Abstract

Three-dimensional cell-based tissue models have been increasingly useful in the fields of tissue engineering, drug discovery, and cell biology. While techniques for building these tissue models have been advanced, there have been increasing demands for imaging techniques that are capable of assessing complex dynamic three-dimensional cell behavior in real-time and at larger depths in highly-scattering scaffolds. Understanding these cell behaviors requires advanced imaging tools to progress from characterizing two-dimensional cell cultures to complex, highly-scattering, thick three-dimensional tissue constructs. Optical coherence tomography (OCT) is an emerging biomedical imaging technique that can perform cellular-resolution imaging in situ and in real-time. In this study, we demonstrate that it is possible to use OCT to evaluate dynamic cell behavior and function in a quantitative fashion in four dimensions (three-dimensional space plus time). We investigated and characterized in thick tissue models a variety of cell processes, such as chemotaxis migration, proliferation, de-adhesion, and cell-material interactions. This optical imaging technique was developed and utilized in order to gain new insights into how chemical and/or mechanical microenvironments influence cellular dynamics in multiple dimensions. With deep imaging penetration and increased spatial and temporal resolution in three-dimensional space, OCT will be a useful tool for improving our understanding of complex biological interactions at the cellular level.

© 2006 Optical Society of America

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    [CrossRef] [PubMed]
  4. R. G. M. Breuls, A. Mol, R. Petterson, C. W. J. Oomens, F. P. T. Baaijens, and C. V. C. Bouten, "Monitoring local cell viability in engineered tissues: A fast, quantitative, and nondestructive approach," Tissue Eng. 9, 269-281 (2003).
    [CrossRef] [PubMed]
  5. D. S. Gareau, P. R. Bargo, W. A. Horton, and S. L. Jacques, "Confocal fluorescence spectroscopy of subcutaneous cartilage expressing green fluorescent protein versus cutaneous collagen autofluorescence," J. Biomed. Opt. 9, 254-258 (2004).
    [CrossRef] [PubMed]
  6. B. R. Masters, P. T. So, and E. Gratton, "Multiphoton excitation microscopy of in vivo human skin. Functional and morphological optical biopsy based on three-dimensional imaging, lifetime measurements and fluorescence spectroscopy," Ann. N. Y. Acad. Sci. 838, 58-67 (1998).
    [CrossRef] [PubMed]
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  21. D. L. Marks, A. L. Oldenburg, J. J. Reynolds, and S. A. Boppart, "Study of an ultrahigh-numerical-aperture fiber continuum generation source for optical coherence tomography," Opt. Lett. 27, 2010-2012 (2002).
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    [CrossRef]
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    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]
  26. N. L’Heureux, S. Paquet, R. Labbe, L. Germain, and F. A. Auger. "A completely biological tissue-engineered human blood vessel," FASEB J. 12, 47-56 (1998).
  27. H. W. Ouyang, S. L. Toh, J. Goh, T. E. Tay, and K. Moe, "Assembly of bone marrow stromal cell sheets with knitted poly (L-Lactide) scaffold for engineering ligament analogs," J. Biomed. Mat. Res. 75, 264-271 (2005).
  28. W. Tan, A. Sendmir-Urkmez, L. J. Fahrner, R. Jamison, D. Leckband, and S. A. Boppart, "Structural and functional optical imaging of three-dimensional engineered tissue development," Tissue Eng. 10, 1747-1756 (2004).
    [CrossRef]

2006 (1)

2005 (1)

H. W. Ouyang, S. L. Toh, J. Goh, T. E. Tay, and K. Moe, "Assembly of bone marrow stromal cell sheets with knitted poly (L-Lactide) scaffold for engineering ligament analogs," J. Biomed. Mat. Res. 75, 264-271 (2005).

2004 (3)

W. Tan, A. Sendmir-Urkmez, L. J. Fahrner, R. Jamison, D. Leckband, and S. A. Boppart, "Structural and functional optical imaging of three-dimensional engineered tissue development," Tissue Eng. 10, 1747-1756 (2004).
[CrossRef]

D. S. Gareau, P. R. Bargo, W. A. Horton, and S. L. Jacques, "Confocal fluorescence spectroscopy of subcutaneous cartilage expressing green fluorescent protein versus cutaneous collagen autofluorescence," J. Biomed. Opt. 9, 254-258 (2004).
[CrossRef] [PubMed]

C. Mason, J. F. Markusen, M. A. Town, P. Dunnill, and R. K. Wang, "The potential of optical coherence tomography in the engineering of living tissue," Phys. Med. Biol. 49, 1097-1115 (2004).
[CrossRef] [PubMed]

2003 (6)

X. Xu, R. K. Wang, and A. El Haj, "Investigation of changes in optical attenuation of bone and neuronal cells in organ culture or three-dimensional constructs in vitro with optical coherence tomography: relevance to cytochrome oxidase monitoring," Eur. Biophys. J. 32, 355-362 (2003).
[CrossRef] [PubMed]

J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nat. Biotechnol. 21, 1361-1367 (2003).
[CrossRef] [PubMed]

M. J. Friedrich, "Studying cancer in three dimensions: 3-D models foster new insights into tumorigenesis," JAMA 290, 1977-1979 (2003).

