Sagnella Sharon, Kligman Faina, Marchant Roger E, Kottke-Marchant Kandice
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
J Biomed Mater Res A. 2003 Dec 1;67(3):689-701. doi: 10.1002/jbm.a.10035.
We have developed a series of extracellular matrix (ECM)-like biomimetic surfactant polymers to improve endothelial cell adhesion and growth on vascular biomaterials. These polymers provide a single-step procedure for modifying the surface of existing biomaterials and consist of a poly(vinyl amine) (PVAm) backbone with varying ratios of cell-binding peptide (RGD) to carbohydrate (maltose), ranging from 100% RGD:0% maltose to 50% RGD:50% maltose. Three biomimetic surfaces, as well as a fibronectin (FN)-coated glass surface were seeded at confluence with human pulmonary artery endothelial cells (HPAECs) and exposed to shear stresses ranging from 0-40.6 dyn/cm2 for periods of 2 h and 6 h. Surfaces were examined for HPAEC coverage and cytoskeletal arrangement as a function of time and shear stress. In general, after 6 h of shear exposure, EC retention on 100% RGD > FN > 75% RGD > 50% RGD. The 100% RGD surface maintained more than 50% of its initial EC monolayer at low to moderate shear stresses whereas all other surfaces dropped to approximately 40% or less in the same shear stress range. The most stable surface, 100% RGD, showed a significant increase in cytoskeletal organization at all shear stresses greater than 2.5 dyn/cm2. In contrast, there was no real change in cytoskeletal organization on the FN surface, and there was a decrease on the 75% RGD surface over time. These results indicate that increasing surface peptide density can control EC shear stability. Furthermore, improved shear stability increases with increasing peptide density and is related to the EC's ability to reorganize its cytoskeleton.
我们研发了一系列细胞外基质（ECM）样的仿生表面活性剂聚合物，以改善内皮细胞在血管生物材料上的黏附与生长。这些聚合物为修饰现有生物材料表面提供了一种单步程序，由具有不同细胞结合肽（RGD）与碳水化合物（麦芽糖）比例的聚乙烯胺（PVAm）主链组成，比例范围从100% RGD:0%麦芽糖到50% RGD:50%麦芽糖。将三种仿生表面以及纤连蛋白（FN）包被的玻璃表面接种汇合的人肺动脉内皮细胞（HPAECs），并使其暴露于0 - 40.6达因/平方厘米的剪切应力下2小时和6小时。检测表面上HPAEC的覆盖情况和细胞骨架排列随时间和剪切应力的变化。一般来说，在剪切暴露6小时后，内皮细胞在100% RGD表面的保留率 > FN > 75% RGD > 50% RGD。在低至中等剪切应力下，100% RGD表面维持了其初始内皮细胞单层的50%以上，而在相同剪切应力范围内，所有其他表面降至约40%或更低。最稳定的表面，即100% RGD表面，在所有大于2.5达因/平方厘米的剪切应力下，细胞骨架组织显著增加。相比之下，FN表面的细胞骨架组织没有实际变化，并且75% RGD表面随时间有所减少。这些结果表明，增加表面肽密度可以控制内皮细胞的剪切稳定性。此外，随着肽密度的增加，剪切稳定性提高，这与内皮细胞重组其细胞骨架的能力有关。
