Enhanced angiogenesis by gelatin hydrogels incorporating basic fibroblast growth factor in rabbit model of hind limb ischemia

Abstract

Recently we have developed new sustained release system of basic fibroblast growth factor (bFGF) using gelatin hydrogel as a carrier. Using this system, we examined the effect of topical sustained release of bFGF on angiogenesis and tissue blood perfusion in a rabbit model of hind limb ischemia. Thirty-two rabbits underwent excision of right femoral artery under general anesthesia. Two weeks later the rabbits were randomized into four groups (n = 8 each): no treatment, intramuscular injection of gelatin hydrogel alone, and intramuscular injection of gelatin hydrogel incorporating 30 microg and 100 microg of bFGF. Four weeks after each treatment, selective angiography, tissue blood flowmetry using laser Doppler perfusion imaging, and histological examination of thigh muscle were performed. In groups treated with bFGF incorporating gelatin hydrogel, tissue blood flow, number of arterioles, and vascular density were significantly increased in a dose-dependent manner 4 weeks after the treatment. Serum concentrations of bFGF and vascular endothelial growth factor were not elevated 4 weeks after the treatment. In conclusion, sustained release of bFGF using gelatin hydrogel augmented angiogenesis and improved tissue blood flow after excision of the femoral artery.

Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

“…Alginate microspheres within an injectable collagen matrix have also been used to deliver stromal cell-derived factor-1 (SDF-1) (Kuraitis et al, 2011), while VEGF-loaded alginate microparticles in a collagen-fibronectin scaffold were used to deliver endothelial cells (Jay et al, 2008). Gelatin hydrogels have been employed to deliver basic fibroblast growth factor (bFGF) (Doi et al, 2007;Layman et al, 2007), and fibrin scaffolds were utilized to deliver bFGF and granulocyte-colony stimulating factor (G-CSF) along with bone marrow cells. More recently, VEGF-mimetic peptides were delivered using assembling peptide amphiphiles (Webber et al, 2011).…”

“…Biomaterial-based strategies have recently been explored. Currently, only poly(d,l-lactide-co-glycolide) (PLGA), collagen-fibronectin, alginate, gelatin, fibrin, and peptide amphiphiles have been examined (Doi et al, 2007;Jay et al, 2008;Kong et al, 2008;Layman et al, 2007;Lee et al, 2010;Ruvinov et al, 2010;Silva and Mooney, 2007;Webber et al, 2011). PLGA microspheres in alginate hydrogels have been utilized to deliver vascular endothelial growth factor (VEGF) (Lee et al, 2010), and alginate hydrogels have been explored for delivery of hepatocyte growth factor (HGF) (Ruvinov et al, 2010), VEGF (Silva and Mooney, 2007), and pDNA encoding for VEGF (Kong et al, 2008).…”

Immunoexpression of aquaporin-1 in the rat periodontal ligament during experimental tooth movement

“…Extracellular matrices surrounding blood vessels have been thought to play crucial roles in neovascularization (6). Although the key angiogenic molecules including vascular endothelial growth factor (VEGF) can induce the sprouting of blood vessels (21), neovascularization occurs without VEGF in certain conditions, including hind limb ischemia (8) and retinopathy (25). The mechanism of revasculature incident to tissue remodeling in the periodontal ligament constitutes one subject for a future study.…”

Local Sustained Release of Prostaglandin E1 Induces Neovascularization in Murine Hindlimb Ischemia

“…Local SR of several growth factors is effective for myocardial ischemia and limb ischemia without systemic side-effects. 7,8,[11][12][13][14][15] In addition, SR of PGE1 potentiated the angiogenesis induced by SR of basic fibroblast growth factor. 12 These treatment strategies improve efficacy without systemic side-effects.…”