D. J. Stephens and V. J. Allan, "Light microscopy techniques for live cell imaging," Science 300, 82-86 (2003).
[CrossRef] [PubMed]

R. G. M. Breuls, A. Mol, R. Petterson, C. W. J. Oomens, F. P. T. Baaijens, and C. V. C. Bouten, "Monitoring local cell viability in engineered tissues: A fast, quantitative, and nondestructive approach," Tissue Eng. 9, 269-281 (2003).
[CrossRef] [PubMed]

A. S. P. Lin, T. H. Barrows, S. H. Cartmella, and R. E. Guldberg, "Microarchitectural and mechanical characterization of oriented porous polymer scaffolds," Biomaterials 24, 481-489 (2003).
[CrossRef]

2002 (2)

I. Constantinidis, C. L. Stabler, R. Long, and A. Sambanis, "Noninvasive monitoring of a retrievable bioartificial pancreas in vivo," Ann. N. Y. Acad. Sci. 961, 298-301 (2002).
[CrossRef] [PubMed]

D. L. Marks, A. L. Oldenburg, J. J. Reynolds, and S. A. Boppart, "Study of an ultrahigh-numerical-aperture fiber continuum generation source for optical coherence tomography," Opt. Lett. 27, 2010-2012 (2002).
[CrossRef]

2001 (1)

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

2000 (2)

A. G. Podoleanu, J. A. Rogers, D. A. Jackson, and S. Dunne, "Three dimensional OCT images from retina and skin," Opt. Express 7, 292-298 (2000).
[CrossRef] [PubMed]

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Ann. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

1999 (1)

J. M. Schmitt, "Optical coherence tomography (OCT): a review," IEEE J. Select. Topics.Quantum Electon. 5, 1205-1215 (1999).
[CrossRef]

1998 (3)

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "In vivo cellular optical coherence tomography imaging," Nat. Med. 4, 861-865 (1998).
[CrossRef] [PubMed]

B. R. Masters, P. T. So, and E. Gratton, "Multiphoton excitation microscopy of in vivo human skin. Functional and morphological optical biopsy based on three-dimensional imaging, lifetime measurements and fluorescence spectroscopy," Ann. N. Y. Acad. Sci. 838, 58-67 (1998).
[CrossRef] [PubMed]

N. L’Heureux, S. Paquet, R. Labbe, L. Germain, and F. A. Auger. "A completely biological tissue-engineered human blood vessel," FASEB J. 12, 47-56 (1998).

1997 (1)

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography," Proc. Natl. Acad. Sci. USA 94, 4256-4261 (1997).
[CrossRef] [PubMed]

1996 (1)

S. A. Boppart, M. E. Brezinski, B. E. Bouma, G. J. Tearney, and J. G. Fujimoto, "Investigation of developing embryonic morphology using optical coherence tomography," Dev. Biol. 177, 54-63 (1996).
[CrossRef] [PubMed]

1995 (1)

H. Steller, "Mechanisms and genes of cellular suicide," Science 267, 1445-1449 (1995).
[CrossRef] [PubMed]

1993 (1)

R. Langer and J. P. Vacanti, "Tissue engineering," Science 260, 920-926 (1993).
[CrossRef] [PubMed]

1992 (1)

P. A. DiMilla, J. A. Quinn, S. M. Albelda, and D. A. Lauffenburger, "Measurement of individual cell migration parameters for human tissue cells," Amer. Inst. Chem. Engr. J. 38, 1092-1104 (1992).
[CrossRef]

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

1989 (1)

H. Michna, "Induced locomotion of human and murine macrophages: a comparative analysis by means of the modified Boyden-chamber system and the agarose migration assay," Cell Tissue Res. 255, 423-429 (1989).
[CrossRef] [PubMed]

Albelda, S. M.

P. A. DiMilla, J. A. Quinn, S. M. Albelda, and D. A. Lauffenburger, "Measurement of individual cell migration parameters for human tissue cells," Amer. Inst. Chem. Engr. J. 38, 1092-1104 (1992).
[CrossRef]

Allan, V. J.

D. J. Stephens and V. J. Allan, "Light microscopy techniques for live cell imaging," Science 300, 82-86 (2003).
[CrossRef] [PubMed]

Auger, F. A.

N. L’Heureux, S. Paquet, R. Labbe, L. Germain, and F. A. Auger. "A completely biological tissue-engineered human blood vessel," FASEB J. 12, 47-56 (1998).

Baaijens, F. P. T.

R. G. M. Breuls, A. Mol, R. Petterson, C. W. J. Oomens, F. P. T. Baaijens, and C. V. C. Bouten, "Monitoring local cell viability in engineered tissues: A fast, quantitative, and nondestructive approach," Tissue Eng. 9, 269-281 (2003).
[CrossRef] [PubMed]

Bargo, P. R.

