Haritz Jasper L, Pflaum Michael, Güntner Hans J, Katsirntaki Katherina, Hegermann Jan, Hehnen Felix, Lommel Michael, Kertzscher Ulrich, Arens Jutta, Haverich Axel, Ruhparwar Arjang, Wiegmann Bettina
Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Lower Saxony Center for Biomedical Engineering, Implant Research and Development, Stadtfelddamm 34, 30625, Hannover, Germany.
Adv Sci (Weinh). 2025 Feb;12(6):e2408976. doi: 10.1002/advs.202408976. Epub 2024 Dec 20.
Although left ventricular assist devices (LVADs) are an alternative to heart transplantation, their artificial surfaces often lead to serious thrombotic complications requiring high-risk device replacement. Coating blood-contacting surfaces with antithrombogenic endothelial cells is considered an effective strategy for preventing thrombus formation. However, this concept has not yet been successfully implemented in LVADs, as severe cell loss is to be expected, especially on the impeller surface with high prothrombogenic supraphysiological shear stress. This study presents a strategy that exploits the magnetic attraction of the impeller on ECs loaded with iron oxide nanoparticles (IONPs) to minimize shear stress-induced cell detachment from the rotating magnetic impeller while ensuring antithrombogenic EC adhesion, especially as a bridge until they formed their adhesion-promoting matrix. In contrast to polyvinylpyrrolidone (PVP)-coated IONPs, more efficient and safer cell loading is achieved with sodium citrate (Cit)-stabilized IONPs, where incubation with 6.6 µg iron mL-1 Cit-IONPs for 24 h resulting in an average internalization of 23 pg iron per cell. Internalization of Cit-IONP significantly improved cell attraction to the highly magnetic impeller surface without affecting cell viability or antithrombogenic function. This protocol is key for the development of a biohybrid LVAD impeller that can prevent life-threatening thrombosis and hemorrhage in a future clinical application.
尽管左心室辅助装置(LVAD)是心脏移植的一种替代方案,但其人工表面常常导致严重的血栓形成并发症,需要进行高风险的装置更换。用抗血栓形成的内皮细胞覆盖血液接触表面被认为是预防血栓形成的有效策略。然而,这一概念尚未在LVAD中成功实施,因为预计会出现严重的细胞损失,尤其是在具有高促血栓形成的超生理剪切应力的叶轮表面。本研究提出了一种策略,利用叶轮对负载有氧化铁纳米颗粒(IONP)的内皮细胞的磁吸引力,以最小化剪切应力诱导的细胞从旋转磁叶轮上脱落,同时确保抗血栓形成的内皮细胞粘附,特别是作为桥梁,直到它们形成促进粘附的基质。与聚乙烯吡咯烷酮(PVP)包被的IONP相比,柠檬酸钠(Cit)稳定的IONP能实现更高效、更安全的细胞负载,用6.6 μg铁/mL的Cit-IONP孵育24 h,平均每个细胞内化23 pg铁。Cit-IONP的内化显著提高了细胞对高磁性叶轮表面的吸引力,而不影响细胞活力或抗血栓形成功能。该方案对于开发一种生物杂交LVAD叶轮至关重要,这种叶轮在未来的临床应用中可以预防危及生命的血栓形成和出血。