The effect of the controlled release of basic fibroblast growth factor from ionic gelatin-based hydrogels on angiogenesis in a murine critical limb ischemic model
The effect of the controlled release of basic fibroblast growth factor from ionic gelatin-based hydrogels on angiogenesis in a murine critical limb ischemic model
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DOI：
10.1016/j.biomaterials.2007.01.044
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发表时间：
2007-06-01
期刊：
影响因子：
14
通讯作者：
Andreopoulos, Fotios M.
中科院分区：
文献类型：
--
作者：
Layman, Hans;Spiga, Maria-Grazia;Andreopoulos, Fotios M.
外源性血管生成生长因子的局部递送已成为外周动脉疾病（PAD）和严重肢体缺血的有前途的替代治疗方法。在本研究中，我们描述了一种新型控释载体的开发，以促进小鼠危重肢体缺血模型中的血管生成。通过明胶或聚-L-谷氨酸分子的羧基分别与聚-L-赖氨酸或明胶分子的胺基之间的碳二亚胺介导的酰胺化反应制备了离子型明胶水凝胶。合成水凝胶的溶胀程度根据 EDC/NHS 比率和平衡介质 pH 值进行评估，同时在人成纤维细胞培养物中评估碱性成纤维细胞生长因子 (FGF-2) 的释放动力学曲线。当 EDC 浓度从 0.75 变化到 2.5 mg/ml 时，肿胀度 (DS) 从 26.5 +/- 1.7 降低到 18.5 +/- 2.4。在 28 天的时间内，80% 的 FGF-2 以受控速率从明胶聚赖氨酸 (gelatin-PLL) 和明胶聚谷氨酸 (gelatin-PLG) 水凝胶支架中释放。细胞粘附研究表明，与明胶-PLL 和对照明胶表面相比，带负电荷的明胶-PLG 水凝胶表面表现出优异的粘附能力。激光多普勒灌注成像以及 CD31 + 毛细血管免疫染色表明，与生长因子的推注给药相比，FGF-2 从离子明胶基水凝胶中的受控释放在促进血管生成方面更有效。 4 周内，释放 FGF-2 的明胶-PLG 水凝胶表现出明显的再灌注，多普勒比率为 0.889 (+/- 0.04)，比对照组高 69.3%。 (c) 2007 Elsevier Ltd. 保留所有权利。
The localized delivery of exogenous, angiogenic growth factors has become a promising alternative treatment of peripheral artery disease (PAD) and critical limb ischemia. In the present study, we describe the development of a novel controlled release vehicle to promote angiogenesis in a murine critical limb ischemic model. Ionic, gelatin-based hydrogels were prepared by the carbodiimide-mediated amidation reaction between the carboxyl groups of gelatin or poly-L-glutamic acid molecules and the amine groups of poly-L-lysine or gelatin molecules, respectively. The degree of swelling of the synthesized hydrogels was assessed as a function of EDC/NHS ratios and the pH of the equilibrating medium, while the release kinetic profile of basic fibroblast growth factor (FGF-2) was evaluated in human fibroblast cultures. The degree of swelling (DS) decreased from 26.5 +/- 1.7 to 18.5 +/- 2.4 as the EDC concentration varied from 0.75 to 2.5 mg/ml. Eighty percent of the FGF-2 was released at controlled rates from gelatin-polylysine (gelatin-PLL) and gelatin-polyglutamic acid (gelatin-PLG) hydrogel scaffolds over a period of 28 days. Cell adhesion studies revealed that the negatively charged surface of the gelatin-PLG hydrogels exhibited superior adhesion capabilities in comparison to gelatin-PLL and control gelatin surfaces. Laser Doppler perfusion imaging as well as CD31 + capillary immunostaining demonstrated that the controlled release of FGF-2 from ionic gelatin-based hydrogels is superior in promoting angiogenesis in comparison to the bolus administration of the growth factor. Over 4 weeks, FGF-2 releasing gelatin-PLG hydrogels exhibited marked reperfusion with a Doppler ratio of 0.889 (+/- 0.04) which was 69.3% higher than in the control groups. (c) 2007 Elsevier Ltd. All rights reserved.