Rational Design of Artificial Cellular Niches for Tissue Engineering - Tissue Engineering: Computer Modeling, Biofabrication and Cell Behavior - page 127

1 The Importance of the Cellular Niche in Tissue
Engineering
Tissue Engineering is a promising emerging field that studies the intrinsic regener-
ative potential of the human body and uses it to restore functionality of damaged
organs or tissues unable of self-healing due to illness or ageing.
Every living cell is affected by the surrounding microenvironment, known as the
extracellular matrix (ECM) [ 1 ]. Many recent studies reveal that biophysical and bio-
chemical features of the ECM such as stiffness, biochemical composition and matrix
topography can influence and also dictate cellular response [ 2 - 4 ]. The cellular niche
is also relevant for modulating cellular forces exerted on the ECM [ 5 ]; these forces
activate specific signaling pathways, which further trigger transcription factors that
control gene expression in the nucleus [ 6 ]. This effect, known as mechanotrans-
duction, affects cell adhesion, proliferation, motility, differentiation and apoptosis
[ 7 , 8 ].
Therefore, the design of controlled artificial cellular niches has a tremendous im-
portance to direct cells towards specific functions. Using Tissue Engineering strate-
gies, the artificial niche will have to recapitulate the natural ECM. As a result, the
engineered construct will serve as a physical scaffold for the cells, allowing their
three-dimensional (3D) spatial organization; it will also ensure the mechanical sta-
bility of the whole construct; finally, it will provide biochemical and biophysical
cues which will have an impact on cellular growth, migration, differentiation and
synthesis of natural ECM.
For a rational design of artificial ECMs, we propose to start by studying the
properties of the native tissue. Characterizing healthy tissues and identifying their
differences compared to damaged ones has shown potential to facilitate disease de-
tection and development of novel targets for regenerative medicine [ 9 , 10 ]. Special
attention should be paid to the biophysical aspects (biochemical composition and
mechanical properties) as well as the macro-, micro- and nanoscopic structure of
the ECM [ 11 , 12 ], since both have remarkable effects on cellular responses.
During the last decades, great contributions have been made by a growing
scientific community in the field of Tissue Engineering. Although this field has
required—and still does—substantial economical investments during extended pe-
riods of time, these funds have not always been sufficient to translate research ad-
vances into new clinical therapies. To a greater extent, scientists in this field are
aware of the need of more rationale before carrying out complex, expensive and
time-consuming in vitro and in vivo trials.
This chapter will recall the importance of the development of better models, high-
lighting computer modeling and novel biofabrication techniques as critical key play-
ers for a rational design of artificial cellular niches in Tissue Engineering. It will also
review the latest efforts towards the development of human-on-chip models thanks
to the progression of microfluidics.