Sustained release of a synthetic structurally-tailored glycopolymer modulates endothelial cells for enhanced endothelialization of materials
Sustained release of a synthetic structurally-tailored glycopolymer modulates endothelial cells for enhanced endothelialization of materials
复制标题
合成结构定制的糖聚合物的持续释放可调节内皮细胞以增强材料的内皮化
DOI：
10.1039/c9tb00714h
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发表时间：
2019-07-07
影响因子：
7
通讯作者：
Brash, John L.
中科院分区：
文献类型：
--
作者：
Jiang, Shuaibing;Wu, Jingxian;Brash, John L.
糖胺聚糖（Glycosaminoglycans，GAG）通过与参与细胞信号传导的关键蛋白质相互作用在各种细胞功能的调节中起着至关重要的作用，并且可以在生物材料的设计中用作生物活性剂。然而，可用于此目的的可用的“天然”GAG具有许多缺点，包括结构异质性和杂质的存在。或者，GAG模拟聚合物已显示出用于修饰生物材料以支持粘附细胞的行为和功能的前景。在本文报道的研究中，使用一种新的“单元重组”策略合成了一系列定制结构的糖共聚物。这些预期作为表面改性剂用于促进表面内皮化。通过4-乙烯基苯磺酸钠（作为磺酸盐单元）和2-甲基丙烯酰胺基吡喃葡萄糖（作为糖单元）的共聚，将来自GAG的结构单元的两个关键结构单元磺酸盐和糖“重组”以得到GAG类似物。调整共聚物的组成和分子量以获得最大的内皮细胞（EC）增殖。发现具有磺酸盐和糖单元的比例约为1.0且分子量为9.8kDa的糖共聚物是最佳的。有趣的是，数据强调了糖单元在GAG生物活性中的关键作用，而不是通常认为的磺酸酯单元的决定性作用。通过同轴静电纺丝将优化的含糖共聚物引入纤维状聚己内酯（PCL）材料中。这些材料显示出GAG模拟聚合物在长时间内的受控释放。与未改性的PCL纤维毡相比，经二元共聚物改性的PCL纤维毡上EC的增殖、迁移和功能均得到了明显的改善。这些改善的可能机制是糖共聚物显著增强血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）与其细胞膜上的受体的结合。这些研究结果表明，这些结构定制的糖共聚物调节EC粘附材料的功能，并可能是有效的改性剂，促进血液接触植入物的内皮化。
Glycosaminoglycans (GAG) play a vital role in the regulation of various cellular functions through their interactions with key proteins involved in cell signaling and can be useful as bioactive agents in the design of biomaterials. However available "natural" GAG that might be used for this purpose suffer a number of drawbacks including structural heterogeneity and the presence of impurities. Alternatively, GAG-mimicking polymers have shown promise for the modification of biomaterials to support the behavior and function of adherent cells. In the study reported herein, a series of glycopolymers of tailored structure were synthesized using a novel "unit-recombination" strategy. These were intended as surface modifiers for the promotion of surface endothelialization. Two key structural units, sulfonate and saccharide, from the building blocks of GAG, were "recombined" to give GAG analogues by copolymerization of sodium 4-vinylbenzenesulfonate (as the sulfonate unit) and 2-methacrylamido glucopyranose (as the saccharide unit). The composition and molecular weight of the copolymers were adjusted to obtain maximum endothelial cell (EC) proliferation. The glycopolymer with sulfonate and saccharide units in a ratio of approximately 1.0 and a molecular weight of 9.8 kDa was found to be optimal. Interestingly, the data emphasized the key role of saccharide units in GAG bioactivity, rather than the commonly believed decisive role of sulfonate units. The optimized glycopolymer was incorporated into fibrous polycaprolactone (PCL) materials by coaxial electrospinning. These materials showed controlled release of the GAG-mimicking polymers over prolonged periods. The proliferation, migration and function of EC on the glycopolymer-modified PCL fiber mats were greatly improved compared to those on unmodified PCL mats. A likely mechanism underlying these improvements is that the glycopolymers significantly enhance the binding of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to their receptors on the cell membrane. These findings demonstrate that these structurally-tailored glycopolymers modulate the functions of EC adherent to materials and may be effective as modifiers for the promotion of endothelialization of blood-contacting implants.