Biomedical Engineering Reference
In-Depth Information
viscoelastic properties. This can be easily understood since water retention is an important
function of GAGs in tissues (Lovekamp et al., 2006). Moreover, GAG content plays a key
biological role in cellular signaling and communication. Thus, decreasing GAG content
leads to an impaired tissue response and repair. Therefore, the decellularization protocol has
to be carefully chosen depending on the tissue type as well as the targeted application.
Ideally, the process should remove all cellular antigens without compromising the structure
and mechanical properties of the tissue.
Liao
et al.
(Liao et al., 2008) investigated the effect of three decellularization protocols on the
mechanical and structural properties on porcine aortic valve leaflets. These protocols were
based on the use of SDS, Trypsin and Triton X-100. They showed that decellularization
resulted in collagen network disruption, and that the ECM pore size varied as a function of
the protocol used. For example, leaflets treated with SDS displayed a dense ECM network
and small pore sizes, characteristics that may have an impact on the recolonization of
interstitial cells.
It has been demonstrated that decellularization of bovine pericardium with SDS causes
irreversible denaturation, swelling and a decrease in tensile strength compared to native
tissue (Courtman et al. 1994; García-Paéz et al., 2000; Mendoza-Novelo et al., 2009). Because
of these deleterious effects on pericardial tissue, non-ionic detergents are preferred for
decellularization processes (Mendoza-Novelo et al., 2010 ). Nevertheless, some issues may
be encountered with the use of non-ionic detergents. Indeed, toxic effects (Argese et al.,
1994) and estrogenic effects (Soto et al., 1991; Jobling et al., 1993) have been reported after
the use of non-ionic detergents such as alkylphenol ethoxylates.
Decellularization mediates alterations of the structural and mechanical properties of the
tissue, but this impact varies depending on the protocol used. For instance, Mirsadraee
et al.
(Mirsadraee et al., 2006) did not observe any significant changes using an SDS-based
decellularization protocol in the ultimate tensile strength compared to native tissue on
human pericardial tissue. They also observed an increased extensibility of the tissue when
cut parallel to collagen bundles.
Tissue decellularization reduces the cellular and humoral immune response targeted against
the bioprosthesis (Meyer et al., 2005). However, removing cells does not ensure adequate
removal of xenoantigens, nor mitigation of the immune response (Goncalves et al., 2005;
Kasimir et al., 2006; Simon et al., 2003; Vesely et al., 1995). For this reason, decellularization
protocols have turned to antigen removal protocols (Ueda et al., 2006; Kasimir et al., 2005). The
presence of cell membrane antigens, such as oligosaccharide beta-Gal has been reported to
lead to an immune response that can be prevented by effective decellularization (Badylak et
al., 2008). Interestingly, Griffiths
et al.
(Griffiths et al., 2008) used an immunoproteomic
approach to study the ability of bovine pericardium to generate a humoral immune response.
They identified thirty one putative protein antigens. Some of them, such as albumin,
hemoglobin chain A and beta hemoglobin have been identified as xenoantigens. Recently,
Ariganello
et al.
provided evidence that decellularized bovine pericardium induced less
differentiation of the monocytes to macrophages compared to polydimethylsiloxane or
polystyrene surfaces (Ariganello et al., 2010; 2011). Nevertheless, the effects of the host
immune response to acellular pericardium remain to be fully characterized. Understanding
this phenomenon is necessary to develop new pericardium preparations and thus improve
biological scaffold integration and clinical safety (Badylak & Gilbert, 2008).
Overall, no optimal decellularization treatment has been identified so far, but depending on
the target tissue as well as the implantation site, the protocol can be adapted to provide the
