SURVEY ARTICLE

-.

FLUID TRANSPORT AND MECHANICAL PROPERTIES OF

ARTICULAR CARTILAGE: A REVIEW

VAN C. Mow,* MARK H. HOLMES* and W. MICH.AEL LN*

Rensselaer Polytechnic Institute. Troy. N1’ 12181. C.S.A.

.Abstract--This review is aimed at unifying our understanding of cartilage liscoelastic propertics in

compression. in particular the role of compression-dependent permeability in controllinr interstitial fluid
Ho\\ and its contribution to the observed viscoelastic etfects. During the pre\ious decade. Tt was shown that
compression causes the Frmeability ofcartilage to drop in a functional manner described by i, = !q, cxpic.~f~
u here X, and .\I were defined as intrinsic permeability parameters and E is the dilatation of the solid matrix (F
= crVu).Since permeability is inversely related to the diffusive drag coefftcient of relattve Iluid motion utth
respect to the porous solid matrix, the measured load-deformation response of the tissue must thereforealso
depend on the non-linearly permeable nature of the tissue. We have summarized in this review our
understanding of this non-linear phenomenon. This understanding of these flow-dependent viscoelastic
etTectsare put rnto the historical perspectiveofacomprehensive litcraturc rcvica ofcarlierattcmpts to model
the compressive viscoelastic properties of articular cartilage.

ISTRODKCTION mechanics, and advanced mathematics. We intend in

Diarthrodial joints, such as the knee and shoulder, are
one of the three types of joints in the human body; the
others are fibrous joints or synarthroses, which have
no relative motion (e.g. the coronal suture of the skull),
and cartilaginous joints or amphiarthroses, which have
little or no relative motion (e.g. the vertebral body-
intervertebral disk-vertebral body joints). A diart-
hrodial joint is characterized by its large degree of
motion; consequently. one of its primary functions is
to facilitate body movement and locomotion (see for
example Warwick and Williams, 1973; Sokoloff, 1978,
1980). Under normal conditions, it is an amazingly
efficient bearing system, capable of providing a nearly
frictionless performance with little, if any, wear for the
entire lifespan of the individual. Although their indi-
vidual anatomical forms and material properties vary
considerably. there are two components common to all
diarthrodial joints: synovial fluid and connective
tissue. In the latter category are articular cartilage,
meniscus, ligaments and tendons. The biomechanical
characterizations of these soft connective tissues (for
example, Hayes and Bodine, 1978; Kempson ct al.,
1971; Kempson, 1980; Wooer al., 1979,198l; MOWet
al., 1980; Roth and Mow, 1980; Lanir, 1983) and
attempts to develop dynamic interaction models
(Higginson et al., 1976; Higginson, 1978; Dowson et
al.. 1981; Mow and Lai, 1979, 1980; Collins, 1982) are
currently active areas of interdisciplinary research,
incorporating concepts from biochemistry, continuum
Re~riwcl IS MOJ 1983: in rehwf jorm 7 fkwmhrr 1983.
*Department of Mechanical Engineering. Aeronautical
Engineering and Mechanics.
+Depnrtment oi Mathematical Sciences.
377
this article to review some of the experimental and
theoretical research projects we have pursued over the
past decade and to discuss some of the unresolved
questions in the study of the structure and function of
just one of the major connective tissues of the joint:
articular cartilage. In particular. we intend to focus on
the role of the non-linear permeability function in
controlling the rate of interstitial fluid flow. which in
turn governs the biphasic compressive viscoelastic
properties of the tissue. Reviews of work on synovial
fluid can be found in Lai cr al. (1978) and some of the
dynamic interaction problems that may arise within
diarthrodial joints between cartilage and synovial fluid
can be found in Mow and Lai (1979, 1980).
Articular cartilage is a white, dense, connective
tissue, from 1 to 5 mm thick, that covers the bony
articulating ends inside the joint. In biomechanical
terms, it is a multi-phasic, non-linearly permeable,
viscoelastic material, consisting of two principal
phases: a solid organic matrix, which is composed
predominately of collagen fibrils and proteoglycan
macromolecules, and a movable interstitial fluid phase,
which is predominately water (Linn and Sokoloff,
1965; Venn and Maroudas, 1977; Muir. 1980;
Armstrong and Mow, 1982a.b). The importance of the
integrity of the tissue in maintaining the health of the
joint and of the deformational characteristics of the
tissue as a whole has been appreciated for over at least
half a century (Hirsch, 1944; Sokoloff, 1969; Mankin.
1974; Muir, 1977; Schofield and Weightman, 1978;
Moskowitz rt al., 1979). However, only recently has the
importance of the role of the movement of interstitial
fluid through the porous matrix and the subsequent
interaction of the interstitial fluid with the porous solid
378 VAN C. Mow, MARK H. HOLMES and W. MICHAEL LAI

matrix in controlling the deformational characteristics

of the tissue as a whole been established (Maroudas,
1975a.b; IMOWrt ul., 1980; Holmes et n/., in press).
Principally, the fluid movement plays a fundamental
role in: (1) the biological processes by augmenting the
transport of nutrients into, and of waste products out
of, the tissue (Ekholm and Norback. 1951; Maroudas
er al., 1968; McKibbin and Maroudas, 1979; Honner
and Thompson, 1971; Salter et al., 1980); (2) the
deformational processes by controlling the mechan- Inters*i:tY 1’ ‘Proteogiycan
ism, through a non-linear interaction process, of the Water - Asregates

rate of fluid transport through the deforming tissue

Fig. 1. Schematic representation of articularcartilage depict-
(Maroudas, 1975b; Mansour and Mow, 1976; Lai and ing a porous, composite organic solid matrix swollen with
Mow, 1980; Lai et al., 1981; Mow YI al., 1982); and water. The major organic components of the matrix are
(3) the functional processes by providing the lubricant collagen fibrils and proteoglycrtn aggregates (Mow and Lai,
for the conformational gap between the articulating 19801.
surfaces of the joint, through exudation and imbibition
caused by the deformation of the tissue during joint
articulation (McCutchen, 1962, 1978; Malcom. 1976;
Torzilli and Mow, 1976a,b; Armstrong and Mow,
1980; Dowson et al., 1981; Collins. 1982; Mow and
Mak, in press). The portion of cartilage mechanics that
we will review here will be those derived from com- 30 I- .:~:0,,5+022* -I
35

pressive theory describing the behavior of articular

cartilage.
Recent advances from these investigations have
codified the various roles of interstitial fluid movement
on the various compressive responses of the tissue.
These fundamental and simple concepts may now be
summarized in a coherent manner to promote an
understanding of the role of interstitial fluid flow
through articular cartilage, or any other biphasic tissue
(meniscus, nasal cartilage, ligaments, etc.), under a
more complex deformational field. Thus the objective
of this review is to provide a comprehensive elucid-
ation of the role of interstitial fluid flow in controlling Fig. 2. Variation of porosity C;,’YTand solid content V,/ V,
the compressive deformational characteristics of carti- with depth from the surface. Note that the top 204; of the
laginous tissues. tissue has the most fluid (Lipshitz er at.. 1976).

