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Neo-artery In vivo Re-growth Using a Tissue-engineered Hyaluronan Biodegradable Scaffold

Sandro Lepidi, Jr.¹, Vincenzo Vindigni, Jr.², Barbara Zavan, Jr.³, Roberta Cortivo, Sr.³, Giovanni Paolo Deriu, Sr.¹, Franco Grego, Sr.¹, Giovanni Abbatangelo, Sr.^1
1Division of Vascular Surgery, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova Medical School, Padova, Italy;²Division of Plastic Surgery, University of Padova Medical School, Padova, Italy;³Department of Histology, Microbiology and Medical Biotechnologies, University of Padova Medical School, Padova, Italy.

OBJECTIVES: The development of cardiovascular tissue engineering introduced the possibility of a living biological graft that might mimic the functional elastic properties of native vessels. In previous studies we showed that a biodegradable tissue-engineered Hyaluronan-based graft (HYAFF 11™) replacing the infrarenal rat aorta was able to guide the complete regeneration of a well functioning small diameter (2 mm) neo-artery. The aim of this study was to test the ability of HYAFF 11™ biodegradable grafts to develop a neo-vessel of larger sizes (5 mm) in a porcine model, focusing on extracellular matrix remodelling and elastin biosynthesis.

METHODS: HYAFF 11™ grafts (diameter 5 mm, length 4 cm) were implanted in an end-to-end fashion in the common carotid artery of 10 pigs. Grafts were analyzed for patency using Duplex-scan every 15 days. Results were evaluated by histology and immunohistochemistry at 1, 2, 3, 4 and 5 months. RT-PCR was used to semi-quantify the relative expression of tropoelastin, collagen type I, MMP1 and MMP2 genes.

RESULTS: All the animals survived the observation period without complications. Three grafts occluded, at 45, 60 and 90 days respectively. Intimal hyperplasia (starting from the anastomotic site) and graft thrombosis were the cause of occlusion as demonstrated by histological examination. There were no signs of stenoses or aneurysms in the remaining grafts. At 5 months, the biomaterial was almost completely degraded and replaced by a neo-artery segment composed of mature smooth muscle cells (MLCK+), collagen and elastin fibres organized in layers, and completely covered on the luminal surface by endothelial cells (vWF+). Collagen type I and MMP2 gene expression showed a time-dependent increase, whereas MMP1 and tropoelastin gene expression decreased from month 1 to 5, in association with elastic fibres organization [Figure 1].

CONCLUSIONS: Although patency rates seem to be inferior to those obtained in previous small animal studies, Hyaluronan-based grafts of larger size confirmed the ability to guide the development of a well functioning neo-artery, with the remarkable property of forming organized layers of elastin fibres. Improvement in the design of the bioengineered HYAFF graft and larger studies are required before introducing this new vascular conduit into the clinical setting.

AUTHOR DISCLOSURES: S. Lepidi, None; V. Vindigni, None; B. Zavan, None; R. Cortivo, None; G.P. Deriu, None; F. Grego, None; G. Abbatangelo, None.