Biomedical Engineering Reference
In-Depth Information
importantly, linear microcrack accumulation resulted in further toughness loss if
the fracture crack initiated from the compressive rather than tensile side [
10
].
Results from these studies illustrate that microdamage formation is an energy
dissipation mechanism. Application of loading during regular/strenuous activities
leads to the formation of in vivo microdamage. This microdamage helps to avert
fracture and is removed by bone remodeling. However, deficiency in remodeling
or age-related changes in the bone matrix (see next section for details) cause
increased bone fragility through inefficient repair and alteration in the magnitude
as well as morphology of microdamage formation.
5 The Effect of Changes in Bone Matrix Quality
on Microdamage
Bone derives its resistance to fracture from collagen deformation [
67
] and by its
ability to form microdamage [
62
] and uncracked ligament bridges during crack
propagation [
65
]. Collagen deformation, microcracking (magnitude and mor-
phology), and uncracked ligaments are the primary toughening mechanisms in
bone and any changes in these mechanisms will influence bone toughness. Several
studies are currently ongoing to establish precise mechanisms by which particular
modifications in bone matrix components (e.g. mineral, collagen, non-collagenous
proteins) affect microdamage formation and cause increased bone fragility with
aging, disease, and/or pharmaceutical treatment. A representative example of
modification in bone collagen and its effect on microdamage formation and bone
fragility is discussed below.
Collagen, a key structural component of bone's extracellular matrix, undergoes
biochemical changes such as non-enzymatic glycation with aging [
68
,
69
]orbis-
phosphonate-based pharmaceutical treatments for osteoporosis [
70
,
71
]. Non-enzymatic
glycation creates crosslinks within and between collagen fibers that are collec-
tively known as advanced glycation end products (AGEs) [
72
,
73
]. AGEs accu-
mulate with age, and their accumulation deteriorates the mechanical properties
of bone [
74
-
77
]. Particularly, non-enzymatic glycation of collagen modifies
bone's post-yield properties [
78
] and thus may play a crucial role in skeletal
fragility [
72
,
79
,
80
].
In context of toughening mechanisms including collagen deformation and
microcracking, Vashishth et al. [
78
] and Tang et al. [
26
] showed that accumulation
of AGEs causes stiffening of the collagen matrix in both cortical and cancellous
bone. Also, AGE accumulation leads to decreased deformation and increased
fracture propensity with aging [
26
] and bisphosphonate-treatment [
71
]. Further-
more, in a recent study conducted by Tang and Vashishth, results indicated that
AGEs affect both the morphology and magnitude of microdamage formation. They
found that in vitro ribosylated cancellous bone specimens had increased amounts
of linear microcracks whereas controls had relatively more diffuse damage [
27
].
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