COMPOSITION AND ULTRASTRUCTURE OF ARTICULAR

CARTILAGE
As a biomaterial, articular cartilage may be consid-
ered as a porous composite organic solid matrix
swollen by water, Fig. 1. In the water, a variety of
mobile electrolytes, which maintain the charge neut-
rality condition of the ionized proteoglycan aggregates
of this matrix, are distributed (Sokoloff, 1963;
Schubert and Hamerman, 1968; Maroudas, 1970). The
interstitial concentrations of the counterions and ions
are governed by the Donnan equilibrium concept
(Maroudas, 1970, Urban et al., 1979). The specific
composition of cartilage varies with joint age and the
topographical and depth location in the joint, as well as
with the specific type ofjoint (Venn, 1978; Muir, 1980).
In normal adult cartilage, the fluid content makes up
approximately 85 o/0of the total mass by wet weight in
the most superficial 25% of the cartilage, and then
decreases in a nearly linear manner to about 70 7: at the
subchondral bone (Lipshitz et al., 1976a), Fig. 2.
Pathological conditions can also have a significant
effect on the water content ofcartilage. For example, in
osteoarthritic human cartilage, the water content is
above normal (Ballet and Nance, 1966; Maroudas,
1976,1979; McDevitt and Muir, 1976; Armstrong and
Mow, 1982a.b)and the water concentration is higher in
the central region of the tissue rather than in the
superficial zone (Venn and Maroudas, 1977; Venn.
1978). This increase of water content has been found to
be the earliest observable change in tissue in animal
models of osteoarthritis (McDevitt and Muir, 1976)
and this increase has been correlated to the observed
decrease of the compressive equilibrium modulus in
animal models as well as in human autopsy materials
from aging joints (Armstrong and Mow, 1982b).
The largest component of the organic solid matrix is
collagen (Muir, 1980). Cartilage collagen, which ac-
counts for about half of the tissue mass by dry weight,
occurs in a highly specific ultrastructural arrangement,
forming four principal layers (McCall, 1968; Clarke,
 Properties 0i articular cartilage: a rsbleu 3-9

minoglycans are relatively short chains of repeatmg

disaccharide units of sulphated hexosamines. In car-
tilage. proteoglycans are bound to a linear chain of
hyaluronic acid to form an enormous aggregate with a
molecular weight of up to 2 x 10R and a length of
approximately 2 pm (Hardingham and Muir, 1974:
Rosenberg t’l (II.. 1975). It appears that most of the
proteoglycans in normal cartilage are in these aggre-
gated forms. However, in aging and diseased tissues.
the molecular architecture of this aggregate is altered
in a number of ways (Brandt and Palmoski. 1976:
Fig. 3. Representation of collagen tibril ultrastructure
Muir, 1977).
throughout the depth of the cartilage depicting the distinct
idwlized zones: (a) a superticial tangential zone composed of
Jen\i‘j packed collagen ribrils in sheets parallel to the surface. PHYSICOCHE~IICAL BASIS OF FLUID FLOQ ASD
tb)n randomly arrayed middle zone with abundant inter- C.~RTIL.\GE DEFORSIATIOS
tibrlllar space to accommodats the proteoglycan and water.
and ICI~ radial deep zone where collagen tibrils appear to
In normal adult cartilagc.collagen is woven together
snactomose into larger bundles as they insert into thecalcified
zoner. The cartilage. i.e. the non-calcified and calcified zones, to form a fibrous network in which the huge pro-
rests upon a stitl’ subchondral plats supported by the soft teoglycan aggregates are trapped. Together they form
wnceilous-marrow composite structure (Mow er [I/., 1974). a cohesive porous composite organic solid matrix. The
collagen network is characterized by its great tensile
197-l: Mcachim and Stockwell, 1979). The superficial stiffness (Kempson et (II., 1973; Woo er rll.. 1976, 1979.
tangential zone, which is near the articular surface. 1980: Roth and Mow, l980), but due to the high
consists of sheets of tightly woven collagen fibrils slenderness ratio of each segment of the collagen fibril.
(Mow ef ~1.. 1974; Clarke, 1971, 1974; Ghadially et al., the network is relatively weak in compression. It also
19761. This region accounts for the highest concentra- has a negligible net charge density at neutral pH
tion of collagen. Based on recent X-ray diffraction (Bowes and Kenten. 1948). On the other hand, the
studies (Aspden and Hukins, 1951) and polarized light proteoglycans contain a high concentration of fixed.
and electron microscopy studies (Bullough and negatively charged groups, giving them a propensity to
Goodfellow. 1968; Sprerand Dahners, 1979), the fibers expand and occupy a large solution domain. Since
on the surface seem to be aligned to the split-line these macromolecules are enmeshed in the collagen
patterns.* The tibers of the middle zone, on the other matrix, which prevents them from reaching their fully
hand. are randomly oriented and homogeneously extended solution volume, their closely spaced charged
dispersed. In the deep zone the fibers come together to groups, 5-15 A, together with the high concentration
form larger. radially oriented fiber bundles. These of freely mobile counterions in the interstitial fluid
bundles enter the calcified zone. crossing the tidemark. (Donnan osmotic pressure), endow the tissue with a
to form an interlocking network that anchors the high capacity to swell and gain or lose water when the
tissue to the bony substrate, Fig. 3. external ionic or mechanical environment is altered
The major noncollagenous components of the solid (Schubert and Hamerman, 1968; Pasternack rf ul..
phase of articular cartilage are proteoglycan macromo- 1974; Maroudas, 1976.1979; Hascall, 1977; \low et al..
leculss, which in normal adult cartilage make up 1981; Grodzinsky YItrl., I98 I; Myers et (II.. in press a.b).
approximately 2&30”, of the total dry weight of the In human femoral heads, it has been estimated that the
tissue. However, unlike the collagen and water content, internal osmotic pressure can range up to 0.2 \IN m _ ’
the percentage of proteoglycans is lowest near the (Maroudas, 1979). At equilibrium, this swelling force is
articular surface and increases with depth. These balanced by the tensile strength of the surrounding
macromolecules consist of a protein core on which collagen matrix. Consequently, even in an unloaded
50-100 glycosaminoglycan chains are bonded (Muir, state, the in sifu collagen network of articular cartilage
1950: Buckwalter and Rosenberg, 1982). The glycosa- is under a tensile prestress (Maroudas, 1976).
The hydrophilic nature of the proteoglycans and the
*The oreanization of the collagen fiber network of ar- architecture of the collagen network give the tissue its
titular cartilnee has been of interest to scientists for a long micro-porous characteristic. Very little of the water in
time. Early rn-icroanatomists believed that the extracellular cartilage is intracellular, and a sizable amount of this
substance of the tissue was homogeneous. Hultkrantz (1898)
water, about 30 00, appears to be associated with the
demonstrated the regular split-line patterns on the articular
buriaces by puncturing them with an awl. The appearance of
collagen fibrils (Torzilli rl (II., 1992). Therefore. most of
this regular array of’split lines’on the surfaceofcartilage was the water is in the intermolecular space and is free to
taken as ebidrnce of the surface collagen fiber ultrastructure. move through the tissue. The ‘pores’ through which it
Tncnty-seven years later. BenninghotT(l925)used these split Rows have been estimated to have a diameter of
lincsand pol,irired light techniques to investigate thearrange-
- 60A (McCutchen, 1962); the derivation of this
ment of the collagen fibers and the whole tissue. From this he
postulated the well-known ‘arcade’ theory of collagen fiber estimate will be concisely described below. The hy-
architecture. draulic permeability of the tissue, as well as the
380 VANC. Mow. MARK H. HOLMES and W. MICHAEL LM

aggegate equilibrium compression modulus, are

.
highly dependent on both the water content and the
uranic acid content, hence providing the physicoche-
mica1 basis for the observed decrease of the tissue
permeability with increased compression (Maroudas,
1975a.b; Mansour and Mow, 1976; Armstrong and
Mow. 1982a), Figs 4a-d.
During compression, as the mmhanical strain in-
creases, the concentration of the organic material and
the charge density both increase, since the interstitial
fluid is forced to flow from the matrix. A new
equilibrium state is reached when the charge density,
collagen tension and applied load are in balance. It is
generally believed that this equilibrium compressive

O70 75 80 95 90 95 100

WATER CGNTENT (Z’

Fig. 4(c). Variation of apparent permeability in m’:N’s

units as a function of native uater content of aging human
patellar specimens (Armstrong and Liow, 1982a).

0 01 02 OS
Fixed-charge density (m equiv./cm5)

Fig. 4(a). Variation of permeability in cm’sg-’ units as a

function of tixcd-charge density in m equiv. cm-” of the tissue o,
(Maroudas. 197Sb).

