Effect of controlled release of fibroblast growth factor-2 from chitosan/fucoidan micro complex-hydrogel on in vitro and in vivo vascularization

✍ Scribed by Shingo Nakamura; Masaki Nambu; Takamitsu Ishizuka; Hidemi Hattori; Yasuhiro Kanatani; Bonpei Takase; Satoko Kishimoto; Yoshiko Amano; Hiroshi Aoki; Tomoharu Kiyosawa; Masayuki Ishihara; Tadaaki Maehara

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 316 KB
• Volume: 85A
• Category: Article
• ISSN: 1549-3296
• DOI: 10.1002/jbm.a.31563

✦ Synopsis

Abstract

We produced a chitosan/fucoidan micro complex‐hydrogel as a carrier for controlled release of heparin binding growth factors such as fibroblast growth factor (FGF)‐2. Material consisting of a soluble chitosan (CH‐LA) mixed with fucoidan yielded a water‐insoluble and injectable hydrogel with filamentous particles. In this study, we examined the ability of the chitosan/fucoidan complex‐hydrogel to immobilize FGF‐2 and to protect its activity, as well as the controlled release of FGF‐2 molecules. The chitosan/fucoidan complex‐hydrogel has high affinity for FGF‐2 (K~d~ = 5.4 × 10^−^^9^M). The interaction of FGF‐2 with chitosan/fucoidan complex‐hydrogel substantially prolonged the biological half‐life time of FGF‐2. It also protected FGF‐2 from inactivation, for example by heat and proteolysis, and enhance FGF‐2 activity. When FGF‐2‐containing complex‐hydrogel was subcutaneously injected into the back of mice, significant neovascularization and fibrous tissue formation were induced near the site of injection at 1 week, and the complex‐hydrogel was biodegraded and disappeared by 4 weeks. These findings indicate that controlled release of biologically active FGF‐2 molecules is caused by both slow diffusion and biodegradation of the complex‐hydrogel, and that subsequent induction of vascularization occurs. FGF‐2‐containing chitosan/fucoidan micro complex‐hydrogel is thus useful and convenient for treatment of ischemic disease. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008