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Immobilization of glycoproteins, such as VEGF, on biodegradable substrates.

机译:将糖蛋白(例如VEGF)固定在可生物降解的底物上。

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Attachment of growth factors to biodegradable polymers, such as poly(lactide-co-glycolide) (PLGA), may enhance and/or accelerate integration of tissue engineering scaffolds. Although proteins are commonly bound via abundant amino groups, a more selective approach may increase bioactivity of immobilized molecules. In this research, exposed carboxyl groups on acid-terminated PLGA were modified with dihydrazide spacer molecules. The number of hydrazide groups available for subsequent attachment of protein was dependent on dihydrazide length, with shorter molecules present at significantly greater surface densities. The potent angiogenic glycoprotein vascular endothelial growth factor (VEGF) was oxidized with periodate and the aldehyde moieties allowed to react with the hydrazide-derivatized PLGA. Derivatization initially affected the amount of protein bound to the surfaces, but differences were substantially reduced following overnight incubation in saline. More importantly, use of shorter dihydrazide spacers significantly enhanced accessibility of immobilized VEGF for binding neutralizing antibody and soluble VEGF receptor. Furthermore, immobilized growth factor enhanced endothelial cell proliferation, with surfaces having the shortest and longest spacers stimulating greater effects. The present work has not only demonstrated an alternative approach to immobilizing growth factors on biodegradable materials, but the scheme can be used to alter the amount of protein bound as well as its availability for subsequent biointeractions.
机译:将生长因子附着于可生物降解的聚合物(例如聚(丙交酯-共-乙交酯)(PLGA))可增强和/或加速组织工程支架的整合。尽管蛋白质通常通过丰富的氨基键合,但更具选择性的方法可能会增加固定分子的生物活性。在这项研究中,酸封端的PLGA上暴露的羧基被二酰肼间隔分子修饰。可用于后续蛋白质附着的酰肼基团的数量取决于二酰肼的长度,较短的分子以明显更高的表面密度存在。用高碘酸盐氧化有效的血管生成糖蛋白血管内皮生长因子(VEGF),并使醛基与酰肼衍生的PLGA反应。衍生作用最初会影响结合到表面的蛋白质量,但是在盐水中孵育过夜后,差异会大大减少。更重要的是,使用较短的二酰肼间隔基可显着提高固定化VEGF与中和抗体和可溶性VEGF受体结合的可及性。此外,固定化的生长因子增强了内皮细胞的增殖,而具有最短和最长间隔基的表面刺激了更大的作用。目前的工作不仅证明了将生长因子固定在可生物降解材料上的替代方法,而且该方案可用于改变结合的蛋白质的数量及其后续生物相互作用的可用性。

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