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

Motoyuki Kumagai, Akira Marui, Yasuhiko Tabata, Takahide Takeda, Masaya Yamamoto, Atsushi Yonezawa, Shiro Tanaka, Shigeki Yanagi, Toshiko Ito-Ihara, Takafumi Ikeda, Toshinori Murayama, Satoshi Teramukai, Toshiya Katsura, Kazuo Matsubara, Koji Kawakami, Masayuki Yokode, Akira Shimizu, Ryuzo Sakata

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)713-721
Number of pages9
JournalHeart and Vessels
Volume31
Issue number5
DOIs
Publication statusPublished - 2016 May 1

Keywords

  • Angiogenesis
  • Basic fibroblast growth factor
  • Critical limb ischemia
  • Drug delivery system

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia'. Together they form a unique fingerprint.

  • Cite this

    Kumagai, M., Marui, A., Tabata, Y., Takeda, T., Yamamoto, M., Yonezawa, A., Tanaka, S., Yanagi, S., Ito-Ihara, T., Ikeda, T., Murayama, T., Teramukai, S., Katsura, T., Matsubara, K., Kawakami, K., Yokode, M., Shimizu, A., & Sakata, R. (2016). Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia. Heart and Vessels, 31(5), 713-721. https://doi.org/10.1007/s00380-015-0677-x