Synthetic Morphogens and Pro-morphogens for Aided Tissue Regeneration - Biologically Responsive Biomaterials for Tissue Engineering - page 50

not all have been successful in improving the quality of nerve repair. Some success
was reported in the publications by Piquilloud et al. [ 26 ] and Barras et al. [ 27 ] show-
ing significant evidence in support of the NGF effect.

3.6.2 Limitation in the Use of Growth Factors

in Clinical Intervention

In therapeutic applications, the use of growth factors is limited by their purification
costs, batch-to-batch reproducibility, known instability under storage conditions
and short lifespan in physiological conditions. In addition, their ability to stimulate
cells tightly depends on their bioavailability. In most of the cases, short lifespan and
sufficient bioavailability require the administration of relatively high dose of these
growth factors. Such doses are not only very expensive, but they also increase the
risks of tumours. Safety concerns are also caused by the risk of transmittable dis-
eases from donor to recipient. While the costs and risks of transmittable diseases
have been tackled by the synthesis of recombinant proteins, problems still remain
about the stability under storage and administration conditions as well as about the
relatively high dosage.
It is thought that by improving the growth factor stability in vivo, relatively
lower doses will become therapeutically efficacious. Delivery systems which are
able to preserve the native conformation of these growth factors and to provide
appropriate concentrations and gradients in the extracellular space have been
designed for this purpose. For example, growth factors for bone repair have been
delivered through the use of polymeric, ceramics and composite biomaterials. The
review papers by Lee and Shin [ 22 ] and by Seeherman and Wozney [ 28 ] offer an
overview of the various combinations of biomaterials and growth factors employed
for this purpose. In all these methods the slow delivery of these growth factors
relies upon the physico-chemical properties of the carriers which are far to mimic
the docking sites for morphogens and growth factors present in the ECM of both
embryonic and adult tissues.
FGF-1 localised delivery has also been pursued through the entrapment of the
growth factor in a fibrin/hydroxyapatite composite. In vivo this system was capable
of delivering biologically active FGF-1 for a longer period of time leading both to
enhanced angiogenesis and infiltration of osteoprogenitor cells [ 29 ] .
Similarly, FGF-2 release from p(HEMA-co-VP), while showing that FGF-2 was
able to enhance bone formation by increasing bone volume, did not show a protracted
effect after surgery [ 30 ] .
The methods of NGF delivery proposed by Piquillod et al. [ 26 ] rely on a degradation-
linked release effect from the polymeric matrix, while the approach followed by
Barras et al. [ 27 ] capitalises on the diffusion of the entrapped growth factor from the
neural guide mesh. As outlined above, these methods of delivering present significant
limitations as, for example, degradation-driven release may limit the growth factor