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Biodegradable Synthetic Small-calibre Vascular Grafts: Long-term Results after Replacement of the Rat Aorta
Beat H. Walpoth1, Damiano Mugnai1, Jean-Christophe Tille2, Francesco Innocente1, Benjamin Nottelet3, Corinne Berthonneche4, Xavier Montet5, Sarra de Valence3, Michael Moeller3, Robert Gurny3, Afksendiyos Kalangos1; 1Dept. of Cardiovascular Surgery, University Hospital of Geneva, Geneva, Switzerland; 2Dept. of Pathology, University Hospital of Geneva, Geneva, Switzerland; 3Dept. of Pharmaceutics & Biopharmaceutics EPGL, Geneva, Switzerland; 4Dept. of Medicine, University Hospital of Lausanne, Lausanne, Switzerland; 5Dept. of Radiology, University Hospital of Geneva, Geneva, Switzerland
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Objective: Shelf-ready synthetic small calibre grafts are needed for coronary artery bypass grafting. Biodegradable scaffolds resistant to degradation-induced aneurysm formation in the systemic arterial circulation have been developed for in vivo vascular tissue engineering. Our aim is to assess the long-term results of synthetic, biodegradable small-calibre vascular grafts compared to ePTFE for aortic replacement in the rat model.
Methods: Ten anaesthetised Sprague Dawley rats (male, 275g), received an infrarenal aortic graft (5 biodegradable; 5 ePTFE) replacement (end-to-end; 2mm ID; 20mm long) and 5 rats served as shame controls. Biodegradable grafts (polycaprolactone = PCL) were produced by random nano-fibre (porosity 80%) electro-spinning. After 1-year survival in vivo high resolution ultra-sonography (Visualsonics; see figure) and angiography were performed to assess patency, stenosis, aneurysm formation, intimal hyperplasia and compliance. After explantation micro CT calcification quantification, histology, immuno-histology, scanning electron microscopy (SEM) and morphometry were carried out.
Results: All grafts (PCL and ePTFE) showed 100% patency at 12 months. No aneurysmal dilation or stenoses were found in the PCL group by angiography. Ultra-sonography showed minimal peri-anastomotic intimal hyperplasia in PCL compared to ePTFE grafts. In vivo compliance revealed a marked reduction between the native abdominal aorta (7-9%) and PCL (3-5%) or ePTFE grafts (1-2%). Micro-pet calcifications were present in both grafts (2-6% of total graft volume) and absent in the native aorta. Histologically low cellular ingrowth was found in ePTFE grafts, whereas PCL grafts showed good homogenous cellularity producing collagen and extra-cellular matrix replacing the PCL scaffold. SEM revealed a confluent neoendothelialisation of the PCL grafts, unlike ePTFE.
Conclusion: Synthetic biodegradable small calibre nano-fibre polycaprolactone grafts show excellent results after 1-year of aortic replacement and compare favourably with the clinically used ePTFE grafts. Thus, such novel in situ tissue engineered grafts could become a future option for clinical applications such as coronary artery bypass grafting.

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