Synthetic Morphogens and Pro-morphogens for Aided Tissue Regeneration - Biologically Responsive Biomaterials for Tissue Engineering - page 58

Fig. 3.3 Schematic
representation of a dendrimer
obtained by liquid-phase
synthesis. Gn indicates the
number of branching
generations (Figure kindly
provided by Dr. Steven
Meikle, University of
Brighton)
Fig. 3.4 Schematic
representation of a semi-
dendrimer (dendron) obtained
by a solid-phase method. Gn
indicates the number of
branching generations
(Figure kindly provided by
Dr. Steven Meikle, University
of Brighton)
Conversely, when the synthesis is performed on a solid phase the branching poly-
mer develops a dome-like (semi-sphere) or a tree-like structure, the semi-dendrimer
(or dendron) [ 70 ] (Fig. 3.4 ).
By both methods it is possible to obtain dendrimers (or dendron) with several
branching levels (generations, Gn) (Figs. 3.3 and 3.4 ). The synthesis of dendrimers
up to G9 has been reported [ 71 ]. From a biotechnological viewpoint both dendrim-
ers and dendrons offer a unique opportunity to expose functionalities able to favour
bio-interactions by a nanostructurally controlled manner. Dendrimers have been
mainly proposed as carriers for the delivery of contrast agents to tissues as well as
of nucleic acid drugs to cells (e.g. US patent no 689056 [ 72 ] ). In particular, PAMAM
dendrimers can bind DNA because of their overall positive charge and nano-archi-
tecture (US patent no. 0130191). For these reasons, PAMAM dendrimers have been
commercialised as plasmid vectors in cell transfection (Superfect™, Quiagen).
Recently, dendrons have been used to increase the affinity of specific bioligands to
cell receptors by functionalising the last branching of the dendrimer with the tar-
geted bioligand [ 73 ]. A patent application has been filed by the University of
Brighton in which bi-functional, bio-tethered dendrons are used to functionalise the
surface of medical implants (PCT/GB2007/050741) (Fig. 3.5 ).
This patent application ensures the correct orientation of the dendron at material
surfaces, thus maximising the exposure of cell bioligands and docking sites for
morphogens and growth factors and increasing their density for area unit considered.
These nanostructured biomaterials could therefore be considered and termed as