Suggestion of potential stent design parameters to reduce restenosis risk driven by foreshortening or dogboning due to non-uniform balloon-stent expansion.

The foreshortening or dogboning of a stent that occurs due to transient non-uniform balloon-stent expansion can induce a vascular injury, resulting in restenosis of the coronary artery. However, previous studies rarely considered the effects of transient non-uniform balloon expansion on analysis of the mechanical properties and behaviors of stents during stent deployment, nor did they determine design parameters to minimize the restenosis risk driven by foreshortening or dogboning. The aim of the current study was, therefore, to suggest potential design parameters capable of reducing the possibility of restenosis risk driven by foreshortening or dogboning through a comparative study of seven commercial stents using finite element (FE) analyses of a realistic transient non-uniform balloon-stent expansion process. The results indicate that using stents composed of opened unit cells connected by bend-shaped link structures, in particular the MAC Plus stent, and controlling the geometrical and morphological features of the unit cell strut or the link structure at the distal ends of stent may prevent restenosis risk caused by foreshortening or dogboning. This study provides a first look at the realistic transient non-uniform balloon-stent expansion by investigating the mechanical properties, behaviors, and design parameters capable of reducing the possibility of restenosis risk induced by the foreshortening or the dogboning.

Coating with paclitaxel improves graft survival in a porcine model of haemodialysis graft stenosis.

BACKGROUND: Most commonly resulting from intimal hyperplasia at the venous anastomosis, stenosis leading to thrombosis is a major cause of failure of polytetrafluoroethylene (PTFE) dialysis grafts. We recently reported that coating haemodialysis grafts with paclitaxel could reduce neointimal hyperplasia. This study tested whether paclitaxel-coating could prolong graft survival in a porcine model. METHODS: PTFE grafts were double-coated with paclitaxel. Bilateral grafts were created between the carotid arteries and the external jugular veins, and we evaluated graft survival by weekly measurements of blood flow for 12 weeks. RESULTS: We successfully implanted four pairs of paclitaxel-coated grafts and four pairs of control grafts in eight Landrace pigs. One control pig had to be euthanized at 4 weeks after graft placement. The grafts in the other three controls and four paclitaxel pigs survived until harvesting of the grafts. All paclitaxel-coated grafts remained patent for 12 weeks without decrease of blood flow. Median blood flow was 702 ml/min at three weeks and 818 ml/min at 12 weeks after placement. In contrast, the four control grafts lost luminal patency at 5, 6, 6 and 8 weeks, respectively. In Kaplan-Meier analysis, paclitaxel-coated grafts showed better survival than uncoated grafts (P = 0.011). CONCLUSIONS: Double-coating with paclitaxel improved graft survival. Coated PTFE grafts may be effective for the prevention of graft failure in patients on haemodialysis.

A novel technique for loading of paclitaxel-PLGA nanoparticles onto ePTFE vascular grafts.

The major cause of hemodialysis vascular access dysfunction (HVAD) is the occurrence of stenosis followed by thrombosis at venous anastomosis sites due to the aggressive development of venous neointimal hyperplasia. Local delivery of antiproliferative drugs may be effective in inhibiting hyperplasia without causing systemic side effects. We have previously demonstrated that paclitaxel-coated expanded poly(tetrafluoroethylene) (ePTFE) grafts, by a dipping method, could prevent neointimal hyperplasia and stenosis of arteriovenous (AV) hemodialysis grafts, especially at the graft-venous anastomoses; however, large quntities of initial burst release have remained a problem. To achieve controlled drug release, paclitaxel (Ptx)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Ptx-PLGA-NPs) were prepared by the emulsion-solvent evaporation method and then transferred to the luminal surface and inner part of ePTFE vascular grafts through our micro tube pumping and spin penetration techniques. Scanning electron microscope (SEM) images of various stages of Ptx-PLGA-NPs unequivocally showed that micro tube pumping followed by spin penetration effectively transferred Ptx-PLGA-NPs to the inner part, as well as the luminal surface, of an ePTFE graft. In addition, the in vitro release profiles of paclitaxel demonstrated that this new system achieved controlled drug delivery with a reduced initial burst release. These results suggest that loading of Ptx-PLGA-NPs to the luminal surface and the inner part of an ePTFE graft is a promising strategy to ultimately inhibit the development of venous neointimal hyperplasia.

Paclitaxel-coated expanded polytetrafluoroethylene haemodialysis grafts inhibit neointimal hyperplasia in porcine model of graft stenosis.

BACKGROUND: The main pathology of haemodialysis graft stenosis is venous neointimal hyperplasia at graft-venous anastomoses. Neointimal hyperplasia is also observed in cases of coronary artery in-stent restenosis. Paclitaxel is a chemotherapeutic agent used to treat cancer, and has been proven to inhibit neointimal hyperplasia of coronary artery in-stent restenosis. In this study, we examined whether a paclitaxel-coated haemodialysis graft could inhibit neointimal hyperplasia and prevent stenosis. METHODS: We dip-coated paclitaxel on expanded polytetrafluoroethylene (ePTFE) grafts at a dose density of 0.59 microg/mm(2). In vitro release tests showed an initial paclitaxel burst followed by a long-term slow release. Using ePTFE grafts with (coated group, n = 8) or without a paclitaxel coating (control group, n = 11), we constructed arteriovenous (AV) grafts connecting the common carotid artery and the external jugular vein in Landrace pigs. RESULTS: After excluding seven pigs for technical failure, cross-sections of graft-venous anastomoses obtained 6 weeks after placing the AV grafts were analysed. Percentage luminal stenosis, ratios of intima to media in whole cross-sections, areas of intima in the peri-junctional areas (within 2 mm above and 2 mm below the graft-venous junction), and the mean thickness of intima within venous sides of cross-sections, were 60.5% (range, 41.5-60.7), 13.0 (range, 8.6-20.4), 23.7 mm(2) (range, 10.8-32.1) and 2.1 mm (range, 1.1-3.0), respectively, in the control group, whereas corresponding median values in the coated group were 10.4% (range, 1.0-17.8), 1.0 (range, 0.7-5.1), 1.6 mm(2) (range, 0.2-8.0) and 0.3 mm (range, 0.1-2.2). All parameters were significantly different between the two groups (P<0.05 by Mann-Whitney test). CONCLUSION: Paclitaxel-coated ePTFE grafts could prevent neointimal hyperplasia and the stenosis of AV haemodialysis grafts.