Synthetic Morphogens and Pro-morphogens for Aided Tissue Regeneration - Biologically Responsive Biomaterials for Tissue Engineering - page 59

a

DD

D

D

B

b

AB AB AB AB AB AB AB AB

DD DD DD DD D

AB AB

D D

D D D

D D D D D

AB AB AB AB

B B B B B

a b c d

BIOMATERIAL SURFACE

- electrostatic bond
- covalent bond

Fig. 3.5 Schematic representation of dendrons for biomaterial surface functionalisation according
to patent application PCT/GB2007/050741. ( a ) Single bi-functional G1 dendron, ( b ) biomaterial
surface functionalisation with bi-functional dendrimers exposing bioactive molecules with differ-
ent strategies: from left to right electrostatic interaction, covalent interactions, entrapment, combi-
nation of all. B: Bridging functionality able to recognise and bind the surface of a given biomaterial.
D: Docking site for bioactive molecules, (AB): bioactive molecule. Adapted from patent applica-
tion PCT/GB2007/050741

synthetic pro-morphogens. In their functions these macromolecules would be poten-
tially beneficial both to cell adhesion as they can lead to the spaced distribution of
the bioligands interacting with the cell membrane receptors (Fig. 3.1 , lower path-
way) and to the generation of domains of high concentration of morphogens and
growth factors (Fig. 3.1 , upper pathway). In the case of cell bioligands, their presen-
tation through an ordered branching of the dendrons is also likely to generate a
surface nano-topography able to enhance cell adhesion. Docking sites can be
obtained, for example, through the functionalisation of biomaterial scaffold by hep-
aran sulphate oligomers derived from the ECM as those which have been reported
to regulate morphogen gradients in developing tissues (see Sect. 3.3 ) [ 11 ] . Indeed,
heparin has already been shown to be able to form macromolecular complexes with
VEGF and to play a fundamental role in controlling tissue angiogenesis [ 74 ] .