D. S. Gareau, P. R. Bargo, W. A. Horton, and S. L. Jacques, "Confocal fluorescence spectroscopy of subcutaneous cartilage expressing green fluorescent protein versus cutaneous collagen autofluorescence," J. Biomed. Opt. 9, 254-258 (2004).
[CrossRef] [PubMed]

Barrows, T. H.

A. S. P. Lin, T. H. Barrows, S. H. Cartmella, and R. E. Guldberg, "Microarchitectural and mechanical characterization of oriented porous polymer scaffolds," Biomaterials 24, 481-489 (2003).
[CrossRef]

Berland, K. M.

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Ann. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

Boppart, S. A.

T. S. Ralston, D. L. Marks, P. S. Carney, and S. A. Boppart, "Inverse scattering for optical coherence tomography," J. Opt. Soc. Am. A 23, 1027-1037 (2006).
[CrossRef]

W. Tan, A. Sendmir-Urkmez, L. J. Fahrner, R. Jamison, D. Leckband, and S. A. Boppart, "Structural and functional optical imaging of three-dimensional engineered tissue development," Tissue Eng. 10, 1747-1756 (2004).
[CrossRef]

D. L. Marks, A. L. Oldenburg, J. J. Reynolds, and S. A. Boppart, "Study of an ultrahigh-numerical-aperture fiber continuum generation source for optical coherence tomography," Opt. Lett. 27, 2010-2012 (2002).
[CrossRef]

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "In vivo cellular optical coherence tomography imaging," Nat. Med. 4, 861-865 (1998).
[CrossRef] [PubMed]

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography," Proc. Natl. Acad. Sci. USA 94, 4256-4261 (1997).
[CrossRef] [PubMed]

S. A. Boppart, M. E. Brezinski, B. E. Bouma, G. J. Tearney, and J. G. Fujimoto, "Investigation of developing embryonic morphology using optical coherence tomography," Dev. Biol. 177, 54-63 (1996).
[CrossRef] [PubMed]

Bouma, B. E.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "In vivo cellular optical coherence tomography imaging," Nat. Med. 4, 861-865 (1998).
[CrossRef] [PubMed]

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography," Proc. Natl. Acad. Sci. USA 94, 4256-4261 (1997).
[CrossRef] [PubMed]

S. A. Boppart, M. E. Brezinski, B. E. Bouma, G. J. Tearney, and J. G. Fujimoto, "Investigation of developing embryonic morphology using optical coherence tomography," Dev. Biol. 177, 54-63 (1996).
[CrossRef] [PubMed]

Bouten, C. V. C.

R. G. M. Breuls, A. Mol, R. Petterson, C. W. J. Oomens, F. P. T. Baaijens, and C. V. C. Bouten, "Monitoring local cell viability in engineered tissues: A fast, quantitative, and nondestructive approach," Tissue Eng. 9, 269-281 (2003).
[CrossRef] [PubMed]

Breuls, R. G. M.

R. G. M. Breuls, A. Mol, R. Petterson, C. W. J. Oomens, F. P. T. Baaijens, and C. V. C. Bouten, "Monitoring local cell viability in engineered tissues: A fast, quantitative, and nondestructive approach," Tissue Eng. 9, 269-281 (2003).
[CrossRef] [PubMed]

Brezinski, M. E.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "In vivo cellular optical coherence tomography imaging," Nat. Med. 4, 861-865 (1998).
[CrossRef] [PubMed]

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography," Proc. Natl. Acad. Sci. USA 94, 4256-4261 (1997).
[CrossRef] [PubMed]

S. A. Boppart, M. E. Brezinski, B. E. Bouma, G. J. Tearney, and J. G. Fujimoto, "Investigation of developing embryonic morphology using optical coherence tomography," Dev. Biol. 177, 54-63 (1996).
[CrossRef] [PubMed]

Carney, P. S.

Cartmella, S. H.

A. S. P. Lin, T. H. Barrows, S. H. Cartmella, and R. E. Guldberg, "Microarchitectural and mechanical characterization of oriented porous polymer scaffolds," Biomaterials 24, 481-489 (2003).
[CrossRef]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Constantinidis, I.

I. Constantinidis, C. L. Stabler, R. Long, and A. Sambanis, "Noninvasive monitoring of a retrievable bioartificial pancreas in vivo," Ann. N. Y. Acad. Sci. 961, 298-301 (2002).
[CrossRef] [PubMed]

Cukierman, E.

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

DiMilla, P. A.

P. A. DiMilla, J. A. Quinn, S. M. Albelda, and D. A. Lauffenburger, "Measurement of individual cell migration parameters for human tissue cells," Amer. Inst. Chem. Engr. J. 38, 1092-1104 (1992).
[CrossRef]

Dong, C. Y.

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Ann. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

Dunne, S.

Dunnill, P.

