The Transport of Insulin-Like Growth Factor through Cartilage - Porous Media: Applications in Biological Systems and Biotechnology - page 445

include a series of biological processes taking place within cartilage involv-
ing IGF transport, IGF interaction with its binding proteins (IGFBPs),
IGF and interstitial fluid flow induced matrix biosynthesis, and the trans-
port of matrix molecules. The model was validated using several indepen-
dent experimental data sets. Of particular significance was that by using
this model, all the available experimental data that is comparable, can be
reproduced using only a single set of model parameters. The results of this
new biosynthesis model show that IGF-I and mechanical loading are able
to stimulate aggrecan synthesis independently, but when applied simultane-
ously, the degree of aggrecan stimulation is greater than that achieved by
either IGF-I or mechanical loading alone. The dynamic balance of aggre-
can metabolism and catabolism in cartilage depends on the IGF-I concen-
tration in synovial fluid, and aggrecan production can be rapidly “switched
on” when the concentration of IGF-I reaches a certain threshold. This model
may prove useful in understanding normal homeostatic processes in carti-
lage, and in identifying optimal cell density distributions for ecient pro-
tein synthesis and more uniform cartilage distributions in tissue engineered
constructs.

11.7 References

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[2] Krishnan, R., Seonghun, F., Park, E., and Ateshian, G. A. (2003). Inho-
mogeneous cartilage properties enhance superficial interstital fluid support
and frictional properties, but do not provide a homogenous state of stress.
Journal of Biomechanical Engineering , 125 :569-577.

[3] Mow, V. C. and Lai, W. M. (1980). Recent developments in synovial joint
biomechanics. Siam Review , 22 :275-317.

[4] Maroudas, A. and Kuettner, K. (1990). Methods in Cartilage Research.
Academic Press, San Diego.

[5] Grodzinsky, A. J., Levenston, M. E., Jin, M., and Frank, E. H. (2000).
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Review of Biomedical Engineering , 2 :691-713.

[6] Bachrach, N. M., Valhmu, W. B., Stazzone, E., Ratcliffe, A., Lai, W.
M., and Mow, V. C. (1995). Changes in proteoglycan synthesis of chon-
drocytes in articular cartilage are associated with the time-dependent
changes in their mechanical environment. Journal of Biomechanics , 28 :
1561-1569.