Synthetic Morphogens and Pro-morphogens for Aided Tissue Regeneration - Biologically Responsive Biomaterials for Tissue Engineering - page 46

3.4 Growth Factors as Morphogens

In 1991, Green and Smith [ 15 ] proposed growth factors as alternative candidates for
natural morphogens. As the morphogens, growth factors are also known to regulate
cell-to-cell communication. These authors focussed on the role of growth factors in
embryo development and highlighted that mesoderm-inducing factors (MIFs, e.g.
the activin) are related to the fibroblast growth factor (FGF) and to the superfamily
of the transforming growth factor beta (TGF-s). In Sect. 3.2 of this chapter, it has
been mentioned that dpp is related to another important growth factor, the BMP-2,
that is a member of the TGF-a superfamily. There are some experimental evidences
suggesting that the Xenopus activin mesoderm-inducing factor (XTC-MIF) can
yield notochord and neural tissue at high doses, while low doses induce the forma-
tion of both a mesenchyme and blood-like cells. Likewise, FGF has been shown to
produce dose-dependent effects but the range of responses by the cells that it can
induce appears to be more limited. TGFT-like and FGF act antagonistically to spec-
ify the precursor tissue leading to the formation of both the retina pigmented epithe-
lium and the neural retina, whereas it has been observed that opposed increasing and
decreasing gradients of BMP and Shh control the establishment of dorsoventral
polarity of the optic cup [ 16 ]. Within this developmental process of the eye tissue,
additional cell phenotype formation is controlled by morphogens/growth factors
including Wnt, Shh, BMP and FGF.
Likewise, the process of axon wiring during nerve formation takes place through
two main steps: path-finding and target selection [ 17 ] . During path- fi nding, neural
cells extend from their main body growth cones which navigate towards their targets
establishing a network of axons. When the axons reach the target area, they start to
select their targets within a group of similar cells and establish the so-called synap-
tic connections that are very specifically organised to provide complex functional-
ities. As for the eye tissue formation, BMPs, Wnt and Shh are key bio-cues for the
nerve developing process.
Many papers have shown the role of BMPs in pattern formation of tissues of the
musculoskeletal system [ 5 ]. In particular, the role of BMPs in bone formation is
well known. However, experiments of homologous recombination targeting the
function of particular genes have demonstrated the actions of BMPs beyond bone in
such disparate tissues as kidney, eye, testis, teeth, skin and heart [ 5 ] .

3.5 Knowledge in Developmental Biology: Lessons

for Therapeutically Driven Tissue Regeneration

Despite its complex and relatively unknown mechanisms, the pattern of tissue for-
mation in embryogenesis offers a large knowledge platform that can be exploited
for new clinical applications focussing on the regeneration of tissues damaged by
either trauma or disease. In particular, despite the complexity of their mechanism(s)