Non-destructive label-free monitoring of collagen gel remodeling using optical coherence tomography.

Matrix remodeling plays a fundamental role in physiological and pathological processes, as well as in tissue engineering applications. In this paper, optical coherence tomography (OCT), a non-destructive optical imaging technology, was used to image collagen gel remodeling by smooth muscle cells (SMCs). The optical scattering properties of collagen-SMC gels were characterized quantitatively by fitting OCT data to a theoretical model. Matrix remodeling over 5 days produced a 10-fold increase in the reflectivity of the collagen gels, corresponding to a decrease in scattering anisotropy from 0.91 to 0.46. The increase in reflectivity was corroborated in confocal mosaic images. Blocking matrix degradation in collagen-SMC gels with doxycycline, a non-specific matrix metalloproteinases (MMPs) inhibitor, impeded the decrease in scattering anisotropy and resulted in few macroscopic signs of remodeling. Causing matrix degradation in acellular gels with a 3 h treatment of MMP-8 (collagenase 2) partially mimicked the decrease in anisotropy measured in collagen-SMC gels after 5 days. These results suggest that the decrease in scattering anisotropy in the collagen-SMC gels was due to MMP activity that degrades collagen fibrils into smaller fragments.

[1]  E Bell,et al.  Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Z. Werb.  ECM and Cell Surface Proteolysis: Regulating Cellular Ecology , 1997, Cell.

[3]  G. Davis,et al.  This Review Is Part of a Thematic Series on Vascular Cell Diversity, Which Includes the following Articles: Heart Valve Development: Endothelial Cell Signaling and Differentiation Molecular Determinants of Vascular Smooth Muscle Cell Diversity Endothelial/pericyte Interactions Endothelial Extracellu , 2022 .

[4]  M. Selman,et al.  Matrix metalloproteases in aberrant fibrotic tissue remodeling. , 2006, Proceedings of the American Thoracic Society.

[5]  A. Halpern,et al.  Confocal reflectance mosaicing of basal cell carcinomas in Mohs surgical skin excisions. , 2007, Journal of biomedical optics.

[6]  Jan P. Stegemann,et al.  Phenotype Modulation in Vascular Tissue Engineering Using Biochemical and Mechanical Stimulation , 2003, Annals of Biomedical Engineering.

[7]  David Levitz,et al.  Quantitative characterization of developing collagen gels using optical coherence tomography. , 2010, Journal of biomedical optics.

[8]  James Varani,et al.  Looking older: fibroblast collapse and therapeutic implications. , 2008, Archives of dermatology.

[9]  G. Hou,et al.  Doxycycline alters vascular smooth muscle cell adhesion, migration, and reorganization of fibrillar collagen matrices. , 2006, The American journal of pathology.

[10]  Stephen J. Weiss,et al.  Regulation of Cell Invasion and Morphogenesis in a Three-Dimensional Type I Collagen Matrix by Membrane-Type Matrix Metalloproteinases 1, 2, and 3 , 2000, The Journal of cell biology.

[11]  Daniel S Gareau,et al.  Feasibility of digitally stained multimodal confocal mosaics to simulate histopathology. , 2009, Journal of biomedical optics.

[12]  J. Schuman,et al.  Optical coherence tomography. , 2000, Science.

[13]  E. Hay,et al.  Guidebook to the extracellular matrix and adhesion proteins , 1995 .

[14]  Massimo Coletta,et al.  Characterization of the mechanisms by which gelatinase A, neutrophil collagenase, and membrane-type metalloproteinase MMP-14 recognize collagen I and enzymatically process the two alpha-chains. , 2007, Journal of molecular biology.

[15]  Debby Gawlitta,et al.  Properties of engineered vascular constructs made from collagen, fibrin, and collagen-fibrin mixtures. , 2004, Biomaterials.

[16]  P. Libby,et al.  Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. , 1994, The Journal of clinical investigation.

[17]  A Rollins,et al.  In vivo video rate optical coherence tomography. , 1998, Optics express.

[18]  R. Wolowacz,et al.  Tetracycline-Based MMP Inhibitors Can Prevent Fibroblast-Mediated Collagen Gel Contraction In Vitro , 1998, Advances in dental research.

[19]  H. M. Lee,et al.  Minocycline reduces gingival collagenolytic activity during diabetes. Preliminary observations and a proposed new mechanism of action. , 1983, Journal of periodontal research.

[20]  M. Moses,et al.  Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  W. Steen.  Absorption and Scattering of Light by Small Particles , 1999 .

[22]  David Levitz,et al.  Optically characterizing collagen gels made with different cell types , 2009, BiOS.

[23]  R K Wang,et al.  The potential of optical coherence tomography in the engineering of living tissue. , 2004, Physics in medicine and biology.

[24]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[25]  Zachary M. Eastman,et al.  Confocal mosaicing microscopy in Mohs skin excisions: feasibility of rapid surgical pathology. , 2008, Journal of biomedical optics.

[26]  D. Kaplan,et al.  Guide to collagen characterization for biomaterial studies. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[27]  Steven L. Jacques,et al.  Low coherence interferometry of the cochlear partition , 2006, Hearing Research.

[28]  Robert M. Nerem,et al.  The Role of Matrix Metalloproteinase-2 in the Remodeling of Cell-Seeded Vascular Constructs Subjected to Cyclic Strain , 2001, Annals of Biomedical Engineering.

[29]  Frederick Grinnell,et al.  Fibroblast biology in three-dimensional collagen matrices. , 2003, Trends in cell biology.

[30]  S. Weiss,et al.  Secreted Versus Membrane-anchored Collagenases , 2009, The Journal of Biological Chemistry.

[31]  Robert A. Brown,et al.  Ultrarapid Engineering of Biomimetic Materials and Tissues: Fabrication of Nano‐ and Microstructures by Plastic Compression , 2005 .

[32]  Giulio Gabbiani,et al.  Perspective Article: Tissue repair, contraction, and the myofibroblast , 2005, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[33]  T. Salo,et al.  Matrix metalloproteinases (MMPs) in oral diseases. , 2004, Oral diseases.

[34]  Adam Wax,et al.  Biomedical Applications of Light Scattering , 2009 .

[35]  B. Hinz,et al.  Myofibroblasts and mechano-regulation of connective tissue remodelling , 2002, Nature Reviews Molecular Cell Biology.

[36]  J. D’Armiento,et al.  Matrix metalloproteinases in development and disease. , 2006, Birth defects research. Part C, Embryo today : reviews.