Review paper: The importance of consideration of collagen cross-links in computational models of collagen-based tissues

Collagen as the main protein in Extra Cellular Matrix (ECM) is the main load-bearing component of fibrous tissues. Nanostructure and architecture of collagen fibrils play an important role in mechanical behavior of these tissues. Extensive experimental and theoretical studies have so far been performed to capture these properties, but none of the current models realistically represent the complexity of network mechanics because still less is known about the collagen's inner structure and its effect on the mechanical properties of tissues. The goal of this review article is to emphasize the significance of cross-links in computational modeling of different collagen based tissues, and to reveal the need for continuum models to consider cross-links properties to better reflect the mechanical behavior observed in experiments. In addition, this study outlines the limitations of current investigations and provides potential suggestions for the future work.