Castellanos Maria Isabel, Guillem-Marti Jordi, Mas-Moruno Carlos, Díaz-Ricart Maribel, Escolar Ginés, Ginebra Maria Pau, Gil Francisco Javier, Pegueroles Marta, Manero Jose María
Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, ETSEIB, Technical University of Catalonia (UPC), Barcelona, 08028, Spain.
Centre for Research in NanoEngineering (CRNE), UPC, Barcelona, 08028, Spain.
J Biomed Mater Res A. 2017 Apr;105(4):973-983. doi: 10.1002/jbm.a.35988. Epub 2017 Jan 18.
Immobilization of bioactive peptide sequences on CoCr surfaces is an effective route to improve endothelialization, which is of great interest for cardiovascular stents. In this work, we explored the effect of physical and covalent immoblization of RGDS, YIGSR and their equimolar combination peptides on endothelial cells (EC) and smooth muscle cell (SMC) adhesion and on thrombogenicity. We extensively investigated using RT-qPCR, the expression by ECs cultured on functionalised CoCr surfaces of different genes. Genes relevant for adhesion (ICAM-1 and VCAM-1), vascularization (VEGFA, VEGFR-1 and VEGFR-2) and anti-thrombogenicity (tPA and eNOS) were over-expressed in the ECs grown to covalently functionalized CoCr surfaces compared to physisorbed and control surfaces. Pro-thrombogenic genes expression (PAI-1 and vWF) decreased over time. Cell co-cultures of ECs/SMCs found that functionalization increased the amount of adhered ECs onto modified surfaces compared to plain CoCr, independently of the used peptide and the strategy of immobilization. SMCs adhered less compared to ECs in all surfaces. All studied peptides showed a lower platelet cell adhesion compared to TCPS. Covalent functionalization of CoCr surfaces with an equimolar combination of RGDS and YIGSR represented prevailing strategy to enhance the early stages of ECs adhesion and proliferation, while preventing SMCs and platelet adhesion. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 973-983, 2017.
将生物活性肽序列固定在钴铬表面是改善内皮化的有效途径，这对心血管支架具有重要意义。在本研究中，我们探讨了RGDS、YIGSR及其等摩尔组合肽的物理和共价固定对内皮细胞（EC）和平滑肌细胞（SMC）黏附以及血栓形成性的影响。我们使用RT-qPCR广泛研究了在功能化钴铬表面培养的内皮细胞中不同基因的表达情况。与物理吸附表面和对照表面相比，在共价功能化的钴铬表面生长的内皮细胞中，与黏附相关的基因（ICAM-1和VCAM-1）、血管生成相关的基因（VEGFA、VEGFR-1和VEGFR-2）以及抗血栓形成相关的基因（tPA和eNOS）均过度表达。促血栓形成基因的表达（PAI-1和vWF）随时间下降。内皮细胞/平滑肌细胞的共培养发现，与普通钴铬表面相比，功能化增加了修饰表面上黏附的内皮细胞数量，这与所使用的肽和固定策略无关。在所有表面上，平滑肌细胞的黏附都比内皮细胞少。与组织培养聚苯乙烯相比，所有研究的肽都表现出较低的血小板细胞黏附。用RGDS和YIGSR的等摩尔组合对钴铬表面进行共价功能化是增强内皮细胞黏附与增殖早期阶段、同时防止平滑肌细胞和血小板黏附的主要策略。© 2017威利期刊公司。《生物医学材料研究杂志》A部分：105A：973 - 983，2017年。
