The Transport of Insulin-Like Growth Factor through Cartilage - Porous Media: Applications in Biological Systems and Biotechnology - page 401

The mechanical properties of cartilage are determined, directly and indi-
rectly, primarily by the collagen and proteoglycan components [5]. Chondro-
cytes also determine cartilage mechanical properties indirectly by regulating
the cartilage composition through the synthesis and degradation of matrix
components [5]. Chondrocytes do this by responding to their chemical and
mechanical “microenvironment” [6]. Proteoglycans produced by chondrocytes
carry a strong negative charge, and the repulsion between these molecules
(electrical and osmotic pressures act in various proportions), giving cartilage
a tendency to swell and so resist compressive forces [7-9]. A collagen network
within the cartilage (which is anchored in the underlying bone) provides car-
tilage with tensile strength, and constrains the swelling of proteoglycans, and
slows the movement of the proteoglycans in the tissue. In other words, equi-
librium is achieved with the collagen in a state of tensile prestress that is
induced by the proteoglycans in a state of compressive prestress [5]. If the col-
lagen matrix is compromised (e.g., perhaps due to excessive mechanical loads
or inflammatory processes), the cartilage can swell and proteoglycans can
escape from the cartilage tissue [10]. These structural changes in the cartilage
in turn lead to excessive cartilage deformation and so an abnormal chemi-
cal and mechanical microenvironment for the chondrocytes. The cartilage is
then prone to increased rates of wear and degradation. When this occurs the
joint is said to be diseased [11,12]. Recently, it was shown that this process of
degradation can be very rapid following high-impact loads [13].
Unlike neighboring bone, articular cartilage lacks nerves to sense poten-
tially damaging loads, and also lacks blood vessels to deliver nutrients and
growth factors to the chondrocytes. As a consequence the cartilage has lim-
ited ability to repair itself. In many disease processes arising from mechanical
damage (e.g., trauma) or biochemical injury (e.g., inflammatory processes) or
both, there is a loss of proteoglycans and the cartilage degrades. When the car-
tilage wears away suciently, movement at an articular joint becomes painful,
and now a days many diseased joints are replaced with artificial prostheses
[14]. However, these prostheses require an expensive operation and all too fre-
quently fail (revision rates are currently about 15%) [15]. Alternate techniques
to treat cartilage defects include chondrocyte seeding (e.g., so-called autolo-
gous grafting [16]) and surgical damage to the subchondral bone to promote
tissue repair [17], but fibrous rather than hyaline cartilage develops in about
25% of these cases [18]. Another approach, entering clinical trials in some
countries, is growing neo-cartilage using cell-seeded scaffolds [19] though no
such “tissue engineered” solutions are yet widely accepted [5]. While some
approaches are very promising, all of them are basically a “let us try it and
see” strategy. This approach stems from an absence of a fundamental under-
standing of the physical and chemical conditions that promote and maintain
healthy cartilage tissue. It is quite conceivable that cartilage behavior is too
complex to yield to intuition alone. Instead, computational modeling, which
integrates mechanical, fluid, and biochemical processes, is essential to develop
rational methodologies for developing new treatments. Understanding quanti-
tatively the relative importance of these factors would substantially increase