Biomedical Engineering Reference
In-Depth Information
between fascicles via shearing of the interfascicular matrix, but it appears that the
load sharing between fascicles is highly inhomogeneous. Strains within individual
fascicles of an Achilles tendon sample were highly variable, even when the applied
macroscopic loading was constant [ 123 ]. To date, very little research has addressed
modeling the mesocale fascicle interactions, thus this remains as an open modeling
challenge. Given that vascular perfusion and innervation occur at this level [ 84 , 174 ],
the need for further research and development in this area is particularly high.
Force transmission from the mesocale fascicle level to the microscale fiber level
has been the subject of a number of experimental studies. As previously discussed,
strain at the microscale fiber level is highly inhomogeneous, with uncrimping and
sliding of adjacent fibers being the dominant modes of deformation. In fact, strains
resulting from sliding of adjacent fibers actually exceeded that of strains measured
within individual fibers. As a result, the fiber strain was considerably less than the
macroscopic fascicles strain. Given this information, it appears that the largest strains
are experienced at the macroscale, followed by the mesoscale fascicle and again
followed by the microscale fiber. Since fibroblasts anchor to individual or multiple
fibers, this suggests that even large macroscale tendon strains may result in relatively
low microscale fiber, and thus fibroblast strains. As mechanotransduction occurs
within individual fibroblast, modeling both the meso- and microscale interactions
may be a necessity. The explicit representation of fibroblast cell bodies may prove
especially insightful, as they will provide the mechanical environment “seen” by cells
in response to macroscale joint loading, which can then yield insights into cellular
mechanotransduction.
There has been very little investigation of force transmission within individual
fibers. This is a result of challenges related to the extremely small physical scale of
fibers. Unlike fascicles, fibers are difficult to isolate [ 159 ]. If fibers are isolated suc-
cessfully, they may be damaged by the process. Furthermore, the diffraction limit of
light limits the achievable resolution of optical imaging modalities, making it diffi-
cult to study the interaction of individual fibrils in a dynamically strained fiber. Most
information regarding force transmission within fibers has been inferred from SEM
and TEM microscopy. In TEM, the distribution and shapes of fibril cross sections
have been studied, indicating both modal and bimodal distributions of fibril diameters
[ 10 , 87 , 175 ]. TEM has also been used to study the distribution of PGs (e.g., decorin)
within tendon and ligament tissue, as they have been hypothesized to play a role as
cross-linkers and spacers between adjacent fibrils [ 105 , 106 , 176 - 181 ]. Although a
number of studies have refuted their role as cross-linking agents [ 100 , 102 ], their
role as mechanical spacers may still be significant. SEM imaging has revealed that
fibrils appear to be very long and display minimal amounts of splitting, weaving, and
merging [ 93 ]. Several studies have measured the change in D-band of fibrils resulting
from macroscopic loading using synchrotron radiation and found that fibril strains
are correlated with applied macroscopic strains [ 182 ]. In order to accurately model
the force transfer within single fibers, more experimental information will be needed
regarding the morphology of fibrils (e.g., the extent of interweaving and crossing)
as well as possible cross-linking mechanisms. This will be particularly relevant for
studies that seek to understand how certain genetic diseases (e.g., Ehlers-Danlos
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