Delivery of Osteogenic Regulatory Growth Factors - Engineered Bone: Tissue Engineering Intelligence Unit - page 110

Figure 1. Pharmacokinetics of various rhBMPs combined in three different carriers in the rat ectopic assay.
10 µ g of iodinated rhBMP were implanted for 3h, 1, 4, 7, 10 and 14 days. The protein-bound radioactivity
from the explants was then measured to determine the percent retention of the implanted rhBMP dose.
Figure adapted from Ref .29. Copyright© 2000 John Wiley & Sons. Reprinted by permission of John Wiley
& Sons, Inc.
The presence of specific chemical binding groups like heparin-binding domain might in-
fluence the binding of growth factors to a carrier. Heparin as well as heparan sulfate proteoglycans
in the extracellular matrix bind to numerous polypeptide growth factors with high affinity.
These growth factors, usually named “heparin-binding growth factors” include BMPs, FGFs,
IGF, EGF and VEGF. Physiologically, this binding activity is important in sequestering growth
factors in the extracellular matrix, allowing the localisation of growth factor activity, the pre-
vention of growth factor degradation, and in some cases, the enhancement of growth factor
binding to cell surface receptors. 30-32 To exploit this binding affinity, some investigators com-
bined growth factors to heparin to stabilise the proteins. 33 Heparin was also immobilised to a
matrix, acting as an affinity site to bind and slowly release growth factors in the healing site.
This drug delivery system consisted of the combination of growth factor, heparin and
heparin-binding peptides covalently immobilised within a fibrin matrix. 34
Kinetics of Growth Factors Released from the Carrier
There are two major mechanisms of growth factor release: material degradation and carrier
diffusion. The mechanism is highly dependent on the choice of material and the method of
loading the growth factor into the matrix (e.g., soaking in the carrier or mixing with the carrier
substance before moulding). Physical hindrance and chemical interaction are two means by
which matrices could delay growth factor release and diffusion. 35-37 These properties serve to