Drug Delivery to the Cardiovascular System - Applications of Biotechnology in Cardiovascular Therapeutics - page 55

matrices presenting protease-degradable sites, cell-adhesion motifs, and growth
factors have been shown to induce the growth of vasculature in vivo (Phelps et al.
2010 ). Compared to injection of soluble VEGF, these matrices can deliver sus-
tained in vivo levels of VEGF over 2 weeks as the matrix degrades. When implanted
subcutaneously in rats, degradable constructs containing VEGF and arginine-glycine-
aspartic acid tripeptide induce a significant number of vessels to grow into the
implant at 2 weeks with increasing vessel density at 4 weeks. The mechanism of
enhanced vascularization is likely cell-demanded release of VEGF, as the hydrogels
may degrade substantially within 2 weeks. In a mouse model of hind limb ischemia,
delivery of these matrices produced significantly increased rate of reperfusion.
These results support the application of engineered bioartificial matrices for deliv-
ery of vascular growth factors to promote vascularization in regenerative therapies
for peripheral ischemic disease.
Immune Modulation Therapy for Peripheral Arterial Disease
Vasogen's Celacade ™ technology involves the ex vivo exposure of a sample of
autologous blood to three oxidative stress factors (heat, an oxidative environment,
and ultraviolet light), followed by intramuscular reinjection. A double-blind, placebo-
controlled pilot study has assessed the effect of Celacade ™ technology on skin
blood flow in patients with symptomatic peripheral arterial occlusive disease
(Edvinsson et al. 2003 ). No significant differences were detected between various
groups for resting or peak postischemic laser Doppler fluxmetry values for dorsal
foot skin blood flow. Patients randomized to Celacade ™ experienced a progressive
decrease in the time to peak postischemic skin blood flow, reaching statistical sig-
nificance at 2 months. Treated patients experienced a 26.1 s decrease in time to
peak blood flow compared to a 7.9 s decrease in the placebo group. Similar but less
striking results were achieved for tcpO 2 recovery time to 50% of pre-ischemia val-
ues (treated group, p = 0.035; placebo group, p = ns). The improved recovery rates
of postischemic dorsal foot skin blood flow in a group of patients with moderately
advanced peripheral arterial disease was probably due to improved endothelial
function.
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Edvinsson LI, Edvinsson ML, Angus Deveber G. Vasogen's immune modulation therapy improves
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