Research Papers

Changes in Collagen With Aging Maintain Molecular Stability After Overload: Evidence From an In Vitro Tendon Model

[+] Author and Article Information
Thomas L. Willett1

Bone Biology Laboratory, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canadawillett@lunenfeld.ca

Rosalind S. Labow

Department of Biochemistry, Microbiology and Immunology, Division of Cardiac Surgery, University of Ottawa Heart Institute, University of Ottawa, Ottawa, ON, K1Y 4W7, Canadarlabow@ottawaheart.ca

Ian G. Aldous

School of Biomedical Engineering, Dalhousie University, Halifax, NS, B3M 3J5, Canadaialdous@dal.ca

Nick C. Avery

Matrix Biology Research Group, School of Clinical Veterinary Medicine, University of Bristol, Bristol BS40 5DU, UKnick.avery@bristol.ac.uk

J. Michael Lee

Department of Applied Oral Sciences, School of Biomedical Engineering, Dalhousie University, Halifax, NS, B3H 3J5, Canadamichael.lee@dal.ca


Corresponding author.

J Biomech Eng 132(3), 031002 (Feb 03, 2010) (8 pages) doi:10.1115/1.4000933 History: Received April 04, 2009; Revised December 22, 2009; Posted January 04, 2010; Published February 03, 2010; Online February 03, 2010

Soft tissue injuries are poorly understood at the molecular level. Previous work using differential scanning calorimetry (DSC) has shown that tendon collagen becomes less thermally stable with rupture. However, most soft tissue injuries do not result in complete tissue rupture but in damaging fiber overextension. Covalent crosslinking, which increases with animal maturity and age, plays an important role in collagenous fiber mechanics. It is also a determinant of tissue strength and is hypothesized to inhibit the loss of thermal stability of collagen due to mechanical damage. Controlled overextension without rupture was investigated to determine if overextension was sufficient to reduce the thermal stability of collagen in the bovine tail tendon (BTT) model and to examine the effects of aging on the phenomenon. Baseline data from DSC and hydrothermal isometric tension (HIT) techniques were compared between two groups: steers aged 24–30 months (young group), and skeletally mature bulls and oxen aged greater than five years (old group). Covalent crosslinks were quantified by ion exchange chromatography. Overextension resulted in reduced collagen thermal stability in the BTT model. The Young specimens, showing detectably lower tissue thermomechanical competence, lost more thermal stability with overextension than did the old specimens. The effect on old specimens, while smaller, was detectable. Multiple overextension cycles increased the loss of stability in the young group. Compositional differences in covalent crosslinking corresponded with tissue thermomechanical competence and therefore inversely with the loss of thermal stability. HIT testing gave thermal denaturation temperatures similar to those measured with DSC. The thermal stability of collagen was reduced by overextension of the tendon—without tissue rupture—and this effect was amplified by increased cycles of overextension. Increased tissue thermomechanical competence with aging seemed to mitigate the loss of collagen stability due to mechanical overextension. Surprisingly, the higher tissue thermomechanical competence did not directly correlate with the concentration of endogenous enzymatically derived covalent crosslinking on a mole per mole of collagen basis. It did, however, correlate with the percentage of mature and thermally stable crosslinks. Compositional changes in fibrous collagens that occur with aging affect fibrous collagen mechanics and partially determine the nature of mechanical damage at the intermolecular level. As techniques develop and improve, this new information may lead to important future studies concerning improved detection, prediction, and modeling of mechanical damage at much finer levels of tissue hierarchy than currently possible.

Copyright © 2010 by American Society of Mechanical Engineers
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Figure 1

Representation of the HIT test. Tissue is held under isometric constraint in a bath of distilled, deionized water. The temperature is increased from ambient temperature to 90°C at approximately 1°C/min during which the kinetic energy of the water bound to the collagen molecules and of the peptide chains of the molecules increases. The denaturation temperature Td and temperature of maximum isometric force TMIF are shown.

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Figure 2

Stress-strain curves for five overextension cycles. The mechanical testing machine was controlled to ramp the deformation at a set strain rate (1%/s) while monitoring the slope of the force versus deformation data until a slope of zero was detected (as suggested by the horizontal gray line), indicative of the start to tissue failure. At this point, the machine reversed at the same rate back to the zero position. This process was used once for one cycle specimens, and five times for the five cycle specimens.

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Figure 3

DSC curves versus HIT curves (normalized to peak heat flow and peak force, respectively) demonstrating differences in the thermal and thermomechanical behavior of young and old specimens as measured by these techniques. Measured parameters were determined as described in the text and in Fig. 1.

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Figure 4

HIT curves (Load versus temperature) from young steer tail tendons demonstrating the effect of five cycles of damaging overextension. Note that both the Td and TMIF decreased, which is the typical result in the young group.




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