PubMed]

Yu, T.

W. Zhou, S. M. Kuebler, K. L. Braun, T. Yu, J. K. Cammack, C. K. Ober, J. W. Perry, and S. R. Marder, “An Efficient Two-Photon-Generated Photoacid Applied to Positive-Tone 3D Microfabrication,” Science 296(5570), 1106–1109 (2002).
[CrossRef] [PubMed]

Zhang, X.

S. Wang, C. Wong Po Foo, A. Warrier, M. M. Poo, S. C. Heilshorn, and X. Zhang, “Gradient lithography of engineered proteins to fabricate 2D and 3D cell culture microenvironments,” Biomed. Microdevices 11(5), 1127–1134 (2009).
[CrossRef] [PubMed]

Zhou, W.

W. Zhou, S. M. Kuebler, K. L. Braun, T. Yu, J. K. Cammack, C. K. Ober, J. W. Perry, and S. R. Marder, “An Efficient Two-Photon-Generated Photoacid Applied to Positive-Tone 3D Microfabrication,” Science 296(5570), 1106–1109 (2002).
[CrossRef] [PubMed]

Zigler, J. S. J.

D. Balasubramanian, X. Du, and J. S. J. Zigler., “The reaction of singlet oxygen with proteins, with special reference to crystallins,” Photochem. Photobiol. 52(4), 761–768 (1990).
[CrossRef] [PubMed]

Zou, C.

X. Chen, M. A. Brewer, C. Zou, and P. J. Campagnola, “Adhesion and migration of ovarian cancer cells on crosslinked laminin fibers nanofabricated by multiphoton excited photochemistry,” Integr Biol (Camb) 1(7), 469–476 (2009).
[CrossRef] [PubMed]

Adv Healthc Mater (1)

J. J. Rice, M. M. Martino, L. De Laporte, F. Tortelli, P. S. Briquez, and J. A. Hubbell, “Engineering the regenerative microenvironment with biomaterials,” Adv Healthc Mater 2(1), 57–71 (2013).
[CrossRef] [PubMed]

Adv Photochem (1)

D. F. Eaton, “Dye sensitized photopolymerization,” Adv Photochem 13, 427–487 (1986).
[CrossRef]

Adv. Polym. Sci. (1)

H. B. Sun and S. Kawata, “Two-photon photopolymerization and 3D lithographic microfabrication,” Adv. Polym. Sci. 170, 169–273 (2006).
[CrossRef]

Ann. Biomed. Eng. (1)

N. J. Sniadecki, R. A. Desai, S. A. Ruiz, and C. S. Chen, “Nanotechnology for cell-substrate interactions,” Ann. Biomed. Eng. 34(1), 59–74 (2006).
[CrossRef] [PubMed]

Annu Rev Chem Biomol Eng (1)

C. A. DeForest and K. S. Anseth, “Advances in bioactive hydrogels to probe and direct cell fate,” Annu Rev Chem Biomol Eng 3(1), 421–444 (2012).
[CrossRef] [PubMed]

Appl. Opt. (1)

Biomacromolecules (3)

S. Basu, C. W. Wolgemuth, and P. J. Campagnola, “Measurement of Normal and Anomalous Diffusion of Dyes within Protein Structures Fabricated via Multiphoton Excited Cross-linking,” Biomacromolecules 5(6), 2347–2357 (2004).
[CrossRef] [PubMed]

P. J. Su, Q. A. Tran, J. J. Fong, K. W. Eliceiri, B. M. Ogle, and P. J. Campagnola, “Mesenchymal Stem Cell Interactions with 3D ECM Modules Fabricated via Multiphoton Excited Photochemistry,” Biomacromolecules 13(9), 2917–2925 (2012).
[CrossRef] [PubMed]

S. Basu, L. P. Cunningham, G. D. Pins, K. A. Bush, R. Taboada, A. R. Howell, J. Wang, and P. J. Campagnola, “Multiphoton Excited Fabrication of Collagen Matrixes Cross-linked by a Modified Benzophenone Dimer: Bioactivity and Enzymatic Degradation,” Biomacromolecules 6(3), 1465–1474 (2005).
[CrossRef] [PubMed]

Biomaterials (2)

J. J. Moon, J. E. Saik, R. A. Poché, J. E. Leslie-Barbick, S. H. Lee, A. A. Smith, M. E. Dickinson, and J. L. West, “Biomimetic hydrogels with pro-angiogenic properties,” Biomaterials 31(14), 3840–3847 (2010).
[CrossRef] [PubMed]

