Significant advances in design of biocompatible metals allowed development of bare metallic stents (BMSs) utilizing these metals for the treatment of vascular diseases. However, restenosis, caused by abnormal accumulation of smooth muscle cells (SMCs) near BMSs, has hindered BMSs to have confidence in their clinical efficacy and safety, and continuously demanded a new type of the stent. Drug eluting stents (DESs) suggested pharmacological methods to tackle with restenosis, however, anti-restenotic agents not only inhibit SMCs but also adversely affect vascular endothelial cells (VECs) which are essential for recovery of blood vessels by inducing re-endothelialization after stent implantation. Therefore, a different strategy to selectively inhibit the accumulation of SMCs is highly required for the stent application. Here, we suggest a new inert metal (NiTi)/biodegradable metal (Mg-Zn alloy) hybrid stent utilizing hydrogen peroxide (H2O2) spontaneously generated from the galvanic coupling of two metals as a SMCs-inhibitive agent. H2O2, one of reactive oxygen species (ROS) in vivo, can be easily formed near the surface of NiTi stent body through oxygen-reduction-reaction (ORR) as degradable Mg-Zn alloys work as sacrificial electron sources. The amount of H2O2 generation can be controlled via the engineering of biodegradation kinetics through Mg-Zn alloy design. We confirm that the optimized amount of H2O2 released from Mg-NiTi connected system selectively inhibited proliferation and function of smooth muscle cells (SMCs) without harming vascular endothelial cells (VECs). Furthermore, for proving high feasibility of our Mg-NiTi stent to be applied in vivo, we introduce surface engineering of Mg thin film coated on the NiTi stent. Because the stent requires to be significantly expanded after implanted to the vessel, interfacial stability of Mg-NiTi interfaces is highly important. Through investigation of delamination phenomenon of Mg thin film coated on the NiTi stent by using both experimental and simulational (finite element analysis) stretching test, we optimize coating pattern of Mg that can stably maintain the adhesion with NiTi stent even after highly deformed condition. Our achievement offers a new insight on development of metallic stents by proposing a simple but novel approach to solve restenosis, which has been a major constraint on clinical application of the stent.

Biodegradability and surface engineering of fully metallic stent enabling controllable generation of reactive oxygen species for antirestenosis

2019 Fall National Meeting

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