CARTILAGE 3D PRINTING - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 260

For patients more than 60 years of age with end-stage arthritis, artificial joint replacement is the recom-
mended treatment ( Grayson and Decker, 2012; Noble et al., 2005; Wylde et al., 2012 ). For younger pa-
tients with focal lesions, biological or cell-based procedures are employed such as microfracture ( Goyal
et al., 2014, 2013; Sherman et al., 2014 ), autologous chondrocyte implantation ( Kon et al., 2012 ), or
osteochondral grafting ( Sherman et al., 2014 ). However, these approaches do not restore long-lasting
healthy cartilage with the major issues being lack of regeneration of the zonal structure of hyaline articular
cartilage and poor integration with host tissue ( Clar et al., 2005; Rasanen et al., 2007; Zeifang et al., 2010 ).
Over the past 10-14 years, much effort has been devoted to prefabrication of neotissues in several
laboratories using various scaffolds systems and bioreactors ( Tuan et al., 2013 ). These tissue engineer-
ing approaches typically involve cell harvesting and isolation, cell expansion, and an in vitro phase
of 3D culture to produce a neotissue graft ( Roelofs et al., 2013 ). The general concept of maturing a
cultured 3D graft tissue before implantation is to ensure development of the desired cartilage mechani-
cal properties ( Mohanraj et al., 2013; Pabbruwe et al., 2009; Theodoropoulos et al., 2011 ). However,
integration of mature cartilage with the host tissue is limited or not consistently demonstrated due to
a number of parameters including lack of vascularity, mismatch between the properties of the ECM
structure of the native tissue and implanted graft, cell death, inadequate differentiation of the cells, and
the type of biomaterial or scaffold used ( Khan et al., 2008 ). Only recently have efforts toward translat-
ing engineered cartilage tissue into human clinical trials been initiated, such as Denovo ET (Engineered
Tissue Graft) and NeoCart (see clinicaltrials.gov). Outcomes of the NeoCart phase-II prospective, ran-
domized clinical trial were similar to that of microfracture surgery and were associated with greater
clinical efficacy at two years after treatment ( Crawford et al., 2012; Fedorovich et al., 2012 ). However,
longer-term clinical outcomes are pending.
Overall, current strategies to engineer cartilage have failed to fabricate new repair tissue in vivo
that is indistinguishable from native cartilage in terms of mechanical properties, zonal organization,
and ECM ( Klein et al., 2009; Schuurman et al., 2013a ). The detailed characterization of cartilage
ECM composition throughout cartilage (as detailed earlier); knowledge of cartilage biology in terms of
cartilage structure and organization ( Grogan et al., 2009; Miosge et al., 1994; Poole et al., 1996; Wald-
man et al., 2003 ), and cartilage zonal phenotype ( Grogan et al., 2013a ); and the availability of various
promising cells sources (e.g. MSC and ESC) as alternative sources for cartilage tissue regeneration
( Bulman et al., 2013; Filardo et al., 2013; Olee et al., 2014 ); coupled with advances in biomaterials
(scaffolds, hydrogels) that support cartilage formation and possess mechanical properties approaching
cartilage ( Spiller et al., 2011; Tuan et al., 2013 ) are collectively very valuable in resolving the present
challenges facing cartilage repair. 3D bioprinting is an emerging technology with the ability to deliver
cells and ECM proteins to organized repair tissues with the desired cell densities, zones, and variation
in ECM properties to mimic normal articular cartilage. If successful, 3D bioprinting can overcome the
major hurdles preventing successful repair such as inadequate reproduction of the tissue structure and
organization, and poor integration with host tissue.
12.1.3 3D BIOPRINTING AND CELL PRINTING APPROACHES
A number of techniques have been developed for 3D bioprinting, most of which are based on tradi-
tional 3D printing or rapid prototyping technologies. The primary methods in development today are
extrusion and ink-jet; however, stereolithography and laser-assisted direct-writing techniques are also
active areas of research. The modes of action for each technology are outlined in Figure 12.3 .