Arginine functionalization of hydrogels for heparin bindingua supramolecular approach to developing a pro-angiogenic biomaterial
Arginine functionalization of hydrogels for heparin bindingua supramolecular approach to developing a pro-angiogenic biomaterial
复制标题
DOI：
10.1002/bit.24598
复制
发表时间：
2013-01-01
影响因子：
3.8
通讯作者：
MacNeil, Sheila
中科院分区：
文献类型：
--
作者：
Gilmore, Louisa;Rimmer, Stephen;MacNeil, Sheila
我们的目标是通过利用肝素结合和释放血管内皮生长因子(VEGF)的能力来合成一种刺激血管生成的生物材料，用于组织工程应用。采用的方法包括用带正电的多肽(寡聚氨酸或寡精氨酸)修饰水凝胶，以实现肝素结合。通过N-乙烯基吡咯烷酮、二甘醇双烯丙基碳酸酯和丙烯酸(PNDA)的共聚反应制备了前驱体水凝胶，并用三赖氨酸或三精氨酸多肽(PNDKKK和PNDRRR)活化羧基后使其官能化。两种水凝胶都能结合和释放具有生物活性的VEGF165，精氨酸修饰的水凝胶效果优于赖氨酸修饰的水凝胶。水凝胶与原代人真皮成纤维细胞和人真皮微血管内皮细胞(HUDMECs)体外细胞相容性得到证实。三精氨酸功能化水凝胶可促进HUDMECs的增殖，一旦负载肝素和血管内皮生长因子，赖氨酸功能化水凝胶对HUDMECs增殖的刺激作用较小。这些数据表明，肝素结合水凝胶为促进血管生成的生物材料提供了一种很有前途的方法。生物技术。比昂斯。2013年；110%：296317。(C)2012年威利期刊公司。
Our aim was to synthesize a biomaterial that stimulates angiogenesis for tissue engineering applications by exploiting the ability of heparin to bind and release vascular endothelial growth factor (VEGF). The approach adopted involved modification of a hydrogel with positively charged peptides (oligolysine or oligoarginine) to achieve heparin binding. Precursor hydrogels were produced from copolymerization of N-vinyl pyrolidone, diethylene glycol bis allyl carbonate and acrylic acid (PNDA) and functionalized after activation of the carboxylic acid groups with trilysine or triarginine peptides (PNDKKK and PNDRRR). Both hydrogels were shown to bind and release bioactive VEGF165 with arginine-modified hydrogel outperforming the lysine-modified hydrogel. Cytocompatibility of the hydrogels was confirmed in vitro with primary human dermal fibroblasts and human dermal microvascular endothelial cells (HUDMECs). Proliferation of HUDMECs was stimulated by triarginine-functionalized hydrogels, and to a lesser extent by lysine functionalized hydrogels once loaded with heparin and VEGF. The data suggests that heparin-binding hydrogels provide a promising approach to a pro-angiogenic biomaterial. Biotechnol. Bioeng. 2013; 110: 296317. (C) 2012 Wiley Periodicals, Inc.