Vascular regeneration by pinpoint delivery of growth factors using a microcatheter reservoir system in a rabbit hind-limb ischemia model

Abstract

Abstract. The purpose of this study was to compare the results of delivering low doses of growth factor iteratively (20 µg x5) via a reservoir system with results obtained following a single administration of 100 µg of growth factor. The delivery systems using gelatin microspheres (GMS) facilitate the controlled release of drugs. The controlled release of growth factors at specific sites is essential for vascular regeneration. An ischemic hind-limb model was established in nine rabbits. A reservoir system was implanted in each rabbit. GMS impregnated with basic fibroblast growth factor (bFGF) through an indwelling 2-Fr catheter was infused in the reservoir system. The rabbits were divided into three equal groups: group 1 received 20 µg iteratively (x5) via the reservoir, a single dose of 100 µg growth factor was administered to group 2 and group 3 was the saline control. The therapeutic effects were evaluated by measuring the thigh temperature, blood pressure and blood flow. An immunohistological analysis was also performed for CD31. No significant difference was observed between preand post-treatment (4 weeks following bFGF infusion) in the thigh temperature, blood pressure and blood flow results from each group. Pathological analysis revealed that the number of regenerated vessels was significantly higher in the group treated iteratively with low-dose bFGF.

Syndecan-4 Proteoliposomes Enhance Revascularization in a Rabbit Hind Limb Ischemia Model of Peripheral Ischemia

“…This finding is in contrast to multiple studies that have found enhancement of revascularization in the ischemic hindlimbs of healthy rabbits using FGF-2. [25][26][27][28][29][30][31][32] The results from the advanced rabbit model are consistent with the lack of efficacy for FGF-2 treatments in clinical trials for intermittent claudication 8 and suggests that the optimized rabbit model may provide better correlation with clinical outcomes.…”

Similar in vitro effects and pulp regeneration in ectopic tooth transplantation by basic fibroblast growth factor and granulocyte‐colony stimulating factor

“…Furthermore, bFGF activates in vivo the plasminogen activator (Presta et al, 1986), facilitating migration and proliferation of vascular endothelial cells by dissolution of the vascular basement membrane (Gospodarowicz et al, 1987). It also promotes in vivo the revascularization, tubule formation, and capillary regeneration (Folkman and Klagsbrun, 1987;Saksela et al, 1987) and the formation of granulation tissue (Okumura et al, 1996), enhancing the collateral blood flow in a rabbit hindlimb ischemic model (Nitta et al, 2012), and inducing cartilage in a model of auricular cartilage defect (Morotomi et al, 2012). Finally, the enhancement of the proliferation and differentiation of mesenchymal stem cells by bFGF has been demonstrated to promote fracture healing (Kawaguchi, 2009).…”