Stable and Thin-Polymer-Based Modification of Neurovascular Stents with 2-Methacryloyloxyethyl Phosphorylcholine Polymer for Antithrombogenicity

Author:

Inuzuka Naoki12,Shobayashi Yasuhiro2,Tateshima Satoshi3ORCID,Sato Yuya4ORCID,Ohba Yoshio5,Ishihara Kazuhiko6ORCID,Teramura Yuji578ORCID

Affiliation:

1. R&D Department, Japan Medical Device Startup Incubation Program, 3-7-2 Nihonbashihon-cho, Chuo-ku, Tokyo 103-0023, Japan

2. R&D Department, N.B. Medical Inc., 3-7-2 Nihonbashihon-cho, Chuo-ku, Tokyo 103-0023, Japan

3. Division of Interventional Neuroradiology, Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles (UCLA), Ronald Reagan UCLA Medical Center, 757 Westwood Plaza, Suite 2129, Los Angeles, CA 90095, USA

4. Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan

5. Cellular and Molecular Biotechnology Research Institute (CMB), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tsukuba Central 5, 1-1-1 Higashi, Ibaraki, Tsukuba 305-8565, Japan

6. Division of Materials & Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan

7. Department of Immunology, Genetics and Pathology (IGP), Uppsala University, Dag Hammarskjölds väg 20, 751 85 Uppsala, Sweden

8. Master’s/Doctoral Program in Life Science Innovation (T-LSI), University of Tsukuba, 1-1-1 Tennodai, Ibaraki, Tsukuba 305-8577, Japan

Abstract

The advent of intracranial stents has revolutionized the endovascular treatment of cerebral aneurysms. The utilization of stents has rendered numerous cerebral aneurysm amenable to endovascular treatment, thereby obviating the need for otherwise invasive open surgical options. Stent placement has become a mainstream approach because of its safety and efficacy. However, further improvements are required for clinically approved devices to avoid the frequent occurrence of thrombotic complications. Therefore, controlling the thrombotic complications associated with the use of devices is of significant importance. Our group has developed a unique stent coated with a 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer. In this study, the surface characteristics of the polymer coating were verified using X-ray photoelectron spectroscopy and atomic force microscopy. Subsequently, the antithrombotic properties of the coating were evaluated by measuring platelet count and thrombin–antithrombin complex levels of whole human blood after 3 h of incubation in a Chandler loop model. Scanning electron microscopy was utilized to examine thrombus formation on the stent surface. We observed that MPC polymer-coated stents significantly reduced thrombus formation as compared to bare stents and several clinically approved devices. Finally, the coated stents were further analyzed by implanting them in the internal thoracic arteries of pigs. Angiographic imaging and histopathological examinations that were performed one week after implantation revealed that the vascular lumen was well maintained and coated stents were integrated within the vascular endothelium without inducing adverse effects. Thus, we demonstrated the efficacy of MPC polymer coating as a viable strategy for avoiding the thrombotic risks associated with neurovascular stents.

Publisher

MDPI AG

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