Biomedical Engineering Reference
In-Depth Information
in their niche
[32]. Even though sometimes that`s exactly what is needed to be avoided (e.g.
Central Nervous System ECM has been shown to contain molecules which inhibit axonal
growth and hinders tissue regeneration [33,34]), ECM has been considered a great option for
tissue engineering.
Recently, it has been shown that cell sensibility towards ECM chemical composition is higher
than previously expected. For instance, Tsai et al. showed that MG63, an osteoblast like cell
lineage, behaves differently when grown in collagen or gelatin electrospun matrices. When
grown in electrospun collagen, MG63 did not show variation on cell attachment or
proliferation rates. On the other hand, cells seeded on electrospun collagen showed increased
expression of osteogenic genes such as Osteopontin and alkaline phosphatase. Collagen and
gelatin present high chemical composition similarity, varying mainly in secondary and tertiary
structure. Such fact underscores the strikingly cell sensitivity to all aspects of ECM chemical
and physical composition [62]. It also underscores the potential of decellularized matrices on
tissue engineering.
Decellularized tissues have been used in regenerative medicine approaches since the early
eighties [38], specially focused on treating cardiovascular diseases by engineering vascular
grafts. Most of the grafts produced, derived from synthetic and natural sources suffered from
several limitations. When the issue of natural graft calcification and immunological recognition
were related to residual cellular components of unmodified biological materials, decellulari‐
zation techniques began to be developed [38,39].
Initially, decellularization was considered for tissue grafts. Developed techniques are con‐
tinuously evolving, as every cell removal agent and method currently available alters
ECM composition and cause some degree of ultrastructure disruption. Decellularization
agents include chemical, biological and physical agents, each of them with different
mechanisms of action.
More specifically: acids and bases promote hydrolytic degradation of biomolecules; hypotonic
solutions lyses cells through osmosis with minimal changes in matrix molecules and tissue
architecture; hypertonic solutions dissociates DNA from proteins; ionic, non-ionic, and
zwitterionic detergents solubilize cell membranes leading to effective removal of cellular
material from tissue; solvents, such as alcohol and acetone, promote either cell lysis by
dehydration or solubilization and removal of lipids and biological agents, such as enzymes,
and chelating agents act through protein cleavage and disrupting cell adhesion to ECM.
Finally, physical agents promote cell lysis through freezing and thawing cycles, electropora‐
tion or pressure [32].
The most effective agents for decellularization of each tissue and organ will depend upon many
factors, including the tissue's cellularity, density, lipid content, and thickness [32].
Lately, whole organ decellularization began to be performed, offering an interesting option
for modular organs such as the heart, lung and kidneys. In 2008, Ott et al. not only performed
whole heart decellularization, but also recellularized the organ with neonatal cardiomyocytes
and obtained organ function [17]. This groundbreaking work highlighted the possibilities of
decellularized matrix-based whole organ tissue engineering.
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