Institute of Biochemistry, Faculty of Life Sciences , Leipzig University , Brüderstrasse 34 , 04103 Leipzig , Germany.
Leibniz-Institute of Surface Engineering (IOM) , Permoserstrasse 15 , 04318 Leipzig , Germany.
Bioconjug Chem. 2019 Oct 16;30(10):2664-2674. doi: 10.1021/acs.bioconjchem.9b00573. Epub 2019 Sep 30.
Common interventional therapies for cardiovascular occlusive diseases, such as the implantation of stents, are at risk of complications like thrombosis or restenosis. Drug-eluting stents have improved patency but simultaneously worsen the endothelialization of the implant. Here, we present a novel peptide coating derived from three proteins of the extracellular matrix named fibronectin, laminin, and elastin. Their active sequences RGD, SIKVAV, and VGVAPG were immobilized onto titanium surfaces by a carrier peptide containing l-3,4-dihydroxyphenylalanine (DOPA). Simultaneous functionalization of the carrier peptide with cyclic c[RGDfK] and SIKVAV had the most potent influence on adhesion, proliferation, viability, and angiogenesis of endothelial cells. By presentation of two adhesion peptides in one molecule, a synergistic enhancement of cell-surface interactions was achieved. Overall, this work clearly demonstrates the advantages of spatially defined peptide coatings for the endothelialization of titanium and thus describes a promising approach for the coating of stents.
心血管闭塞性疾病的常见介入治疗方法,如支架植入术,存在血栓形成或再狭窄等并发症的风险。药物洗脱支架提高了通畅率,但同时恶化了植入物的内皮化。在这里,我们提出了一种源自细胞外基质三种蛋白质的新型肽涂层,分别是纤连蛋白、层粘连蛋白和弹性蛋白。它们的活性序列 RGD、SIKVAV 和 VGVAPG 通过含有 l-3,4-二羟基苯丙氨酸 (DOPA) 的载体肽固定在钛表面上。载体肽同时用环 c[RGDfK] 和 SIKVAV 进行功能化,对内皮细胞的黏附、增殖、活力和血管生成有最强烈的影响。通过在一个分子中呈现两个黏附肽,实现了细胞表面相互作用的协同增强。总的来说,这项工作清楚地表明了空间限定肽涂层在钛内皮化方面的优势,因此描述了一种有前途的支架涂层方法。