0
.o 75 80 @5 90 35 100
‘NAT’R CiVEFIT (7.)

Fig. 4(d). Variation of intrinsicequilibrium modulus in MPa

units as a function of native water content of aging human
patellar specimens (Armstrong and Mow, 1982a).

stiffness of the tissue is derived from the Donnan

osmotic effect associated with the closely spaced,
negatively charged sulphate and carboxyl groups on
the glycosaminoglycans. as well as from the resistance
to bulk compression of the neutral composite
proteoglycan-collagen solid matrix (Maroudas,
1975b; Parsons and Black, 1979; Armstrong and Mow,
1982b; Myers and Mow, 1953). The ‘flow-independent
shear rigidity’ of cartilage is derived from the collagen
fibriis that apparently carry the tensile stress rendered
3 90 80 m 60 55 by the spatial nature of the collagen ultrastructure
Cortiloge hydration expressed within the tissue when it is sheared, Fig. 5 (Hayes and
OS % of initiol weight Bodine, 1978; Mow et al., 1982, 1983). Because the
Fig. 4(b). Variation of permeability in cm3 sg-’ units as a
proteoglycan aggregates alone do not provide signili-
function of hydration as percentage of initial weight of the cant shear resistance, they must interact with the
tissue (Maroudas, 1975b). collagen network to produce a solid matrix with
 Properties of articular
Fig. 5. Schematic depiction of functional role of collagen
tibrils in resisting the shear deformation of a unit block of
articularcartilage. The existence ofa composite solid matrix is
nccessar); for the collagen fibrils to play an active role during
shear.
sufhcient shear strength (Armstrong et al., 1981; Mow
er LI/.,in press 1983). Similarly, the tensile stitfness of
cartilage is derived primarily from the intrinsic col-
lagen fibril properties. the strength of collagen cross-
linking. and, secondarily, from collagen-proteoglycan
interactions. These equilibrium behaviors are ‘tlow-
independent’. When interstitial fluid flow becomes
significant, the frictional drag or diffusive resistance of
relative fluid flow causes the observed flow-dependent
viscoelastic effects, i.e. creep and stress relaxation. In
compression, it has been shown that this biphasiceffect
is the dominant mechanism responsible for the ob-
served compressive viscoelastic behavior of cartilagin-
ous tissues (Mow er al., 1980, Lai et ~1..198 I; Holmes rr
LJ., in press).
From the discussion of these rather simple notions,
it is apparent that the general deformation of articular
cartilage is very complex, involving the mechanical
entanglement of collagen and proteoglycan, the tensile
resistance of the collagen network, the compressive
resistance of the proteoglycans, and the diffuse resist-
ance generated as the fluid flows through the matrix.
The details of the internal equilibration mechanisms
between the collagen network, proteoglycan swelling
pressure, and fluid flow are presently largely un-
resolved, although some progress has been made in the
last few years (Maroudas, 1979; Mow et al., 1980;
Grodzinsky er ol., 1981). In this review we intend to
present some of the findings concerning the role of
interstitial fluid flow in cartilage deformation and, in
particular, the non-linear interaction between cartilage
deformation and interstitial fluid flow as it is man-
ifested in the non-linear, intrinsic permeability
function.
The physicochemical characteristics of the counter-
ion within the interstitial fluid, e.g. valency and concen-
tration, also have a significant effect on the response of
articular cartilage to imposed stresses and strains. For
example, an increase of interstitial Na’ concentration
causes a charge-shielding effect on the closely spaced
( - 5-I 5 A) anionic groups on the glycosaminoglycans.
This, in turn, can cause the proteoglycans to contract
from their extended solution volume (Pasternack et al.,
1974). Macroscopically, this results in a measurable
cartilage: a review 381
shrinkage in tissue size and a decrease m tis,ue mass
caused by the decrease in tissue hydration, %loreover.
recent experimental and theoretical evidence shows
that the modulation of intra- and inter-molecular
electrostatic repulsion forces among the proteoglycan
charge groups (Mow and Lai, 1980), and or disruption
of collagen-proteoglycan electrostatic interactions
(Muir, 1980) by changes in the counterion environ-
ment in the interstitial fluid. can atfcct compressive
(Sokoloff, 1963; Maroudas. 1979; Parsons and Black.
1979) tensile (Kempson. 1980; Myers t’r LJ.. in prrsh
a-b), and shear (Hayes and Bodine, 1978; Mow t’t tr!.,
1983) properties of the tissue. It is clear from these
studies that both the movement of interstitial fluid and
the rates of ion transport in cartilage arc of predomi-
nant importance in the functioning of the tissue.
FLL’ID FLOH: SLTRITIO\
The importance ofinterstitial fluid flow. particularly
as it affects the nutrition of cartilage, was appreciated
as early as the nineteenth century. Later the role of
fluid flow was more popularly expounded by
Benninghoff (1924.1925)and by Ekholm and Norback
(1951). However. even though there was a great deal of
speculation that the deformation of cartilage was
strongly influenced by the exudation and imbibition of
interstitial fluid, its exact role was not understood in
the early studies on the elasticity of cartilage (Bsr,
1926; Giicke, 1927: Hirsch, 1944). For example. Hirsch
conjectured that the ‘circulation of tissue juices’ de-
creased as the cartilage lost its elasticity. thereby
reducing the mechanism for its nutrition. At the same
time, he could not explain why he obtained a creep-like
response and an incomplete recovery in his indentation
tests of cartilage, giving rise to a phenomenon which
became known as ‘imperfect elasticity’. He apparently
did not realize the importance of the exuded fluid that
he observed on the articular surface around the
indenting probe. Nevertheless, Hirsch hypothesized
that there should be a strong connection between
mechanical strain and tluid Row, being aware of the
ideas of Hildebrand (1921) and Policard (1936) that
fluid movement can be induced from a ‘suction and
pressure effect’ of repeated loading of the cartilage
surface.
The role of a pumping mechanism for the transport
of nutrients through cartilage has been questioned by
Maroudas et a/. (1968) and by McKibbin and
Maroudas (1979). During their intermittent compres-
sion experiments, they found that the penetration of
methylene blue into cartilage is no more than they
believed would be expected from simple diffusion with
no intermittent compression. Consequently. they con-
cluded that for small solutes, such as glucose. diffusion
is the controlling mechanism, whereas a mechanical
pumping action probably governs the transport of
solutes of a larger molecular weight. such as serum
albumin. One of the arguments used in support of a
382 VAN C. Mow. MARK
pumping mechanism is that when the joint is in-
capacitated, so there is no rhythmic stressing, the
cartilage shows signs of degeneration (Honner and
Thompson. 1971: Salter et al., 1980; Brandt. 1981).
However. there is also the possibility that the synovial
fluid ‘stagnates’ at the articular surfaces in such a
situation, thereby reducing the nutrients available for
transport by diffusion. The experimental evidence to
date supports the fact that low molecular weight
solutes are transported by simple diffusion, but there
has not yet been a complete coherent theoretical
analysis to assess the relative importance of the
mechanical pumping effect vs the ditfusive transport
mechanism for cartilage (Lai and Mow, 1978).
CONTISL’USl ~IODELISC OF ARTICULAR CARTILAGE
Single phase: elastic
In studying the deformational characteristics of
articular cartilage under mechanical loading, one of
the central concerns has been the determination of the
‘elastic modulus’ of this thin layer of tissue at the ends
of the bone in a diarthrodial joint. Because of its
anatomical form and its thinness, the indentation
experiment was the choice of many investigators
(Hirsch, 1944; Sokoloff, 1966; Kempson et al., 1971;
Colctti et al., 1972; Hayes et al., 1972; Hori and
Mockros, 1976). The first attempts to find the Young’s
modulus usually involved the application of the Hertz
solution for the contact between two elastic bodies of
infinite depth. Although the justification for this is
usually vague, Hirsch (1944), who was aware of the
possible influence of the multiphasic nature of car-
tilage on its deformational characteristics, justified his
analysis on Gildemeister’s (1914) work on the contact
between gels.
Another approach was taken by Sokoloff (1966),
who considered cartilage to be comparable, in terms of
its mechanical response, to medium-hard rubber. For
this latter material, the ‘mean instantaneous deforma-
tion’ is apparently not very sensitive to the thickness if
it is thick enough, in this case more than about 2 mm
(Livingston rr a[., 1961). Since the cartilage specimens
used by Sokoloff were approximately 3 mm thick, he
assumed that the Young’s modulus E for cartilage
could be determined from the relation
P
E (1)
=2.67w,a1
where P is the constant applied load, we is the depth of
penetration, and a is the radius of the plane-ended,
cylindrical indenter. This comes from the solution of
the elastic punch problem for a linearly elastic medium
of infinite depth at equilibrium and with a shear
modulus of
P(1 -v)
/L=p.
4W, a
In his analysis, Sokoloff further assumed cartilage is
H. HOLMES and W. MICHAEL LAr
incompressible, so v = 1,‘2and E = 311.Inserting these
values into equation (2). one obtains equation (1) used
