Synthetic Morphogens and Pro-morphogens for Aided Tissue Regeneration - Biologically Responsive Biomaterials for Tissue Engineering - page 47

of action, morphogens stem out as of key importance in the signalling process that
is required for tissue formation. Two main aspects of the morphogen role are worth
noting:

• Their number appears to be relatively limited when compared to the number of

functions they can exert on the developing embryo. From the examples provided
in Sect. 3.4 , it is obvious that a variety of tissues can be generated by only a few
types of morphogens/growth factors. Indeed, it is significant that some of them
are structurally and functionally related to growth factors controlling the tissue
signalling pathways in adult organisms.
Their interactions with the macromolecules of the ECM appear to be important •

in the regulation of the tissue formation. In particular, docking sites are necessary
to control the diffusion and the local concentrations of the morphogens that are
indicated as the main mechanisms for cell interpretation of the biosignalling.
Their recognition by the cells appears to be a regulator not only of the cell •

function, but also of their gradients and local concentrations.
Their actions through concentration gradients, opposing gradients and cell biorec-

•

ognition are mainly exerted on stem cells presenting a totipotent or multipotent
phenotype that allows them to differentiate in various types of tissue cells.

Most of these controlling mechanisms can be regarded as lessons to be transferred
to the study of tissue repair and regeneration in adult organisms and to clinical appli-
cations aiming at the repair of tissues damaged by either trauma or disease.

3.6 Growth Factors in Adult Tissue Repair and Regeneration

Unlike embryo development, adult human morphogenesis during the process of
tissue repair is guided by a variety of signals produced by different types of cells
(e.g. inflammatory cells and tissue cells). Indeed, following damage, tissue repair
is promoted by cytokines and growth factors that interact with tissue cells to
regulate their genes and in turn their metabolic activity [ 18 ] . Traumatic events
(accidental or surgical) and diseases cause the loss of the tissue architectural, bio-
chemical, cellular and homeostatic properties [ 19 ]. Indeed, the ECM is mainly
composed of structural proteins (e.g. collagens, fibronectin) and polysaccharides
(e.g. glycosaminoglycans) which preserve cell viability and the delicate homeo-
static balance of the tissue (Fig. 3.2a ).
As discussed in Sect. 3.3 , any change in the ECM structure can alter the distribution
of the morphogens and therefore their action. As a consequence of its disruption it is
likely that the biosignalling during healing may negatively impact the ability of the
ECM macromolecules to control the morphogen/growth factor gradients.
The restoration of these properties in spontaneous healing is gradual and takes
place through a number of phases starting from the arrest of the bleeding by the clot
which is gradually digested by inflammatory cells and proteolytic enzymes to give