Biomedical Engineering Reference
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125 I-IGFs (
0.003 nM) in adult bovine articular cartilage discs (3 mm
diameter
m depth), which were equilibrated in solutions for 48 hours
containing both radiolabeled 125 I-IGFs and unlabeled IGFs. Their results indi-
cate that the binding of IGFs to cartilage, through the IGFBPs, regulates the
transport of IGFs in cartilage, probably contributing to the control of their
bioavailability.
Garcia et al. [58] experimentally and theoretically studied the role of
IGFBPs on the transport and binding of IGF-I within the cartilage tissue.
125 I-IGF-I was allowed to diffuse across a 400 µ m-thick cartilage disk. It was
observed that the transport of 125 I-IGF-I was dramatically slowed by binding
of IGF-I to its IGFBPs. Garcia et al. [58] also presented a theoretical model
based on the Langmuir isotherm to predict the equilibrium binding behavior
of IGF-I. Together, the studies of Bhakta et al. [29] and Garcia et al. [58],
provide strong evidence that IGFBPs can potentially influence the transport
of IGFs in cartilage.
Recently, Barta and Maroudas [27] modeled the cartilage as a two-layer
continuum, namely a thin surface layer exposed to synovial fluid and a deeper
layer with impermeable bony endplate to study the diffusion of IGF-I, its
interaction with soluble binding protein and fixed binding sites on ECM, as
well as cell receptor binding and internalization. However, without the imple-
mentation of the porous mechanics theory coupled with reactive transport,
Barta and Maroudas's study cannot fully explore the effect of physiologically
relevant loading on IGF transport.
In this section, the basic solute transport presented in the previous sec-
tion is extended by including solute binding, and then governing equations
are particularized to the specific geometry of a cylindrical cartilage disc
undergoing unconfined axial loading with radial transport of IGF-I. Finally,
model predictions are compared with the experimental findings [29].
×
400
µ
11.3.2 Interaction between IGF-I and Its IGFBPs
The total solute concentration ( c I ) is comprised of both “free” and “bound”
solute, that is,
c I = c I + c I
(11.32)
where c I is the concentration of free (or unbound) solute and c I represents
the concentration of solute bound onto the solid phase (e.g., via binding
proteins). Both concentrations are given with respect to the overall RVE
volume.
11.3.2.1
Law of Mass Action
Assuming that IGF-I can combine with IGFBP to form an IGF/IGFBP com-
plex and that the complex can also break into its original constituents (i.e., the
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