Biomedical Engineering Reference
In-Depth Information
3.5.3 Platelet derived growth factor (PDGF)
this is secreted in the form of dimer with different combinations of a, B, C
and d chains. it is present in platelet a-granules, monocytes, macrophages,
endothelial cells and osteoblasts.
103
PDGF acts both in the first phase of
bone repair, stimulating the proliferation of osteoprogenitors, and during
the differentiation stage. pdGF is released by platelet a-granules during the
early phases of fracture healing
104
and afterwards by the cells of the bone
repair site. pdGF-BB is generally considered more effective than pdGF-
aa in stimulating mitogenic activity on the skeleton,
105
but pdGF-aa also
influences bone healing, together with BMP-2 and TGF-b.
106
3.5.4 Vascular endothelial growth factor (VEGF)
this is produced by endothelial cells and osteoblasts. in the early stages
of bone repair, vEGF is also released by platelet a-granules. Even if
angiogenesis is the most known effect of vEGF, it is also required for osteoblast
proliferation and differentiation.
107
vEGF is involved in the conversion of
cartilage to bone callus during fracture repair
108
and increases the number
of osteoblasts.
109
vEGF also favours osteoclastogenesis inducing raNK
expression in osteoclast precursors.
110
3.5.5 Insulin-like growth factors (IGF)
two
insulin-like growth factors (IGF) have been identified (IGF-I or
somatomedin C and iGF-ii). the serum concentration of iGF-i is mainly
regulated by the growth hormone (Gh) and the biological actions of iGF
are modulated in a cell-specific manner by IGF-binding proteins.
iGF-i is primarily produced by liver cells in response to Gh. other sources
are the bone matrix, endothelial cells, osteoblasts and chondrocytes. the
target tissue of iGF-i are muscle, cartilage, bone, liver, kidney, nerves, skin
and lungs. iGF-i is more potent than iGF-ii and has been localized in healing
fractures,
111
even if iGF-ii is the most abundant growth factor in bone. in the
first phases of bone repair, IGF-I stimulates osteoblast proliferation
112
and
promotes bone matrix formation by fully differentiated osteblasts.
113
iGF-ii
acts at a later stage of endochondral bone formation and stimulates type i
collagen production, cartilage matrix synthesis and cell proliferation.
114
iGF
is regarded as a link between bone formation and bone resorption.
115
3.5.6 Protein therapy with recombinant growth factors
the rationale for the therapeutic use of GF to stimulate bone healing is
based on the hypothesis that the selection of an appropriate signalling GF
