The Transport of Insulin-Like Growth Factor through Cartilage - Porous Media: Applications in Biological Systems and Biotechnology - page 402

Solutes
(e.g., growth factors, oxygen)

Fluid & deformation

Loss

Transport

Transport & bind
to matrix structure

Binding Proteins

Competitive binding

ECM Production
Growth factors

Chondrocytes ECM Degradation

Cytokines

Enhance

Mechanical stimuli

Applied Load/Strain

Decrease

Material Properties

FIGURE 11.1
Schematic of feedback loops that control the mechanical and chemical envi-
ronment sensed by chondrocytes embedded within the cartilage matrix; these
feedback loops are at the “tissue level,” but there exists many more feedback
loops at the intercellular and intracellular levels, which enable cartilage to
perform its physiological function.

our ability to coax cartilage toward ongoing health, or to optimize the condi-
tions for cartilage repair once it is damaged.
As indicated earlier the current limitation in our understanding of car-
tilage homeostasis is largely due to the large number of complex processes
occurring simultaneously. To illustrate this point diagrammatically, some of
the key tissue level processes are shown in Figure 11.1. The transport of solutes
(e.g., oxygen, growth factors, and cytokines) to the chondrocytes (which forms
part of the chemical microenvironment “seen” by the cell), as well as the
transport of newly synthesized matrix components [20] are coupled to the
mechanical microenvironment, both directly through advective transport and
indirectly through changes in the matrix physical properties (e.g., mechani-
cal stiffness, diffusion properties, and hydraulic conductivity) due to changes
in biosynthesis of proteoglycans. The system is further complicated by the
presence of families of binding proteins, competitor growth factors, and cell
surface receptors.
Approximately, 60%-80% of proteoglycans within the cartilage are
believed to be in stable forms (i.e., effectively immobilized within the ECM)
[20]. Newly synthesized proteoglycan monomers, secreted by the chondro-
cytes, are initially mobile until the majority become bound to hyaluronan