by Sokoloff for E. From this. for human patella.
Sokoloff found the ‘instantaneous Young’s modulus’
(which uses w,, at 0.S s after application of the load) to
be 2.28 MPa. Also. the’equilibrium Young’s modulus’,
which uses we at one hour, was found to be 0.69 MPa.
Moreover, he observed that the deformation of ar-
ticular cartilage was non-linear, even for strains of
IO 9,. which is contrary to the basic assumptions
employed in deriving the expressions for E and /I, i.e.
equations (1) and (2).
The analysis for a plane-ended, as well as for a
spherical-ended, indenter on a layer of linearly elastic
material attached to a rigid foundation was carried out
by Hayes et al. (1972) and by Hori and Mockros (1976).
Using the approach of Lebedev and Ufliand (1958) of
reducing the problem to the inversion of a Fredholm
integral equation of the second kind. Hayes it al. were
able to determine the displacement field of the elastic
layer at equilibrium. For the case of a plane-ended
indenter, the Young’s modulus was found to be given
as
E _ P(l -G)
2w,ai(a, h, v) ’
where the function K comes from the solution of the
integral equation. From their analysis. Hayes et al.
concluded that the depth of indentation is very sensit-
ive to the aspect ratio, a/h, since the radius of the
indenter is less than the thickness in most indentation
tests, Fig. 6. To illustrate, with the assumption that
cartilage is incompressible, it can be shown that for
cartilage on a rigid foundation, the instantaneous
Young’s modulus was 30 :,, less than that calculated by
Sokoloff. This shows that in Sokoloff‘s calculations,
the stitfness of the underlying bone was lumped into
the cartilage stiffness, giving an erroneously high
Young’s modulus value (Mow er al., 19S2).
Singlr phase: rkcoelasric
The assumption that cartilage is purely elastic
applies, at best, only at equilibrium because there
Subchondral
Bone
Fig. 6. Representation ofa plane-ended indenter applied to a
thin layer ofarticular cartilage. Cartilage has been modeled as
a single-phase elastic medium (Sokoloff. 1966). a layered,
single-phase elastic medium (Hayes et (II.. 1972: Kempson et
(2)
NI., 1979). a single-phase viscoelastic medium (Coletti er ul..
1972; Parsons and Black, 1977). and a layered, biphasic
medium (Mow rr al.. 1991t.
 Properties of articular
would bc no dissipative et%ct due to the movement of
the interstitial fluid. However, it was not until the early
1960’s that the systematic study of the role of fluid flow
on the function of cartilage actually began. Elmore e’t
al. ( 1963). in one of the Hurststudies, showed that the
creep response observed in the indentation testing of
cartilage is largely due to the eRlux of interstitial fluid
from the tissue. Their obsenation resolved the prob-
lem of the ‘imperfect’ elasticity of cartilage that had
been observed 3Oyr earlier by Hirsch. They also
observed that after removal of the load, complete
recovery occurs only if the fluid is present to enter the
cartilage. This study was extended by Linn and
Sokoloff (1965), who correlated the magnitude of the
creep response and the amount of fluid exuded from
the tissue. and by Sokoloff (1966). who studied the
topographical variations of these properties. This
latter problem has also been examined by Hirsch
(1944). Kempson er ol. (1971). and Cameron t’r 01.
(1975). While most investigators had by then realized
that interstitial fluid flow is intrinsically linked to
cartilage deformation, no theoretical attempts were
made to consider these effects in a continuum model.
Most investigators, except Torzilli and Mow (1976a.b)
continued to use single-phase viscoelastic models to
describe the compressive creep response of cartilage.
In the indentation tests of cartilage, after a sudden
application of static load, a rapid compression takes
place which is followed by a slow creep process toward
equilibrium over the next 60 min or so. One method
used to account for this is to use a lumped-parameter,
single-phase, spring-and-dashpot, viscoelastic model
without regard for the interstitial fluid flow and
internal redistribution of the organic matrix and the
compaction within the cartilage specimen (Camosso
and Marotti, 1962; Hayes and Mockros. 1971; Coletti
ZI al., 1972; Parsons and Black, 1977, 1979).
Kempson (‘Ial. (1971,19SO), in examining the results
of their indentation experiments, used an expression
for what they refer to as a ‘two-second creep modulus’
for cartilage, based on a study by Waters (1965) on the
indentation of thin sheets ofvulcanized natural rubber.
The latter assumes that the classical Hertzian solution
for a semi-intinite elastic layer can simply be multiplied
by an appropriate dimensionless function to account
for a tit-rite depth. For a plane-ended indenter, he
concluded that
(4)
where 4 was determined experimentally. This result is
functionally equivalent to equation (3), but this empi-
rical approach says nothing about the displacement
tield of the elastic layer and little about physical
constraints, such as boundary conditions. In any case,
from the measurement of the indentation, two seconds
after application of the load, Kempson used equation
(4) to determine E. The resulting value, the’two-second
creep modulus’, is supposed to include the initial elastic
response as well as a small portion of the creep. This is,
cartilage: a review x3
however. inconsistent with the equilibrium condition
used to derive equation (4). and it clearly violates the
assumption that the material is purely elastic. Further,
the expression is quite sensitive to the Poisson’s ratio.
see equation (3). and had to be guessed at in order to
calculate E from equation (4). It is not surprising that
Simon (1971). from his indentation tests on canine
tibia1 cartilage, obtained inconsistent results using the
‘two-second creep modulus’ concept. A similar diff-
culty was encountered by Hori and Mockros (1976) in
using equation (3); they found there was considerable
dispersion in their values for E. which they suggested
was due to the non-linear, anisotropic and inhomoge-
neous nature of articular cartilage. This type of
analysis has been extended by Parsons and Black
(1977) to include linear viscoelasticity, using a genera-
lized Kelvin model to describe the transient portion of
the creep curve under a constant indenting load. The
concepts of ‘unrelaxed and relaxed modulus’ were
introduced to determine the instantaneous and
equilibrium values of the modulus using equation (3)
where the Poisson’s ratio was assumed to be 0.4. With
appropriate reinterpretation (Mak PI al., 1987; Mow YL
al.. 1982). these unrelaxed and relaxed moduli can be
used to estimate the intrinsic elastic moduli of the solid
organic matrix of the biphasic model for cartilage of
Mow et al. (1980) without an a priori assumption on
the value of the Poisson’s ratio. The retardation
spectrum also can be reinterpreted to yield the perme-
ability of the solid matrix. Thus we see that the
evolution of our understanding of cartilage deforma-
tion, experimental and theoretical, leads us naturally
into a multiphasic model for the tissue.
A comprehensive application of viscoelastic theory
to cartilage in tension has been made by Woo er al.
(1979, 1980). From their experiments on the stretching
properties of articular cartilage, they developed a
quasi-linear viscoelastic model, which assumes that the
kernel of the stress-strain-history integral is a function
of strain and time. This is similar to biomechanical
models for other types of soft tissues (Fung, 1981).
From it Woo er al. found that they could accurately
predict the relaxation and cyclic behavior, but at the
same time, they were unable to obtain a reasonable
value for the elastic stress if the strain rates were low.
At higher strain rates. the biphasic viscoelastic effects
would begin to dominate, and the movement of
interstitial fluid must therefore be taken into account.
Recently, Li er al. (1983) produced experimental
evidence, which correlated well with a biphasic analysis
of cartilage strips in tension, that interstitial fluid flow
could be important if the strain rates of the tensile
experiment are sufficiently high, Fig. 7.
Mulliphnsic theories
It is apparent from experimental results. such as
those obtained from indentation tests, that the move-
ment of the interstitial fluid plays a fundamental role in
the dynamic deformational behavior of the tissue. In
other words, to obtain a realistic rheological model for
3Y4 VAN C. i%tow.MARK H.
c fluid phase and the solid phase, and ps is the apparent
LONGITUDINAL STRAIN (%I
Fig. 7. The stress-strain data for superficial-zone articular
cartilage at three difkrent strain rates. The strain rate and the
number of specimens tested at each strain are shown on the
figure. Those data are for the small-strain region. For small
strains, the biphasic model predicts that the load per unit area
on the specimen is
2 = h2F:
A
irE
’
+
-4
k,H,
where E, and II, are the Young’s
A0 - c’ A, exp( -2,2”2 ~~k,,r/h*)
“=I
modulus and aggregate
modulus of the solid matrix and k, and h are the specimen
permeability and thickness. respectively. and
A ,, . A,. and sI,are constantsdependent on the moduli
of the solid matrix (Li et al.. 1983).
biomechanical studies on articuiar cartilage. it is
necessary to account for the fluid component as a
distinct phase of the system within the tissue. This
means that, at the very least, cartilage should be
modeled as a biphasic (two-phase) material, with the
solid matrix and the interstitial fluid as the two phases.
