UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey.
Biomaterials. 2011 Dec;32(34):8797-805. doi: 10.1016/j.biomaterials.2011.08.018. Epub 2011 Aug 31.
Metal-based scaffolds such as stents are the most preferred treatment methods for coronary artery disease. However, impaired endothelialization on the luminal surface of the stents is a major limitation occasionally leading to catastrophic consequences in the long term. Coating the stent surface with relevant bioactive molecules is considered to aid in recovery of endothelium around the wound site. However, this strategy remains challenging due to restrictions in availability of proper bioactive signals that will selectively promote growth of endothelium and the lack of convenience for immobilization of such signaling molecules on the metal surface. In this study, we developed self-assembled peptide nanofibers that mimic the native endothelium extracellular matrix and that are securely immobilized on stainless steel surface through mussel-inspired adhesion mechanism. We synthesized Dopa-conjugated peptide amphiphile and REDV-conjugated peptide amphiphile that are self-assembled at physiological pH. We report that Dopa conjugation enabled nanofiber coating on stainless steel surface, which is the most widely used backbone of the current stents. REDV functionalization provided selective growth of endothelial cells on the stainless steel surface. Our results revealed that adhesion, spreading, viability and proliferation rate of vascular endothelial cells are remarkably enhanced on peptide nanofiber coated stainless steel surface compared to uncoated surface. On the other hand, although vascular smooth muscle cells exhibited comparable adhesion and spreading profile on peptide nanofibers, their viability and proliferation significantly decreased. Our design strategy for surface bio-functionalization created a favorable microenvironment to promote endothelial cell growth on stainless steel surface, thereby providing an efficient platform for bioactive stent development for long term treatment of cardiovascular diseases.
基于金属的支架，如支架，是治疗冠状动脉疾病的最首选的方法。然而，支架管腔表面内皮化受损是一个主要的局限性，偶尔会导致长期的灾难性后果。在支架表面涂覆相关的生物活性分子被认为有助于在伤口部位周围恢复内皮。然而，由于缺乏适当的生物活性信号来选择性地促进内皮生长，以及缺乏将这些信号分子固定在金属表面上的便利性，这种策略仍然具有挑战性。在这项研究中，我们开发了模拟天然内皮细胞外基质的自组装肽纳米纤维，并通过贻贝启发的粘附机制将其牢固地固定在不锈钢表面上。我们合成了 Dopa 修饰的肽两亲物和 REDV 修饰的肽两亲物，它们在生理 pH 下自组装。我们报告说，Dopa 修饰使纳米纤维能够涂覆在不锈钢表面上，这是目前支架最广泛使用的支架。REDV 功能化提供了内皮细胞在不锈钢表面上的选择性生长。我们的结果表明，与未涂覆的表面相比，血管内皮细胞在肽纳米纤维涂覆的不锈钢表面上的粘附、扩散、活力和增殖率显著提高。另一方面，尽管血管平滑肌细胞在肽纳米纤维上表现出相似的粘附和扩散特征，但它们的活力和增殖显著降低。我们的表面生物功能化设计策略创造了一个有利的微环境，促进了不锈钢表面上内皮细胞的生长，从而为心血管疾病的长期治疗提供了一种有效的生物活性支架开发平台。
