Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland.
COOK Ireland Limited, Limerick, Ireland.
J Biomed Mater Res A. 2021 Sep;109(9):1549-1559. doi: 10.1002/jbm.a.37150. Epub 2021 Feb 24.
While drug-eluting stents containing anti-proliferative agents inhibit proliferation of smooth muscle cells (SMCs), they also delay the regrowth of the endothelial cells which can result in subsequent development of restenosis. Acidic extracellular environments promote cell anchorage and migration by inducing conformational change in integrins, the main cell adhesion proteins. This study addresses the feasibility of a citric acid (CA) functionalized nitinol stent for improving vascular biocompatibility, specifically enhancing endothelialization. CA functionalized nitinol vascular stents are compared to commercial bare metal (Zilver Flex) and paclitaxel eluting stents (Zilver PTX) in terms of re-endothelialization. To study the effect of stent coatings, a stent conditioned media methodology was developed in an attempt to represent in vivo conditions. Overall, distinct advantages of the CA functionalized nitinol stent over commercial Zilver PTX DES and Zilver Flex BMS stents in terms of endothelial cell adhesion, migration, and proliferation are reported. These novel findings indicate the potential of a CA functionalized stent to serve as a bioactive and therapeutic surface for re-endothelialization, perhaps in combination with a SMC proliferation inhibitor coating, to prevent restenosis.
尽管含有抗增殖剂的药物洗脱支架可以抑制平滑肌细胞 (SMCs) 的增殖,但它们也会延迟内皮细胞的再生,从而导致随后发生再狭窄。酸性细胞外环境通过诱导整合素的构象变化来促进细胞附着和迁移,整合素是主要的细胞粘附蛋白。本研究探讨了柠檬酸 (CA) 功能化镍钛诺支架改善血管生物相容性的可行性,特别是增强内皮化。从再内皮化的角度,将 CA 功能化镍钛诺血管支架与商业裸金属支架 (Zilver Flex) 和紫杉醇洗脱支架 (Zilver PTX) 进行了比较。为了研究支架涂层的影响,开发了一种支架条件培养基方法,试图模拟体内条件。总的来说,与商业的 Zilver PTX DES 和 Zilver Flex BMS 支架相比,CA 功能化镍钛诺支架在促进内皮细胞黏附、迁移和增殖方面具有明显优势。这些新发现表明,CA 功能化支架具有作为再内皮化的生物活性和治疗性表面的潜力,也许可以与平滑肌细胞增殖抑制剂涂层结合使用,以预防再狭窄。