Biomedical Engineering Reference
In-Depth Information
that basing composition-function relationships on major ECM components alone
does not provide a complete picture. The importance of cross-linking collagen to
achieve mechanically mature network has also been shown in cardiovascular tissue
engineering [
2
,
96
].
There is another key factor that contributes to tissue mechanical properties.
Several experimental studies have suggested that enhanced structural organisation
of the collagen network could contribute to the elevated stiffness values observed
in bioreactor studies [
44
,
58
,
70
,
74
]. The effect of structural alterations is however
difficult to investigate experimentally, since tissue structure is not easily altered in
a tightly controlled manner, biochemical and biomechanical alterations are com-
monly not easily uncoupled and certain structural features aside from fibre ori-
entation are difficult to quantify. However, from extensive studies on a wide range
of load bearing soft tissues, it has become apparent that the collagen architecture in
these tissues is not only optimised for the particular load bearing duties but is also
able to adapt to changes in the loading environment [
33
,
63
,
97
]. Understanding
the mechanisms of tissue remodelling will potentially allow us to design biore-
actors to control the structure and organisation of engineered tissues.
4.3.2 Modelling the Influence of the Collagen Architecture in Tissue
Engineered Cartilage
Several studies exist that model cartilage structure. Collagen remodelling
algorithms developed in the cardiovascular biomechanics field have been suc-
cessfully applied to predict the collagen organisation in tibial plateau cartilage
[
115
]. Khoshgoftar et al. [
62
] evaluated deformation fields in cartilaginous con-
structs undergoing various loading protocols: unconfined compression, sliding
indentation and combined compression-sliding indentation. Based on the predicted
strain fields the latter was hypothesised to provide the most suitable stimulation
for the development of a Benninghoff-like zonal structure in the engineered
constructs. This native cartilage architecture, in which collagen fibres arcade from
an alignment perpendicular to the articular surface in the deep zone to an orien-
tation parallel to the surface in the superficial zone, is crucial for cartilage struc-
ture-function relationships and has proven difficult to recapitulate in engineered
tissues [
64
]. The influence of postnatal collagen reorientation on the confined
compression behaviour of articular cartilage was investigated with a composition
based constitutive model in van Turnhout et al. [
112
]. Klisch et al. [
65
] developed
a cartilage growth mixture model in which proteoglycans and collagen can grow
independently of each other via volumetric mass deposition but are constrained to
move together during deformation. More advanced constitutive relations were
incorporated later on that included the balance between stresses generated by the
proteoglycans and those in the collagen network [
66
]. The model was successfully
validated against biochemical content, tissue volume and tensile moduli from in
vitro growth experiments [
66
]. The effect of collagen orientation on the equilib-
rium properties of charged and neutral biphasic tissues was investigated in Nagel
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