In vivo chronic scaffolding force of a resorbable magnesium scaffold.

The aim of this study is to qualitatively characterize the in vivo chronic scaffolding force of the Magmaris® Resorbable Magnesium Scaffold (RMS). This important parameter of scaffolds must be balanced between sufficient radial support during the healing period of the vessel and avoidance of long-term vessel caging. A finite element model was established using preclinical animal data and used to predict the device diameter and scaffolding force up to 90 days after implantation. To account for scaffold resorption, it included backbone degradation as well as formation of discontinuities as observed in vivo. The predictions of the model regarding acute recoil and chronic development of the device diameter were in good agreement with the preclinical data, supporting the validity of the model. It was found that after 28 and 90 days, the Magmaris® RMS retained 90 % and 47 % of its initial scaffolding force, respectively. The reduction in scaffolding force was mainly driven by discontinuities in the meandering segments. Finite element analysis combined with preclinical data is a reliable method to characterize the chronic scaffolding force.

Antibody-mediated PCSK9 neutralization worsens outcome after bare-metal stent implantation in mice.

AIMS: Despite advances in pharmacotherapy and device innovation, in-stent restenosis (ISR) and stent thrombosis (ST) remain serious complications following percutaneous coronary intervention (PCI) procedure with stent implantation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme involved in plasma cholesterol homeostasis and recently emerged as a therapeutic target for hypercholesterolemia. Antibody-based PCSK9 inhibition is increasingly used in different subsets of patients, including those undergoing PCI. However, whether PCSK9 inhibition affects outcome after stent implantation remains unknown. METHODS AND RESULTS: 12 to 14 weeks old C57Bl/6 mice underwent carotid artery bare-metal stent implantation. Compared to sham intervention, stent implantation was associated with increased expression of several inflammatory mediators, including PCSK9. The increase in PCSK9 protein expression was confirmed in the stented vascular tissue, but not in plasma. To inhibit PCSK9, alirocumab was administered weekly to mice before stent implantation. After 6 weeks, histological examination revealed increased intimal hyperplasia in the stented segment of alirocumab-treated animals compared to controls. In vitro, alirocumab promoted migration and inhibited the onset of senescence in primary human vascular smooth muscle cells (VSMC). Conversely, it blunted the migration and increased the senescence of endothelial cells (EC). CONCLUSION: Antibody-based PCSK9 inhibition promotes in-stent intimal hyperplasia and blunts vascular healing by increasing VSMC migration, while reducing that of EC. This effect is likely mediated, at least in part, by a differential effect on VSMC and EC senescence. The herein-reported data warrant additional investigations concerning the use of PCSK9 inhibitors in patients undergoing PCI with stent implantation.

Preclinical evaluation of the degradation kinetics of third-generation resorbable magnesium scaffolds.

BACKGROUND: The novel sirolimus-eluting resorbable scaffold DREAMS 3G was designed as a third-generation development of its predecessor, the Magmaris scaffold. AIMS: This preclinical study aimed to examine the qualitative and temporal course of the degradation of the DREAMS 3G relative to the Magmaris scaffold. METHODS: Forty-nine DREAMS 3G and 24 Magmaris scaffolds were implanted into 48 mini swine for degradation kinetics analysis. Another DREAMS 3G was implanted into one mini swine for crystallinity analysis of the degradation end product after 730 days. Degradation kinetics were determined at 28, 90, 120, 180, and 365 days. RESULTS: Discontinuity density in DREAMS 3G was significantly lower than that in Magmaris scaffolds for the follow-up timepoints of 90 and 120 days. Planimetric analysis indicated 99.6% backbone degradation for DREAMS 3G at 12 months. Compared to the Magmaris scaffold, individual strut degradation in DREAMS 3G showed less variability and the remaining backbone core was more homogeneous. The degradation end product of DREAMS 3G manifested as calcium phosphate with a minor share of aluminium phosphate. CONCLUSIONS: DREAMS 3G showed almost complete degradation after one year, with amorphous calcium and aluminium phosphate as the end products of degradation. Despite its thinner struts, scaffold discontinuity was significantly lower in the DREAMS 3G than in the Magmaris scaffold, likely providing a longer scaffolding time.