The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.While vascular endothelial growth factor (VEGF) is an acknowledged potent pro-angiogenic agent there is a need
to deliver it at an appropriate concentration for several days to achieve angiogenesis. The aim of this study was
to produce microspheres of biodegradable polylactic-co-glycolic acid (PLGA) tailored to achieve sustained release
of VEGF at an appropriate concentration over seven days, avoiding excessive unregulated release of VEGF
that has been associated with the formation of leaky blood vessels. Several formulations were examined to
produce microspheres loaded with both human serum albumin (HSA) and VEGF to achieve release of VEGF
between 3 and 10 ng per ml for seven days to match the therapeutic window desired for angiogenesis. In vitro
experiments showed an increase in endothelial cell proliferation in response to microspheres bearing VEGF.
Similarly, when microspheres containing VEGF were added to the chorionic membrane of fertilised chicken eggs,
there was an increase in the development of blood vessels over seven days in response, which was significant for
microspheres bearing VEGF and HSA, but not VEGF alone. There was an increase in both blood vessel density
and branching – both signs of proangiogenic activity. Further, there was clearly migration of cells to the VEGF
loaded microspheres. In summary, we describe the development of an injectable delivery vehicle to achieve
spatiotemporal release of physiologically relevant levels of VEGF for several days and demonstrate the angiogenic
response to this. We propose that such a treatment vehicle would be suitable for the treatment of ischemic
tissue or wounds
