Repair of Osteochondral Lesions - Engineered Bone: Tissue Engineering Intelligence Unit - page 166

Throughout the tissue, both cells and matrix present a highly organised distribution within
successive layers known as the superficial, transitional, radial and calcified zones. Chondrocytes
within each layer are characterised by distinct size, shape and space orientation. Also collagen
fibers follow a rigorous structural pattern, forming a network of parallel, arcade-like and per-
pendicular fibers from superficial to deeper zones. Such structural organisation both at the
cellular and molecular levels is indicative of specialised functions.
Focal Lesions and Natural Repair of Articular Cartilage
Traumatic cartilage lesions affect mostly young subjects often involved in sustained sport
activities. During these traumas, shear forces lead to a separation of cartilage between the radial
and the calcified layers. 3 Focal defects are classified as either chondral or osteochondral. Chon-
dral lesions lie entirely within the cartilage and do not penetrate beyond the calcified zone into
the subchondral bone. The vasculature being unreached, these lesions do not heal spontane-
ously and are analogous to those observed during the early phases of osteoarthritis. 4,5 Osteo-
chondral defects penetrate the articular surface in depth through the vascularised subchondral
bone. Some spontaneous attempts of repair can be observed as mesenchymal chondroprogenitor
stem cells invade the lesion, differentiate into chondrocytes and form cartilage. 6 However,
repair of full-thickness defects ends up to be only transient: the repair tissue is fibrous in nature,
does not have the functional properties of native hyaline cartilage, and thus results more vul-
nerable to the action of free radicals, metalloproteinases and catabolic cytokines including IL-1
and TNF- α . 7,8 Matrix breakdown often leads to evident clefts and fissures on the articular
surface and subsequently to the onset of degenerative joint diseases such as osteoarthritis. 9
It is thus clear that articular cartilage has a limited capacity for self-regeneration after injury.
Intrinsic biological features of the tissue itself are the limiting factors:
1. the mature chondrocytes have a relatively low metabolic activity and proliferation capacity
and the abundant extracellular matrix may provide a barrier for their migration to the defect;
2. articular cartilage being neither vascularised nor penetrated by lymphatic vessels, there is no
direct access to progenitor cells; furthermore, the supply of growth and differentiation pro-
moting factors is ensured only by diffusion from the synovial fluid;
3. some of the proteoglycans of the matrix have anti-adherent properties and may prevent cell
adhesion, further undermining any tentative repair process; 10 herein may also lie the diffi-
culty of achieving a good integration between repair tissue and native cartilage;
4. finally, articular cartilage is not innervated and thus insensitive to early injuries that can
readily progress to degeneration much before evident clinical symptoms emerge.
Total joint replacement using artificial prostheses generally eliminates pain and partially
restores functionality, but is limited by the durability of the device. Thus, particularly for young
individuals, it is mandatory to identify alternative procedures to permanently repair cartilage
injuries or at least to delay the implantation of an artificial joint replacement. The complexity
of articular cartilage structure and the peculiarity of its biological/biophysical features explain
the large repertoire of most diversified therapeutic approaches that have been developed and
are being investigated to regenerate osteochondral lesions and restore joint functionality. In the
following sections, the reader is provided with an overview of these techniques.
Current Clinical Treatments of Osteochondral Lesions
Microfracturing
Microfracturing is the most widely used cartilage repair technique, with more than 76,000
procedures reported in 1999 in the U.S. only. 11 The procedure, which is generally performed
arthroscopically, consists in perforating the subchondral plate of (osteo)chondral defects by
multiple holes, thus allowing marrow-derived mesenchymal progenitor cells to reach the lesion
and form new cartilaginous matrix 12 (Fig. 1A). The popularity of the technique derives from
the low morbidity and an overall clinical improvement of symptoms. However, the tissue
generated after microfracturing was shown to lack the structure, composition, mechanical