J. L. Charest, L. E. Bryant, A. J. Garcia, and W. P. King, “Hot embossing for micropatterned cell substrates,” Biomaterials 25(19), 4767–4775 (2004).
[CrossRef] [PubMed]

Biomed. Microdevices (1)

S. Wang, C. Wong Po Foo, A. Warrier, M. M. Poo, S. C. Heilshorn, and X. Zhang, “Gradient lithography of engineered proteins to fabricate 2D and 3D cell culture microenvironments,” Biomed. Microdevices 11(5), 1127–1134 (2009).
[CrossRef] [PubMed]

Cancer Res. (1)

L. A. Liotta and W. G. Stetler-Stevenson, “Tumor invasion and metastasis: an imbalance of positive and negative regulation,” Cancer Res. 51(18Suppl), 5054s–5059s (1991).
[PubMed]

Cell (1)

P. Friedl and S. Alexander, “Cancer invasion and the microenvironment: plasticity and reciprocity,” Cell 147(5), 992–1009 (2011).
[CrossRef] [PubMed]

Cell Mol Bioeng (1)

X. Chen, Y. D. Su, V. Ajeti, S. J. Chen, and P. J. Campagnola, “Cell adhesion on micro-structured fibronectin gradients fabricated by multiphoton excited photochemistry,” Cell Mol Bioeng 5(3), 307–319 (2012).
[CrossRef] [PubMed]

Dis. Model. Mech. (1)

T. R. Cox and J. T. Erler, “Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer,” Dis. Model. Mech. 4(2), 165–178 (2011).
[CrossRef] [PubMed]

Integr Biol (Camb) (1)

X. Chen, M. A. Brewer, C. Zou, and P. J. Campagnola, “Adhesion and migration of ovarian cancer cells on crosslinked laminin fibers nanofabricated by multiphoton excited photochemistry,” Integr Biol (Camb) 1(7), 469–476 (2009).
[CrossRef] [PubMed]

J. Biomed. Mater. Res. A (1)

S. Basu and P. J. Campagnola, “Properties of crosslinked protein matrices for tissue engineering applications synthesized by multiphoton excitation,” J. Biomed. Mater. Res. A 71(2), 359–368 (2004).
[CrossRef] [PubMed]

J. Cell Biol. (1)

P. Lu, V. M. Weaver, and Z. Werb, “The extracellular matrix: a dynamic niche in cancer progression,” J. Cell Biol. 196(4), 395–406 (2012).
[CrossRef] [PubMed]

Lab Chip (1)

G. Kumi, C. O. Yanez, K. D. Belfield, and J. T. Fourkas, “High-speed multiphoton absorption polymerization: fabrication of microfluidic channels with arbitrary cross-sections and high aspect ratios,” Lab Chip 10(8), 1057–1060 (2010).
[CrossRef] [PubMed]

Laser Photon Rev (1)

S. Maruo and J. T. Fourkas, “Recent progress in multiphoton microfabrication,” Laser Photon Rev 2(1-2), 100–111 (2008).
[CrossRef]

Lect. Notes Comput. Sci. (1)

C. Lorenz, I. C. Carlsen, T. M. Buzug, C. Fassnacht, and J. Weese, “A multi-scale line filter with automatic scale selection based on the Hessian matrix for medical image segmentation,” Lect. Notes Comput. Sci. 1252, 152–163 (1997).
[CrossRef]

Macromolecules (1)

J. D. Pitts, P. J. Campagnola, G. A. Epling, and S. L. Goodman, “Reaction efficiencies for sub-micron multi-photon freeform fabrications of proteins and polymers with applications in sustained release,” Macromolecules 33, 1514–1523 (2000).
[CrossRef]

Nat. Mater. (3)

C. E. Olson, M. J. Previte, and J. T. Fourkas, “Efficient and robust multiphoton data storage in molecular glasses and highly crosslinked polymers,” Nat. Mater. 1(4), 225–228 (2002).
[CrossRef] [PubMed]

C. A. DeForest, B. D. Polizzotti, and K. S. Anseth, “Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments,” Nat. Mater. 8(8), 659–664 (2009).
[CrossRef] [PubMed]

R. G. Wylie, S. Ahsan, Y. Aizawa, K. L. Maxwell, C. M. Morshead, and M. S. Shoichet, “Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels,” Nat. Mater. 10(10), 799–806 (2011).
[CrossRef] [PubMed]

Nat. Photonics (1)

C. M. Soukoulis and M. Wegener, “Past achievements and future challenges in the development of three-dimensional photonic metamaterials,” Nat. Photonics 5, 523–530 (2011).

