Yang C F, Yasukawa T, Kimura H, Miyamoto H, Honda Y, Tabata Y, Ikada Y, Ogura Y
Department of Ophthalmology and Visual Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Ophthalmic Res. 2000 Jan-Feb;32(1):19-24. doi: 10.1159/000055582.
The study was designed to investigate the feasibility of using an acidic gelatin hydrogel as a biodegradable vehicle for basic fibroblast growth factor (bFGF). bFGF was incorporated by polyion complexation into a biodegradable hydrogel prepared by cross-linking acidic gelatin with the isoelectric point of 4.9. The dried hydrogel (sized to 2x1 mm) was hydrated with bFGF aqueous solution including different doses of bFGF (20, 50, 125, 250 and 500 ng) and implanted into a rabbit corneal pocket (2.5x2 mm). As a control group, the gelatin hydrogel without bFGF or bFGF alone (500 ng) was used. Corneal angiogenesis was evaluated by biomicroscopy, corneal fluorescein angiography and histology for 21 days. Photographs were taken and corneal angiogenesis was evaluated by image analysis. The hydrogel degraded with time after its implantation into the corneal pocket. Experimental eyes receiving the hydrogel containing more than 50 ng of bFGF demonstrated significant corneal angiogenesis. Control eyes and eyes receiving the hydrogel containing 20 ng of bFGF showed no corneal angiogenesis. Corneal angiogenesis, which occurred on the 3rd or 4th day after implantation, reached maximal growth on about day 7 and regressed from day 10 after implantation. The area of angiogenesis showed a dose-dependency on bFGF. The gelatin hydrogel itself induced neither angiogenesis nor inflammation. These results suggested that acidic gelatin hydrogel releases bioactive bFGF with its biodegradation, resulting in corneal neovascularization.
本研究旨在探讨使用酸性明胶水凝胶作为碱性成纤维细胞生长因子（bFGF）的可生物降解载体的可行性。通过聚离子络合将bFGF掺入到由等电点为4.9的酸性明胶交联制备的可生物降解水凝胶中。将干燥的水凝胶（尺寸为2×1毫米）用包含不同剂量bFGF（20、50、125、250和500纳克）的bFGF水溶液水合，然后植入兔角膜袋（2.5×2毫米）中。作为对照组，使用不含bFGF的明胶水凝胶或单独的bFGF（500纳克）。通过生物显微镜检查、角膜荧光素血管造影和组织学对角膜血管生成进行了21天的评估。拍摄照片并通过图像分析评估角膜血管生成。水凝胶植入角膜袋后随时间降解。接受含有超过50纳克bFGF的水凝胶的实验眼表现出明显的角膜血管生成。对照组眼和接受含有20纳克bFGF的水凝胶的眼未显示角膜血管生成。植入后第3天或第4天出现的角膜血管生成在大约第7天达到最大生长，并在植入后第10天开始消退。血管生成面积对bFGF呈剂量依赖性。明胶水凝胶本身既不诱导血管生成也不诱导炎症。这些结果表明，酸性明胶水凝胶在其生物降解过程中释放生物活性bFGF，导致角膜新生血管形成。
