RSS-Feed abonnieren
DOI: 10.1055/s-0035-1544362
In-vivo Monitoring of Tissue-Engineered Vascular Grafts
Objectives: Tissue engineering has the potential to significantly improve the treatment of patients with cardiovascular disease. The capability of online monitoring of position and performance of tissue-engineered constructs after implantation could foster the successful clinical translation. Non-invasive imaging techniques and suitable materials enable the in-vivo implant monitoring. We here present the successful production, subsequent implantation and non-invasive monitoring of tissue-engineered vascular grafts, labeled with ultrasmall superparamagnetic iron oxide (USPIO) particles, in a sheep model.
Methods: Composite small caliber vascular grafts (n = 12) were fabricated by molding of fibrin/cell mixture supported by a macroporous polyvinylidene fluoride (PVDF) warp-knitted mesh. For six of the grafts, the mesh had been previously labeled with USPIOs (0.2% w/w). After 2 weeks of in-vitro conditioning in a bioreactor system the tissue-engineered vascular grafts (n = 6) were implanted as carotid artery interponate in the adult sheep model, 3 with labeled mesh and 3 with unlabeled mesh. The remaining grafts served as control. Implants were imaged 4 and 8 weeks after implantation by MRI and 1 and 3 weeks after implantation by PET/CT. Animals were sacrificed after 9/10 weeks after implantation to perform tissue analysis. All grafts (n = 12), implanted and control were analyzed by quantification of collagen content, histological and immunohistological stainings, scanning (SEM) and transmission (TEM) electron microscopy.
Results: Tissue-engineered vascular grafts containing USPIO-labeled PVDF scaffolds were successfully visualized in-vivo over a time span of 8 weeks using T2* and proton weighted MR imaging without any signal loss. USPIO-labeling was stable under physiological conditions and the intactness of the textile mesh was proven. Patency was verified by MRI angiography. 5 grafts were patent and showed no signs of thrombosis, stenosis or aneurysm formation after 2 months of implantation. Tissue development was not influenced by USPIO-labeling of the PVDF mesh. Extracellular matrix analysis revealed a native-like collagen content. Luminal lining with endothelial cells was evident.
Conclusions: USPIO-labeled tissue-engineered vascular grafts were successfully implanted as interposition grafts in the sheep carotid artery with subsequent non-invasive imaging by MRI and PET/CT. Online monitoring of grafts might improve the post-operative follow-up of implants.