Nat. Protoc. (1)

D. Qin, Y. Xia, and G. M. Whitesides, “Soft lithography for micro- and nanoscale patterning,” Nat. Protoc. 5(3), 491–502 (2010).
[CrossRef] [PubMed]

Opt. Express (1)

Photochem. Photobiol. (2)

J. D. Pitts, A. R. Howell, R. Taboada, I. Banerjee, J. Wang, S. L. Goodman, and P. J. Campagnola, “New photoactivators for multiphoton excited three-dimensional submicron cross-linking of proteins: bovine serum albumin and type 1 collagen,” Photochem. Photobiol. 76(2), 135–144 (2002).
[CrossRef] [PubMed]

D. Balasubramanian, X. Du, and J. S. J. Zigler., “The reaction of singlet oxygen with proteins, with special reference to crystallins,” Photochem. Photobiol. 52(4), 761–768 (1990).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (2)

B. Kaehr, R. Allen, D. J. Javier, J. Currie, and J. B. Shear, “Guiding neuronal development with in situ microfabrication,” Proc. Natl. Acad. Sci. U.S.A. 101(46), 16104–16108 (2004).
[CrossRef] [PubMed]

X. Jiang, D. A. Bruzewicz, A. P. Wong, M. Piel, and G. M. Whitesides, “Directing cell migration with asymmetric micropatterns,” Proc. Natl. Acad. Sci. U.S.A. 102(4), 975–978 (2005).
[CrossRef] [PubMed]

Rev. Sci. Instrum. (1)

M. Sridhar, S. Basu, V. L. Scranton, and P. J. Campagnola, “Construction of a laser scanning microscope for multiphoton excited optical fabrication,” Rev. Sci. Instrum. 74(7), 3474–3477 (2003).
[CrossRef]

Science (1)

W. Zhou, S. M. Kuebler, K. L. Braun, T. Yu, J. K. Cammack, C. K. Ober, J. W. Perry, and S. R. Marder, “An Efficient Two-Photon-Generated Photoacid Applied to Positive-Tone 3D Microfabrication,” Science 296(5570), 1106–1109 (2002).
[CrossRef] [PubMed]

Tissue Eng. Part A (1)

J. A. Santiago, R. Pogemiller, and B. M. Ogle, “Heterogeneous differentiation of human mesenchymal stem cells in response to extended culture in extracellular matrices,” Tissue Eng. Part A 15(12), 3911–3922 (2009).
[CrossRef] [PubMed]

Other (2)

R. E. Burgeson, “Basement Membranes,” in Dermatology in General Medicine, T. B. Fitzpatrick, A. Z. Eisen, K. Wolff, I. M. Freedberg, and K. F. Austen, eds. (McGraw-Hill, 1987), pp. 288–303.

J. Fourkas, “Multiphoton lithography, processing and fabrication of photonic structures,” Woodh Pub Ser Elect, 139–161 (2012).

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Figures (6)

Fig. 1
Fig. 1

Optical Configuration for the purpose built fabrication system, incorporating separate EOMs for power control and rapid shuttering and an FPGA for optimized control of the fabrication process.

Fig. 2
Fig. 2

Flowchart showing the steps required for the fabrication process.

Fig. 3
Fig. 3

Example of image processing used in scaffold design. Far left is the original SHG image of the collagen in the stroma from an ovarian tissue malignancy. The middle image results from a threshold to remove the background noise. The far right image is obtained by calculating the Eigenvectors of the Hessian matrix of the SHG image to better accentuate fiber structures. Scale bar = 40 microns.

Fig. 4
Fig. 4

Single optical section of Col IV immunofluorescence and resulting fabricated structures. (a) Original immunofluorescence image,(b) immunofluorescence of BSA/FN fabricated structure created through modulated raster scanning, (c) two color overlap of (a) and (b), where white indicates high overlap, and (d) two-color overlap of (a) and structure created through a STL model, where the contrast was from Rose Bengal fluorescence. The green shows the regions which were not reproduced in the fabrication process. Scale bar = 30 microns.

Fig. 5
Fig. 5

3D renderings of confocal image (a) derived from FN in mouse left ventricle and resulting fabricated structure created through modulated raster scanning (b). The large feature indicated by the arrow is a blood vessel. The contrast was FN immunofluorescence in both images. Scale bar = 30 microns.

Fig. 6
Fig. 6

3D renderings of SHG image (a)) and fabricated structure (b) from a human ovarian cancer. Scale bar = 50 microns. (c) SEM of the fabricated structure taken at 600X magnification.

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