NEW STRATEGY OF THERAPEUTIC ANGIOGENESIS INDUCED BY PROTEIN DELIVERY OF BASIS FIBROBLAST GROWTH FACTOR AGAINST LIMB ISCHEMIA

Abstract

Purpose of study: We developed a biodegradable hydrogel composed of acidic gelatin to enable basic fibroblast growth factor (bFGF) to be released at the site of action for an extended time period with protein delivery. We examined whether the topical use of gelatin hydrogel incorporating bFGF (hydrogel bFGF) facilitates the formation of collateral vessels and improves blood flow in diabetic rat hindlimb ischemia. Methods used: One week after diabetes induced by injection of streptozotocin once, ischemia was induced in the hindlimb of 15 rats by removal of the femoral artery. Two weeks later, they were divided into 2 groups: group A had just the femoral artery removed (n=7), group B had hydrogel bFGF 100 μg injected intramuscularly (n=8). We compared improvement of the local blood flow before and 4weeks after the treatment between group A and B. Summarize results: In histological assessment, the number of capillaries and arterioles around the muscle were seen larger in group B than in group A (group A: 58±13/mm2 vs. group B: 123±14/mm2, P<0.01). Moreover, recovery in limb perfusion as assessed by laser Doppler perfusion imaging were also better in group B than in group A (group A: 73° 10%, group B: 94±8%, P<0.01). Serum bFGF did not significantly increase in both groups before and after treatment. In conclusion, the controlled release system of hydrogel bFGF for topical use facilitated angiogenesis effectively. We believe that this therapy helps preventing limbs from amputation.