C. Mason, J. F. Markusen, M. A. Town, P. Dunnill, and R. K. Wang, "The potential of optical coherence tomography in the engineering of living tissue," Phys. Med. Biol. 49, 1097-1115 (2004).
[CrossRef] [PubMed]

El Haj, A.

X. Xu, R. K. Wang, and A. El Haj, "Investigation of changes in optical attenuation of bone and neuronal cells in organ culture or three-dimensional constructs in vitro with optical coherence tomography: relevance to cytochrome oxidase monitoring," Eur. Biophys. J. 32, 355-362 (2003).
[CrossRef] [PubMed]

Fahrner, L. J.

W. Tan, A. Sendmir-Urkmez, L. J. Fahrner, R. Jamison, D. Leckband, and S. A. Boppart, "Structural and functional optical imaging of three-dimensional engineered tissue development," Tissue Eng. 10, 1747-1756 (2004).
[CrossRef]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Friedrich, M. J.

M. J. Friedrich, "Studying cancer in three dimensions: 3-D models foster new insights into tumorigenesis," JAMA 290, 1977-1979 (2003).

Fujimoto, J. G.

J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nat. Biotechnol. 21, 1361-1367 (2003).
[CrossRef] [PubMed]

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "In vivo cellular optical coherence tomography imaging," Nat. Med. 4, 861-865 (1998).
[CrossRef] [PubMed]

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography," Proc. Natl. Acad. Sci. USA 94, 4256-4261 (1997).
[CrossRef] [PubMed]

S. A. Boppart, M. E. Brezinski, B. E. Bouma, G. J. Tearney, and J. G. Fujimoto, "Investigation of developing embryonic morphology using optical coherence tomography," Dev. Biol. 177, 54-63 (1996).
[CrossRef] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Gareau, D. S.

D. S. Gareau, P. R. Bargo, W. A. Horton, and S. L. Jacques, "Confocal fluorescence spectroscopy of subcutaneous cartilage expressing green fluorescent protein versus cutaneous collagen autofluorescence," J. Biomed. Opt. 9, 254-258 (2004).
[CrossRef] [PubMed]

Germain, L.

N. L’Heureux, S. Paquet, R. Labbe, L. Germain, and F. A. Auger. "A completely biological tissue-engineered human blood vessel," FASEB J. 12, 47-56 (1998).

Goh, J.

H. W. Ouyang, S. L. Toh, J. Goh, T. E. Tay, and K. Moe, "Assembly of bone marrow stromal cell sheets with knitted poly (L-Lactide) scaffold for engineering ligament analogs," J. Biomed. Mat. Res. 75, 264-271 (2005).

Gratton, E.

B. R. Masters, P. T. So, and E. Gratton, "Multiphoton excitation microscopy of in vivo human skin. Functional and morphological optical biopsy based on three-dimensional imaging, lifetime measurements and fluorescence spectroscopy," Ann. N. Y. Acad. Sci. 838, 58-67 (1998).
[CrossRef] [PubMed]

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Guldberg, R. E.

A. S. P. Lin, T. H. Barrows, S. H. Cartmella, and R. E. Guldberg, "Microarchitectural and mechanical characterization of oriented porous polymer scaffolds," Biomaterials 24, 481-489 (2003).
[CrossRef]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Horton, W. A.

D. S. Gareau, P. R. Bargo, W. A. Horton, and S. L. Jacques, "Confocal fluorescence spectroscopy of subcutaneous cartilage expressing green fluorescent protein versus cutaneous collagen autofluorescence," J. Biomed. Opt. 9, 254-258 (2004).
[CrossRef] [PubMed]

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Jackson, D. A.

Jacques, S. L.

D. S. Gareau, P. R. Bargo, W. A. Horton, and S. L. Jacques, "Confocal fluorescence spectroscopy of subcutaneous cartilage expressing green fluorescent protein versus cutaneous collagen autofluorescence," J. Biomed. Opt. 9, 254-258 (2004).
[CrossRef] [PubMed]

Jamison, R.

W. Tan, A. Sendmir-Urkmez, L. J. Fahrner, R. Jamison, D. Leckband, and S. A. Boppart, "Structural and functional optical imaging of three-dimensional engineered tissue development," Tissue Eng. 10, 1747-1756 (2004).
[CrossRef]

L’Heureux, N.

N. L’Heureux, S. Paquet, R. Labbe, L. Germain, and F. A. Auger. "A completely biological tissue-engineered human blood vessel," FASEB J. 12, 47-56 (1998).

Labbe, R.

N. L’Heureux, S. Paquet, R. Labbe, L. Germain, and F. A. Auger. "A completely biological tissue-engineered human blood vessel," FASEB J. 12, 47-56 (1998).

Langer, R.

R. Langer and J. P. Vacanti, "Tissue engineering," Science 260, 920-926 (1993).
[CrossRef] [PubMed]

Lauffenburger, D. A.

