Supplementary Material for: VEGF and IGF Delivered from Alginate Hydrogels Promote Stable Perfusion Recovery in Ischemic Hind Limbs of Aged Mice and Young Rabbits

Biomaterial-based delivery of angiogenic growth factors restores
perfusion more effectively than bolus delivery methods in rodent models
of peripheral vascular disease, but the same success has not yet been
demonstrated in clinically relevant studies of aged or large animals.
These studies explore, in clinically relevant models, a therapeutic
angiogenesis strategy for the treatment of peripheral vascular disease
that overcomes the challenges encountered in previous clinical trials.
Alginate hydrogels providing sustained release of vascular endothelial
growth factor (VEGF) and insulin-like growth factor-1 (IGF) were
injected into ischemic hind limbs in middle-aged and old mice, and also
in young rabbits, as a test of the scalability of this local growth
factor treatment. Spontaneous perfusion recovery diminished with
increasing age, and only the combination of VEGF and IGF delivery from
gels significantly rescued perfusion in middle-aged (13 months) and old
(20 months) mice. In rabbits, the delivery of VEGF alone or in
combination with IGF from alginate hydrogels, at a dose 2 orders of
magnitude lower than the typical doses used in past rabbit studies,
enhanced perfusion recovery when given immediately after surgery, or as a
treatment for chronic ischemia. Capillary density measurements and
angiographic analysis demonstrated the benefit of gel delivery. These
data together suggest that alginate hydrogels providing local delivery
of low doses of VEGF and IGF constitute a safe and effective treatment
for hind-limb ischemia in clinically relevant animal models, thereby
supporting the potential clinical translation of this concept.