Preclinical evaluation of degradation kinetics and elemental mapping of first- and second-generation bioresorbable magnesium scaffolds

Abstract

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 strut-based 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.