This point of view has been taken by a number of
investigators such as Fessler (1960). McCutchen
(1962), Zarek and Edwards (1964), Torzilli and Mow
(1976a.b). and Higginson cl al. (1976). It should be
pointed out that even though a two-phase model is
adequate for the description of the motion found in
most mechanical testing done so far, a more involved
model of articular cartilage would be multiphasic,
taking into account the influence of the mobile elec-
trolytes and the collagen-proteoglycan solid phase as a
fiber-reinforced composite porous matrix (Myers et
(II., in press).
A biphasic model for articular cartilage was begun
by Torzilli and Mow (1976a.b) and extended by MOW
and Lai (1979) and Mow et al. (1980). based on the
mixture theory of Craine et al. (1970) and Bowen
(1976). In essence, this model depicts articular cartilage
as a soft, porous and permeable, elastic solid filled with
water. Assuming that both phases are intrinsically
incompressible, the continuity equation for this binary
mixture is
divv’+cxdivv”+rl(v’-v/)-grad
where v’ and v” are, respectively, the velocities of the
HOLMES and W. MICHAEL LAI
density of the solid. The coeRicient z is defined as the
solid content, which is given by the ratio of solidity
r’,/ C; to porosity C;/ C; of the tissue. Here I’,. C’,.and
V, are the solid, fluid and total volume of the tissue,
respectively. The momentum balance equations for the
two components of the mixture. omitting inertial
forces, are
divd-k’(v’-vyl) = 0, @a)
and
div 0’ + K (9 - vJ ) = 0. (6b)
where d and u/are the apparent stress tensors for the
solid and fluid phases, respectively. The second term in
equations (6) represents the diffusive drag arising from
the relative velocities between the fluid and solid
components. Even in the unloaded state, the diffusive
coefIicient K has values on the order of 10L5N .s rnmS,
which helps explain why the inertial terms are omitted
in equations (6). Under slow flow conditions, the
diffusive coefficient is related to the permeability k of
the tissue by the inverse relation (Lai and MOW, 1980)
k=----
1
(1 +a)*K’
In the simple version of the biphasic theory used to
A,, model articular cartilage, known as the KLM model
for cartilage, the solid phase is assumed to be isotropic
and linearly elastic, and the interstitial fluid is inviscid
(Mow and Lai, 1980). Accordingly, assuming small
strains, the isotropic stress-strain relationship for the
first order theory for the solid phase is
d = - apl + i.,eI + Q,e, @a)
and for the fluid phase it is
flf = -PI, (W
where p is the apparent fluid pressure, A,, pr are the
intrinsic elastic moduli of the solid matrix in the
mixture, and e is the infinitesimal strain tensor describ-
ing the deformation of the solid matrix. It is also
assumed that the tissue is spatially homogeneous, SO i.,
and y, are constants.
Because of the generality of the formulation of this
biphasic model, other terms can be included in the
linearized constitutive laws, equations (8). which can
incorporate, for example, a viscoelastic solid matrix,
diffusive couples and capillary forces. Also, the iso-
tropic case is presented here, but formulae for the more
general case of biphasic anisotropic stress-strain laws
can be found in Mow and Lai (1979). These extensions
are important to remember because the assumptions of
the linear KLM model are only approximately correct.
For example, cartilage appears to have a significant
anisotropic structure, as manifested by the split-line
patterns and anisotropic tensile properties (WOO ef a!..
1976; Kempson, 1980; Roth and Mow, 1980). Also, it
has been found that in shear the organic solid matrix is
In p’= 0, (5)
slightly viscoelastic (Hayes and Bodine, 1978; MOW et
al., 1982). So a more accurate model of articular
 Properties of articuhr cartilage: a review
cartilage would have to include terms to describe the
mtrinsic viscoelastic behavior of the solid matrix.
However, in compression the predominant mechanism
giving rise to the observed viscoelastic behavior of
cartilage appears to arise primarily from the diffusive
drag caused by the interstitial fluid flow through the
solid matrix, and depends only secondarily on the
v iscorlastic properties of the solid matrix itself. In fact.
we have found that the linear KLM theory can
adequately describe the observed creep and stress-
rslaxation behavior of articular cartilage and nasal
cartilage, as well 3s meniscus. under isothermal and
constant electrolytic conditions (Mow and Lai. 1980;
Mow er al.. 1980; Mow and Schoonbeck. 1982;
Favenesi t’r (11.. 1983).
PER%lE.ABILITY
The permeability of the tissue is a macroscopic
measure of the ease with which fluid can flow through
the matrix. One of the first studies of permeability was
made by McCutchen (1962). who examined the uni-
axial compressive properties of cartilage by creep-
testing cylindrical plugs of bovine shoulder cartilage.
For the surface layer, he found the average value of the
permeability to be 5.g x IO-” mJ/N.s and he ob-
served a decrease in the permeability with depth from
the articular surface. This dependence on depth was
also examined by Maroudas t’t al. (1968). who found
the permeability for human femoral condyle cartilage
to increase from the supcrticial region to the middle
region by about 35 “,,. then to decrease from the middle
region to the deep region of the tissue by about X0”,.
This inhomogeneity has been attributed to the dense
network ofcollagen fibers in the superficial zone (Muir
cr a/., 1970) and to the increase in charge density in the
deep zone (Maroudas rr al., 1969). In fact, Maroudas
(1975b) found that the decrease of permeability below
the surface layer correlates significantly well with the
observed increase of the fixed-charge density, Fig. 4a.
This dependence of the permeability on the ionic
content of the bathing solution was first demonstrated
by Edwards (1967) on cartilage from the hips of dogs.
He found that by increasing the ionicconcentration. by
changing from normal saline to normal Ringer’s, the
permeability increased by a factor of about three. The
dependence of the permeability of articular cartilage
c-n the compressive strain in the tissue was first shown
by Mansour and Mow (1976). More recently, ad-
ditional data were obtained, and this compression-
strain-dependent permeability was shown empirically
to depend on the applied compressive strain and the
applied pressure gradient in an exponential manner,
Fig. 8. It was found that there is a non-linear decrease
in the permeability with increased compressive strain,
which leads to a significant reduction in the ability of
the fluid to flow through the matrix. This latter
measurement was a simple mechanical method to
verify the correlation of permeability to fixed-charge
density obtained earlier by Maroudas er al., since with
$85
compression. the fixed-charge density of the tissue
increased while the permeability decreased.
The approach in all these studies of cartilage
permeability is basically the same. Fluid is forced to
flow through a cylindrical disc of cartilage that has
been removed from the bone by applying a direct fluid
pressure P,, across the tissue. For a one-dimensional
flow through a sample of thickness h, the apparent
permeability k0 measured in these permeation experi-
ments is determined from the empirical Darcy’s law,
which states that
(9)
where Q is the volume flux of permeated fluid through
a permeating area A of the specimen. The difficulty in
determining the permeability of soft biological tissues
with this procedure is that the permeation process
gives rise to a drag force (i.e. the force exerted by the
fluid on the solid as it flows through the specimen) of
significant magnitude to compact the soft, permeable
solid matrix in a non-uniform manner. This compac-
tion decreases the permeability within the tissue, and
the decrease varies with the distance from the surface.
making the measured value of k,, an average. lumped-
parameter value. This effect is particularly important
for soft tissues such as articular cartilage, where
substantial compaction of the matrix can easily occur.
Experimentally, this is manifested by the dependence
of Lo on the driving pressure P, that was first observed
for articular cartilage by Mansour and Mow (1976).
Note that for porous, permeable elastic materials
where the solid matrix is very stiff, e.g. soils or sintered
metallic materials, this effect is negligible or non-
existent. Thus this flow-limiting effect appears to be
particularly important only in soft biological multip-
basic materials.
To separate the effects of the clamping strain E, used
to hold the specimen discs in the permeation exper-
iment and the applied pressure PA, Mow and Lai
(1980) obtained a family of permeability curves L,(E,:
PA) with PA as the parameter. In doing this. it was
empirically demonstrated that there is an exponential
decrease of the permeability function with sc. Figure 8
shows how the permeability changes as a function of E,
for various parametric values of the constant pressure
drop PA used to maintain steady permeation. The
empirical exponential law used to curve-fit the data
was
k, = A(P,)exp[-W,)s,)]. ( 10)
where A(P,) and a(P,) are also shown in Fig. 8.
To incorporate this result into the biphasic theory,
Lai and Mow (1980) introduced the concept of in-
trinsic permeability, k, defined as
X-= lim k,(s,; P,4) = li,exp(Ms), (II)
P,-0
where k, = A(0). .V = a(0). and E = -E, is the dila-
tation field. It is important to note that this function is
386 VAN C. Mow, MARK H. HOLMES and W. IMICHAEL LAI

