Controlled release of fibroblast growth factor-2 from an injectable 6-O-desulfated heparin hydrogel and subsequent effect on in vivo vascularization

✍ Scribed by Shingo Nakamura; Masayuki Ishihara; Kiyohaya Obara; Kazunori Masuoka; Takamitsu Ishizuka; Yasuhiro Kanatani; Bonpei Takase; Takemi Matsui; Hidemi Hattori; Tomoya Sato; Yutaka Kariya; Tadaaki Maehara

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 323 KB
• Volume: 78A
• Category: Article
• ISSN: 1549-3296
• DOI: 10.1002/jbm.a.30688

✦ Synopsis

Abstract

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