Biomedical Engineering Reference
In-Depth Information
similar levels of inlet flow. They could also explain the higher flow rates necessary
to stimulate cells in 2D compared to a 3D environment [
4
,
52
].
This brief selection of numerical studies on tissue differentiation in scaffolds
seeded with mesenchymal stem cells provides a small insight into how quantitative
engineering analyses can help understand the heterogeneity of microscopically
induced deformations with peak values significantly exceeding macroscopically
applied loads. They present a valuable tool to balance the various competing
design criteria for scaffolds in a more systematic way compared to experimental
trial and error to achieve optimal tissue growth and regeneration. The application
will dictate whether a micromechanically accurate representation of the scaffold is
necessary or whether the use of a smeared continuum treatment is sufficient.
4.3 Modelling the Bioreactor Environment: From Structure
to Function in Engineered Cartilage
4.3.1 Importance of Structure and Composition for Mechanical Fitness
While these studies demonstrate a role of models in predicting phenotypical
changes, the mechanical environment also influences the organisation of the tissue.
A biomimetic recapitulation of tissue structure has relevance for those tissues in
which the architecture is optimised for their loadbearing duties, such as articular
cartilage. Cartilage tissue engineering is based either on chondrocytes or pro-
genitor cells induced to undergo chondrogenesis and differentiate towards a
chondrocyte-like cell. The chondrocytes then synthesise cartilage specific extra-
cellular matrix components to establish a functional and viable tissue. Common
assessment of this functionality is usually based on measuring glycosaminoglycan
and collagen II content as well as performing compression tests to determine tissue
mechanical properties. Both in native and in engineered cartilage various tissue
stiffness measures have been found to correlate with the amount of these two main
components constituting the cartilage extracellular matrix. Yet, this correlation of
composition and functionality is an oversimplification and neglects the structure-
function relationships present. This becomes apparent when considering experi-
ments [
5
,
44
,
45
,
70
,
73
] that report a stiffer cartilage matrix when the constructs
were mechanically loaded during bioreactor culture than when it was kept
unloaded, but found no differences in the collagen and sulphated GAG content.
Yan et al. [
117
] investigated structure-function relations in tissue engineered
cartilage, including minor ECM components and cross-linking proteins into their
analysis. They found strong correlations between these usually omitted constitu-
ents and the mechanical properties of the constructs as well as an increase in their
concentration due to loading. They concluded that low levels of collagen IX and
mature collagen cross-linking are a major contributing factor to poor mechanical
properties of in vitro engineered cartilage. Thus it could be shown experimentally
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