Obara Kiyohaya, Ishihara Masayuki, Ishizuka Toshiaki, Fujita Masanori, Ozeki Yuichi, Maehara Tadaaki, Saito Yoshio, Yura Hirofumi, Matsui Takemi, Hattori Hidemi, Kikuchi Makoto, Kurita Akira
Department of Surgery II, National Defence Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Biomaterials. 2003 Sep;24(20):3437-44. doi: 10.1016/s0142-9612(03)00220-5.
Application of ultraviolet light (UV-) irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution including fibroblast growth factor-2 (FGF-2) resulted within 30s in an insoluble, flexible hydrogel. About 20% of the FGF-2molecules were released from the FGF-2-incorporated chitosan hydrogel into phosphate buffered saline (PBS) within 1 day, after which no further significant release occurred under in vitro non-degradation conditions of the hydrogel. The FGF-2molecules retained in the chitosan hydrogel remained biologically active, and were released from the chitosan hydrogel upon the in vivo biodegradation of the hydrogel. In order to evaluate its accelerating effect on wound healing, full thickness skin incisions were made on the back of healing-impaired diabetic (db/db) mice and their normal (db/+) littermates. Application of the chitosan hydrogel significantly induced wound contraction and accelerated wound closure in both db/db and db/+ mice. However, the addition of FGF-2 in the chitosan hydrogel further accelerated wound closure in db/db mice, although not in db/+ mice. Histological examination also has demonstrated an advanced granulation tissue formation, capillary formation and epithelialization in wounds treated with FGF-2-incorporated chitosan hydrogels in db/db mice.
将紫外线(UV)照射应用于包含成纤维细胞生长因子-2(FGF-2)的可光交联壳聚糖(Az-CH-LA)水溶液,30秒内即可形成不溶性的柔性水凝胶。在1天内,约20%的FGF-2分子从含FGF-2的壳聚糖水凝胶中释放到磷酸盐缓冲盐水(PBS)中,此后在水凝胶的体外非降解条件下没有进一步的显著释放。保留在壳聚糖水凝胶中的FGF-2分子保持生物活性,并在水凝胶体内生物降解时从壳聚糖水凝胶中释放出来。为了评估其对伤口愈合的促进作用,在愈合受损的糖尿病(db/db)小鼠及其正常(db/+)同窝小鼠的背部制作全层皮肤切口。壳聚糖水凝胶的应用显著诱导了db/db和db/+小鼠的伤口收缩并加速了伤口闭合。然而,在壳聚糖水凝胶中添加FGF-2进一步加速了db/db小鼠的伤口闭合,尽管在db/+小鼠中没有。组织学检查还表明,用含FGF-2的壳聚糖水凝胶处理的db/db小鼠伤口中,肉芽组织形成、毛细血管形成和上皮化均有所进展。