Interdisciplinary Research Centre on Biomaterials (CRIB), Naples, Italy.
Acta Biomater. 2010 Jul;6(7):2532-9. doi: 10.1016/j.actbio.2009.12.050. Epub 2010 Jan 4.
Understanding the influence of a controlled spatial distribution of biological cues on cell activities can be useful to design "cell instructive" materials, able to control and guide the formation of engineered tissues in vivo and in vitro. To this purpose, biochemical and mechanical properties of the resulting biomaterial must be carefully designed and controlled. In this work, the effect of covalently immobilized RGD peptide gradients on poly(ethylene glycol) diacrylate hydrogels on cell behaviour was studied. We set up a mechanical device generating gradients based on a fluidic chamber. Cell response to RGD gradients with different slope (0.7, 1 and 2 mM cm(-1)) was qualitatively and quantitatively assessed by evaluating cell adhesion and, in particular, cell migration, compared to cells seeded on hydrogels with uniform distribution of RGD peptides. To evaluate the influence of RGD gradient and to exclude any concentration effect on cell response, all analyses were carried out in a specific region of the gradients which displayed the same average concentration of RGD (1.5 mM). Results suggest that cells recognize the RGD gradient and adhere onto it assuming a stretched shape. Moreover, cells tend to migrate in the direction of the gradient, as their speed is higher than that of cells migrating on hydrogels with a uniform distribution of RGD and increases by increasing RGD gradient steepness. This increment is due to an augmentation of bias speed component of the mean squared speed, that is, the drift of the cell population migrating on the anisotropic surface provided by the RGD gradient.
了解生物信号的受控空间分布对细胞活动的影响对于设计“细胞指令性”材料非常有用，这种材料能够控制和引导体内和体外工程组织的形成。为此，必须仔细设计和控制所得生物材料的生化和机械性能。在这项工作中，研究了共价固定化 RGD 肽梯度对聚（乙二醇）二丙烯酸酯水凝胶对细胞行为的影响。我们设置了一种基于流体室的机械装置来产生梯度。通过评估细胞黏附和细胞迁移（特别是细胞迁移），对具有不同斜率（0.7、1 和 2 mM cm(-1)) 的 RGD 梯度的细胞反应进行了定性和定量评估，与在 RGD 肽均匀分布的水凝胶上接种的细胞进行了比较。为了评估 RGD 梯度的影响并排除细胞反应的任何浓度效应，所有分析都在梯度的特定区域进行，该区域显示出相同的 RGD 平均浓度（1.5 mM）。结果表明，细胞识别 RGD 梯度并附着在其上，呈现出伸展的形状。此外，细胞倾向于沿梯度迁移，因为它们的速度高于在具有 RGD 均匀分布的水凝胶上迁移的细胞的速度，并且随着 RGD 梯度陡度的增加而增加。这种增加是由于均方速度的偏置速度分量的增加，即细胞群体在由 RGD 梯度提供的各向异性表面上的漂移。
