Interfaces in Composite Materials - Biointerfaces: Where Material Meets Biology - page 166

subchondral bone, and both chondrocytes hypertrophy and endochondral
ossification occur (Figure 7.2). 132 These changes in both subchondral bone
and cartilage are associated with joint pain, tenderness, swelling and
stiffness.
The prevalence of osteoarthritis increases with increasing age and obesity
of the population; it affects approximately 8million people in UK but nearly
27million in USA. 133 Treatment guidelines generally first recommend a non-
operative approach (weight loss, exercise and anti-inflammatory drugs) be-
fore surgical options such as joint replacement. Unlike bone, cartilage re-
generation is limited. 134 Currently there is no widely accepted treatment to
repair osteochondral defects 135 although tissue engineering is emerging as a
promising future option. Simultaneous engineering of articular cartilage
and subchondral bone with a stable interface, that separates these two
histologically, mechanically and functionally different tissues, is very chal-
lenging, however. Designing stratified, i.e., bilayered 136-141 or multi-
layered, 142-147 scaffolds with spatially controlled, continuous gradients
of materials composition/properties and growth factors 148 to mimic the
complex elegance of native tissue is likely to be essential for effective re-
generation of the osteochondral interface (Figure 7.3). For the construction
of stratified scaffolds, polymeric composites (e.g., silk-fibroin sponge 142 or
collagen-hyaluronic acid-fibrin gel 134 ) or polymeric-ceramic composites
(e.g., polycaprolactone-b-tricalcium phosphate nanoparticles) 149 or com-
bination of both (e.g., chitosan-gelatin for cartilage layer but hydroxyapatite-
chitosan-gelatin for bone layer 136 ) have been used. For effective tissue
regeneration, pore sizes of 100-200 mm and 300-450 mm has been shown to
be optimal for the chondral and osseous layer respectively. 150
To engineer the complex osteochondral tissues, the native cross-talk be-
tween chondrocytes and osteoblasts 132 and the innate capacity of stem cells
to proliferate and then differentiate into a variety of lineages 151 have been
employed. The traditional strategy relies on culturing each phase of the
scaffold with its specific cells; the differentiated phases can then be joined
(e.g., using fibrin glue 136 or self-assembling peptides 142,152 ) and co-cultured
to form the osteochondral construct. Co-culturing allows the cross-talk be-
tween different cell populations and formation of a more complete osteo-
chondral construct with an interface of hypertrophic chondrocytes, type X
collagen and MMP-13. 142,152 In vivo implantation of bilayered integrated,
spatially controlled composites supported the osteochondral regeneration in
a lapine knee defect. 136,153
Growth factors, e.g., transforming growth factor-b1 (TGF-b1) and bone
morphogenetic protein-2 (BMP-2) have also been incorporated within the
scaffold to enhance stem cell differentiation. 154-156 Yet, the dose and spatial
distribution of growth factors within the scaffolds is dicult to control.
Furthermore, the dual release of growth factors [i.e., both TGF-b3 and in-
sulin growth factor-1 (IGF-1)] does not necessarily synergistically enhance
the quality of engineered osteochondral tissues over the single release (e.g.,
IGF-1). 156 More importantly, the growth factor proteins are unstable and

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