Department of Chemical Engineering, 212 Ross Hall, Auburn University, AL 36849, USA.
Acta Biomater. 2013 Sep;9(9):8279-89. doi: 10.1016/j.actbio.2013.05.023. Epub 2013 Jun 13.
This study investigated the dynamic adhesion of endothelial progenitor cells (EPCs) to peptide-grafted poly(ethylene glycol) diacrylate (PEGDA) hydrogels and determined the relative ability of RGDS, REDV and YIGSRG peptides to reduce the velocity of EPC rolling. Circulating EPCs are key mediators of endothelium repair and have been shown to accelerate re-endothelialization, which is important in reducing the incidence of restenosis following stent placement and occlusion of small diameter vascular grafts. However, to exploit these capabilities for tissue engineering applications, more knowledge is needed about EPC binding to the vascular wall under shear and, in particular, whether the incorporation of peptide ligands into biomaterials can support the process of EPC rolling or maintain EPC adhesion. This study specifically examined one type of EPCs endothelial colony forming cells (ECFCs), based on their ability to be expanded in culture and differentiate into mature endothelial cells. The amount of grafted PEG-peptide was shown to be dependent on the concentration of PEG-peptide grafting solution photopolymerized onto the hydrogel surface. The ECFC strength of adhesion on PEG-RDGS grafted hydrogels exceeded 350 dyn cm(-2) for 85% of adherent cells. PEG-RGDS grafted hydrogels supported ECFC rolling, whereas ECFC velocity on the negative control PEG-RGES grafted hydrogels and on the "blank slate" PEGDA hydrogels was substantially higher than the cutoff velocity for cell rolling. The ECFC rolling velocity on PEG-RDGS grafted hydrogels depended on the shear rate; as shear rate was increased from 20 s(-1) to 120 s(-1), ECFC rolling velocity increased from 103±3 μm s(-1) to 741±28 μm s(-1). REDV and YIGSRG, which are known to preferentially support endothelial cell adhesion, also supported ECFC rolling. Interestingly, the rolling velocity of ECFCs on PEG-REDV grafted hydrogels was significantly lower than on PEG-YIGSRG or on PEG-RGDS grafted hydrogels. Understanding the dynamic adhesion of ECFCs to peptide-grafted hydrogels is the first step towards understanding the similarities and differences of EPCs from mature endothelial cells and improving the ability to sequester EPCs to biomaterial surfaces in order to promote intravascular re-endothelialization.
本研究探讨了内皮祖细胞（EPC）与肽接枝聚乙二醇二丙烯酸酯（PEGDA）水凝胶的动态黏附，并确定了 RGDS、REDV 和 YIGSRG 肽降低 EPC 滚动速度的相对能力。循环 EPC 是内皮修复的关键介质，已被证明可加速再内皮化，这对于减少支架放置后和小直径血管移植物闭塞后的再狭窄发生率非常重要。然而，为了将这些能力应用于组织工程应用，需要更多关于 EPC 在切变下与血管壁结合的知识，特别是将肽配体掺入生物材料是否可以支持 EPC 滚动过程或维持 EPC 黏附。本研究特别研究了一种类型的 EPCs——内皮集落形成细胞（ECFCs），基于其在培养中扩增和分化为成熟内皮细胞的能力。接枝 PEG-肽的量取决于光聚合到水凝胶表面的 PEG-肽接枝溶液的浓度。PEG-RDGS 接枝水凝胶上 EPC 的黏附强度超过 350 dyn cm(-2)，对于 85%的黏附细胞。PEG-RGDS 接枝水凝胶支持 ECFC 滚动，而在阴性对照 PEG-RGES 接枝水凝胶和“空白石板”PEGDA 水凝胶上，ECFC 的速度远高于细胞滚动的截止速度。PEG-RDGS 接枝水凝胶上 ECFC 的滚动速度取决于剪切速率；当剪切速率从 20 s(-1)增加到 120 s(-1)时，ECFC 的滚动速度从 103±3 μm s(-1)增加到 741±28 μm s(-1)。已知优先支持内皮细胞黏附的 REDV 和 YIGSRG 也支持 ECFC 滚动。有趣的是，ECFC 在 PEG-REDV 接枝水凝胶上的滚动速度明显低于 PEG-YIGSRG 或 PEG-RGDS 接枝水凝胶。了解 ECFC 与肽接枝水凝胶的动态黏附是理解 EPC 与成熟内皮细胞相似性和差异性的第一步，并提高将 EPC 隔离到生物材料表面以促进血管内再内皮化的能力。
