Institute for Experimental Molecular Imaging, Faculty of Medicine, RWTH Aachen University, Forckenbeckstraße 55, 52074 Aachen, Germany.
Department of Biohybrid & Medical Textiles, AME-Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Forckenbeckstraße 55, 52074 Aachen, Germany.
Biomaterials. 2024 Dec;311:122669. doi: 10.1016/j.biomaterials.2024.122669. Epub 2024 Jun 17.
Biohybrid tissue-engineered vascular grafts (TEVGs) promise long-term durability due to their ability to adapt to hosts' needs. However, the latter calls for sensitive non-invasive imaging approaches to longitudinally monitor their functionality, integrity, and positioning. Here, we present an imaging approach comprising the labeling of non-degradable and degradable TEVGs' components for their in vitro and in vivo monitoring by hybrid H/F MRI. TEVGs (inner diameter 1.5 mm) consisted of biodegradable poly(lactic-co-glycolic acid) (PLGA) fibers passively incorporating superparamagnetic iron oxide nanoparticles (SPIONs), non-degradable polyvinylidene fluoride scaffolds labeled with highly fluorinated thermoplastic polyurethane (F-TPU) fibers, a smooth muscle cells containing fibrin blend, and endothelial cells. H/F MRI of TEVGs in bioreactors, and after subcutaneous and infrarenal implantation in rats, revealed that PLGA degradation could be faithfully monitored by the decreasing SPIONs signal. The F signal of F-TPU remained constant over weeks. PLGA degradation was compensated by cells' collagen and α-smooth-muscle-actin deposition. Interestingly, only TEVGs implanted on the abdominal aorta contained elastin. XTT and histology proved that our imaging markers did not influence extracellular matrix deposition and host immune reaction. This concept of non-invasive longitudinal assessment of cardiovascular implants using H/F MRI might be applicable to various biohybrid tissue-engineered implants, facilitating their clinical translation.
生物杂交组织工程血管移植物(TEVGs)由于其适应宿主需求的能力而具有长期耐用性。然而,后者需要敏感的非侵入性成像方法来纵向监测其功能、完整性和定位。在这里,我们提出了一种成像方法,包括对不可降解和可降解 TEVG 成分进行标记,以便通过混合 H/F MRI 进行体外和体内监测。TEVG(内径 1.5 毫米)由可生物降解的聚(乳酸-共-乙醇酸)(PLGA)纤维组成,这些纤维被动地掺入超顺磁性氧化铁纳米粒子(SPIONs),不可降解的聚偏二氟乙烯支架用高度氟化热塑性聚氨酯(F-TPU)纤维标记,含有纤维蛋白混合物的平滑肌细胞和内皮细胞。在生物反应器中以及在大鼠皮下和肾下植入后对 TEVG 进行 H/F MRI 显示,SPIONs 信号的减少可以准确监测 PLGA 的降解。F-TPU 的 F 信号在数周内保持不变。PLGA 的降解由细胞的胶原蛋白和α-平滑肌肌动蛋白沉积来补偿。有趣的是,只有植入腹主动脉的 TEVG 才含有弹性蛋白。XTT 和组织学证明,我们的成像标志物不会影响细胞外基质的沉积和宿主的免疫反应。使用 H/F MRI 对心血管植入物进行非侵入性纵向评估的这一概念可能适用于各种生物杂交组织工程植入物,从而促进它们的临床转化。