Biomedical Engineering Reference
In-Depth Information
1981; 1985), or, even more unusually, ostrich (Maestro et al., 2006) or kangaroo pericardium
(Neethling et al., 2000; 2002). However, those exogenous grafts raise several issues, and
especially the immune response against the bioprosthesis as well as the viral status of the
graft.
Human autologous pericardium is thus an interesting option, presenting several advantages
over allografts since it is free of donor-derived pathogens and does not induce any immune
response (Mirsadraee et al., 2007), is easily available, easily handled and of low cost.
Ultimately, these characteristics allow for shorter and less aggressive pericardial processing
before implantation of the bioprosthesis. However, because of intermittent reports of its
tendency to retract or become aneurysmal, the general opinion has been negative (Edwards
et al., 1969, Bahnson et al., 1970). For cusp tissue replacement or valve tissue replacement,
stabilization of pericardium is performed with a solution of 0,2% to 0,6% glutaraldehyde in
order to prevent secondary shrinkage (Duran et al., 1998; Al-Halees et al., 1998, 2005; Goetz
et al., 2002).
3. Processing of pericardium
As allografts have been the main source for pericardial bioprostheses currently in use,
significant processing steps have to be performed prior to clinical use. In particular, as
xenogeneic cellular antigens induce an immune response or an immune-mediated rejection
of the tissue, decellularization protocols are widely used to reduce the host tissue response
(Gilbert et al., 2006.). Once decellularized, the free-cell pericardial tissue is composed of
extracellular matrix proteins which are generally conserved among species, and thus can be
easily used as a scaffold for the host cell attachment, migration and proliferation (Schmidt &
Baier, 2000). This scaffold considerably accelerates tissue regeneration. Overall, tissue
decellularization aims at reducing tissue antigenicity and host response while preserving
the mechanical integrity, biological activity and composition of the ECM (Simon et al., 2006;
Gilbert et al., 2006).
3.1 Extracellular matrix decellularization methods
Most decellularization protocols include a combination of various methods, such as
physical, enzymatic or chemical treatments (Gilbert et al., 2006; Crapo et al., 2011). Physical
methods can either rely on snap freezing (Jackson et al., 1988; Roberts et al., 1991),
mechanical force (Freytes et al., 2004) or mechanical agitation (Schenke-Layland et al., 2003),
whereas enzymatic protocols employ nucleases, calcium chelating agents or protease
digestion (Teebken et al., 2000; Bader et al., 1998; McFetridge et al., 2004; Gamba et al., 2002).
Regarding physical decellularization processes, sonication, based on the use of ultrasounds
to disrupt the cell membrane, has been investigated. Such treatment considerably affects the
pericardial architecture and full decellularization cannot be achieved. Thus sonication has to
be carried out simultaneously with chemical treatments in order to fully decellularize the
pericardial tissue and remove cellular debris. However, this combination leads to alterations
of the extracellular matrix (ECM) architecture.
For the enzymatic procedure, the main enzyme employed is trypsin, cleaving peptide
bonds on the C-side of arginine and lysine and thus allowing separation of the cells from
the ECM.
Chemical protocols involve use of alkaline and acid treatments (Freytes et al., 2004), ionic
detergents, sodium dodecyl sulfate (SDS), sodium deoxycholate and Triton X-200 (Rieder et
