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Controlled release of fibroblast growth factor‐2 from an injectable 6‐O‐desulfated heparin hydrogel and subsequent effect on in vivo vascularization
Author(s) -
Nakamura Shingo,
Ishihara Masayuki,
Obara Kiyohaya,
Masuoka Kazunori,
Ishizuka Takamitsu,
Kanatani Yasuhiro,
Takase Bonpei,
Matsui Takemi,
Hattori Hidemi,
Sato Tomoya,
Kariya Yutaka,
Maehara Tadaaki
Publication year - 2006
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.30688
Subject(s) - in vivo , fibroblast growth factor , materials science , in vitro , fibroblast , self healing hydrogels , biophysics , heparin , controlled release , basic fibroblast growth factor , incubation , growth factor , biochemistry , chemistry , polymer chemistry , biology , nanotechnology , receptor , microbiology and biotechnology
We prepared a 6‐O‐desulfated (DS‐) heparin (Hep) hydrogel as an excellent carrier for the controlled release of Hep‐binding growth factors, such as fibroblast growth factor (FGF)‐2. This material, which is partially derived from photoreactive groups, such as cinnamate, is easily crosslinked upon ultraviolet light (UV)‐irradiation, resulting in a water‐insoluble, viscous, and injectable hydrogel. In the present study, we examined the capacity of 6‐O‐DS‐Hep hydrogel to immobilize FGF‐2, as well as the controlled release of FGF‐2 molecules from this hydrogel in vitro and in vivo . Only 10% of FGF‐2 was gradually released from the FGF‐2‐containing 6‐O‐DS‐Hep hydrogel (photocrosslinked 6‐O‐DS‐Hep (4%; w/w) hydrogel containing 50 μg/mL FGF‐2) into PBS (phosphate‐buffered saline) within first 7 days. The 6‐O‐DS‐Hep hydrogel in vitro maintained the original form through 1 weeks incubation in PBS, but it was gradually fragmented and could not maintain the original form by 2–3 week‐washing. When the FGF‐2‐containing 6‐O‐DS‐Hep hydrogel was subcutaneously injected into the back of rats, significant neovascularization and fibrous tissue formation were induced near the injected site from day 3 after the injection. And, the hydrogel had been biodegraded and completely disappeared from the injected sites in vivo within about 15–20 days after the injection. These findings indicate a controlled release of biologically active FGF‐2 molecules together with fragmentation and biodegradation of 6‐O‐DS‐Hep hydrogel and the subsequent induction of neovascularization in vivo . © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006