Vascular healing and integration of a fully bioresorbable everolimus-eluting scaffold in a rabbit iliac arterial model.

AIMS: We aimed to investigate a fully bioresorbable poly-l-lactide (PLLA) scaffold to assess vascular remodelling in comparison to a permanent polymeric metal DES. METHODS AND RESULTS: Twenty-five New Zealand white rabbits received an Absorb bioresorbable vascular scaffold (BVS, 1.0 and 1.1) or a CYPHER sirolimus-eluting stent (SES) in the iliac arteries. Twelve arteries were harvested at one month for scanning electron microscopy (SEM) analysis (BVS 1.1). The other implanted (BVS 1.0) arteries (n=32) were explanted at three, six and 36 months for light microscopic analysis. Re-endothelialisation assessed at one month was incomplete in both BVS and SES by SEM, with a trend towards greater coverage in SES (endothelialisation above strut: 32.2% vs. 60.6%, p=0.10). However, light microscopic analysis at later time points revealed greater endothelial coverage in BVS than in SES at 36 months (100.0% vs. 93.3%, p=0.05). Inflammation scores were comparable between arteries implanted with BVS and SES at three months (1.1 vs. 1.1, p=0.99), which decreased over time in the BVS implanted arteries (36 months: 0.0 vs. 0.2, p=0.05). At 36 months, BVS were completely resorbed, and resorption sites were replaced by connective tissue. CONCLUSIONS: BVS in the rabbit iliac artery model demonstrated ongoing vascular healing at three and six months, and complete vessel restoration, re-endothelialisation and no to minimal vascular inflammation at 36 months.

Long-term safety of an everolimus-eluting bioresorbable vascular scaffold and the cobalt-chromium XIENCE V stent in a porcine coronary artery model.

BACKGROUND: The Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb) has shown promising clinical results; however, only limited preclinical data have been published. We sought to investigate detailed pathological responses to the Absorb versus XIENCE V (XV) in a porcine coronary model with duration of implant extending from 1 to 42 months. METHODS AND RESULTS: A total of 335 devices (263 Absorb and 72 XV) were implanted in 2 or 3 main coronary arteries of 136 nonatherosclerotic swine and examined by light microscopy, scanning electron microscopy, pharmacokinetics, and gel permeation chromatography analyses at various time points. Vascular responses to Absorb and XV were largely comparable at all time points, with struts being sequestered within the neointima. Inflammation was mild to moderate (with absence of inflammation at 1 month) for both devices, although the scores were greater in Absorb at 6 to 36 months. Percent area stenosis was significantly greater in Absorb than XV at all time points except at 3 months. The extent of fibrin deposition was similar between Absorb and XV, which peaked at 1 month and decreased rapidly thereafter. Histomorphometry showed expansile remodeling of Absorb-implanted arteries starting after 12 months, and lumen area was significantly greater in Absorb than XV at 36 and 42 months. These changes correlated with dismantling of Absorb seen after 12 months. Gel permeation chromatography analysis confirmed that degradation of Absorb was complete by 36 months. CONCLUSIONS: Absorb demonstrates comparable long-term safety to XV in porcine coronary arteries with mild to moderate inflammation. Although Absorb was associated with greater percent stenosis relative to XV, expansile remodeling was observed after 12 months in Absorb with significantly greater lumen area at ≥ 36 months. Resorption is considered complete at 36 months.

Lumen gain and restoration of pulsatility after implantation of a bioresorbable vascular scaffold in porcine coronary arteries.

OBJECTIVES: Using intravascular ultrasound (IVUS) and histomorphometry, this study sought to evaluate the potential of nonatherosclerotic porcine coronary arteries to undergo progressive lumen gain and a return of pulsatility after implantation with an everolimus-eluting bioresorbable vascular scaffold (BVS). BACKGROUND: Unique benefits such as lumen gain and restored vasomotion have been demonstrated clinically after treatment with BVS; however, a more rigorous demonstration of these benefits with a randomized clinical trial has not yet been conducted. METHODS: Seventy nonatherosclerotic swine received 109 everolimus-eluting BVS and 70 everolimus-eluting metal stents randomized among the main coronary arteries. Arteries were evaluated in vivo by angiography and IVUS and post-mortem by histomorphometry at time points from 1 to 42 months. RESULTS: From 1 to 6 months, both BVS- and everolimus-eluting metal stent-implanted arteries demonstrated stable lumen areas (LAs). From 12 months to 42 months, there was a progressive increase in the LA of arteries implanted with a BVS as assessed by histomorphometry and IVUS. This lumen gain in the implanted segment corresponded to an increase in the reference vessel LA. Normalization in the in-segment LA (LA:reference vessel LA) was observed qualitatively by angiography and quantitatively by IVUS. Additionally, BVS-implanted arteries demonstrated restored in-segment pulsatility on the basis of IVUS assessment of the differences in the mid-scaffold area between end-diastole to end-systole. CONCLUSIONS: Starting at 12 months, BVS-implanted porcine coronary arteries underwent progressive lumen gain and showed restored pulsatility. These benefits demonstrated preclinically may translate into improvements in long-term clinical outcomes for patients treated with BVS compared with conventional drug-eluting stents.