Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia

Abstract

As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I-IIa study that 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) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 ± 8.4 vs. 46.2 ± 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger's disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI.

Association of FGF-2 Concentrations with Atheroma Progression in Chronic Kidney Disease Patients

“…In our study, lower FGF-2 levels are associated with the appearance of new plaques, but were not associated with the baseline presence of atheroma plaques, agreeing with the notion of a protective role for FGF-2 in the early stages of atheroma plaque formation. Indeed, clinical trials using FGF-2 as a treatment for revascularization have not shown any effect aggravating atherosclerotic disease (46,47). Our results disclosing a higher odds ratio (OR) for atheromatosis progression in patients with CKD stages 4-5 and on dialysis than in patients with CKD stage 3 may appear discordant with those of Rigatto et al (48) observing lower progression of atheromatosis in later CKD stages.…”

Collagen/Heparin Bi‐Affinity Multilayer Modified Collagen Scaffolds for Controlled bFGF Release to Improve Angiogenesis In Vivo

“…However, bFGF usually has a short half‐life (≈46 min) because of enzymolysis, and it easily and rapidly diffuses away from the injured site. This has forced investigators to introduce massive doses or frequent dosing of bFGF into the body, which risks systemic toxicity, possible renal failure, tumor growth, and poor patient compliance with increased cost . In recent years, more and more researchers have focused on developing localized controlled release bFGF delivery systems, which have fewer side effects.…”

Intramyocardial delivery of VEGF165 via a novel biodegradable hydrogel induces angiogenesis and improves cardiac function after rat myocardial infarction

“…Several growth factors, such as vascular endothelial growth factor(VEGF) [7][8][9][10][11][12], fibroblast growth factor (FGF) [7,13], hepatocyte growth factor (HGF) [14] and platelet-derived growth factor (PDGF), have been generated in the presence of MI to resist ischemia and irreversible heart death. As the loss is highly localized, the endogenous response may be insufficient to repair the damaged blood vessels.…”