P. A. DiMilla, J. A. Quinn, S. M. Albelda, and D. A. Lauffenburger, "Measurement of individual cell migration parameters for human tissue cells," Amer. Inst. Chem. Engr. J. 38, 1092-1104 (1992).
[CrossRef]

Leckband, D.

W. Tan, A. Sendmir-Urkmez, L. J. Fahrner, R. Jamison, D. Leckband, and S. A. Boppart, "Structural and functional optical imaging of three-dimensional engineered tissue development," Tissue Eng. 10, 1747-1756 (2004).
[CrossRef]

Lin, A. S. P.

A. S. P. Lin, T. H. Barrows, S. H. Cartmella, and R. E. Guldberg, "Microarchitectural and mechanical characterization of oriented porous polymer scaffolds," Biomaterials 24, 481-489 (2003).
[CrossRef]

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Long, R.

I. Constantinidis, C. L. Stabler, R. Long, and A. Sambanis, "Noninvasive monitoring of a retrievable bioartificial pancreas in vivo," Ann. N. Y. Acad. Sci. 961, 298-301 (2002).
[CrossRef] [PubMed]

Marks, D. L.

Markusen, J. F.

C. Mason, J. F. Markusen, M. A. Town, P. Dunnill, and R. K. Wang, "The potential of optical coherence tomography in the engineering of living tissue," Phys. Med. Biol. 49, 1097-1115 (2004).
[CrossRef] [PubMed]

Mason, C.

C. Mason, J. F. Markusen, M. A. Town, P. Dunnill, and R. K. Wang, "The potential of optical coherence tomography in the engineering of living tissue," Phys. Med. Biol. 49, 1097-1115 (2004).
[CrossRef] [PubMed]

Masters, B. R.

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Ann. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

B. R. Masters, P. T. So, and E. Gratton, "Multiphoton excitation microscopy of in vivo human skin. Functional and morphological optical biopsy based on three-dimensional imaging, lifetime measurements and fluorescence spectroscopy," Ann. N. Y. Acad. Sci. 838, 58-67 (1998).
[CrossRef] [PubMed]

Michna, H.

H. Michna, "Induced locomotion of human and murine macrophages: a comparative analysis by means of the modified Boyden-chamber system and the agarose migration assay," Cell Tissue Res. 255, 423-429 (1989).
[CrossRef] [PubMed]

Moe, K.

H. W. Ouyang, S. L. Toh, J. Goh, T. E. Tay, and K. Moe, "Assembly of bone marrow stromal cell sheets with knitted poly (L-Lactide) scaffold for engineering ligament analogs," J. Biomed. Mat. Res. 75, 264-271 (2005).

Mol, A.

R. G. M. Breuls, A. Mol, R. Petterson, C. W. J. Oomens, F. P. T. Baaijens, and C. V. C. Bouten, "Monitoring local cell viability in engineered tissues: A fast, quantitative, and nondestructive approach," Tissue Eng. 9, 269-281 (2003).
[CrossRef] [PubMed]

Oldenburg, A. L.

Oomens, C. W. J.

R. G. M. Breuls, A. Mol, R. Petterson, C. W. J. Oomens, F. P. T. Baaijens, and C. V. C. Bouten, "Monitoring local cell viability in engineered tissues: A fast, quantitative, and nondestructive approach," Tissue Eng. 9, 269-281 (2003).
[CrossRef] [PubMed]

Ouyang, H. W.

H. W. Ouyang, S. L. Toh, J. Goh, T. E. Tay, and K. Moe, "Assembly of bone marrow stromal cell sheets with knitted poly (L-Lactide) scaffold for engineering ligament analogs," J. Biomed. Mat. Res. 75, 264-271 (2005).

Pankov, R.

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

Paquet, S.

N. L’Heureux, S. Paquet, R. Labbe, L. Germain, and F. A. Auger. "A completely biological tissue-engineered human blood vessel," FASEB J. 12, 47-56 (1998).

Petterson, R.

R. G. M. Breuls, A. Mol, R. Petterson, C. W. J. Oomens, F. P. T. Baaijens, and C. V. C. Bouten, "Monitoring local cell viability in engineered tissues: A fast, quantitative, and nondestructive approach," Tissue Eng. 9, 269-281 (2003).
[CrossRef] [PubMed]

Pitris, C.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "In vivo cellular optical coherence tomography imaging," Nat. Med. 4, 861-865 (1998).
[CrossRef] [PubMed]

Podoleanu, A. G.

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Quinn, J. A.

P. A. DiMilla, J. A. Quinn, S. M. Albelda, and D. A. Lauffenburger, "Measurement of individual cell migration parameters for human tissue cells," Amer. Inst. Chem. Engr. J. 38, 1092-1104 (1992).
[CrossRef]

Ralston, T. S.

Reynolds, J. J.

Rogers, J. A.

Sambanis, A.

I. Constantinidis, C. L. Stabler, R. Long, and A. Sambanis, "Noninvasive monitoring of a retrievable bioartificial pancreas in vivo," Ann. N. Y. Acad. Sci. 961, 298-301 (2002).
[CrossRef] [PubMed]

Schmitt, J. M.

