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Therapeutic angiogenesis induced by controlled release of fibroblast growth factor‐2 from injectable chitosan/non‐anticoagulant heparin hydrogel in a rat hindlimb ischemia model
Author(s) -
Fujita Masanori,
Ishihara Masayuki,
Shimizu Masafumi,
Obara Kiyohaya,
Nakamura Shingo,
Kanatani Yasuhiro,
Morimoto Yuji,
Takase Bonpei,
Matsui Takemi,
Kikuchi Makoto,
Maehara Tadaaki
Publication year - 2007
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2006.00185.x
Subject(s) - heparin , fibroblast growth factor , self healing hydrogels , angiogenesis , chemistry , wound healing , ischemia , chitosan , basic fibroblast growth factor , pharmacology , medicine , growth factor , surgery , biochemistry , polymer chemistry , receptor
The addition of non‐anticoagulant heparin [periodate‐oxidized (IO 4 ) heparin] and fibroblast growth factor (FGF)‐2 to a viscous water‐soluble chitosan (CH‐LA) aqueous solution produces an injectable FGF‐2/CH‐LA/IO 4 ‐heparin hydrogel. The purpose of this study was to examine the ability of the injected FGF‐2/CH‐LA/IO 4 ‐heparin hydrogel to induce vascularization and fibrous tissue formation. FGF‐2/CH‐LA/IO 4 ‐heparin hydrogels (100 μL of hydrogel consisting of 20 mg/mL of CH‐LA, 2 mg/mL of IO 4 ‐heparin, and 50 μg/mL of FGF‐2) were subcutaneously injected into the backs of wound healing‐impaired diabetic ( db/db ) mice. Furthermore, the effect of percutaneous injection of FGF‐2/CH‐LA/IO 4 ‐heparin hydrogel at eight sites (25 μL/site) into ischemic left lower limbs of rats was examined from day 4 to at least day 28 postinjection. The injection of FGF‐2/CH‐LA/IO 4 ‐heparin hydrogels into the backs of db/db mice resulted in significant increases in blood vessel formation, significant vascularization, and fibrous tissue formation near the injection site. Injection of FGF‐2/CH‐LA/IO 4 ‐heparin hydrogel into ischemic left lower limbs of rats also significantly recovered and increased blood flow and blood oxygen in the calf and thigh. These results indicate that the controlled release of biologically active FGF‐2 molecules from FGF‐2/CH‐LA/IO 4 ‐heparin induces angiogenesis and possibly collateral circulation in db/db mice and the ischemic limbs of rats.