Novel Polymer-Free Everolimus-Eluting Stent Fabricated using Femtosecond Laser Improves Re-endothelialization and Anti-inflammation

In-Ho Bae,In-Ho Bae,In-Ho Bae,Kyung Seob Lim,Kyung Seob Lim,Kyung Seob Lim,Jun-Kyu Park,Jun-Kyu Park,Kwang Hwan Oh,Mi Rim Jin,Myung Ho Jeong,Mi Rim Jin,Dae Sung Park,Dae Sung Park,Dae Sung Park,Dae Sung Park,Jae Won Shim,Jae Won Shim,Jae Won Shim,Doo Sun Sim,Doo Sun Sim,Doo Sun Sim

doi:10.1038/s41598-018-25629-9

Abstract

The aim of this study was to fabricate a novel polymer-free everolimus-eluting stent with nanostructure using a femtosecond laser (FSL). The stent were coated with everolimus (EVL) using FSL and electrospinning processes. The surface was rendered hydrophobic, which negatively affected both platelet adhesion (82.1%) and smooth muscle cell response. Animal study was performed using a porcine coronary restenosis model. The study groups were divided into 1) bare metal stent (BMS), 2) poly(L-lactide) (PLA)-based EVL drug eluting stent (DES), 3) commercial EVL-eluting DES, and 4) FSL-EVL-DES. After four weeks of stent implantation, various analyses were performed. Quantitative analysis showed that the amount of in-stent restenosis was higher in the BMS group (BMS; 27.8 ± 2.68%, PLA-based DES; 12.2 ± 0.57%, commercial DES; 9.8 ± 0.28%, and FSL-DES; 9.3 ± 0.25%, n = 10, p < 0.05). Specifically, the inflammation score was reduced in the FSL-DES group (1.9 ± 0.39, n = 10, p < 0.05). The increment in re-endothelialization in the FSL-DES group was confirmed by immunofluorescence analysis. Taken together, the novel polymer-free EVL-eluting stent fabricated using FSL can be an innovative DES with reduced risk of ISR, thrombosis, and inflammation.

Highlights

The advantages of FSL, such as the ability to regulate cellular processes and accumulation of data regarding the utility of FSL-based medical devices, data on surface modification of stents is scarce
Synthetic polymer-based everolimus-eluting DES have been widely used for effective treatment of obstructive coronary artery disease and prevention of in stent restenosis (ISR) that is mainly caused by hyperproliferation of smooth muscle cells[20]
Several histological studies show that inflammatory reactions play a pivotal role in the proliferation of neointimal hyperplasia and restenosis after stent implantation, which support the results of this report[25,26]

Summary

Introduction

The advantages of FSL, such as the ability to regulate cellular processes and accumulation of data regarding the utility of FSL-based medical devices, data on surface modification of stents is scarce. We have reported that a protein can be incorporated inside the nanoscaled pores on the surfaces of medical devices by a simple loading process[16]. Owing to its ability to reduce restenosis, it has been extensively studied and widely used in patients with coronary artery diseases[17,18,19]. The aim of this study was to fabricate a novel polymer-free DES with nanopatterns and nanopores using FSL. The cellular response regulatory ability of the nanopatterns and drug storage capacity of the nanopores were evaluated. The feasibility of FSL was verified by investigating the alteration of mechanical properties post-FSL and in a preclinical animal study

Objectives

Methods

Results

Conclusion