J. M. Schmitt, "Optical coherence tomography (OCT): a review," IEEE J. Select. Topics.Quantum Electon. 5, 1205-1215 (1999).
[CrossRef]

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Sendmir-Urkmez, A.

W. Tan, A. Sendmir-Urkmez, L. J. Fahrner, R. Jamison, D. Leckband, and S. A. Boppart, "Structural and functional optical imaging of three-dimensional engineered tissue development," Tissue Eng. 10, 1747-1756 (2004).
[CrossRef]

So, P. T.

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Ann. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

B. R. Masters, P. T. So, and E. Gratton, "Multiphoton excitation microscopy of in vivo human skin. Functional and morphological optical biopsy based on three-dimensional imaging, lifetime measurements and fluorescence spectroscopy," Ann. N. Y. Acad. Sci. 838, 58-67 (1998).
[CrossRef] [PubMed]

Southern, J. F.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "In vivo cellular optical coherence tomography imaging," Nat. Med. 4, 861-865 (1998).
[CrossRef] [PubMed]

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography," Proc. Natl. Acad. Sci. USA 94, 4256-4261 (1997).
[CrossRef] [PubMed]

Stabler, C. L.

I. Constantinidis, C. L. Stabler, R. Long, and A. Sambanis, "Noninvasive monitoring of a retrievable bioartificial pancreas in vivo," Ann. N. Y. Acad. Sci. 961, 298-301 (2002).
[CrossRef] [PubMed]

Steller, H.

H. Steller, "Mechanisms and genes of cellular suicide," Science 267, 1445-1449 (1995).
[CrossRef] [PubMed]

Stephens, D. J.

D. J. Stephens and V. J. Allan, "Light microscopy techniques for live cell imaging," Science 300, 82-86 (2003).
[CrossRef] [PubMed]

Stevens, D. R.

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Tan, W.

W. Tan, A. Sendmir-Urkmez, L. J. Fahrner, R. Jamison, D. Leckband, and S. A. Boppart, "Structural and functional optical imaging of three-dimensional engineered tissue development," Tissue Eng. 10, 1747-1756 (2004).
[CrossRef]

Tay, T. E.

H. W. Ouyang, S. L. Toh, J. Goh, T. E. Tay, and K. Moe, "Assembly of bone marrow stromal cell sheets with knitted poly (L-Lactide) scaffold for engineering ligament analogs," J. Biomed. Mat. Res. 75, 264-271 (2005).

Tearney, G. J.

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography," Proc. Natl. Acad. Sci. USA 94, 4256-4261 (1997).
[CrossRef] [PubMed]

S. A. Boppart, M. E. Brezinski, B. E. Bouma, G. J. Tearney, and J. G. Fujimoto, "Investigation of developing embryonic morphology using optical coherence tomography," Dev. Biol. 177, 54-63 (1996).
[CrossRef] [PubMed]

Toh, S. L.

H. W. Ouyang, S. L. Toh, J. Goh, T. E. Tay, and K. Moe, "Assembly of bone marrow stromal cell sheets with knitted poly (L-Lactide) scaffold for engineering ligament analogs," J. Biomed. Mat. Res. 75, 264-271 (2005).

Town, M. A.

C. Mason, J. F. Markusen, M. A. Town, P. Dunnill, and R. K. Wang, "The potential of optical coherence tomography in the engineering of living tissue," Phys. Med. Biol. 49, 1097-1115 (2004).
[CrossRef] [PubMed]

Vacanti, J. P.

R. Langer and J. P. Vacanti, "Tissue engineering," Science 260, 920-926 (1993).
[CrossRef] [PubMed]

Wang, R. K.

C. Mason, J. F. Markusen, M. A. Town, P. Dunnill, and R. K. Wang, "The potential of optical coherence tomography in the engineering of living tissue," Phys. Med. Biol. 49, 1097-1115 (2004).
[CrossRef] [PubMed]

X. Xu, R. K. Wang, and A. El Haj, "Investigation of changes in optical attenuation of bone and neuronal cells in organ culture or three-dimensional constructs in vitro with optical coherence tomography: relevance to cytochrome oxidase monitoring," Eur. Biophys. J. 32, 355-362 (2003).
[CrossRef] [PubMed]

Xu, X.

X. Xu, R. K. Wang, and A. El Haj, "Investigation of changes in optical attenuation of bone and neuronal cells in organ culture or three-dimensional constructs in vitro with optical coherence tomography: relevance to cytochrome oxidase monitoring," Eur. Biophys. J. 32, 355-362 (2003).
[CrossRef] [PubMed]

Yamada, K. M.

