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International Journal of Bioprinting                                 3D printing with drug for vascular repair




            that the simultaneous administration of multiple drugs,   significant improvements in hindlimb ischemia, marked
            as opposed  to the  introduction of a single agent, may   by enhanced recovery speed and blood flow. These findings
            contribute to a synergistic effect, thereby facilitating   highlight the potential of statin- and curcumin-loaded
            the treatment of ischemic diseases. Further research   nanoparticles as a promising approach for controlled drug
            and optimization of nanoparticle delivery systems are   delivery and regeneration of functional blood vessels.
            warranted to fully understand their mechanisms of action   Further research and optimization are required to fully
            and explore their clinical potential.              explore their clinical potential and pave the way for future
                                                               therapeutic applications.
               The successful fabrication of nanoparticle-laden ABVs
            using 3D printing technology is a significant advancement   Acknowledgments
            in the field of tissue engineering. The ability to create
            ABVs with customizable sizes and integrated nanoparticles   None.
            opens new possibilities for targeted drug delivery and
            localized therapy (Figure 4). The preserved viability and   Funding
            proliferative capacity of cells within ABVs indicate their   This work was supported by a grant from the National
            potential for supporting vascular regeneration. In the in   Research Foundation (NRF2020R1A2C2101297 and
            vivo  transplantation  experiment,  necrosis  was  observed   2022R1A5A2027161) funded by the Korean government.
            in the control group that received ABVs without cells or
            nanoparticles,  highlighting  the  importance  of  utilizing   Conflict of interest
            combination  therapy  encompassing  cells  and  drugs.
            However, the groups that received ABVs loaded with cells   The authors declare no conflicts of interest.
            and nanoparticles exhibited remarkable recovery from
            hindlimb ischemia. At 28 days, the EPC@NP@BV group   Author contributions
            exhibited significantly pronounced vascular recovery   Conceptualization:  Eun Ji Lee, Jaewoo Choi, Woong Bi
            ability, whereas the EPC@NPSC@BV group attained the   Jang, Sang-Mo Kwon
            fastest recovery, marked by almost complete recovery   Formal analysis: Eun Ji Lee, Jaewoo Choi, Woong Bi Jang
            within 14 days. The EPC@NPSC@BV group demonstrated   Investigation: Eun Ji Lee, Jaewoo Choi, Woong Bi Jang, Hye
            the most significant improvements in terms of recovery   Ji Lim
            speed and blood flow, attesting to the synergistic effects   Methodology: Eun Ji Lee, Jaewoo Choi, Woong Bi Jang, Hye
            of statin and curcumin in cell-based therapy (Figure   Ji Lim, Deokhyeon Yoon, Dong Myoung Lee, Donggu
            5B–E). These findings suggest that EPCs enhance their   Kang,  Jeong-Seok Lee,  Hojun Jeon, Kyeong  Hyeon
            functionality and proliferative capacity through the   Lee, Yong-Il Shin, Sang-Cheol Han
            uptake of therapeutic agents, thus assuming a critical   Writing – original draft: Eun Ji Lee, Jaewoo Choi, Woong
            role in facilitating vascular recovery subsequent to ABV   Bi Jang
            transplantation (Figure 3). Histological analysis revealing   Writing – review & editing: Sang-Mo Kwon
            enhanced expression of vascular-related markers, such as
            α-SMA and CD31, in the EPC@NPSC@BV group further   Ethics approval and consent to participate
            supported these outcomes (Figure 5F–I). These findings   Human umbilical cord blood was collected from healthy
            point to the capability of the combination therapy in   volunteers after obtaining informed consent according to
            facilitating the regeneration of functional blood vessels,   the protocol approved by the Institutional Review Board
            which leads to improved angiogenesis.              of Pusan National University Yangsan Hospital, Republic
                                                               of Korea (Approval No. PNUYH-05-2017-053). Animal
            5. Conclusion                                      treatment and maintenance were performed in accordance
            In this study, we successfully prepared NPS and NPC,   with the Principles of Laboratory Animal Care, and animal
            which were in consistent spherical shape and demonstrate   experiments were performed in accordance with protocols
            sustained release profiles. The nanoparticles exhibited   approved by the Pusan National University Institutional
            excellent biocompatibility and promoted the proliferative   Animal Use and Care Committee (Approval No. PNU-
            capacity and functionality of EPC. The integration of these   2022-0212).
            nanoparticles within ABVs using 3D printing technology
            allows for customizable and functional constructs capable   Consent for publication
            of promoting vascular regeneration. In in vivo models, the   In accordance with the guidelines for publication involving
            transplantation  of  nanoparticle-loaded  ABVs  resulted  in   human subjects, we obtained written consent from


            Volume 10 Issue 2 (2024)                       344                                doi: 10.36922/ijb.1857
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