Vascularization in vivo caused by the controlled release of fibroblast growth factor-2 from an injectable chitosan/non-anticoagulant heparin hydrogel.
Addition of various heparinoids to the lactose-introduced, water-soluble chitosan (CH-LA) aqueous solution produces an injectable chitosan/heparinoid hydrogel. In the present work, we examined the capability of the chitosan/non-anticoagulant heparin (periodate-oxidized (IO(4)-) heparin) hydrogel to immobilize fibroblast growth factor (FGF)-2, as well as the controlled release of FGF-2 molecules from the hydrogel in vitro and in vivo. The hydrogel was biodegraded in about 20 days after subcutaneous injection into the back of a mouse. When the FGF-2-incorporated hydrogel was subcutaneously injected into the back of both mice and rats, a significant neovascularization and fibrous tissue formation were induced near the injected site. These results indicate that the controlled release of biologically active FGF-2 molecules is caused by biodegradation of the hydrogel, and that subsequent induction of the vascularization occurs.
Fujita
Masanori
M
Department of Surgery II, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. BXB01424@nifty.ne.jp
Ishihara
Masayuki
M
Simizu
Masafumi
M
Obara
Kiyohaya
K
Ishizuka
Toshiaki
T
Saito
Yoshio
Y
Yura
Hirofumi
H
Morimoto
Yuji
Y
Takase
Bonpei
B
Matsui
Takemi
T
Kikuchi
Makoto
M
Maehara
Tadaaki
T
D000818:Animals; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry*; D048271:Chitosan; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage* / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry; D006496:Heparinoids / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007267:Injections; D008297:Male; D008422:Materials Testing; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D006496:Heparinoids; D020100:Hydrogels; D016222:Fibroblast Growth Factor 2; D002686:Chitin; D048271:Chitosan