Structure-function relationships of postnatal tendon development: a parallel to healing

Abstract

This review highlights recent research on structure-function relationships in tendon and comments on the parallels between development and healing. The processes of tendon development and collagen fibrillogenesis are reviewed, but due to the abundance of information in this field, this work focuses primarily on characterizing the mechanical behavior of mature and developing tendon, and how the latter parallels healing tendon. The role that extracellular matrix components, mainly collagen, proteoglycans, and collagen cross-links, play in determining the mechanical behavior of tendon will be examined in this review. Specifically, collagen fiber re-alignment and collagen fibril uncrimping relate mechanical behavior to structural alterations during development and during healing. Finally, attention is paid to a number of recent efforts to augment injured tendon and how future efforts could focus on recreating the important structure-function relationships reviewed here.

Figure 1

(a) Hierarchical structure of tendon spanning from the single collagen molecule up to fibrils, fascicles, and whole tendon. Inset image describes the structure of fibril-associated proteoglycans, the most abundant of which is decorin in tendon. Image reproduced from Voleti et al., 2012. (b) Histological section (4x) of the rat supraspinatus tendon-to-bone insertion site, highlighting the transition zone. Image reproduced from Thomopoulos et al., 2002.

Figure 2

Typical stress-strain curve of tendon shows an elongated toe region with a low stiffness transitioning to a high stiffness linear region. Inset are two mechanisms of tendon's response to load within the toe region, notably (A) the uncrimping of collagen fibrils, and (B) the re-alignment of collagen fibrils, represented by a decrease in the variance of the distribution of fiber angles from the toe to the linear region.

Figure 3

Representative transmission electron microscopy images of transverse sections of collagen fascicles from the anterior (A) and posterior (B) aspect of the human patellar tendon. Posterior fascicles tended to have smaller fibril cross-sectional area (C) Graph showing typical stress-strain properties of one anterior compared with one posterior tendon fascicle from the patellar tendon of one patient. On average, anterior fascicles were stronger and stiffer than posterior fascicles. (D) First-order linear regression plot of fibril cross-sectional area against peak stress of anterior versus posterior fascicles. There was no association between fascicle strength and fibril cross-sectional area. Figures reproduced from Hansen et al., 2010