Rational Design of Artificial Cellular Niches for Tissue Engineering - Tissue Engineering: Computer Modeling, Biofabrication and Cell Behavior - page 134

StarPEG-heparin hydrogels were tailored for storage and controlled release of
high affinity GAG-binding proteins, in a fashion that closely resembles the mecha-
nisms occurring within natural tissue [ 53 ].
3.3 Natural Microenvironments: Decellularized ECMs
Decellularization of natural ECMs is particularly relevant within the field of organ
engineering, where whole-organ development is pursued. Despite the remarkable
achievements and extensive work already performed by tissue engineers in heart,
kidney, pancreas and lung regeneration, a complete functionality of the whole or-
gans has not yet been reached [ 54 ]. The first step in this process consists on the
removal of every cell in a donor organ by the perfusion of detergents, proteases and
chemicals; the aggressiveness of the process can damage the structure and compo-
sition of the resulting acellular 3D matrix, thus, altering the host response of these
scaffolds regarding to the organ reconstruction [ 55 ]. In the second step of the pro-
cess, a selection of cell populations are seeded in the acellular matrix, considering
the different cell types that are present in complex tissues and organs, in order to re-
generate every structure such as the parenchyma and vasculature. Many alternatives
are being evaluated as potential cell sources, including pluripotent stem cells, adult
progenitor cells or, in particular cases, tissue-derived differentiated cells; moreover,
autologous versus allogeneic cell sources are under study [ 56 ]. Finally, in order to
enhance the repopulation of the construct, specific culture conditions, adequate for
the organ in reconstruction, must be ensured. This is commonly achieved by means
of bioreactors, which can perfuse the culture media in the construct for the nutrient
and oxygen supply, and they can even provide the system with biophysical stimula-
tion as mechanical or electrical stimuli.
3.4 Model Implementation: Tissues- and Organs-on-a-Chip
In this section, a selection of a few significant examples of model implementations
of tissues- and organs-on-a-chip will be brought up from the literature to illustrate
the great potential of in vitro microdevices for Tissue Engineering.
Moraes and co-workers have recently used the term tissue-on-a-chip to identify
any micro-engineered system with controlled properties that achieves the forma-
tion of tissue constructs using cells, soluble factors, fluid shear or perfused culture
medium [ 57 ]. Similarly, organ-on-a-chip is used to designate a more complex mi-
croengineered system that is able to recapitulate the in vivo milieu at an organ level,
frequently applying microscale compartmentalization strategies [ 57 ]. Their work
nicely reviews the last advances towards developing functional organs-on-a-chip .
Work conducted at the Griffith Laboratory reported as early as in 2002 on the
design, fabrication, and performance of a bioreactor for both morphogenesis of 3D