Thorac Cardiovasc Surg 2015; 63 - OP110
DOI: 10.1055/s-0035-1544362

In-vivo Monitoring of Tissue-Engineered Vascular Grafts

F. Wolf 1, H. Schnöring 2, K. Chalabi 3, M.E. Mertens 4, A. Morgenroth 5, V.N. Gesche 6, S. Koch 1, A. Vogg 5, O.H. Winz 5, R. Autschbach 2, J. Frese 1, P. Mela 1, F. Kiessling 4, F.M. Mottaghy 5, T. Lammers 4, S. Jockenhövel 1, 6
  • 1Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Tissue Engineering & Textile Implants, Aachen, Germany
  • 2Klinik für Thorax-, Herz- und Gefäßchirurgie der Uniklinik Aachen, Aachen, Germany
  • 3Institut National de Chirurgie Cardiaque et de Cardiologie Interventionnelle, Luxembourg, Luxembourg
  • 4University Clinic and Helmholtz Institute for Biomedical Engineering, Department of Experimental Molecular Imaging, Aachen, Germany
  • 5Klinik für Nuklearmedizin, Uniklinik RWTH Aachen, Aachen, Germany
  • 6Institut für Textiltechnik der RWTH Aachen University, Aachen, Germany

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.