In vivo evaluation of polyurethane-PDMS based small diameter vascular grafts reinforced with a Nitinol mesh

Introduction Peripheral artery disease and related revascularization procedures are increasing due to the aging population and growing incidence of diabetes mellitus. Up to now, autologous saphenous vein represents the conduit of choice for peripheral by-pass. Synthetic vascular graft in polyethylene terephthalate (Dacron®) and expanded polytetrafluoroethylene (ePTFE) are used when the vein is not available. These grafts are successfully used to replace large diameter vessels, but they have shown poor patency rates when used in small-diameter sizes (<6 mm) or low-flow locations due to thrombosis and intimal hyperplasia. The aim of this study was to prepare a polymeric small diameter vascular graft reinforced with an highly flexible Nitinol mesh (Kips Bay Medical Inc, Minneapolis, MN, USA) to prevent circumferential dilatation and kinking. Materials and Methods Poly(ether)urethane-PDMS grafts were fabricated by spray, phase-inversion technique. which allowed to incorporate the mesh during graft fabrication and to obtain a composite device1. The in vivo experiments were performed in the sheep carotid artery by-pass model to assess grafts performance in term of patency and tissue compatibility. In particular, a 7 cm long, 4 mm I. D. composite graft was interposed (double end-to-side anastomosis) with a continuous suture and the carotid segment was excised. Graft patency was checked by Eco-Color Doppler the day after implant and once weekly thereafter. After 1, 3 and 6 months grafts (n=4) were explanted, opportunely fixed and serially sectioned for histological analysis. Stevenel's/Van Gieson stain was employed to evaluate tissue response, in particular the presence of macrophages and neovascularization, Masson Trichrome to assess the production of collagen and extracellular matrix. Results No signs of seroma, infection or necrosis were observed in any of the animals. Eco-Color Doppler showed grafts patency at each controls, moreover no dilatation or aneurismatic formation were observed. Macroscopical observation of grafts explanted showed all grafts to be patent with a thrombus-free luminal surface. At 1 and 3 months graft extremities were covered by an endoluminal white tissue, while the mid-portion appeared covered by a thin layer of reddish fibrinous material. At 6 months grafts appeared almost completely covered by white tissue. None of the grafts showed signs of calcification. Histological analysis showed an internal lining of endothelial-like cells, containing fibroblasts or myofibroblasts cells, grew from the adjacent carotid over the graft material and external sign of neoadventitia formation with a slight inflammatory reaction. No intimal hyperplasia was observed at anastomoses in any samples. Discussion and Conclusions The animal experimentation of the composite grafts showed good handling, optimal patency, mechanical stability, neointimal formation, tissue integration and absence of calcification.