CARTILAGE 3D PRINTING - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 258

et al., 1996 ) are found in higher concentrations in the SZ, including decorin, biglycan, asporin, lumican,
and fibromodulin, which modulate many processes including metabolism, growth factor signaling,
and maintaining tissue integrity ( Kizawa et al., 2005; Pelletier et al., 2000; Poole et al., 1996; Rough-
ley, 2006 ). Recently a fibulin-like ECM protein (EFEMP1) was found predominately expressed in
the SZ ( Grogan et al., 2013a ) and was postulated to maintain the immature status of chondroprogeni-
tor cells ( Wakabayashi et al., 2010 ), which contributes to the mounting evidence of the presence of
progenitor cell populations residing in this region ( Alsalameh et al., 2004; Dowthwaite et al., 2004;
Grogan et al., 2009 ), which may be critical for replenishing cells and maintaining tissue homeostasis.
The middle zone (MZ) region (40-60% of cartilage thickness; Figure 12.1 ) contains chondrocytes
with more PCM and collagen fibrils that are more randomly dispersed. In comparison to the SZ, the
MZ ECM contains higher levels of aggrecan ( Bayliss et al., 1983 ) and is specifically high in hyaluronic
acid (HA), dermatan sulfate, and collagen type II ( Asari et al., 1994; Buschmann et al., 2000; Franzen
et al., 1981; Maroudas et al., 1969; Ratcliffe et al.; 1984; Schinagl et al., 1997; Wong et al., 1996 ). The
main role of aggrecan is to maintain tissue hydration, which is important for endowing cartilage its
mechanical properties ( Dudhia, 2005 ). Cartilage intermediate layer protein (CILP) is uniquely located
in the MZ ( Lorenzo et al., 1998 ). The ECM protein cartilage oligomeric matrix protein (COMP) is also
mainly seen in MZ and DZ ( DiCesare et al., 1995; Murray et al., 2001 ).
The deepest 30-40% of cartilage thickness is classified as the radial or deep zone (DZ), which con-
tains the lowest cell density and collagen content compared to the SZ and MZ ( Venn, 1978 ). On the other
hand, the proteoglycan content, including aggrecan, keratan sulfate, and chondroitin sulfate, is much
higher than the upper zones ( Asari et al., 1994; Jacoby and Jayson, 1975; Mitrovic and Darmon, 1994;
FIGURE 12.1
Cartilage zonal organization and extracellular matrix (ECM) composition.