Abstract
Collagen is the structural molecule that is most correlated with strength in blood vessels. In this study, we compared the properties of collagen in engineered and native blood vessels. Transmission electron microscopy (TEM) was used to image sections of engineered and native arteries. Band periodicities of engineered and native collagen fibrils indicated that spacing between collagen molecules was similar in engineered and native tissues. Engineered arteries, however, had thinner collagen fibrils and fibers than native arteries. Further, collagen fibrils were more loosely packed within collagen fibers in engineered arteries than in native arteries. The sensitivity of TEM analysis allowed measurement of the relative frequency of observation for alignment of collagen. These observations showed that collagen in both engineered and native arteries was aligned circumferentially, helically, and axially, but that engineered arteries had less circumferential collagen and more axial collagen than native arteries. Given that collagen is primarily responsible for dictating the ultimate mechanical properties of arterial tissue, future efforts should focus on using relative frequency of observation for alignment of collagen as a descriptive input for models of the mechanical properties of engineered or native tissues.
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Armentano R. L., J. Levenson, J. G. Barra, E. I. Cabrera Fischer, G. J. Breitbart, R. H. Pichel, A. Simon 1991 Assessment of elastin and collagen contribution to aortic elasticity in conscious dogs. Am. J. Physiol. 260, H1870–H1877
Aspden R. M., N. H. Bornstein, D. W. Hukins 1987 Collagen organisation in the interspinous ligament and its relationship to tissue function. J. Anat. 155, 141–151
Brodsky B., E. F. Eikenberry, K. Cassidy 1980 An unusual collagen periodicity in skin. Biochim. Biophys. Acta 621(1), 162–166
Canham P. B., H. M. Finlay, D. R. Boughner 1997 Contrasting structure of the saphenous vein and internal mammary artery used as coronary bypass vessels. Cardiovasc. Res. 34(3), 557–567
Canham P. B., E. A. Talman, H. M. Finlay, J. G. Dixon 1991 Medial collagen organization in human arteries of the heart and brain by polarized light microscopy. Connect. Tissue Res. 26(1–2), 121–134
Canty, E. G., T. Starborg, Y. Lu, S. M. Humphries, D. F. Holmes, R. S. Meadows, A. Huffman, E. T. O’toole, and K. E. Kadler. Actin filaments are required for fibripositor-mediated collagen fibril alignment in tendon. J. Biol. Chem. 281(50), 38592–38598, 2006
Cox R. H. 1978 Differences in mechanics of arterial smooth muscle from hindlimb arteries. Am. J. Physiol. 235(6), H649–H656
Dahl S. L. M., R. B. Rucker, L. E. Niklason 2005 Effects of copper and cross-linking on the extracellular matrix of tissue-engineered arteries. Cell Transplant. 14(10), 861–868
Driessen N. J., G. W. Peters, J. M. Huyghe, C. V. Bouten, F. P. Baaijens 2003 Remodelling of continuously distributed collagen fibres in soft connective tissues. J. Biomech. 36(8), 1151–1158
Engelmayr G. C. J., G. D. Papworth, S. C. Watkins, J. E. J. Mayer, M. S. Sacks 2006 Guidance of engineered tissue collagen orientation by large-scale scaffold microstructures. J. Biomech. 39(10), 1819–1831
Finlay H. M., L. McCullough, P. B. Canham 1995 Three-dimensional collagen origanization of human brain arteries at different transmural pressures. J. Vasc. Res. 32, 301–312
Grassl E. D., T. R. Oegema, R. T. Tranquillo 2002 Fibrin as an alternative biopolymer to type-I collagen for the fabrication of a media equivalent. J. Biomed. Mater Res. 60(4), 607–612