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

Amer. Inst. Chem. Engr. J. (1)

P. A. DiMilla, J. A. Quinn, S. M. Albelda, and D. A. Lauffenburger, "Measurement of individual cell migration parameters for human tissue cells," Amer. Inst. Chem. Engr. J. 38, 1092-1104 (1992).
[CrossRef]

Ann. N. Y. Acad. Sci. (2)

I. Constantinidis, C. L. Stabler, R. Long, and A. Sambanis, "Noninvasive monitoring of a retrievable bioartificial pancreas in vivo," Ann. N. Y. Acad. Sci. 961, 298-301 (2002).
[CrossRef] [PubMed]

B. R. Masters, P. T. So, and E. Gratton, "Multiphoton excitation microscopy of in vivo human skin. Functional and morphological optical biopsy based on three-dimensional imaging, lifetime measurements and fluorescence spectroscopy," Ann. N. Y. Acad. Sci. 838, 58-67 (1998).
[CrossRef] [PubMed]

Ann. Rev. Biomed. Eng. (1)

P. T. So, C. Y. Dong, B. R. Masters, and K. M. Berland, "Two-photon excitation fluorescence microscopy," Ann. Rev. Biomed. Eng. 2, 399-429 (2000).
[CrossRef]

Biomaterials (1)

A. S. P. Lin, T. H. Barrows, S. H. Cartmella, and R. E. Guldberg, "Microarchitectural and mechanical characterization of oriented porous polymer scaffolds," Biomaterials 24, 481-489 (2003).
[CrossRef]

Cell Tissue Res. (1)

H. Michna, "Induced locomotion of human and murine macrophages: a comparative analysis by means of the modified Boyden-chamber system and the agarose migration assay," Cell Tissue Res. 255, 423-429 (1989).
[CrossRef] [PubMed]

Dev. Biol. (1)

S. A. Boppart, M. E. Brezinski, B. E. Bouma, G. J. Tearney, and J. G. Fujimoto, "Investigation of developing embryonic morphology using optical coherence tomography," Dev. Biol. 177, 54-63 (1996).
[CrossRef] [PubMed]

Eur. Biophys. J. (1)

X. Xu, R. K. Wang, and A. El Haj, "Investigation of changes in optical attenuation of bone and neuronal cells in organ culture or three-dimensional constructs in vitro with optical coherence tomography: relevance to cytochrome oxidase monitoring," Eur. Biophys. J. 32, 355-362 (2003).
[CrossRef] [PubMed]

FASEB J. (1)

N. L’Heureux, S. Paquet, R. Labbe, L. Germain, and F. A. Auger. "A completely biological tissue-engineered human blood vessel," FASEB J. 12, 47-56 (1998).

J. Biomed. Mat. Res. (1)

H. W. Ouyang, S. L. Toh, J. Goh, T. E. Tay, and K. Moe, "Assembly of bone marrow stromal cell sheets with knitted poly (L-Lactide) scaffold for engineering ligament analogs," J. Biomed. Mat. Res. 75, 264-271 (2005).

J. Biomed. Opt. (1)

D. S. Gareau, P. R. Bargo, W. A. Horton, and S. L. Jacques, "Confocal fluorescence spectroscopy of subcutaneous cartilage expressing green fluorescent protein versus cutaneous collagen autofluorescence," J. Biomed. Opt. 9, 254-258 (2004).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A (1)

JAMA (1)

M. J. Friedrich, "Studying cancer in three dimensions: 3-D models foster new insights into tumorigenesis," JAMA 290, 1977-1979 (2003).

Nat. Biotechnol. (1)

J. G. Fujimoto, "Optical coherence tomography for ultrahigh resolution in vivo imaging," Nat. Biotechnol. 21, 1361-1367 (2003).
[CrossRef] [PubMed]

Nat. Med. (1)

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "In vivo cellular optical coherence tomography imaging," Nat. Med. 4, 861-865 (1998).
[CrossRef] [PubMed]

Opt. Express (1)

Opt. Lett. (1)

Phys. Med. Biol. (1)

C. Mason, J. F. Markusen, M. A. Town, P. Dunnill, and R. K. Wang, "The potential of optical coherence tomography in the engineering of living tissue," Phys. Med. Biol. 49, 1097-1115 (2004).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. USA (1)

S. A. Boppart, G. J. Tearney, B. E. Bouma, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, "Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography," Proc. Natl. Acad. Sci. USA 94, 4256-4261 (1997).
[CrossRef] [PubMed]

Quantum Electon. (1)

J. M. Schmitt, "Optical coherence tomography (OCT): a review," IEEE J. Select. Topics.Quantum Electon. 5, 1205-1215 (1999).
[CrossRef]

Science (5)

H. Steller, "Mechanisms and genes of cellular suicide," Science 267, 1445-1449 (1995).
[CrossRef] [PubMed]

E. Cukierman, R. Pankov, D. R. Stevens, and K. M. Yamada, "Taking cell-matrix adhesions to the third dimension," Science 294, 1708-1712 (2001).
[CrossRef] [PubMed]

D. J. Stephens and V. J. Allan, "Light microscopy techniques for live cell imaging," Science 300, 82-86 (2003).
[CrossRef] [PubMed]

