Biosafety and Efficacy Evaluation of a Biodegradable Magnesium based Drug-eluting Stent in Porcine Coronary Artery

Although drug-eluting stent (DES) has become the standard for percutaneous coronary interventions (PCI) based revascularization, stent thrombosis has emerged as a major cause of death and morbidity for those clinical commonly used permanent stents. Drug-eluting bioresorbable stent (BRS) was thus developed as an alternative to DES, which can be completely absorbed after its therapeutic period. Among them, magnesium (Mg) based BRS has attracted great attention due to its suitable mechanical properties, innovative chemical features and well-proven biocompatibility. In the present work, a Mg–Nd–Zn-Zr (JDBM) based drug-eluting BRS loaded with rapamycin was prepared, and its biosafety and efficacy for coronary artery stenosis were evaluated via in vitro and in vivo experiments. The smooth muscle cells adhesion of PDLLA/RAPA coated alloy and the rapamycin pharmacokinetics of JDBM BRS were first assessed in vitro. JDBM BRS and commercial DES Firehawk were then implanted in the coronary arteries of a porcine model. Neointimal hyperplasia was evaluated at 30, 90, and 180 days, and re-endothelialization was evaluated at 30 days. Furthermore, Micro-CT and optical coherence tomography (OCT) analysis were performed to evaluate the technical feasibility and biocompatibility of JDBM alloy based drug-eluting BRS in vivo. The results showed the inhibition ability of PDLLA/RAPA coated JDBM to smooth muscle cells adhesion and moderate drug release rate of JDBM BRS, demonstrating good anti-restenosis ability in vitro. In vivo, low local and systemic risks of JDBM alloy based BRS was demonstrated in the porcine model. We also showed that this novel BRS was associated with a comparable efficacy profile and high anti-restenosis performance. These findings may confer long term advantages for the use of this BRS over a traditional DES.