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Wang, et al.
stents have been demonstrated to facilitate the recovery could be easily tuned by using various combinations of
of vasomotion and reduce the risk of late thrombosis [8,9] . polymer nanofibers and structural designs.
Laser cutting is the conventional manufacturing technique Despite the progress of metal stents coated with
for metal stents and bioresorbable polymeric stents. drug-loaded nanofibers, the performance of drug-loaded
However, laser processing as a thermal process will nanofibers based on bioresorbable stents has not been well
cause heat-affected zones and microcracks and reduce a investigated. Accordingly, to overcome the challenges
stent’s fatigue life, especially for polymeric stents . In associated with DES, such as permanent metallic
[10]
our previous study , we developed a custom-made four- stents and the limitations of antiproliferative agents on
[11]
axis three-dimensional (3D) printing system with a novel endothelialization, we propose a strategy to combine
mini-screw extruder and a rotation mandrel to realize bioresorbable stents with DP-loaded nanofiber coatings
precise extrusion of polymer filaments. We successfully that could prevent in-stent restenosis and promote neo-
developed a novel stent with a zero Poisson’s ratio endothelialization. As depicted in Figure 1, we developed
structure to address the longitudinal foreshortening an integrated stent with the combination of biodegradable
problem of conventional metal stents. Moreover, polymers as the backbone material of 3D-printed stents
bioresorbable polycaprolactone (PCL) stents with and DP-loaded nanofibers as the coating. 3D bioresorbable
adjustable stent structures and shapes were fabricated by stents were fabricated by printing on a rotation mandrel using
3D printing. PCL, and the stents were further coated with DP-loaded
To alleviate the limitations of antiproliferative poly(D,L-lactide) (PDLLA) nanofibers by electrospinning.
agents on endothelialization, drugs that could impede The surface morphology and radial strength of the stents
SMC proliferation and have no detrimental effect on were characterized by scanning electron microscopy (SEM)
endothelial cell viability have been explored as coatings and radial compression tests, respectively. The in vitro drug
for vascular stents. Dipyridamole (DP), an antithrombotic release, degradation, and Fourier transform infrared (FTIR)
and antithrombogenic drug used in the clinic, can impede characterization of PDLLA/DP nanofibers were investigated
the proliferation of SMCs by hindering the uptake of and a long-term sustained release of DP drug over 120 days
adenosine . More importantly, DP has been reported was achieved. In addition, the in vitro hemocompatibility
[12]
to facilitate the proliferation and endothelialization of and biocompatibility results suggested that stents coated
vascular endothelial cells . Therefore, it is reasonable with DP-loaded nanofibers significantly inhibited the
[13]
to develop a biodegradable polymer coating with the proliferation of SMCs and facilitated the endothelializtion
combination of versatile DP to address the dilemma of vascular endothelial cells. Moreover, in vivo evaluation
of current antiproliferative agent-loaded DES. Various of stent implantation was carried out using a porcine
approaches, including dip coating , spray coating [15,16] , and coronary artery model. After implantation for 28 days, the
[14]
electrospinning , have been explored to achieve polymer/ arteries implanted with DP-loaded stents showed reduced
[17]
drug coating with stents. Among them, electrospinning has in-stent restenosis and initial endothelialization.
been reported to be a versatile and economical technology 2. Materials and methods
to produce nanofibers for biomedical applications .
[18]
Compared to DES, stents coated with drug-loaded nanofibers 2.1. Materials
might introduce additional benefits. For example, drug-
loaded nanofibers mimic the microenvironment of the native PCL (average Mn 80000) and DP were purchased from
extracellular matrix and provide a high surface-to-volume Sigma-Aldrich (St. Louis, USA). 1,1,1,3,3,3-hexafluoro-2-
ratio, which is beneficial for cell adhesion and proliferation, propanol (HFIP, 99+%) was supplied by Aladdin Co., Ltd.
more uniform drug release, and higher doses of agents . (Shanghai, China). PDLLA (Mn = 10 kDa) was purchased
[19]
In addition, it is flexible to select different polymers as the from Jinan Daigang Biomaterial Co., Ltd. (Jinan, China).
carrier of agents . Punnakitikashem et al. reported a 2.2. 3D-printed PCL stents coated with PDLLA/
[20]
[21]
biodegradable vascular graft with nanofibrous structures DP nanofibers
electrospun by mixing polyurethane with DP, achieving
sustained release of DP for more than 91 days. Liu et al. A custom-made four-axis 3D printing system with a novel
[22]
fabricated bare-metal stents coated with poly(l-lactide- mini-screw extruder and a rotation mandrel reported in our
co-caprolactone) nanofibers loaded with both heparin and previous study was applied to fabricate tubular PCL stents .
[11]
rosuvastatin using coaxial electrospinning for the treatment As illustrated in Figure 1A(i), the PCL material was molten
of aneurysms. This study demonstrated that nanofibers and extruded through the nozzle into filaments and further
with shell-core structures could load different drugs with deposited on the rotating mandrel. Stents with an inner
adjustable ratios and spatial distribution, suggesting the diameter of 3 mm and a length of 10 mm were fabricated.
flexibility and compatibility of electrospun nanofibers for Subsequently, as illustrated in Figure 1A(ii), PDLLA
drug release. The release rate and drug loading capacity nanofibers loaded with DP were randomly deposited onto

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