Repair of Osteochondral Lesions - Engineered Bone: Tissue Engineering Intelligence Unit - page 165

C HAPTER 12

Repair of Osteochondral Lesions

Ivan Martin, Dirk Schaefer and Beatrice Dozin

Abstract

Trauma and disease of joints frequently involve structural damage to the articular

cartilage surface and the underlying subchondral bone. These pathologies result in
severe pain and disability for millions of people world-wide and represent a major chal-
lenge for the orthopaedic community. Albeit a series of therapeutic approaches has been devel-
oped to treat osteochondral defects, none of them has proved yet to ensure long-lasting regen-
eration. The difficulties encountered mostly rely on the intrinsic biological, biochemical and
biomechanical properties of the articular cartilage. An accurate knowledge of these properties
is mandatory to improve current therapies and/or establish innovative procedures. This chap-
ter will (i) describe some of the structural and functional properties of articular cartilage; (ii)
critically present the current procedures to repair cartilage; (iii) introduce a variety of novel
strategies currently under investigation for cartilage repair and (iv) highlight some of the main
challenges to be addressed in order to improve the clinical treatment of osteochondral lesions.

Introduction

Structure and Function of Articular Cartilage
The structural organisation of articular cartilage in adult organisms reveals a rather simple
architecture, being composed of one single type of highly specialised cell, the chondrocyte,
embedded within a dense extracellular matrix (for a review, see ref. 1). The chondrocytes con-
tribute little to the volume of the tissue, 1-2% in human articular cartilage. In adulthood,
chondrocytes generally do not divide any longer and are aimed at maintaining the integrity of
the articular surface through balanced synthetic and catabolic activities. The matrix itself is
composed of (i) fluid, mostly water (75-80% of the wet weight), gases, metabolites and cations,
and (ii) a framework of macromolecules that include mainly type II collagen (50-73% of the
dry weight), proteoglycans (15-30% of the dry weight), other fibrillar (IX and XI) and nonfibrillar
(type VI and X) collagens and additional noncollagenous molecules. A variety of interactions
bridge the individual macromolecules, in particular noncovalent associations between
proteoglycans and collagens and covalent bonds between different collagen species.
The framework of macromolecules mostly gives the tissue its form and stability. Water and
proteoglycans are dispersed through the collagen framework as a soluble gel, making the matrix
biphasic. Due to their hydrophilic nature, proteoglycans mainly confer resistance to compres-
sion, by attracting a large amount of water into the intramolecular and intermolecular space.
Collagen fibrils withstand the swelling forces of the water-proteoglycan phase and provide the
matrix with high tensile strength. Thus articular cartilage, although it is only a few millimeters
thick, ensures to the joint smooth gliding motion, load transmission, force distribution and
minimised peak focal stress on the subchondral bone. 2 The functional role of noncollagenous
proteins, comprising anchorinCII, fibronectin, tenascin, fibromodulin and cartilage oligomeric
protein, remains as of yet largely unknown.