Faster smooth muscle cell coverage in ultrathin-strut drug-eluting stent leads to earlier re-endothelialization

Dongwoo Hahn; Donghoon Lee; Woonggyu Hyun; Yunnie Cho; Chang-Hwan Yoon; Ki-Hyun Jeon; Si-Hyuck Kang; Tae-Jin Youn; In-Ho Chae

doi:10.3389/fbioe.2023.1207858

Faster smooth muscle cell coverage in ultrathin-strut drug-eluting stent leads to earlier re-endothelialization

Front Bioeng Biotechnol. 2023 May 23:11:1207858. doi: 10.3389/fbioe.2023.1207858. eCollection 2023.

Authors

Dongwoo Hahn¹, Donghoon Lee², Woonggyu Hyun³, Yunnie Cho³, Chang-Hwan Yoon¹, Ki-Hyun Jeon¹, Si-Hyuck Kang¹, Tae-Jin Youn¹, In-Ho Chae¹

Affiliations

¹ Division of Cardiology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
² Cardiovascular center, Asan Chungmu Hospital, Asan, Republic of Korea.
³ College of Medicine, Seoul National University, Seoul, Republic of Korea.

Abstract

Background: The ultrathin-strut drug-eluting stent (DES) has shown better clinical results than thin- or thick-strut DES. We investigated if re-endothelialization was different among three types of DES: ultrathin-strut abluminal polymer-coated sirolimus-eluting stent (SES), thin-strut circumferential polymer-coated everolimus-eluting stent (EES), and thick-strut polymer-free biolimus-eluting stent (BES) to gain insight into the effect of stent design on promoting vascular healing. Methods: After implanting three types of DES in the coronary arteries of minipigs, we performed optical coherence tomography (OCT) at weeks 2, 4, and 12 (n = 4, each). Afterward, we harvested the coronary arteries and performed immunofluorescence for endothelial cells (ECs), smooth muscle cells (SMCs), and nuclei. We obtained 3D stack images of the vessel wall and reconstructed the en face view of the inner lumen. We compared re-endothelialization and associated factors among the different types of stents at different time points. Results: SES showed significantly faster and denser re-endothelialization than EES and BES at weeks 2 and 12. Especially in week 2, SES elicited the fastest SMC coverage and greater neointimal cross-sectional area (CSA) compared to EES and BES. A strong correlation between re-endothelialization and SMC coverage was observed in week 2. However, the three stents did not show any difference at weeks 4 and 12 in SMC coverage and neointimal CSA. At weeks 2 and 4, SMC layer morphology showed a significant difference between stents. A sparse SMC layer was associated with denser re-endothelialization and was significantly higher in SES. Unlike the sparse SMC layer, the dense SMC layer did not promote re-endothelialization during the study period. Conclusion: Re-endothelialization after stent implantation was related to SMC coverage and SMC layer differentiation, which were faster in SES. Further investigation is needed to characterize the differences among the SMCs and explore methods for increasing the sparse SMC layer in order to improve stent design and enhance safety and efficacy.

Keywords: drug-eluting stent (DES); neointimal coverage; optical coherence tomography; re-endothelialization; smooth muscle cell (SMC).

Grants and funding

This work was supported by a grant from the Korean Health Technology R&D project, Ministry of Health and Welfare, Republic of Korea (Grant no. HI19C0655), and the Korea Medical Device Development Fund funded by the Korean Government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health and Welfare, and the Ministry of Food and Drug Safety) (KMDF RS-2020-KD000229 and RS-2020-KD000033).