The Transport of Insulin-Like Growth Factor through Cartilage - Porous Media: Applications in Biological Systems and Biotechnology - page 434

reduces the number of binding sites which then reduces the influence of bind-
ing sites in enhancing IGF-I transport under cyclic loading. Therefore, it is
important to incorporate the competitive binding in the theoretical model.

11.5 An Integrated Model of IGF-I and Mechanical-

Loading-Mediated Biosynthesis in a Deformed

Articular Cartilage
11.5.1 Introduction
In the previous sections a series of models of IGF-I transport into cartilage was
presented. Ultimately the motivation for this work was to understand how the
microenvironment of chondrocytes might be shaped, so that we could begin to
understand how chondrocytes might respond to its chemical and mechanical
environment, and to change the local ECM composition. It would seem natural
then to couple the previous model with a model for matrix biosynthesis in
response to these stimuli. This is our goal of the final section of this chapter,
though only selected aspects of matrix biosynthesis are dealt with here.
A numbers of studies have theoretically modeled the turnover of ECM
macromolecules. Sengers et al. [79] proposed a solute transport and biosyn-
thesis model for cartilage constructs by using the finite element approach.
The matrix synthesis rate was assumed to linearly depend on solute and cell
concentration. However, the model ignored the influence of IGFBPs and the
consumption of solutes by chondrocytes.
Recently, Klein and Sah [80] extended a continuum model of matrix
metabolism and transport developed by DiMicco and Sah [20] to understand
the time and spatially dependent accumulation of proteoglycan in engineered
cartilage constructs. Most importantly, the model considered the matrix
macromolecules as soluble, bound, and degraded components and investigated
the synthesis, binding, and transport behavior of each component, and their
interactions. However, without the implementation of the theory of porous
media, the model cannot describe the mechanical behavior of cartilage and
the influence of mechanical stimuli on matrix biosynthesis.
To construct or biosynthesis model first we need to briefly review some
experimental findings on IGF-I and load induced biosynthesis in cartilage. We
will see that very little is really known about the signaling pathways between
stimulus (e.g., IGF-I, mechanical loading) and the production rate of matrix
molecules. We will therefore tend to use Hill functions to connect these two
processes. Once these matrix molecules are synthesized they need to move
away from the chondrocytes and into the surrounding cartilage. Our model
will also be extended to include these processes as well. We will show that the
equations for this process are very similar to what we have already seen for
IGF-I transport.