Multiscale Modeling of Ligaments and Tendons - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 106

Ligament

Fascicle

Fiber

Fibril

Tropocollagen

Nano
100 nm

Micro
100 µm

Meso
500 µm

Macro
5mm

Fig. 1 Hierarchical organization of ligament from the molecular level to the joint level

fibers form fascicles at the mesoscale and fascicles form the whole tendon or
ligament at the macroscale (Fig. 1 ).
The ECM of ligaments and tendons is formed by self-assembly of cell-secreted
proteins and consists of approximately 70 % water [ 28 ]. The solid phase of these
tissues is primarily composed of type I collagen (60-80 %), with the remainder
consisting of elastin, proteoglycans and glycosaminoglycans (GAGs), other types
of collagen (types III, IV, V, VI), fibrillin and other proteins [ 121 , 125 , 230 ]. Type
I collagen exhibits different organizational motifs at each scale (Figs. 1 and 2 )
[ 121 ]. At the nanoscale, tropocollagen monomers are assembled to form fibrils
(50-200 nm dia.), which display a characteristic d-banding period (67 nm) [ 121 ,
170 , 171 , 224 ]. Tropocollagen monomers are held together by a combination of
hydrogen, ionic and covalent bonds [ 125 , 230 ]. Fibrils are spaced regularly within
healthy tissue and predominantly aligned in parallel [ 31 , 209 , 227 ]. Cross sectional
TEM images reveal that fibrils are well organized and separated by a regular
spacing within healthy tissue. At the microscale , fibrils are assembled into fibers
(20-50 lm dia.) [ 50 , 117 ]. Fibroblasts and tenocytes (10 lm width 9 60 lm
length) are located in the interfiber space [ 121 , 125 ]. Fibroblasts and tenocytes are
responsible for regulating the ECM in response to loading and injury, and
mechanotransduction plays a major role in their function [ 229 ]. The characteristic
crimp pattern is visible at the fiber level, with a period of 50-200 lm[ 112 , 117 ].
Fibers are arranged in a largely parallel fashion [ 121 ]. At the mesoscale , fibers are
assembled into fascicles (100-500 lm dia) [ 50 , 121 , 230 ]. To at least some extent,
crimp is registered between fibers [ 124 , 168 ]. Fascicles are organized in parallel
[ 96 ]. Fascicles and fibers are surrounded by a thin fascia (referred to as endotenon)
[ 85 , 121 , 206 ]. At the macroscale , groups of fascicles are organized into functional
bands (100 lm-1 mm dia) [ 50 ].
Noncollagenous ECM constituents include proteoglycans (PGs) such as decorin
(*1%/wt), biglycan (*0.5%/wt) and others (fibromodulin, lumican, aggrecan,
versican), fibrillin [ 21 , 114 , 125 , 143 - 145 , 167 ] and elastin (1-2%/wt) [ 121 , 125 ,
192 , 206 ]. The large PGs (e.g., aggrecan) contribute to the apparent viscoelastic
material behavior of these tissues by controlling water content and flux [ 114 ].