Inhibition of intimal hyperplasia of the vein graft with degradable poly lactic-co-glycolic acid vascular external sheaths carrying slow-release bosentan

Abstract

OBJECTIVES: Intimal hyperplasia is a major reason for the restenosis of vein grafts. A vascular external sheath was designed to inhibit intimal hyperplasia of vein grafts. METHODS: Using the biodegradable material poly(lactic-co-glycolic acid) and fibrin, a high porosity external sheath carrying bosentan with a stratified internal spiral structure was made by grouping mould extraction and low-temperature deposition techniques. Bosentan, a dual endothelin A and B receptor antagonist, was carried in the new designed external sheath, and could be slowly released. Rabbits underwent carotid bypass with ipsilateral jugular vein without external sheath (control, Group C), with external sheath (Group S) or with external sheath carrying bosentan (Group S + B). RESULTS: Eight weeks after interposition, ultrasonography indicated that the change rate of the diameter of vein grafts of Group C (42.3 ± 5.8%) was much higher than that of Group S (18.5 ± 8.6%) or S + B (1.1 ± 13.2%) (P < 0.01, respectively). The change rate of peak velocity of Group S + B (-0.5 ± 9.8%) was lower than that of Group S (5.7 ± 7.4%) or C (25.6 ± 13.1%) (P < 0.01 vs Group C; P < 0.05 vs Group S). The sheaths degraded completely 9 weeks after interposition and the histological examination showed that the ratio of long/short diameter of vein grafts was much higher in Group C (P < 0.01, respectively). The ratio of the area of intima-media to the area of lumen and the ratio of thickness of intima to the thickness of media of Group S + B were significantly lower (P < 0.01 vs Group C; P < 0.05 vs Group S, respectively). Masson and Alcian Blue staining indicated that the remodelling of collagen and the distribution of proteoglycan in vein grafts of Group S + B were more similar to those of the artery. CONCLUSIONS: The degradable vascular external sheath with slow-release bosentan can inhibit hyperplasia of intima, and improve the shape of experimental vein grafts.