Influence of the extracellular matrix on the frictional properties

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					                                                                                                                                 Matrix Turnover: Mechanisms and Common Denominators         677

Influence of the extracellular matrix on the
frictional properties of tissue-engineered cartilage
M. Plainfosse*, P.V. Hatton*, A. Crawford*1 , Z.M. Jin† and J. Fisher†
*Centre for Biomaterials and Tissue Engineering, University of Sheffield, Sheffield S10 2TA, U.K., and †Institute of Medical and Biological Engineering,
University of Leeds, Leeds LS2 9JT, U.K.

                 Low-friction surfaces are critical for efficient joint articulation. The tribological properties of articular cartilage
                 have been studied extensively in native tissue and joints. Despite their importance, very few studies have
                 examined the frictional properties of tissue-engineered cartilage. We have therefore reviewed the re-
                 lationship between composition, structure and friction in tissue-engineered cartilage.

Introduction                                                                                             matrix. The extracellular matrix of hyaline cartilage is often
Articular cartilage has a crucial role in allowing diversity of                                          described as biphasic because of the two main phases of
movement under high-load-bearing conditions. The func-                                                   which it is composed. One phase is solid, porous and elastic
tional properties of articular cartilage may, however, be                                                in nature and is mainly composed of a dense network
impaired following trauma or degenerative arthritic disease.                                             of collagen fibres enmeshed with highly sulfated proteo-
Conventional treatments rely mainly on pain control,                                                     glycans and hyaluronic acid. Type II collagen accounts
abrasion, micro-fracture and, ultimately, joint replacement.                                             for over 90% of the total collagen [2] and forms a dense
Unfortunately, none of these treatments is entirely satisfact-                                           network of cross-linked fibres which give articular cartilage
ory in the long-term. The complex structure of articular                                                 its tensile properties. Proteoglycans, of which aggrecan
cartilage and its functional properties make it a difficult                                              accounts for approx. 90% [3], form large complexes with
tissue to repair. The replacement of injured cartilage using                                             hyaluronic acid and produce an integrated system enmeshed
tissue-engineered grafts or constructs represents a potential                                            into the collagen network. The hydrophilic properties of
solution. Articular cartilage with hyaline characteristics may                                           proteoglycans generate a swelling pressure that contributes
indeed be engineered in vitro. Its evaluation has, how-                                                  primarily to the compressive properties of the tissue. The
ever, focused more on tissue histology and biochemistry,                                                 second major phase is an incompressible liquid composed of
rather than on functional properties. The evaluation of                                                  interstitial water and electrolytes (mainly Na+ , Cl− , K+ and
the mechanical performance of tissue-engineered cartilage                                                Ca2+ ions) accounting for up to 80% of the tissue wet weight
represents a relatively new challenge for bioengineering. In                                             [4]. The structure of native articular cartilage aids retention
this paper, we review the factors responsible for mechanical                                             of water within the tissue: the collagen fibres form a network
functionality of tissue-engineered cartilage.                                                            able to enmesh and retain the proteoglycans which absorb a
                                                                                                         high level of water because of their hydrophilic properties.
                                                                                                         Most importantly, when load is applied to healthy cartilage,
Composition and structure                                                                                it is carried by the fluid phase of the composite structure,
                                                                                                         resulting in elevated internal fluid pressure and a very low
Native articular cartilage                                                                               coefficient of friction [5].
Chondrocytes are the only cell type in articular cartilage,
representing only 1% of the tissue volume, but are essential
for the synthesis and maintenance of the extracellular                                                   Engineered cartilage
matrix [1]. Although it is well known that intermittent                                                  Various studies have shown that articular cartilage can be
mechanical loading is essential to maintain the integrity of                                             engineered in vitro with structural features in common
articular cartilage, the mechanosensing pathways are unclear.                                            with native articular cartilage. An extensive hyaline-like
Chondrocytes have been reported to have cilia extending                                                  extracellular matrix is synthesized, and we have shown that
into the extracellular matrix which may act as sensors of the                                            the chondrocytes can surround themselves with a pericellular
mechanical environment and may thus be at the origin of a                                                matrix rich in collagen type VI, forming a chondron-like
cellular response [1].                                                                                   structure [6]. It is, however, a common problem that the levels
   The mechanical behaviour of articular cartilage is depend-                                            of matrix components, in particular of type II collagen, do not
ent on the composition and organization of the extracellular                                             reach levels found in native mature articular cartilage. Hence,
                                                                                                         cartilage constructs engineered in vitro may be considered
Key words: cartilage, extracellular matrix, frictional property, joint, tissue engineering, tribology.   to be structurally immature. This immaturity is reflected in
  To whom correspondence should be addressed (email                          the relatively low aggregate or Young’s modulus which is

                                                                                                                            C   The Authors Journal compilation C 2007 Biochemical Society
678   Biochemical Society Transactions (2007) Volume 35, part 4

      obtained for engineered cartilage matrix when subjected to            Figure 1 Light micrographs of tissue-engineered cartilage
      confined or unconfined compression [7].                               sections stained with haematoxylin and eosin
         It has not yet been possible to produce tissue-engineered          Tissue structures before (a) and after (b) initial friction test. Scale bars,
      cartilage with a matrix composition and architecture identical        400 µm.
      with mature tissue in order to replicate its mechanical pro-
      perties. In particular, engineered cartilage should ideally
      contain the appropriate proteoglycan content which, once
      integrated into the collagen network, will form an appropriate
      composite microstructure.

