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International Journal of Bioprinting                                3D bioprinting for nanoparticle evaluation




            patient outcomes through personalized and precise   into artificial blood vessels shows promise in improving
            medical interventions. 60,61                       ischemic repair. Meanwhile, the use of magnetic NPs for
                                                               targeted drug  delivery effectively  addresses  stenosis  in
            4.1. Three-dimensional bioprinted human auricular   blood vessels. Furthermore, the development of cell-laden
            model for cyclosporine A- and coenzyme Q10-        blood vessels with dual drug delivery systems represents
            loaded solid lipid nanoparticles                   a significant leap forward, offering comprehensive
            The study by Yalgın et al.  used 3D bioprinting technology   solutions for vascular regeneration. These interdisciplinary
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            to develop human auricular models for evaluating the   approaches underscore the transformative potential of
            effects of SLNs loaded with cyclosporine A (CycA)   combining 3D bioprinting with nanotechnology in the
            and  coenzyme  Q10  (Q10)  on  cell  growth.  The  authors   field of regenerative medicine.
            employed biocompatible materials such as alginate,
            polylactic acid (PLA), and polyvinyl alcohol (PVA) using   5.1. Bioprinting of artificial blood vessels
            an Ultimaker-2 3D printer to create models that mimic   with rapamycin-loaded nanoparticles for
            human ear structures (Figure 4A). The primary goal is   vascular regeneration
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            to assess the suitability of these 3D-printed models for   The study by Choi et al.  explored an approach using 3D
            NIH-3T3 fibroblast growth in the presence of CycA and   bioprinting technology to fabricate artificial blood vessels
            Q10 SLNs. The 3D printing process involves creating   loaded with rapamycin-loaded NPs. This method aims to
            precise, layer-by-layer models from these biocompatible   address significant clinical challenges posed by vascular
            materials. Alginate, PLA, and PVA were tested for their   diseases, such as restenosis following interventions like
            ability to serve as scaffolds for cell growth. However, due   stent placement. 67–69  The researchers utilized 3D bioprinting
            to mechanical instability, alginate hydrogels were less   to create artificial blood vessels that closely mimic natural
            suitable, while PLA provided a stable scaffold conducive   vascular architecture. This technique allowed for precise
            to NP incorporation. The study utilized a high-shear   control over the dimensions and structure of the vessels,
            homogenization technique to prepare the SLNs, which were   ensuring they were tailored to the specific needs of the
            then incorporated into the PLA models. The incorporation   patient. The customization capabilities of 3D printing are
            of SLNs into the 3D-printed PLA models allowed for a   crucial for creating patient-specific solutions, which are
            controlled release of CycA and Q10, enabling a detailed   more effective and less likely to be rejected by the body.
            evaluation of their effects on cell viability and growth.   One of the significant advancements in this study was the
            MTT assays were used to measure cell viability, showing   integration  of  NPs  within  the  3D-printed  vessels.  These
            that  Q10-SLNs  significantly  enhanced  cell  proliferation   NPs were made from mesoporous silica, characterized
            and mitigated the cytotoxic effects of CycA. Specifically,   by their small size and porous nature, which allowed for
            while CycA-SLNs alone resulted in lower cell viability,   efficient drug loading and controlled release. The study
            the addition of Q10-SLNs to the PLA models improved   focused on rapamycin, a drug known for its potent ability
            cell  viability to  a  substantial  degree  (Figure  4B).  Three-  to prevent restenosis by inhibiting smooth muscle cell
            dimensional bioprinting offers significant advantages for   proliferation. By  encapsulating rapamycin  in NPs,  the
            tissue engineering, particularly in creating patient-specific   authors aimed to achieve sustained and localized drug
            models with complex geometries. This study demonstrates   delivery, thereby enhancing its therapeutic efficacy while
            that 3D-printed PLA auricular models effectively support   minimizing systemic side effects. The bioprinting process
            fibroblast growth and NP delivery, providing a stable   involved creating a bioink composed of a mixture of
            environment for evaluating SLNs. 62                sodium  alginate  and  atelocollagen,  which  was  used  to
                                                               print the vessel’s structure. The core material, a sacrificial
            5. Three-dimensional bioprinted cardiovas-         substance made from Pluronic® F-127, was used to create
            cular and vascular models                          the lumen of the blood vessels. Endothelial progenitor cells
                                                               (EPCs) were also incorporated into the bioink to promote
            Recent advancements in 3D bioprinting technologies   re-endothelialization, a critical process for long-term vessel
            have significantly propelled the field of cardiovascular   functionality and integration into the host tissue.  To
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            and vascular regeneration. These cutting-edge techniques   evaluate the effectiveness of the 3D-printed vessels, Choi et
            enable the fabrication of complex, functional blood   al. included both in vitro and in vivo experiments. In vitro,
            vessel structures, which are crucial for treating various   the researchers assessed the stability and drug release profile
            vascular conditions. 63–66  Key studies have demonstrated   of the rapamycin-loaded NPs. The NPs demonstrated a
            the potential of integrating drug-loaded NPs within   slow and controlled release of rapamycin, maintaining
            3D-bioprinted constructs to enhance therapeutic    its concentration at therapeutic levels over an extended
            outcomes.  The  incorporation  of  rapamycin-loaded  NPs   period. This controlled release is essential for preventing


            Volume 10 Issue 5 (2024)                        12                                doi: 10.36922/ijb.4273
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