PERMEABlLlTY vs. APPLIED STRAIN

p,: . 0 fJF,q MN/,,?

l OS?2 MN/m2

0 I6 24 32 40 l
C
Applied Compressive SlroYn (%I

Fig. 8(a). Experimental curves of permeability versusapplied compressive strain at various levels of applied
pressure for a sample of bovine articular cartilage. The solid curves are least square best fits of the indicated
exponential decay law, equation (10) (Mow er 01.. 1980).

1 I I I )
05 IO I5 20 P
1
Pressvre (MN/m21

Fig. 8(c). Curve of exponent z(PA) vs P, for the same bovine

specimen (Mow et aI., 1980).

through a circular cylinder is used

05 IO I5 20
PressuretMN/m*l
Fig. 8(b). Curve of the amplitude function A(P,) and exper-
imental data points vs P, for the same bovine specimen (Mow
er al., 1980).
defined for the theoretical limit of PA -+ 0, which can be
obtained parametrically from Fig. 8 by extrapolation.
For normal bovine cartilage immersed in normal
Ringer’s solution, we find from the permeation exper-
iment that k, = 1.7 x lO_” m4/N*s and M = 4.3.
Consequently, even for small compressive strains,
there is a significant nonlinear interaction between the
fluid phase and the solid matrix as the tissue deforms.
It is of interest to note how the estimates of the
‘uniform pore size’ of these cartilage specimens, which
appear in the literature, have been obtained
(McCutchen, 1962; Maroudas, 1973). Usually the
Poiseuille formula for steady-volume rate of flow, Q,
P naf PA
A
Q=-gy
Here /Ais the viscosity of the permeating fluid, ai and Ii
are the radius and length of each pore, Fig. 9a, and P,, is
the applied pressure at the upstream end of the tube.
For a specimen whose permeated area is A, and
thickness h. and with n number of pores, the area1
porosity and tortuosity factor would be given by flA
=c;_, A,/A, and di = ii/h, respectively. For a un-
iform Poiseuille model whose pore structure is homo-
geneous and isotropic,
and
,=!!=’
h ii’
where a and I are the assumed constant radius and
length of the ‘circular cylindrical pore’. Inserting these
model assumptions into equation (12) above and

-’ .
 Properties of articular cartilage: a review

lations show that the pore size decreases practically

linearly with the bulk compression. This leads one to
conclude that bulk compression of cartilage is really
achieved by expelling the fluid from the intrrstitium
and that the organic matrix is essentially incom-
pressible. One must warn. however. that this type of
heuristiccalculation may be grossly inaccurate by itself
and should not be used strictly by itself but rather
should be used to supplement other. more rigorously
derived results such as those presented in this review.

Fig. 9(a). A uniform tube Poireuille flow model for assessing

SOS-LINE.aK FLLID SOLID ISTERACTIO\ DL-RISC
the ‘average pore size’ ofsrticular cartilage. In this model, all
circular cylindrical tubes are uniform in size (I, = I and ,-ii CO\lPREsSIOS
= .41. It is assumed that the porosity is isotropic so that the
areal porosity is equal to the volume porosity. The above discussions pertain to steady-state be-
havior ofcartilage during compression or permeation.
They explain the need to consider a nonlinearly
permeable biphasic model for articular cartilage under
compression. This concept of nonlinear, strain-
dependent permeability must be tested in other de-
formational conditions to verify its general validity
(Lai ef al., 1981; Holmes c~ ul., in press). A number of
different testing procedures have been used to ac-
complish this. They generally involve the nonsteady or
X x 0.669 MN/m* dynamic deformational behavior of cartilage; one
method is the in sifu stress-relaxation indentation test
described earlier (Mak er nl., 1982). and another is the
PERMEABILITY
uniaxial confined-compression experiment. A par-
ticular example of thcsc latter experiments arises when
cylindrical ostrochondral plugs arc compressed
03 against a free-draining, rigid. porous filter at the
articular surface. The pores of the filter are small
APPLIED COMPRESSIVE STRAIN (%)
enough so that the filter may be used to compress the
Fig. 9(b). Variation of average pore size as assessed by the solid matrix of the tissue, yet large enough to allow
uniform tube model. The method allows assessment of ‘free’ exudation of the Huid across the surface. At the
change of interstitial pore size with compression and applied same time, the plug of material is inserted into a snugly
pressure. Average solid content z and average porosity /I were
fitting confining chamber to prevent significant
assumed IO be 0.22 and 0.81 respectively. and d = tortuosity
Sactor. amounts of lateral expansion as the tissue is being
compressed normally across the articulating surface of
the specimen, Fig. 10. This experimental protocol was
equating this volume rate of flow with that defined by imposed in an attempt to achieve the theoretical
Darcy’s law, equation (9). the&average pore radius’may condition of one-dimensional confined compression -
be shown to be

