Abstract 16154: Safety and Efficacy of Sustained Release of Basic Fibroblast growth Factor Using Biodegradable Gelatin Hydrogel in Patients With Critical Limb Ischemia
Background: Gene therapy or cell transplantation may be promising in the treatment of critical limb ischemia (CLI). However, there are still concerns for safety of genetic materials, and complex procedures and costs of cell transplantation. To overcome shortcomings or limitations of these methods, we sought to investigate the impact of a sustained release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical CLI.
Methods and Results: This study was a phase I-IIa study which analyzed 10 CLI patients following a 200-μg intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event.[Table] After 24 weeks, TcO2 showed significant improvement (p<0.01). Regarding secondary endpoints, the distance walked in 6 minutes (p=0.02), the Rutherford classification (p=0.02), the rest pain scale (p=0.03) and the cyanotic scale (p<0.01) also showed significant improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n=7, 28.6 ± 10.0 vs 45.8 ± 14.3 mmHg for pretreatment vs after 24 weeks, p<0.01) or Buerger’s disease (n=3, 27.7 ± 4.2 vs 47.2 ± 11.8 mmHg, p=0.05) revealed that TcO2 had improved in both subgroups. TcO2 also had significantly improved in patients with chronic kidney disease (CKD) (n=6, 29.3 ± 10.8 vs 44.3 ± 15.0 mmHg, p<0.01) or without CKD (n=4, 27.0 ± 3.7 vs 49.1 ± 10.4 mmHg, p=0.01) (estimated glomerular filtration rate <60 ml/min/1.73m2).
Conclusions: The sustained release of bFGF from biodegradable gelatin hydrogel may be safe, simple, and effective to offer an angiogenesis in CLI. This method was effective both in patients with ASO and Buerger’s disease regardless of the presence of CKD.
- © 2013 by American Heart Association, Inc.