Synthetic Morphogens and Pro-morphogens for Aided Tissue Regeneration - Biologically Responsive Biomaterials for Tissue Engineering - page 49

by a diabetic mouse model have shown the relatively lower expression of receptors
for the platelet-derived growth factor (PDGF-BB), an important stimulator of
fibroblast proliferation and promoter of tissue repair [ 21 ]. In such a case, the
presence of the growth factor as well as of its diffusion through a gradient may not
be sufficient to ensure tissue repair.

3.6.1 Use of Growth Factors in Clinical Intervention

The use of growth factors as therapeutic tools has widely been explored at research
level and, in some cases, it has reached its clinical use. Relevant to this chapter is
the use of growth factors structurally and functionally related to embryo
morphogens.
The most important class of growth factors used in bone tissue engineering is the
TGF-m superfamily that includes the TGF-1 and the BMPs [ 22 ] . In adults, BMPs
act as a stimulating factor for stem cell differentiation into osteoblasts and direct
osteochondral calcification. BMP-2, also known as OP-1, has been commercialised
by Stryker and used to treat bone critical defects. Conversely, FGF-2 has been inves-
tigated showing conflicting evidences about its bone repair potential.
Alongside these growth factors with morphogen similarities, other growth fac-
tors are worth mentioning because of their therapeutic potential for tissue repair.
The insulin-like growth factor (IGF) is another growth factor that has been carefully
investigated in relation to cartilage and bone repair [ 22 ] .
Together with FGF, the vascular endothelial growth factor (VEGF) is widely
recognised as the principal player in angiogenesis and it has been used to improve
vascularisation of newly formed bone. In addition, it has been demonstrated that
VEGF is also a mediator of various osteoinductive factors such as TGF-b1, thus
providing an indirect stimulus to osteogenesis [ 22 ]. As a potent stimulator of
fibroblast proliferation PDGF-BB has also been proposed as a growth factor in skin
regeneration. The clinical performance of acellular skin grafts such as Biobrane ® ,
Biobrane-L ® and Transcyte ® , bioengineered dermal substitutes, is linked to their
ability to provide growth factors including PDGF-BB [ 23, 24 ] .
Neural growth factor (NGF) is the target of many studies aiming at peripheral
nerve regeneration. NGF is released by the distal end of a damaged nerve to attract
axonal regeneration at the proximal stump. However, only short nerve gaps are
capable of spontaneous repair. In an attempt to address this clinical problem, many
research groups have studied the delivery of NGF into the lumen of a repairing
nerve. One specific example of such an approach is the delivery of NGF into a sili-
cone nerve guide by an osmotic pump [ 25 ]. This method of delivery has been proven
to be successful in improving the quality of nerve repair over a 5 mm gap. However,
it is important to consider that these experiments were performed in a healing model,
thus not proving the clinical potential of this approach. Indeed, the delivery of NGF
into the lumen of nerve guide has been evaluated in many publications. However,