Stem Cell Differentiation Depending on Different Surfaces - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 275

particles with a porous inner matrix and a variable surface. Bioactive molecules
can be captured within the inner matrix. Generally, microspheres have a diameter
of 1-500 lm. Smaller particles (10-1000 nm) are described as nanospheres.
The biodegradable polymer microspheres are embedded in the pores of a ceramic
matrix prior to cultivation. The major advantage of this method compared with the
embedding of bioactive molecules into a polymer coating is the combination of
different polymers with differing degradation profiles. Consequently, it is possible to
create a time-controlled release of multiple growth and differentiation factors.
Therefore, this method can be used to direct the differentiation behavior of MSC. The
time-dependent release can be controlled by variation of the polymer properties. The
most commonly used polymer for this application is poly(lactic-co-glycolic acid)
[ 70 , 71 ]. Moreover, alginates [ 77 ] and chitosans [ 78 ] are frequently applied. An in
vivo microenvironment can be simulated in vitro by applying different bioactive
molecules and polymers with defined release profiles.
Another possibility to create a bioactive surface on a ceramic matrix is its
specific modification with biologic compounds. Early studies showed a function-
alization of the surface with ECM proteins, such as fibronectin and laminin [ 79 ].
These proteins support cell adhesion and proliferation. It is well known that only
specific amino acid sequences of these proteins interact with the integrins of the
cells; therefore, only short amino acid sequences are used for surface modification.
The sequence arginine-glycine-aspartic acid [ 80 - 82 ] supports cell adhesion and
has been studied in detail. Moreover, the amino acid sequences tyrosine-isoleu-
cine-glycine-serine-arginine [ 83 ], arginine-glutamine-aspartic acid-valine [ 84 ],
and isoleucine-lysine-valine-alanine-valine [ 83 ] are used for tissue engineering
surface modification. These sequences can be introduced into the 3D matrix
network by physical, chemical, photochemical, and ionic cross-linking.

5 Sensing the Microenvironment

The modulating effect of matrix stiffness, topography, and geometry upon cellular
responses to biomaterials has been studied in detail over the past decade. It is
obvious that cells have the ability to sense their microenvironment and react to
the properties of their surroundings in a different manner. But what mechanism do
the cells use to identify their substrate and how do they process the information
obtained? Prior to sensing the surface elasticity, roughness, or geometry, the cells
need to adhere to the substrate. The adhesion procedure is modulated by integrins,
which are located in the cell membrane. Three mechanochemical features are
important during the adhesion process [ 85 ]: (1) the biomaterial-integrin binding
forces have to pass a critical threshold, (2) the integrins must mechanically link the
artificial matrix to the cytoskeleton in order to transmit extracellular forces to the
cell interior, and (3) the transmitted forces have to be translated into biochemical
signals (mechanotransduction), resulting in a cellular response. But not only
integrins are involved in the procedure of cell-matrix adhesion and signal