(13)

Here k, is the experimentally determined apparent

permeability, equation (10) or (I 1). With known values
of tissue porosity p-O.8 and water viscosity, Fig. 9b
shows the range of average pore radii for normal
bovine articular cartilage in terms of the tortuosity
factor 6. There is no estimate for the tortuosity
factor-the path length actually traveled by a fluid
particle as it traverses the specimen of thickness h. It
would not be unreasonable to assume that this factor
ranges between one and two. For example, for d = 2, Fig. 10. Schematic depiction of the confined-compression
we see from Fig. 9b that for uncompressed tissues biphasic experiments. The rigid porous loading (with either
prescribed tractions or displacements) allows exudate to flow
(from the intrinsic permeability curve), a - 56 A and
freely into the pores of the tilter. The confining chamber is
with 40”” (clamping or bulk) compression a - 30A used to approximate the one-dimensional theoretical require-
(assuming S = 2 for both cases). These simple calcu- ment assumed in the analysis.
388 VANC. Mow. MARK
and it has been found by Mow et al. (1980) and
Armstrong and Mow (1982a.b) to be a significantly
accurate method to assess the intrinsic material pro-
perties of the solid matrix, its aggregate modulus H,
-_i,+ 2~,, and its linear permeability coefficient k,.
In an extension of the linear KLM biphasic theory
of cartilage to incorporate the nonlinear permeation
process, equation (11). the equation for the one-
dimensional deformation of the solid matrix along the
axis of the plug was shown to follow the non-linear
diffusion equation (Mow and Lai, 1980; Holmes et a!.,
in press).
H, 2 =k, exp
where the intrinsic permeability function, equation
(11). has been used to derive equation (14). Here u(z, t)
is the axial component of the displacement vector
describing the deformation of the solid matrix, Fig. 10.
The axial component of velocity c(z, r) of the intersti-
tial fluid phase is found from the continuity relation-
ship, equation (5), with the boundary condition u = u
=Oatz=h
a relaxation behavior of cartilage, Fig. 12. In these
I+. t) = -a z ufz,1).
A common experiment for the uniaxial compression
configuration involves the determination of the creep
behavior of the material. For the creep test, a constant
load is suddenly applied across the porous filter, and
the subsequent displacement is recorded. In the bip-
basic theory, the appropriate boundary condition at
the articular surface (z = 0) interfaced with the free-
draining rigid porous filter is
0 for tG0
H,gL
i -F. for t> 0,
where Fe is the magnitude of the applied compressive
traction. The resulting mathematical problem, which
includes equation (14), is non-linear, and at present no
analytic solution is known. Therefore either numerical
or asymptotic methods are necessary to obtain a
solution to the non-linear creep problem. We have
done this by examining the short and long-time
behavior of the solution (I-Iolmes, in press). It was
found that, in the initial moments after applying the
load, the creep displacement of the articular surface,
denoted by ue(t), is given as
h2
uo(t)=j30J;,0s t e<--
k,H,’
where for small compressive strains
/I,, =?exp(-$$($)“‘.
This describes the surface displacement for cartilage
with a thickness of 1.5 x 10m3m during the first 120s
or so, which corresponds approximately to the time it
takes the deformation, u(z, t), to diffuse down to the
H. HOLMESand W. MICHAELLAI
tidemark, i.e. the noncalcilied~lcified juncture. In
other words, prior to this time, the compression is
confined near the surface, so the creep response of the
tissue in confined compression is unaffected by the
boundary at the tidemark. For the long-time behavior,
the displacement exponentially approaches its equilib-
rium value of IIF,,/H,~, which is determined by the
aggregate modulus of the linearly elastic solid matrix.
One of the most important aspects of this asymptotic
result is that the early time response of the tissue, as
observed by a creep experiment, is proportional to J;,
irrespective of the load Fe. This behavior can be easily
verified from the creep data. Figure 11 shows some of
(14) our recent experimental data on normal bovine car-
tilage verifying the asymptotic solution given by
equation (17). The other important aspect is that, for
small strains, the equilibrium stress and the equilib-
rium strain in compression are linearly related; this has
been repeatedly verified experimentally (Mow et al.,
1980; Armstrong and Mow, 1982a).
The second confined compression test measures the
uniaxial stress-relaxation behavior of cartilage. This
experiment was first used by Lipshitz et al. (1976b) to
assess the influence of fluid Row on the stress-
(15)
experiments, a ramp-displacement function is imposed
on the articular surface given by
for 0 < t < to (compression phase)
Vet
%3(t) =
1 V&l for t, < c (relaxation phase).
(19)
As with the creep problem, the resultant inhomoge-
neous displacement field must be determined by
solving the nonlinear diffusion equation, equation (14).
An accurate approximation of the solution to this
(16) problem can be obtained for the case of a slow rate of
t
IS-
60-
45-
30-
(17)
(18)
Fig. 11. The measured displacement of the articular surface
during the first 120 s of a confined uniaxial creep experiment
on bovine articular cartilage with an applied load of I.2
x IO’ N m -I. The linearity of these data compares well with
the predicted behavior from the biphasic theory as given by
the asymptotic solution in equation (17).
 Properties of articular cartilage: a review

Control led Romoed Dtsolocement

Stress History During Romp Dispiocement

-w t UP

Timt

Schematic of Fluid Flow During Romp Displacement

EfllUlt Efflux
dir n Equilibrium
Arliculor
Surioct
Articulor
Cortilagt Tidtmorh
HI
E

Fig. I?. The top graph shows a controlled ramp displacement for a confined-compression experiment. The
middlecurve showsa typical stress rise during thecompression phaseand a typical stress-relaxation response
in the relaxation phase. The bottom schematics show that the movement of interstitial fluid predominates the
stress-history response. During the compression phase, fluid exudation gives rise to a peak stress (I,,, and
during the relaxation phase, fluid redistribution gives rise to the relief of the compacted region at the surface,
hence stress relaxation. (For more quantitative details, see Fig. 13.)

compression. For a slow rate, by which we mean
(20)
a nearly uniform state of compression exists in the
tissue (Holmes, 1983.1984). In thiscase, theasymptotic
expansion of the solution for the stress history at the
representing the strain imposed in the experiment.
Based on the known typical permeation values for
normal bovine cartilage, this expression is valid for
experiments in which the compressive phase lasts
longer than loo0 s and, of course, for strains of no
more than about 20 y<. Higher rates of compression or
higher frequency excitations in compression would

h2
articular surface (-_= 0) is given by induce compressive strains beyond the validity of

U;_(I)
-&o
linear infinitesimal strain theory.
H, ~+c,exp(crMt)
1, ----<arcs
Lo4
(214
For this slow rate it is also relatively easy to
determine the solution during the relaxation phase
(Holmes et al., in press). We find that immediately
subsequent to the start of the relaxation process, at the
where
articular surface,
h*
(Zlb) L(t) - a,-.V,J;_ 0 <r-lo < 1 (23a)
co =3koH,1,
where
v,
c’=T. 2ha,
M, = (2W
t,jnH,k,exp(--EoM)’
Here the equilibrium compressive strain .eois given by
I and
pot0
Eo = ~ (22)
h up = -coH,[l +coexp(eoM)]. (23~)
390 VAN C. Mow. MARK H. HOLMES and W. MICHAEL L,u