R. Langer and J. P. Vacanti, "Tissue engineering," Science 260, 920-926 (1993).
[CrossRef] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, "Optical coherence tomography," Science 254, 1178-1181 (1991).
[CrossRef] [PubMed]

Tissue Eng. (2)

R. G. M. Breuls, A. Mol, R. Petterson, C. W. J. Oomens, F. P. T. Baaijens, and C. V. C. Bouten, "Monitoring local cell viability in engineered tissues: A fast, quantitative, and nondestructive approach," Tissue Eng. 9, 269-281 (2003).
[CrossRef] [PubMed]

W. Tan, A. Sendmir-Urkmez, L. J. Fahrner, R. Jamison, D. Leckband, and S. A. Boppart, "Structural and functional optical imaging of three-dimensional engineered tissue development," Tissue Eng. 10, 1747-1756 (2004).
[CrossRef]

Other (1)

B. E. Bouma and G. J. Tearney, editors, Handbook of Optical Coherence Tomography. Marcel Dekker, N.Y. (2001).

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Figures (8)

Fig. 1.
Fig. 1.

Experimental set-up for cell chemotaxis migration studies. A modified Boyden chamber is shown, in expanded view to show the membrane filter, and contained with a microincubator chamber for long-term imaging studies on a microscope stage.

Fig. 2.
Fig. 2.

OCT of cell migration. 3-D OCT images demonstrate the migration of macrophages (a-f). Cells at different points in time are labeled with different colors. The interval time is 40 min between (a/b, b/c, d/e, and e/f), and 120 min between (c/d). Individual OCT images are merged to form composite images of individual cell migration in 3-D space (g,h). Composite (g) is composed of (a-c) and composite (h) is a composed of (d-f). Insets in (g,h) show color-coded single-cell migration. Corresponding histology after the study is shown in (i), with macrophages collecting at the bottom. Scale bar is 200 μm.

Fig. 3.
Fig. 3.

Cell migration validation with confocal microscopy. 3-D confocal images of cell migration through the matrix is shown. Migration direction is upward as the microincubation chamber was inverted on an inverted microscope stage. Note the increasing number of cells entering the top plane of the volume (arrows) over time. Scale bar represents 50 μm.

Fig. 4.
Fig. 4.

OCT of cell proliferation in 3-D scaffolds. Images were acquired with low (5×104 cells) initial cell density. 3-D OCT images (a,d,g) and 2-D (x-z) OCT images (b,e,h) of engineered tissues were acquired on Day 0 (a-c), Day 4 (d-f), and Day 8 (g-i). Histological images stained with H&E (c,f,i) are shown to confirm cell proliferation over time. Scale bar in (i) is applicable for all images.

Fig. 5.
Fig. 5.

OCT of cell de-adhesion. Time-lapse images showing the process of cell de-adhesion and cell layer movement (black arrows) from a calcium-phosphate scaffold. Cells were cultured on the scaffolds for (a) 3 days and (b) 10 days. Continuous images were taken every minute after engineered tissues were soaked in a trypsin solution. (a) OCT images acquired at 10 min and 16 min after placement in trypsin solution. No detectable change was noted before 10 min. Difference images were calculated during cell de-adhesion by subtracting images acquired at later time-points. (b) Time-lapse images showing the process of cell layer de-adhesion (black arrows) from the scaffold (white arrows). De-adhesion of the cell-layer sheet was abrupt between 20 min and 30 min. Scale bars represents 200 μm.

Fig. 6.
Fig. 6.

OCT imaging of cell-substrate interactions with microtopographic feature sizes larger than single cells. 2-D (a,b) and 3-D (c) OCT images of a microgrooved (30 μm × 30 μm × 40 μm) PDMS substrate used for cell culture (d-f). Black arrows show the cells interacting with the substrate microstructure. OCT images are compared with corresponding phase contrast (g), 2-D confocal microscopy (h), and 3-D confocal microscopy (i) images. White arrows show the cross-sectional structure of the microgrooves. Scale bar represents 100 μm in all images.

Fig. 7.
Fig. 7.

OCT imaging of cell-substrate interactions with microtopographic feature sizes smaller than single cells. 3-D OCT images of a microgrooved (10 μm × 10 μm × 5–20 μm) PDMS substrate without (a) and with (b,c) cultured cells. Black arrows indicate cell clusters. Inset in (c) illustrates cell clusters overlying microgrooves. OCT images are compared with corresponding phase contrast (d), 2-D confocal microscopy (e), and 3-D confocal microscopy (f) images. Scale bar represents 50 μm in all images.

Fig. 8.
Fig. 8.

Collagen-dependent changes in OCT. OCT images of tissue models are shown with a constant cell number (~ 5 × 104) and increasing amounts of collagen in the Matrigel matrix. Collagen percentage varies for (a) 0%, (b) 0.05%, (c) 0.1%, (d) 0.15%, and (e) 0.2%. Increasing collagen content increases scattering, reducing imaging depth and contrast between cells and matrix. Scale bar represents 100 μm.

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