      Friction and lubrication

      Hypothesis for joint lubrication
      Many theories have been proposed in attempts to explain
                                                                            most of the load will be carried by the solid phase, and the
      the extremely low friction and wear of articular cartilage.
                                                                            coefficient of friction reaches its maximum.
      Many fluid-film lubrication models have been developed:
      hydrodynamic lubrication [8], squeeze-film lubrication [9]
      and elastohydrodynamic lubrication [10]. Boundary lubric-             Frictional properties of tissue-engineered
      ation models have also been widely described, and various             cartilage
      boundary lubricants have been proposed: hyaluronic acid               Very few detailed studies have investigated the frictional
      [11], glycoproteins such as lubricin [12–14], phospholipids           response of tissue-engineered cartilage. In the last year,
      [15,16] and proteoglycans such as chondroitin sulfate [17].           Morita et al. [24] and Lima et al. [25] have shown that
      Their exact roles and importance are, however, still unclear          engineered cartilage has some frictional behaviours in
      and have been the source of many controversies. Self-                 common with native articular cartilage, particularly the time-
      pressurized hydrostatic and weeping lubrication [18] and              dependent response. They also observed that the culture time
      boosted lubrication [19] are other examples of lubrication            and the maturation of the engineered tissue were some of the
      models proposed over the past century. Mow and Lai [20]               key parameters contributing to the low frictional response of
      developed the work of McCutchen, and proposed a frictional            the engineered tissue.
      model based on the biphasic properties of articular cartilage.           We have performed initial friction tests [5] on engi-
      The pressurization of the interstitium within the tissue is           neered constructs developed using bovine chondrocytes and
      today widely believed to contribute largely to the low friction       poly(glycolic acid) scaffolds [26]. Our results confirmed
      of articular cartilage [21–23].                                       that the coefficient of friction increases with loading time.
                                                                            After 5 s of stationary loading, we observed that the
      Interstitial fluid pressurization and joint                            coefficient of friction for the engineered constructs was
      lubrication                                                           higher (µ5 s = 0.04 ± 0.01) than for the native articular
      The total friction at a cartilage–cartilage interface consists of     cartilage (µ5 s = 0.02 ± 0.01), reflecting a higher resistance to
      two parts, one due to the fluid phase and the other to the solid      the motion. After a longer period (20 min), the tendency was
      contacts [FT (t) = µS × WS (t) + µF × WF (t), where F T (t) is the    reversed and the coefficient of friction for the engineered
      overall friction force, µs is the effective coefficient of friction   tissue became notably lower (µ20 min = 0.11 ± 0.04) than
      attributed to the solid phase, W S (t) is the load carried by the     for the native articular cartilage (µ20 min = 0.20 ± 0.05).
      solid phase, µF is the effective coefficient of friction attributed   Histological evaluation (Figure 1) performed on completion
      to the fluid phase, W F (t) is the load carried by the fluid          of the friction tests showed delamination at the superficial
      phase, and (t) indicates time function dependency] [21]. As           layer of tissue-engineered cartilage. It is thought that the
      the friction of the liquid phase can be neglected before the          debris generated and released in the lubricant during the tests
      friction of the solid phase, it is accepted as a first approxi-       may have reduced the resistance to the motion. As observed
      mation that the total friction is simply dependent on the solid       by Ozturk et al. [27], particles may also have accumulated on
      phase [FT (t) = µS × WS (t)].                                         the steel plate, thus reducing the roughness of the material
         Under a constant load, the initial interstitial fluid              and the resistance to the motion.
      pressurization in cartilage is maximal. The largest proportion           We believe that, in order to develop functional engineered
      of the load is carried by the fluid phase and, consequently,          cartilage, one significant challenge is to replicate more closely
      the coefficient of friction is extremely low. As the loading          the biphasic characteristics of native articular cartilage. In
      time increases, the flow of water exuding from the tissue             particular, the reproduction of the composite microstructure
      increases, and the interstitial fluid pressurization drops.           of enmeshed collagen and proteoglycan networks is most
      The fraction of solid-to-solid contacts increases, and the            likely to be essential in order to improve the retention of
      coefficient of friction goes up. Eventually, the interstitial         water within the tissue and improve the frictional properties.
      fluid pressurization will subside after a certain loading period,     Without the structural retention of integrated components,

      C   The Authors Journal compilation C 2007 Biochemical Society
                                                                                                                    Matrix Turnover: Mechanisms and Common Denominators         679

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   271–279                                                                          Received 18 April 2007

                                                                                                               C   The Authors Journal compilation C 2007 Biochemical Society

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