The Effect of Mechanical Strain on Non-enzymatic Cross-linking of Collagen type II Fibrils in Articular Cartilage

The Effect of Mechanical Strain on Non-enzymatic Cross-linking of Collagen type II Fibrils in Articular Cartilage

Lagrand, Jaap (TU Delft Mechanical, Maritime and Materials Engineering; TU Delft Biomaterials & Tissue Biomechanics; TU Delft Biomechanical Engineering)

Pouran, B. (mentor)
Weinans, H.H. (graduation committee)
Zadpoor, A.A. (graduation committee)
Harlaar, J. (graduation committee)

Delft University of Technology

Biomedical Engineering

2019-08-08

Investigations into mechanotransduction in connective tissue extracellular matrix (ECM) have demonstrated that collagen networks show cell-independent mechanosensitive behavior. It has been suggested that mechanical strain could lead to conformational changes in the molecular structure of collagen, thereby influencing the susceptibility to other molecules. In the process of normal aging, the collagen fibrils in cartilage undergo a non-enzymatic process known as glycation. It involves the accumulation of advanced glycation end products (AGEs) after exposure to sugars, resulting in the formation of cross-links between the collagen fibrils. This process is correlated with increased stiffness and brittleness of the cartilage, making it more prone to mechanical damage. The goal of this thesis was to assess whether mechanical compression has any effects on the formation of non-enzymatic cross-links during the aging of articular cartilage. Two different models have been developed to mimic aging knees that undergo static and dynamic compression. Healthy cartilage explants were exposed to L-threose sugar to induce artificial aging. During incubation, these explants were submitted to either static or dynamic unconfined compression. Treatment with static compression consisted of a 5, 10 or 15\% strain throughout the whole incubation period, using a custom-made bioreactor. Treatment with dynamic compression consisted of multiple loading cycles at a frequency of either 0.01 Hertz (Hz) or 1 Hz, using a Dynamic Mechanical Analyzer (DMA). We conducted cartilage surface color analyses, micro‐indentation tests, dynamic mechanical analyses and biochemical measurements of pentosidine cross‐links to assess the effects of advanced glycation cross‐linking under these different conditions. Dynamic compression at a frequency of 1 Hz was found to affect the formation of non-enzymatic cross-links. Biomechanical and biochemical data showed a similar trend, namely, the average values for equilibrium modulus, dynamic moduli, phase shifts and pentosidine per collagen level were noticeably higher (or lower in case of phase shift) for the 1 Hz treated samples compared to samples of other treatment groups. The results of these studies suggest that compression at the physiological frequency of walking does affect the formation of cross-links in the articular cartilage during aging. These findings contribute to a better understanding of the mechanochemistry of collagen fibrils, which is necessary to develop future strategies against cartilage aging and deterioration.

Cartilage
Collagen
Cross-links
Biomechanical properties
HPLC
Aging
DMA
Indentation
Strain-dependency

http://resolver.tudelft.nl/uuid:26cd823b-217f-42f1-b5bc-7f988f14ae24

Student theses

master thesis

© 2019 Jaap Lagrand