Here CT, denotes the equilibrium compressive stress
attained in the limit I - x given by
0, = c,,H,,. (231 analytical asymptotic solutions for the predicted stress
This shows that at the start of the relaxation phase, the
compressive stress decreases as the square root of time
from the peak compressive stress a, achieved at the end
of the compressive phase. This approximation applies,
roughly, to the first 100 s of the relaxation phase. As
time increases, the compressive stress continues to
decrease, and in fact it approaches exponentially its
equilibrium value of EdH 4determined by the linearly
elastic response of the solid matrix. These results show
that stress relaxation occurs because of an internal
fluid redistribution process, which in turn is governed
by the lower permeability within the compressed
tissue, k, exp( - E,,M), giving rise to a more rapid rate
of relaxation relative to the peak stress op. A summary
of the results obtained from the asymptotic solutions is almost linear time dependence is seen during the
shown in Fig. 13. These results illustrate the fundamen-
tal role of the flow-limiting effect on the deformational
behavior of the non-linearly permeable tissue. It tends
to make the tissue appear stiffer-as with other
viscoelastic materials-with increasing rates of com-
pression by virtue of the increased frictional drag
required to extrude the fluid from the tissue during the
compressive phase of the experiment. Thus the non-
linear, strain-dependent permeability effect appears to
be ideal in the diarthrodial joint loading situation-it
exudes fluid when required, but only with ever-
increasing resistance to flow.
We have performed numerous stress-relaxation
studies following a very strict experimental protocol to
insure the repeatability of the sensitive measurements
(Holmes er a[., in press; McCormack, 1983). The
maximum peak load in all these experiments occurs at
the end of the compressive phase, and it increases with
increasing strain rate t. For the ‘slow’ rate experiment,
typically the maximum peak load is s 4-5 N and the
equilibrium load is about 2-3 N for a 6.35 mm dia-
meter plug ofcartilage. Because of the simplicity of the
history in these experiments, it is relatively easy to
determine the material constants of the model. For the
case at hand, we used a non-linear regression analysis
with equation (2la)as the object function to determine
k, and ?lf. The aggregate modulus H,4is obtained from
the equilibrium stress measured after complete stress
relaxation has occurred. Figure I4 shows an actual set
of data from our experiment where i = 0.0021 y,;s-’
and co = 5OCQs. In this case. we find that k, = 2.51
x 10-1s rn’1N.s. ‘41= 7.83, and H, = 0.41 MPa.
For the typical slow strain-rate stress-history curve
shown in Fig. 14. we see that, as in Fig. 13, immediately
following the onset of the ramp compression, a
parabolic load-vs-time curve is observed. After this, an
compressive portion of the experiment. If we ex-
trapolate this curve back to r = 0, and denote the
intercept with the a-axis. by ue, we have from equation
(21a) u0 = cc,. The contribution of the non-linear
permeability can be seen in Fig. I3 if one compares era
= (cp-c,)/c,7 the normalized difference between
the peak stress up and equilibrium stress uz, with ue. If
the permeability were constant, so M = 0 in equation
(11). uR and u,, would be equal. However, in Fig. 14, it
can be seen that they are not the same; uR is about
100 y,, larger than ue. These stress-rise characteristics
are governed by the rate of compression I’,, thickness
h, aggregate modulus H,, and the intrinsic perme-
ability parameters k, and 121.The non-linear, flow-
limiting parameter M, as defined by Lai et al. (1981). is
responsible for the rise of the stress above and beyond
the values that would be obtained with a constant
permeability. For the strain rates required by the slow-
rate experiment, the deviations are relatively small

10
t

1.
Time (secl

Fig. 14. Non-linear regression analysis, using equation (Zla)

Fig. 13. Depictions of the asymptotic normalized stress- and the experimental data from 3000s to 5000s. is used to
history prrdiction of a slow-rate compression experiment if determine k, and M. These values, together with H, de-
the tissue is non-linearly biphasic. The stress rise in the termined at equilibrium, are used in an exact numerical
compressive phase depends on the sum of a linear time solution (solid line) to predict :he complete stress history. The
function and an exponential time function. The stress inter- agreement is excellent over the entire 8C00 s period. This
cept u0 is different from the total stress decay uR method provides a self-consistency check on the validity of
= c,, exp(e,M) (Holmes et al., in press). For a linearly the model as well as the asymptotic solutions (Holmes rt al.. in
biphasic material. CT”= CJ~ since .LI = 0. press).
 Properties of articular
durmg the compressive phase. However, during the
relaxation phase. the non-linear permeability causes a
significant change in the rate ofstress relaxation. From
equation (73), it is seen that the rate of stress relaxation
is proportional to M,, which depends inversely on the
lower permeability value k. exp( -cc, M) of the com-
pressed tissue. The mechanism of stress relaxation is
indeed fluid redistribution within the tissue, and
interstitiai fluid flow in the compressed tissue must
pass through the matrix with this layer of lower
permeability. Thus a higher stress-relaxation rate is
seen relative to the peak stress op. It should be pointed
out that the material parameters were determined
using the data from the compressive phase of the
experiment; hence, the relaxation phase provides an
internal check on the self-consistency of the biphasic
theory, and, as can be seen in Fig. 14, the agreement is
excellent.
This review has focused on three specific aspects of
our understanding of cartilage biomechanics. First,
relevant biochemical, physicochemical, and ultrastruc-
tural knowledge is presented so that the reader can
interpret the biomechanical properties of this tissue
from a micromechanical point of view. Second, a
detailed historical account is presented of prior at-
tempts to model articular cartilage indentation be-
havior. An appreciation of the evolution of thought on
the development of cartilage deformational theories,
leading up to the development of the biphasic model
for articular cartilage, is both instructive and en-
lightening. Third, a summary of our most recent
investigations on the influence of the non-linear strain-
dependent permeability effect on the compressive
creep and stress-relaxation behavior of the tissue is
presented. We found, by two separate, independent
tests-the steady, direct permeability experiment
and the transient compressive stress-relaxation
experiment-that cartilage permeability must be de-
scribed by the function k = k, exp(EM) where k, and
Mare the intrinsic permeability parametersand Eis the
dilatation given by E = trVu. This non-linear perme-
ability function has profound effects on the compress-
ive creep and stress-relaxation behavior of the tissue,
since these phenomenological viscoelastic effects are
predominately governed by the rate of interstitial fluid
flow. The physicochemical basis for this nonlinear
flow-limiting effect derives from the significant direct
correlation between cartilage permeability and tixed-
charge density from steady-permeation experiments.
Compaction of the tissue will correspondingly increase
its fixed-charge density and hence decrease its perme-
ability. Thus the nonlinearly permeable biphasic
model for cartilage should be used whenever detailed
deformational responses of the tissue in compression
or detailed material-parameter characterizations of the
tissue are desired. Preliminary experimental results
show that, for example, in the stress-relaxation exper-
cartilage: a review 19 I
iment, M is very sensitive to the observed stress peaks.
Thus we expect that this non-linear, flow-limiting
parameter M could provide a sensitive quantitative
indicator of cartilage degeneration in diseases such as
osteoarthritis. Future work in this area must now focus
on the correlation ofchanges of these intrinsic material
properties ofcartilage with data such as: (1) the natural
variation of tissue structure and biochemistry; (2) the
pathological. e.g. osteoarthritic, changes of collagen
fibrillar ultrastructure and proteoglycan conformation
found in diseased tissues; and (3) the variation of
monovalent (Na’), divalent (Ca’ ‘), and other ions in
the interstitium. These problems pose extraordinary
challenges not only to biomechanicians but to a whole
host of allied biomedical scientists.
Arknowlrdgzmml-This material is based on research sup-
ported by National Science Foundation grant MEA
82-11968. National Institute of Arthritis, Diabetes, and
Digestive and Kidney Diseases grants AM 19093 and AM
26440. and the Clark and Crossan endowment 81 Rensselaer
Polytechnic Institute. Any opinions, findings and conclusions
or recommendations expressed in this publication are those
of the authors and do not necessarily represent the wews of
the National Science Foundation. We wish to thank Mr.
Brendan McCormack and Ms. W. B. Zhu for their technical
assistance in obtaining the stress-relaxation and creep data.
Mrs. Lynne Nagengast and Ms. Joyce A. Brock for their
assistance in typing this manuscript. and Ms. Rose .A. Boshoff
for her editorial assistance.
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