Department of Obstetrics, University and University Hospital of Zurich, Laboratory for Cell and Tissue Engineering, Schmelzbergstrasse 12, PATHG 48, Zurich 8091, Switzerland.
Qvanteq AG, Zurich, Switzerland.
Acta Biomater. 2022 Jan 1;137:331-345. doi: 10.1016/j.actbio.2021.10.022. Epub 2021 Oct 19.
Blood-contacting medical implants made of Nitinol and other titanium alloys, such as neurovascular flow diverters and peripheral stents, have the disadvantage of being highly thrombogenic. This makes the use of systemic (dual) anti-platelet/anticoagulant therapies inevitable with related risks of device thrombosis, bleeding and other complications. Meeting the urgent clinical demand for a less thrombogenic Nitinol surface, we describe here a simple treatment of standard, commercially available Nitinol that renders its surface ultra-hydrophilic and functionalized with phosphate ions. The efficacy of this treatment was assessed by comparing standard and surface-treated Nitinol disks and braids, equivalent to flow diverters. Static and dynamic (Chandler loop) blood incubation tests showed a drastic reduction of thrombus formation on treated devices. Surface chemistry and proteomic analysis indicated a key role of phosphate and calcium ions in steering blood protein adsorption and avoiding coagulation cascade activation and platelet adhesion. A good endothelialization of the surface confirmed the biocompatibility of the treated surface. STATEMENT OF SIGNIFICANCE: Titanium alloys such as Nitinol are biocompatible and show favorable mechanical properties, which led to their widespread use in medical implants. However, in contact with blood their surface triggers the activation of the intrinsic coagulation cascade, which may result in catastrophic thrombotic events. The presented results showed that a phosphate functionalization of the titanium oxide surface suppresses the activation of both coagulation cascade and platelets, avoiding the subsequent formation of a blood clot. This novel approach has therefore a great potential for mitigating the risks associated to either thrombosis or bleeding complications (due to systemic anticoagulation) in patients with cardiovascular implants.
由 Nitinol 和其他钛合金（如神经血管血流导向器和外周支架）制成的与血液接触的医疗植入物有高度血栓形成的缺点。这使得全身（双重）抗血小板/抗凝治疗成为必要，相关风险包括器械血栓形成、出血和其他并发症。为满足对低血栓形成 Nitinol 表面的迫切临床需求，我们在此描述了一种简单的标准商业可用 Nitinol 表面处理方法，使其表面具有超亲水性并功能化磷酸盐离子。通过比较标准和表面处理的 Nitinol 盘和编织物（相当于血流导向器）来评估这种处理的效果。静态和动态（Chandler 环）血液孵育试验表明，处理后的器械上血栓形成明显减少。表面化学和蛋白质组学分析表明，磷酸盐和钙离子在引导血液蛋白吸附、避免凝血级联激活和血小板黏附方面起着关键作用。表面的良好内皮化证实了处理表面的生物相容性。
钛合金如 Nitinol 具有生物相容性和良好的机械性能，这导致它们在医疗植入物中得到广泛应用。然而，与血液接触时，其表面会触发固有凝血级联的激活，这可能导致灾难性的血栓事件。所呈现的结果表明，钛氧化物表面的磷酸盐功能化抑制了凝血级联和血小板的激活，从而避免了随后形成的血凝块。因此，这种新方法具有降低心血管植入物患者血栓形成或出血并发症（由于全身抗凝）相关风险的巨大潜力。
