Aims: Because vascular restoration therapy using bioresorbable vascular scaffolds (BRS) remains an appealing concept to restore vasoreactivity, an understanding of biodegradation remains paramount during preclinical testing. We therefore aimed to investigate the qualitative and temporal course of degradation of magnesium alloy-based bioresorbable vascular scaffolds in juvenile swine.Methods and results: Qualitative characterisation of biodegradation was performed in 41 DREAMS 1G up to three years, while degradation kinetics were acquired in 54 DREAMS 2G implanted into porcine coronary arteries for 28, 90 and 180 days, one and two years. Assessment of end product composition was achieved in DREAMS 2G at 180 days. Myocardium was examined, while an OCT attenuation score was derived at strut level from 180 days to two years in DREAMS 2G. Degradation of DREAMS entails two corrosive phases. At one year, 94.8% of the magnesium was bioabsorbed in DREAMS 2G and, at two years, magnesium was completely replaced by amorphous calcium phosphate. Von Kossa staining revealed variable peri-strut mineralisation at all time points and only small focal myocardial emboli observed in one animal in the 180 days cohort. Strut discontinuity density was low at 28 days (0.5±0.57 per mm) and increased to a density above 7.5 per mm up to one year. OCT attenuation score correlated well with strutbased degradation analysis up to two years. Conclusions:While the current set of data supports vascular safety, clinical trials are warranted to prove the concept of vascular restoration following DREAMS implantation.

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Neointimal infiltration with foamy macrophages is recognized as an early and important sign of de-novo atherosclerosis after stent implantation (neoatherosclerosis). Recent histopathological studies have proven that automated quantification of signal attenuation using intravascular optical coherence tomography (OCT) imaging allows for sensitive identification of macrophages in native atherosclerotic disease. Whether this is true for neointimal foam cells in the setting of neoatherosclerosis remains unknown. Autopsy samples of stented coronary arteries (n = 13 cases) were evaluated by histology and OCT. After co-registration with histology, the attenuation rate of emitted laser light was measured in regions with and without neointimal foamy macrophages relative to its peak intensity at the blood-tissue interface. Attenuation index was subsequently determined as slope of a regression curve fitted to individual data points. Receiver operating curve (ROC) analysis was used to establish an optimal cutoff for detecting foamy macrophages in homogenous and non-homogenous neointima, respectively. Finally, the tissue attenuation index was applied to confirm or exclude the presence of neointimal foamy macrophages in symptomatic patients presenting with in-stent restenosis and undergoing intravascular OCT imaging (n = 29 cases). Tissue attenuation index derived from post-mortem samples differed significantly between histologically confirmed regions with and without neointimal foamy macrophages (− 1.23 ± 1.42 vs. − 0.52 ± 1.79, p < 0.05). ROC analysis was able to distinguish neointima with foamy macrophage infiltration from neointima without (93% sensitivity, 73% specificity, cutoff − 0.79, AUC 0.87 for homogenous neointima and 40% sensitivity, 95% specificity, cutoff − 1.93, AUC 0.69 for non-homogenous neointima). In symptomatic patients presenting with in-stent restenosis after stent implantation and undergoing intravascular imaging with OCT, neointimal foamy macrophages were detected in 34.2% of homogenous and 43.6% of non-homogenous neointimal ROI's evaluated. OCT-derived and histopathologically validated tissue attenuation index enables identification of neointimal foamy macrophages in stented coronary arteries. Such image-based post-processing software algorithm may help discern and triage subjects at increased risk for device-related events.

Background: neoatherosclerosis represents an accelerated manifestation of atherosclerosis in nascent neointima after stenting, associated with adverse events. We investigated whether improved reendothelialization using RGD-coated stents results in diminished vascular permeability and reduced foam cell formation compared to standard DeS in atherosclerotic rabbits. Methods and Results: neointimal foam cell formation was induced in rabbits (n = 7). Enhanced endothelial integrity in RGDcoated stents resulted in decreased vascular permeability relative to DES, which was further confirmed by SEM and TEM. Cell culture experiments examined the effect of everolimus on endothelial integrity. increasing concentrations of everolimus resulted in a dose-dependent decrease of endothelial cell junctions and foam cell transformation of monocytes, confirming the relevance of endothelial integrity in preventing permeability of LDL. Conclusion: Incomplete endothelial integrity was confirmed as a key factor of neointimal foam cell formation following stent implantation. pro-healing stent coatings may facilitate reendothelialization and reduce the risk of neoatherosclerosis.