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RESEARCH ARTICLE

3D-printed Bioresorbable Stent Coated with

Dipyridamole-Loaded Nanofiber for Restenosis

Prevention and Endothelialization

Chengjin Wang 1,2,3 , Yang Yang 1,2,3 , Jingyuan Ji 1,2,3 , Yongcong Fang , Liliang Ouyang 1,2,3 ,
1,2
Lei Zhang 1,2,3 *, Wei Sun 1,2,3,4 *

1 Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China
2 Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing 100084, China
3 “Biomanufacturing and Engineering Living Systems” Innovation International Talents Base (111 Base), Beijing 100084, China
4 Department of Mechanical Engineering, Drexel University, Philadelphia, PA 19104, USA

Abstract: Intimal hyperplasia and restenosis caused by excessive proliferation of smooth muscle cells (SMC) are the main
factors for the failure of stent implantation. Drug-eluting stents carried with antiproliferative drugs have emerged as a successful
approach to alleviate early neointimal development. However, these agents have been reported to have an undesirable
effect on re-endothelialization. In this study, we proposed an integrated bioresorbable stent coated with dipyridamole (DP)-
loaded poly(D,L-lactide) (PDLLA) nanofibers. Three-dimensional (3D) bioresorbable stents were fabricated by printing
on a rotation mandrel using polycaprolactone (PCL), and the stents were further coated with PDLLA/DP nanofibers. The
in vitro degradation and drug release evaluation illustrated the potential for long-term release of DP. Stents coated with
PDLLA/DP nanofibers showed excellent hemocompatibility. The cell viability, proliferation, and morphology analysis results
revealed that stents coated with PDLLA/DP nanofibers could prevent the proliferation of SMC and have no adverse effects on
endothelial cells. The in vivo implantation of stents coated with PDLLA/DP nanofibers showed initial patency and continuous
endothelialization and alleviated neointimal formation. The attractive in vitro and in vivo performance indicated its potential
for restenosis prevention and endothelialization.
Keywords: Bioresorbable stent; Nanofiber; Dipyridamole; Anti-restenosis; Endothelialization

*Correspondence to: Lei Zhang, Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China;
stoneszhang@mail.tsinghua.edu.cn; Wei Sun, Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing
100084, China; weisun@mail.tsinghua.edu.cn
Received: January 13, 2022; Accepted: February 19, 2022; Published Online: February 19, 2022
(This article belongs to the Special Issue: Composite/Multi-component Biomaterial Inks and Bioinks)

Citation: Wang, C., Yang, Y., Ji, J., et al., 2022, 3D-Printed Bioresorbable Stent Coated with Dipyridamole-Loaded Nanofiber for Restenosis
Prevention and Endothelialization. Int J Bioprint, 8(2):543. http://doi.org/10.18063/ijb.v8i2.543

1. Introduction and prolonged dual antiplatelet therapy [3,4] . Moreover,
antiproliferative agents loaded in the polymer coating of
In recent years, metallic drug-eluting stents (DES) have
become an effective clinical treatment for coronary artery DES, such as sirolimus and paclitaxel, have been reported
disease, which work by introducing antiproliferative to have an undesirable effect on re-endothelialization,
drug-loaded polymer coatings that can inhibit smooth which may result in long-term endothelial dysfunction [5,6] .
muscle cell (SMC) proliferation and alleviate neointimal To overcome the inherent drawbacks of permanently
development [1,2] . However, residual metallic stents as existing metallic stents, bioresorbable stents have been
foreign objects would cage the vessel permanently, leading developed to provide temporary support with tunable
to late stent thrombosis, impaired coronary vasomotion, degradation rates of stent materials . Bioresorbable
[7]
© 2022 Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and
reproduction in any medium, provided the original work is properly cited.
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