Effect of controlled release of fibroblast growth factor-2 from chitosan/fucoidan micro complex-hydrogel on in vitro and in vivo vascularization.
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 x 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.
Nakamura
Shingo
S
Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Nambu
Masaki
M
Ishizuka
Takamitsu
T
Hattori
Hidemi
H
Kanatani
Yasuhiro
Y
Takase
Bonpei
B
Kishimoto
Satoko
S
Amano
Yoshiko
Y
Aoki
Hiroshi
H
Kiyosawa
Tomoharu
T
Ishihara
Masayuki
M
Maehara
Tadaaki
T
D000818:Animals; D048271:Chitosan; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006207:Half-Life; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007511:Ischemia / Q000188:drug therapy; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011134:Polysaccharides