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Beyond RGD; nanoclusters of syndecan- and integrin-binding ligands synergistically enhance cell/material interactions
Biomaterials ( IF 12.8 ) Pub Date : 2018-10-04 , DOI: 10.1016/j.biomaterials.2018.10.002
Fatemeh Karimi , Varsha Jagannath Thombare , Craig A. Hutton , Andrea J. O'Connor , Greg G. Qiao , Daniel E. Heath

Biomaterials are a powerful platform for directing cellular behaviour. Herein, we employed a biomimetic strategy to synthesize a low-fouling polymer functionalized with nano-scale clusters of ligands that bind both integrin and syndecan-4 receptors, as both receptor types are critical in focal adhesion signalling and mechanotransduction. Our results demonstrate that the presence of both ligand types synergistically increases the adhesion of human umbilical vein endothelial cells (more than a two fold increase after 4 h) and increases the rate of surface endothelialization compared to surfaces functionalized with only one ligand type. Additionally, we observe that the mixed population of ligands regulates endothelial cell migration, likely due to improved focal adhesion formation as observed through confocal microscopy. Furthermore, we illustrate that only endothelial cells cultured on these mixed ligand surfaces exhibit the appropriate morphological changes – elongation and alignment in the direction of flow - when exposed to laminar shear flow, and neither of the individual ligands alone is sufficient. These results illustrate that both receptor types must be engaged for optimum cell-material interactions and are mandatory for appropriate mechanotransduction. The results presented in this manuscript will be critical for the development of next generation biomedical devices and tissue engineering scaffolds.



中文翻译:

超出RGD;多糖与整联蛋白结合配体的纳米簇协同增强细胞/物质相互作用

生物材料是指导细胞行为的强大平台。在这里,我们采用了仿生策略来合成一种低污垢的聚合物,该聚合物被能与整联蛋白和syndecan-4受体结合的纳米级配体簇功能化,因为这两种受体类型在粘着斑信号传导和机械转导中都至关重要。我们的结果表明,两种配体类型的存在协同提高了人脐静脉内皮细胞的粘附性(4 h后增加了两倍以上),并且与仅用一种配体类型进行功能化的表面相比,增加了表面内皮化的速率。此外,我们观察到配体的混合种群调节内皮细胞的迁移,这可能是由于通过共聚焦显微镜观察到的粘着斑形成的改善。此外,我们说明,仅在这些混合的配体表面上培养的内皮细胞在暴露于层流剪切流时会表现出适当的形态变化-在流动方向上的伸长和排列,并且单独的单个配体都不足够。这些结果说明,两种受体类型都必须参与才能实现最佳的细胞-材料相互作用,并且对于适当的机械传导是必不可少的。本手稿中的结果对于下一代生物医学设备和组织工程支架的开发至关重要。这些结果说明,两种受体类型都必须参与才能实现最佳的细胞-材料相互作用,并且对于适当的机械传导是必不可少的。本手稿中的结果对于下一代生物医学设备和组织工程支架的开发至关重要。这些结果说明,两种受体类型都必须参与才能实现最佳的细胞-材料相互作用,并且对于适当的机械传导是必不可少的。本手稿中的结果对于下一代生物医学设备和组织工程支架的开发至关重要。

更新日期:2018-10-04
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