Hofmann H., P. P. Fietzek, K. Kuhn 1978 The role of polar and hydrophobic interactions for the molecular packing of type-I collagen: a three-dimensional evaluation of the amino acid sequence. J. Mol. Biol. 125, 137–165
Holzapfel G. A., T. C. Gasser, M. Stadler. A structural model for the viscoelastic behavior of arterial walls: continuum formulation and finite element analysis. Eur. J. Mech. A/Solids 21: 441–463, 2002
Holzapfel G. A., T. C. Gasser 2000 A new constitutive framework for arterial wall mechanics and a comparative study of material models. J. Elasticity 61, 1–48
Humphrey J.D. 1999 Remodeling of a collagenous tissue at fixed lengths. J. Biomech. Eng. 121, 591–597
Kadler K. 2004 Matrix loading: assembly of extracellular matrix collagen fibrils during embryogenesis. Birth Defects Res. C Embryo Today 72(1), 1–11
Kuhn, K., and R. W. Glanville. Molecular structure and higher organization of different collgaen types. In: Biology of Collagen, edited by A. Viidik and J. Vuust. London: Academic Press Inc., 1980, pp. 1–14
Lanir Y. 1983 Constitutive equations for the lung tissue. Trans. ASME 105, 374–380
Lanir Y. 1983 Constitutive equations for fibrous connective tissues. J. Biomech. 16(1), 1–12
Merrilees M. J., K. M. Tiang, L. Scott 1987 Changes in collagen fibril diameters across artery walls including a correlation with glycosaminoglycan content. Connect. Tissue Res. 16, 237–257
Niklason L. E., W. A. Abbott, J. Gao, B. Klagges, K. K. Hirschi, K. Ulubayram, N. Conroy, R. Jones, A. Vasanawala, S. Sanzgiri, R. Langer 2001 Morphologic and mechanical characteristics of engineered bovine arteries. J. Vasc. Surgery 33(3), 628–638
Niklason L. E., J. Gao, W. M. Abbott, K. Hirschi, S. Houser, R. Marini, R. Langer 1999 Functional arteries grown in vitro. Science 284, 489–493
Rothenburger M., Volker W., Vischer J. P., Berendes E., Glasmacher B., Scheld H. H., Deiwick M. 2002 Tissue engineering of heart valves: formation of a three-dimensional tissue using porcine heart valve cells. ASAIO J. 48(6), 586–591
Roylance D. 1996 Mechanics of Materials. New York: John Wiley & Sons, Inc.
Sacks M. S. 2003 Incorporation of experimentally-derived fiber orientation into a structural constitutive model for planar tissues. Trans. ASME 125, 280–287
Sacks M. S., D. B. Smith, E. D. Hiester 1997 A small angle light scattering device for planar connective tissue microstructural analysis. Ann. Biomed. Eng. 25, 678–689
Shadwick R. E. 1999 Mechanical design in arteries. J. Exp. Biol. 202, 3305–3313
Solan A., S. Mitchell, M. Moses, L. Niklason 2003 Effect of pulse rate on collagen deposition in the tissue-engineered blood vessel. Tissue Eng. 9(4), 579–586
Torp, S., E. Baer, and B. Friedman. Effects of age and of mechanical deformation on the ultrastructure of tendon. In: Structure of Fibrous Biopolymers, edited by E. D. T. Atkins and A. Keller. London: Butterworths, 1975
Wells S. M., T. Sellaro, M. S. Sacks 2005 Cyclic loading response of bioprosthetic heart valves: effects of fixation stress state on the collagen fiber architecture. Biomaterials 26(15), 2611–2619
Acknowledgments
This work was funded by NIH R01 HL63766. Many thanks to the Duke Cancer Center Electron Microscopy Facility for preparing samples for transmission electron microscopy, and for training the authors to use the transmission electron microscope. The authors also wish to thank Frank Baaijens and Niels Driessen for thought-provoking discussions about collagen alignment.
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Dahl, S.L.M., Vaughn, M.E. & Niklason, L.E. An Ultrastructural Analysis of Collagen in Tissue Engineered Arteries. Ann Biomed Eng 35, 1749–1755 (2007). https://doi.org/10.1007/s10439-007-9340-8
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DOI: https://doi.org/10.1007/s10439-007-9340-8