Rational Design of Artificial Cellular Niches for Tissue Engineering - Tissue Engineering: Computer Modeling, Biofabrication and Cell Behavior - page 128

2 Characterization of Natural Microenvironments

2.1 Main Components of the Natural ECM

The natural cellular microenvironment contains both intrinsic and extrinsic signals
that regulate cellular functions: quiescence, self-renewal, proliferation, differenti-
ation, motility, and apoptosis. This microenvironment varies in its characteristics
depending on the tissue it is part of [ 1 ]. Nevertheless, common features of cellu-
lar microenvironments can be recognized: they are 3D complexes consisting of:
(a) a cellular compartment, where different types of cells are found (e.g. for the
bone marrow: fibroblasts, osteoblasts, endothelial cells, stromal cells, etc.) [ 13 ];
(b) an ECM component, which acts as a dynamic support for cell anchorage and
intercellular communication [ 14 ]; and (c) a soluble component, which includes cy-
tokines, growth factors, metalloproteinases, etc. that contribute to matrix remodeling
and cell fate regulation [ 15 ].
In the ECM, different types of proteins are found, such as collagen, fibronectin,
laminin, vitronectin, and tenascin, together with a wide variety of proteoglycans like
hyaluronan, aggrecan, and decorin. Around 28 different molecules of collagen, the
most extensive protein in vertebrates, have already been found. Among them, type
I-III, V, and XI are triple helices of fibril structures (Fig. 1 ).
There is a wide variety of types of ECM in vertebrates, depending on tissues. The
main tissues in vertebrates are nerve, muscle, blood, lymphoid, epithelial and con-
nective tissues. Among them, epithelial and connective tissues are the most distinct
ones in terms of cell density and characteristics of the ECM. In the former, cells
are abundant and form a cell sheet that endures most of the mechanical stresses in

Fig. 1 , Advanced BioMatrix). Left :

Triple helix in type I collagen fibrils using an equipment that combines a Focused Iom Beam (FIB)
module with a Field Emission Gun (FE)-Scanning Electron Microscope (SEM) (FIB/FESEM,
Quanta 3D™ DualBeam™ FEI). Right : Micrograph of fribillar type-I collagen taken with the
same FIB/FESEM instrument. Images courtesy of Laboratory of Tissue Engineering, CEIT, San
Sebastian, Spain

Images of collagen hydrogels of 0.5 mg / mL (PureCol