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3D-printed Stent Coated with Dipyridamole-loaded Nanofiber
3 mm, length: 15 mm) were prepared and sterilized Electrospun fibers loaded with DP have been
using 15 kGy of gamma radiation before implantation. reported to realize sustained release for up to weeks.
Six white minipigs were divided into two groups (group Punnakitikashem et al. developed a nanofibrous
[21]
one and group two). Stents coated with PDLLA/DP scaffold with a higher DP content (10%), which inhibited
nanofibers (n = 3) were implanted into group one, while SMC proliferation and showed no adverse effect on
PCL bare stents (n = 3) were implanted into group two as endothelial cells. A similar concentration of DP in the
the control group. solution was also used to prepare drug-loaded nanofibers
Stents were positioned into the coronary arteries to achieve the antiplatelet effect [28,29] . Here, DP was
of pigs. Balloons with crimped stents were dilated with dissolved in PDLLA/HFIP solution at a concentration
10 atm for 30 s to realize a stent-to-artery diameter of 10% to PDLLA. Thus, the concentration of DP in
ratio of 1.2:1. Coronary angiography was recorded polymer solution was 25 mg/mL. PDLLA/DP nanofibers
after implantation for days 1 and 28. After stents were with an average diameter of 247.01 ± 44.65 nm showed
implanted for 28 days, pigs were euthanized to harvest the a relatively uniform morphology and compact diameter
stented artery samples. Then, samples were fixed in 10% distribution, as shown in Figure 2A(i). In contrast, plain
formalin for 24 h, dehydrated and embedded in paraffin PDLLA nanofibers exhibited an average diameter of
for cross-section slicing. Hematoxylin and eosin (H&E) 685.54 ± 252.23 nm and possessed a bimodal distribution
and Masson staining were performed for histological of fiber diameter, as depicted in Figure S1C.
analysis. Subsequently, FTIR characterization was performed
to investigate the chemical structure of DP, PDLLA
2.10. Statistical analysis nanofibers, and PDLLA/DP nanofibers. Since the
Experimental data are presented as the mean ± standard concentration of DP in the mixture of PDLLA/DP was
deviation (SD). The statistical analysis software GraphPad only 10%, these peaks with low absorbance in the FTIR
Prism 8.0 was used for Student’s t-test. spectra of DP were not obvious in the spectra of PDLLA/
DP. Therefore, we mainly focused on the characteristic
3. Results peaks in each spectrum. As shown in Figure 2B, the
most obvious peak in the spectra of DP was detected at
3.1. Fabrication and characterization of PDLLA/ 1527 cm , which was correlated to C=N bonding and
−1
DP nanofibers absent in the spectra of PDLLA. Similarly, peaks at
−1
−1
The diameter of electrospun fibers typically ranges approximately 1750 cm (C=O), 1185 cm , and 1085
−1
from tens of nanometers to several micrometers . The cm (C-O-C) were detected in the spectra of PDLLA
[26]
morphology of electrospun fibers was influenced by the but absent in the spectra of DP. After the loading of DP
polymer solution composition and processing parameters. into PDLLA fibers, all peaks that were obvious in the
We first optimized the electrospinning process with the base spectra of DP or PDLLA were retained in the spectra of
polymer PDLLA. The morphology of PDLLA nanofibers PDLLA/DP. These results indicated that the PDLLA/DP
was investigated using different concentrations of PDLLA/ nanofibers maintained their chemical stability.
HFIP solutions (100, 150, 200, and 250 mg/mL) and flow The morphologies of PDLLA/DP fibers at different
rates (0.5, 1.0, and 2.0 mL/h). As shown in Figure S1, degradation times were investigated. As presented
in general, PDLLA fibers became more uniform with in Figure 2A(i), fibers possessed a uniform and
the increase of PDLLA concentration. The formation of centralized diameter distribution (247.01 ± 44.65 nm)
beads was observed and gradually became unapparent before degradation (0 week). After degradation for
at concentrations of 100, 150, and 200 mg/mL, while 8 weeks, the diameter of the fibers slightly decreased
uniform nanofibers with smooth surfaces were achieved at (234.73 ± 80.48 nm), and the diameter distribution of
concentrations of 250 mg/mL (Figure S1A). Fong et al. the PDLLA/DP fibers flattened (Figure 2A(ii)). When
[27]
reported that a higher viscosity of polymer solutions could the degradation lasted for 16 weeks, the diameter of
facilitate the formation of fibers without beads, which was the PDLLA/DP fibers showed an obvious decrease to
confirmed by our results. Thus, the PDLLA/HFIP polymer 145.70 ± 66.87 nm compared to that after 8 weeks of
solution concentration was set as 250 mg/mL in the present degradation (Figure 2D). In addition, broken fibers were
work. The effect of the flow rate of polymer solution observed due to accelerated degradation (Figure 2A(iii)).
on the nanofiber morphology was further evaluated. As Furthermore, the representative release curve of DP from
presented in Figure S1B, there was no obvious difference PDLLA/DP nanofibers is presented in Figure 2C, which
in the morphology of PDLLA fibers prepared with flow shows sustained and long-term drug release. In the initial
rates of 0.5, 1.0, and 2.0 mL/h. To achieve a more compact 7 days, the release maintained a relatively fast rate,
structure, we selected a higher flow rate (2.0 mL/h) in the especially in the first 24 h. The release rate gradually
following studies. stabilized in the following days. Approximately 60% of

84 International Journal of Bioprinting (2022)–Volume 8, Issue 2