Abstract
Proper replacement or repair of damaged tendons or ligaments requires functionally engineered tissue that mimics their native mechanical properties. While tendon structure–function relationships are generally assumed, there exists little quantitative evidence of the roles of distinct tendon components in tendon function. Previous work has used linear correlations to assess the independent, univariate effects of one structural or one biochemical variable on mechanics. The current study's objective was to simultaneously and rigorously evaluate the relative contributions of seven different structural and compositional variables in predicting tissue mechanical properties through the use of multiple regression statistical models. Structural, biochemical, and mechanical analysis were all performed on tail tendon fascicles from different groups of transgenic mice, which provide a reproducible, noninvasive, in vivo model of changes in tendon structure and composition. Interestingly, glycosaminoglycan (GAG) content was observed to be the strongest predictor of mechanical properties. GAG content was also well correlated with collagen content and mean collagen fibril diameter. Collagen fibril area fraction was a significant predictor only of material properties. Therefore, in a large multivariate model, GAG content was the largest predictor of mechanical properties, perhaps both through direct influence and indirectly through its correlation with collagen content and fibril structure.
Similar content being viewed by others
REFERENCES
Ault, H. K., and A. H. Hoffman. A composite micromechanical model for connective tissues: Part 1—Theory. J.Biomech.Eng. 114:137–141, 1992.
Birk, D. E., F. H. Silver, and R. L. Trelstad. Matrix Assembly. In: Cell Biology of the Extracellular Matrix, edited by E. D. Hay. New York: Plenum, 1991, pp. 221–254.
Blevins, F. T., M. Djurasovic, E. L. Flatow, and K. G. Vogel. Biology of the rotator cuff tendon. Orthop.Clin.North Am. 28:1–16, 1997.
Bonadio, J., T. L. Saunders, E. Tsai, S. A. Goldstein, J. Morris-Wiman, L. Brinkley, D. F. Dolan, R. A. Altschuler, J. E. Hawkins Jr., and J. F. Bateman. Transgenic mouse model of the mild dominant form of osteogenesis imperfecta. Proc.Natl.Acad.Sci.U.S.A. 87:7145–7149, 1990.
Calabro, A., V. C. Hascall, and R. J. Midura. Adaptation of FACE methodology for microanalysis of total hyaluronan and chondroitin sulfate composition from cartilage. Glycobiology 10:283–293, 2000.
Christiansen, D. L., E. K. Huang, and F. H. Silver. Assembly of type I collagen: Fusion of fibril subunits and the influence of fibril diameter on mechanical properties. Matrix Biol. 19:409–420, 2000.
Craig, A. S., M. J. Birtles, J. F. Conway, and D. A. Parry. An estimate of the mean length of collagen fibrils in rat tail-tendon as a function of age. Connect.Tissue Res. 19:51–62, 1989.
Danielson, K. G., H. Baribault, D. F. Holmes, H. Graham, K. E. Kadler, and R. V. Iozzo. Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility. J.Cell Biol. 136:729–743, 1997.
Derwin, K. A., and L. J. Soslowsky. A quantitative investigation of structure–function relationships in a tendon fascicle model. J.Biomech.Eng. 121:598–604, 1999.
Derwin, K. A., L. J. Soslowsky, J. H. Kimura, and A. H. Plaas. Proteoglycans and glycosaminoglycan fine structure in the mouse tail tendon fascicle. J.Orthop.Res. 19:269–277, 2001.
Devore, J. L. Probability and Statistics for Engineering and the Sciences. Belmont, CA: Duxbury Press, 1991.
Flint, M. H., A. S. Craig, H. C. Reilly, G. C. Gillard, and D. A. Parry. Collagen fibril diameters and glycosaminoglycan con-tent of skins—indices of tissue maturity and function. Connect.Tissue Res. 13:69–81, 1984.
Haut, R. C. The effect of a lathyritic diet on the sensitiv-ity of tendon to strain rate. J.Biomech.Eng. 107:166–174, 1985.
Haut, R. C., R. L. Lancaster, and C. E. DeCamp. Mechanical properties of the canine patellar tendon: Some correlations with age and content of collagen. J.Biomech. 25:163–173, 1992.
Kastellic, J., I. Palley, and E. Baer. A structural model for tendon crimping. J.Biomech. 13:887–893, 1980.
Lin, T. W., P. S. Robinson, P. R. Reynolds, K. A. Derwin, K. G. Danielson, R. V. Iozzo, and L. J. Soslowsky. Quantified structure–function relationships in tendon using transgenic mouse models. Trans.Orthop.Res. 26:698, 2001.
Lin, T. W., S. M. White, P. S. Robinson, K. A. Derwin, A. H. Plaas, R. V. Iozzo, and L. J. Soslowsky. Relating ex-tracellular matrix composition with function—a study using transgenic mouse tail fendon fascicles. Trans.Orthop.Res. 27:45, 2002.
Liu, X., H. Wu, M. Byrne, J. Jeffrey, S. Krane, and R. Jaenisch. A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling. Cell Biol. 130:227–237, 1995.
McBride, D. J., Jr., R. L. Trelstad, and F. H. Silver. Structural and mechanical assessment of developing chick tendon. Int.J.Biol.Macromol. 10:194–200, 1988.
Mikic, B., B. J. Schalet, R. T. Clark, V. Gaschen, and E. B. Hunziker. GDF-5 deficiency in mice alters the ultrastructure, mechanical properties and composition of the Achilles tendon. J.Orthop.Res. 19:365–371, 2001.
Parry, D. A. The molecular and fibrillar structure of collagen and its relationship to the mechanical properties of connective tissue. Biophys.Chem. 29:195–209, 1988.
Parry, D. A., and A. S. Craig. Quantitative electron micro-scope observations of the collagen fibrils in rat-tail tendon. Biopolymers 16:1015–1031, 1977.
Pins, G. D., D. L. Christiansen, R. Patel, and F. H. Silver. Self-assembly of collagen fibers. Influence of fibrillar alignment and decorin on mechanical properties. Biophys.J. 73:2164–2172, 1997.
Scott, J. E. Proteoglycan-fibrillar collagen interactions. Biochem.J. 252:313–323, 1988.
Stegemann, H., and K. Stalder. Determination of Hydroxyproline. Clinica Chimica Acta 18:267–273, 1967.
Trotter, J. A., and T. J. Koob. Collagen and proteoglycan in a sea urchin ligament with mutable mechanical properties. Cell Tissue Res. 258:527–539, 1989.
Vogel, K. G., and D. Heinegard. Characterization of proteogly-cans from adult bovine tendon. J.Biol.Chem. 260:9298–9306, 1985.
Woo, S. L. Mechanical properties of tendons and ligaments. I. Quasi-static and nonlinear viscoelastic properties. Biorheology 19:385–396, 1982.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Robinson, P.S., Lin, T.W., Jawad, A.F. et al. Investigating Tendon Fascicle Structure–Function Relationships in a Transgenic-Age Mouse Model Using Multiple Regression Models. Annals of Biomedical Engineering 32, 924–931 (2004). https://doi.org/10.1023/B:ABME.0000032455.78459.56
Issue Date:
DOI: https://doi.org/10.1023/B:ABME.0000032455.78459.56