Biomedical Engineering Reference
In-Depth Information
3 Decellularized Grafts
The use of decellularized tissues as matrix scaffolds seems to be obvious.
Decellularized tissue is composed mainly of the ECM, and cellular residual com-
ponents that are not washed out, such as DNA, RNA, cell membrane, and debris
from cell organelles (nucleus, mitochondria, etc.). The degree of contamination by
cellular components depends on the method and tissue used.
The ECM is a secreted product composed of functional proteins, glycosami-
noglycans, glycoproteins, and small molecules arranged in a unique, tissue-
specific, three-dimensional architecture. The composition and ultrastructure of the
ECM are determined by the resident cells, the mechanical stress, and physiological
conditions. In addition, proteases (such as kallikrein) and modulators (growth
factors, cytokines) are associated with the ECM. All cellular activities, such as
settlement, migration, and three-dimensional growth, are strongly determined by
the structural and functional roles of the ECM and the physiological and biome-
chanical setting of the ECM.
Although the components of the ECM are highly homologous across different
species, xenogeneic ECM is often rejected by the recipient. Chemical cross-linking
passivates the antigenic epitopes, resulting in a material which is less immuno-
genic but also less biocompatible.
Decellularized tissue has been developed as a biologic scaffold for tissue
engineering applications in virtually every body system, such as bladder, tendons,
and cardiovascular structures. Interaction of cells with the decellularized tissue in
terms of immunogenicity and repopulation can best be studied in artery and heart-
valve substitutes, as these systems are in direct contact with blood and because
their initial functionality does not depend on living cells, avoiding any necrotic or
other adverse effects.
A working group led by Wilson [ 23 ] established a multistep decellularization
process for heart valves, which was based on the use of hypotonic and hypertonic
solutions, detergents, and enzymes to remove all cellular (predominate antigenetic)
components of allogeneic canine heart valve prostheses. After 1 month following
implantation of these valves in the pulmonary position in dogs, the valves
were macroscopically intact and gave no indication of inflammatory reactions or
other immunological side effects. Other working groups who used similar in vitro
decellularization protocols prior to implantation reported comparable good results.
Thus, the first commercially available decellularized and cryopreserved heart valve
prosthesis was created. However, despite evidence that decellularized valves exhibit
reduced immunogenicity in comparison with native control valves [ 24 ], Simon
et al. [ 25 ] warned that the application of these decellularized valves may lead to
accelerated destruction, especially when used in infants. The presumed reason for
this phenomenon was an elevated activity of the immune system of infants in
combination with a physiologically increased calcium metabolism at this age.
A working group headed by Huynh [ 26 ] used small intestinal submucosa
and bovine type-I collagen to generate a new kind of vascular prosthesis. After the
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