The Transport of Insulin-Like Growth Factor through Cartilage - Porous Media: Applications in Biological Systems and Biotechnology - page 435

11.5.1.1 IGF-I and Mechanical-Loading-Mediated

Cartilage Biosynthesis

There are two key biosynthesis experimental results that we will use to con-
struct the biosynthesis model. An important requirement of these experimen-
tal studies is that they are all performed on similar cartilage explants, so as
to avoid variation in chondrocyte behavior due to species or animal age.
The first key experimental results were obtained by Bonassar et al. [30].
They showed that IGF-I increased both proline and sulfate incorporation
within cartilage tissue (a measure of collagen and proteoglycan synthesis)
in a dose-dependent manner. However, it is unclear exactly how IGF-I and
the presence of its complexes stimulate ECM synthesis. IGF-I may stimu-
late synthesis of cartilage matrix components, such as GAG (a component of
aggrecan) and collagen, through binding to chondrocyte membrane receptors
[63]. The binding of IGF-I to receptors is a relatively specific and reversible
process depending on time, pH, temperature, and the concentration of the
components involved [81].
It is known that in the microenvironment of the chondrocytes the mechan-
ical stimuli alone can significantly affect the synthesis and degradation rate
of matrix macromolecules [5]. Clinical research on human knee joints indi-
cated that moderate exercise helped to improve GAG content in the knee
cartilage of patients who were at high risk of developing OA [82]. Experi-
mental studies of Davisson et al. [83] on tissue engineered cartilage constructs
found that static compression diminished aggrecan synthesis whereas dynamic
loading enhanced aggrecan production. Buschmann et al. [32] measured spa-
tially localized changes of aggrecan synthesis in response to a range of cyclic
mechanical loading in bovine cartilage explants. Their results suggested that
the mechanical stimulation was dependent on the flow of interstitial fluid
induced by mechanical loading and a certain threshold of interstitial fluid
velocity. This is the second key biosynthesis experimental result upon which
the model is based.

11.5.2 Biosynthesis Model Construction
The previous sections have introduced a reactive-transport poroelastic porous
media model to investigate the coupled processes of growth factor transport
through cartilage undergoing mechanical deformation. Here the model is fur-
ther extended to include biosynthesis and degradation of matrix molecules.
The model is validated using three independent experimental data sets. It is
found that a single set of parameters can describe the experimental results.
The model is then employed to make predictions about changes in pro-
teoglycan content under a variety of conditions including free, bound, and
degraded conditions. This model may prove useful in predicting the behavior
of tissue engineering constructs, or predicting the outcome of repair processes
in cartilage.