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International Journal of Bioprinting 3D-printed PPDO/GO stents for CHD treatment.

1. Introduction methods for vascular BRSs, such as laser cutting and
braiding, present respective challenges. Overheating
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Congenital heart disease (CHD) is the most common birth during the laser cutting process can significantly impair
defect, with 13.3 million patients worldwide in 2019, and the mechanical properties of the stent. Similarly, braided
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the leading cause of morbidity and mortality in newborns. stents tend to exhibit relatively low radial force. 25,28 3D
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CHD-related vascular stenoses account for approximately printing has become a research focus in the development
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12% of all CHDs, including pulmonary artery or vein of medical implants. This technique offers advantages such
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stenosis, coarctation of the aorta and its branches,
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and postoperative stenosis. In recent years, intravascular as speed, cost-efficiency, flexibility in the manufacturing
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stent implantation has become the preferred treatment location, and material conservation. It enables the
due to its efficacy. Bioresorbable stents (BRSs) have been personalized customization of products with high
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developed to overcome the drawbacks of permanent precision and geometrical complexity, which is well-suited
metal stents that are currently used in clinical practice. for BRSs. Common 3D printing technologies used for
BRSs can provide short- to mid-term radial support to polymeric BRSs include stereolithography (SLA), selective
prevent stenotic vessel recoil and are gradually resorbed laser sintering (SLS), fused deposition modeling (FDM),
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by the body afterward. This reduces the risks of in-stent etc. During SLA, photosensitive resins are polymerized
restenosis, stent thrombosis, and chronic inflammation. 10,11 and cured under ultraviolet (UV) light, but photoinitiators
Most critically for pediatric patients, BRSs are adapted to and photoabsorbers may be toxic. 31,32 SLS uses a laser to
the vascular growth of infants and children, eliminating partially melt powder materials and bond the particles
the need for secondary interventions, as the implanted together, resulting in a rough surface and requiring post-
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segments can perform luminal remodeling without processing. FDM is a cost-effective and user-friendly
stenosis formation. Therefore, BRSs exhibit significant method that involves melting and extruding materials,
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advantages in the treatment of CHD-related vascular which is suitable for printing thermoplastic polymers.
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stenoses. Notably, there are currently no pediatric BRS Lu et al. developed a PPDO/stabaxol-1 stent using FDM
products available worldwide. Many researchers have to treat cerebrovascular disease.
attempted to develop BRSs for pediatric patients. Various However, the inadequate mechanical performance of
bioresorbable materials have been studied, including PPDO stents, as noted in our previous study, remains
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poly-L-lactic acid (PLLA), poly(lactic-co-glycolic acid) an issue due to their low modulus and strength. The
(PLGA), zinc alloy, and nitride iron. 12–15 However, the incorporation of nanofillers has been considered effective
degradation times of all the above-mentioned materials in improving the mechanical properties of polymers.
are over 1 year, mismatching the constructive remodeling Some studies have reported PPDO nanocomposites
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period of vessels (3–6 months). Prolonged degradation reinforced with carbon nanotubes, chitin nanocrystals,
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triggers inflammatory response and delayed vascular and hydroxyapatite nanoparticles. 40–42 Graphene oxide
growth. Another key issue is that, compared to stainless (GO) is a 2D carbon nanomaterial with high modulus
steel and CoCr alloy used in permanent metal stents, and strength. 43,44 Its high specific surface area provides
these bioresorbable materials exhibit inferior mechanical a larger contact area with the composite matrix. Its rich
properties, leading to poor radial strength of the stent. oxygen-containing functional groups (hydroxyl, carboxyl,
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Radial strength is defined as the maximum force that a stent epoxy groups) on the surface enhance the interfacial
can withstand before collapsing and is the most critical interaction with the polymer matrix through covalent
mechanical property of a stent. 19,20 Low radial strength bonds, hydrogen bonds, π–π interactions, etc., facilitating
results in vascular recoil and flow disruptions, which can stress transfer and improving the mechanical performance
lead to worse conditions, including stent restenosis and of the composite. 45,46 The hydrophilicity and surface
stent migration. 10,21 Therefore, it is crucial to develop a BRS negative charge of GO are conducive to protein adsorption
with sufficient radial strength and moderate degradation via electrostatic interaction, hydrogen bonding, and
time for CHD pediatric patients. hydrophobic interaction, which promotes cell adhesion and
Poly(p-dioxanone) (PPDO) is a semi-crystalline proliferation. 47,48 Stent implantation inevitably damages
aliphatic polyester with good bioresorbability and the endothelium, leading to thrombosis and intimal
biocompatibility. Research has demonstrated that the hyperplasia, thereby causing restenosis. It is essential
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degradation time of PPDO is 6 months, and a braided to promote endothelial cell adhesion, migration, and
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PPDO BRS can maintain radial support for at least 3 proliferation to accelerate endothelialization. Studies have
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months during in vitro degradation, which is ideal for reported that GO facilitates the adhesion, proliferation,
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CHD pediatric patients. Recently, PPDO has been explored and migration of human umbilical vein endothelial cells
for application in vascular stents. Traditional fabrication (HUVECs), 50,51 demonstrating good hemocompatibility
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Volume 10 Issue 6 (2024) 318 doi: 10.36922/ijb.4530