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International Journal of Bioprinting 3D bioprinting for nanoparticle evaluation

regeneration of endothelial cells, crucial for the long-term curcumin, aimed at enhancing vascular regeneration,
success of the implanted vessels. 71 was explored. This approach leverages the synergistic
effects of these drugs on EPCs to address challenges in
5.2. Three-dimensional bioprinted pulmonary vein cardiovascular therapy, particularly in the context of
stenosis models for targeted nanoparticle delivery ischemic diseases. The core of the study revolves around
Ning et al. developed an in vitro model of pulmonary the encapsulation of atorvastatin and curcumin into NPs.
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vein stenosis (PVS) using 3D bioprinting technology Atorvastatin is known for its ability to lower cholesterol
(Figure 5B). This study aims to address the limitations and enhance nitric oxide production, promoting
of the current PVS treatments, particularly issues of vasodilation and anti-inflammatory effects. Curcumin,
restenosis and off-target effects, by creating a precise a potent antioxidant, combats reactive oxygen species
and controllable model for studying disease mechanisms (ROS), which are typically elevated in ischemic conditions
and potential therapies. The research team employed and transplantation scenarios. The dual-drug-loaded NPs
digital light processing-based 3D bioprinting to fabricate (NPSC) are designed to provide controlled, sustained
bifurcated pulmonary vein (PV) constructs that closely release of the drugs, enhancing their therapeutic efficacy
mimic the anatomical features of human pulmonary and reducing potential side effects.
veins. These constructs were seeded with human umbilical
vein endothelial cells (HUVECs) and maintained in a To create the artificial blood vessels, the researchers
perfusion bioreactor system, which simulates a dynamic employed a bioprinting technique using bioink composed
flow environment similar to physiological conditions. of EPCs isolated from umbilical cord blood, combined
This setup enabled the formation of a uniform and viable with the NPSC. The bioprinting process allowed for
endothelium within the PV constructs. The study used precise control over the size and shape of the blood
vessels, accommodating various anatomical requirements.
superparamagnetic iron oxide NPs (SPIONs) conjugated This customization is critical for ensuring the successful
with rapamycin, a potent mTOR inhibitor effective in integration and function of the transplanted vessels
reducing vascular cell proliferation. 72–74 The SPIONs were within the host’s circulatory system. The characterization
designed to be magnetically guided to specific regions of of the NPs revealed consistent spherical shapes and
the bioprinted PV constructs using an external magnetic sizes, confirming the stability and reproducibility of the
field. Computational modeling identified the bifurcation
points within the PV constructs as high-risk areas for fabrication process. The sustained release profiles of statin
and curcumin from the NPs were validated using liquid
endothelial cell overgrowth, making them ideal targets for chromatography/mass spectrometry (LC/MS), ensuring
NP delivery. The application of an external magnetic field that the therapeutic agents were available over extended
effectively concentrated the rapamycin-loaded SPIONs at periods. Additionally, the biocompatibility assessments
the bifurcation points, significantly reducing endothelial indicated that the NPs were non-toxic to EPCs even at
cell proliferation. This targeted approach minimized high concentrations, supporting their safe application
adverse side effects associated with systemic drug delivery, in vivo. Upon transplantation into a mouse model of
such as immunosuppression and endothelial damage. hindlimb ischemia, the NPSC-loaded artificial blood
Magnetic targeting allowed for precise localization of vessels demonstrated significant improvements in vascular
therapeutic NPs, enhancing treatment efficacy. The regeneration. The in vivo studies showed enhanced blood
mechanical properties and structural fidelity of the flow recovery and reduced tissue necrosis in the treated
bioprinted PV constructs were thoroughly characterized, groups compared to controls. Histological analyses
demonstrating high precision and reproducibility. The confirmed increased expression of vascular markers,
porous structure facilitated nutrient and oxygen exchange, such as CD31 and alpha-smooth muscle actin (α-SMA),
which is essential for maintaining cell viability over indicating successful angiogenesis and vascular repair.
extended culture periods. The 3D bioprinting technology
also enabled the production of patient-specific models, The study highlights several advantages of using
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increasing the relevance and applicability of the in vitro 3D-bioprinting for vascular regeneration. The ability
system for PVS research. 75 to customize artificial blood vessels ensures better
anatomical fit and integration, while the incorporation
5.3. Three-dimensional bioprinting of dual drug- of NPs allows for localized, sustained drug delivery. This
loaded artificial blood vessels for enhanced approach minimizes systemic side effects and provides a
vascular regeneration targeted therapeutic effect, crucial for treating complex
In the study conducted by Lee et al. the innovative use vascular diseases. The combination of atorvastatin and
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of 3D bioprinting technology to fabricate artificial blood curcumin within the NPs leverages their complementary
vessels incorporating NPs loaded with atorvastatin and mechanisms, enhancing cell function and survival

Volume 10 Issue 5 (2024) 15 doi: 10.36922/ijb.4273