Reduced restenosis and enhanced re-endothelialization of functional biodegradable vascular scaffolds by everolimus and magnesium hydroxide

Abstract

Background Coronary artery disease is a cardiovascular disease with a high mortality and mortality rate in modern society. Vascular stent insertion to restore blood flow is essential to treat this disease. A fully biodegradable vascular scaffold (BVS) is a vascular poly (L-lactic acid) (PLLA) stent that is receiving growing interest as this is biodegradable in the body and does not require secondary removal surgery. However, acidic byproducts composed of PLLA produced during the biodegradation of the BVS can induce an inflammatory response. Magnesium hydroxide, a basic inorganic particle, neutralizes the acidic byproducts of PLLA. Methods In this study, we investigated using a BVS coated with everolimus and surface-modified magnesium hydroxide that suppresses smooth muscle cell proliferation and protects endothelial cells, respectively. The various characteristics of the functional stent were evaluated using in vitro and in vivo analyses. Results The BVS was successfully prepared with evenly coated everolimus and surface-modified magnesium hydroxide. A neutral pH value was maintained by magnesium hydroxide during degradation, and everolimus was released for one month. The coated BVS effectively inhibited protein adsorption and platelet adhesion, demonstrating excellent blood compatibility. In vitro analysis showed that BVS protects endothelial cells with magnesium hydroxide and selectively inhibits smooth muscle cell proliferation via everolimus treatment. The functional BVS was inserted into porcine coronary arteries for 28 days, and the results demonstrated that the restenosis and inflammation greatly decreased and re-endothelialization was enhanced as compared to others. Conclusions This study provides new insights into the design of drug-incorporated BVS stent for coronary artery disease. Graphical Abstract

Restoring endothelial function: shedding light on cardiovascular stent development

“…Additionally, Dong Keun Han et al modified poly( l -lactic acid) stents with everolimus and MH to reduce restenosis and inflammation, thus enhancing re-endothelialization. 135…”

A Study of PLA Thin Film on SS 316L Coronary Stents Using a Dip Coating Technique

“…Approximately 5 million percutaneous coronary interventions (PCI) are performed annually worldwide [ 1 , 2 , 3 ]. Atherosclerosis is one of the most recurring inflammatory problems produced in the coronary arteries in the last years around the world [ 4 , 5 , 6 , 7 ]. Stenting is an important treatment to allow blood to flow through narrowed coronary arteries [ 2 , 8 ].…”

A small-diameter vascular graft immobilized peptides for capturing endothelial colony-forming cells

“…Poly (L)-lactic acid (PLLA) is widely explored in tissue engineering and drug-delivery systems because of its remarkable biodegradability and biocompatibility properties ( Tyler et al, 2016 ). The application of electrospinning PLLA to fabricate artificial vascular scaffolds has been recognized in many studies ( Song et al, 2021 ; Baek et al, 2022 ). Moreover, we presented a strategy to fabricate porous PLLA fabrics with both micro- and nano-pores using a combination of electrospinning PLLA/polyethylene oxide (PEO) blend solution and water etching of PEO in the previous work ( Zhao et al, 2018 ).…”