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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        3D-bioprinted cell-laden blood vessel with

                                        dual drug delivery nanoparticles for advancing
                                        vascular regeneration



                                        Eun Ji Lee 1,2† , Jaewoo Choi 1,2† , Hye Ji Lim , Deokhyeon Yoon , Dong Myoung
                                                                          1,2
                                                                                           1,2
                                        Lee , Donggu Kang , Jeong-Seok Lee , Hojun Jeon , Kyeong Hyeon Lee ,
                                                         3
                                           1,2
                                                                        3
                                                                                                     4
                                                                                    3
                                        Yong-Il Shin , Sang-Cheol Han , Woong Bi Jang *, and Sang-Mo Kwon *
                                                                   6
                                                  4,5
                                                                                                     1,2
                                                                                 1,2
                                        1 Laboratory for  Vascular Medicine and Stem  Cell Biology,  Department  of  Physiology,  Medical
                                        Research Institute, School of Medicine, Pusan National University, Yangsan, Republic of Korea
                                        2 Convergence Stem Cell Research Center, Pusan National University, Yangsan, Republic of Korea
                                        3 Research Institute of Additive Manufacturing and Regenerative Medicine, Baobab Healthcare Inc.,
                                        55 Hanyangdaehak-Ro, Ansan, Gyeonggi-do, South Korea
                                        4 Science of Convergence, School of Medicine, Pusan National University, Yangsan, Republic of
                                        Korea
                                        5 Department  of Rehabilitation  Medicine,  Pusan  National  University Yangsan Hospital, Yangsan,
                                        Republic of Korea
                                        6 CEN Co., Ltd., Nano-Convergence Center, 761 Muan-ro, Miryang, Republic of Korea
                                        (This article belongs to the Special Issue: Nano-enabled 3D Bioprinting for Various Tissue Engineering)
                                        Abstract
            † These authors contributed equally
            to this work.               Vascular regeneration plays a critical role in the treatment of cardiovascular
            *Corresponding authors:     diseases and in tissue engineering applications. In this study, we fabricated and
            Woong Bi Jang               characterized statin/curcumin-loaded nanoparticles for potential applications in
            (jangwoongbi@naver.com)     vascular regeneration. The nanoparticles exhibited consistent spherical shape and
            Sang-Mo Kwon                sizes, indicating reproducibility and stability of the fabrication process. The sustained
            (smkwon323@pusan.ac.kr)
                                        release of the loaded drugs from the nanoparticles indicated their suitability for
            Citation: Lee EJ, Choi J, Lim HJ,   controlled and prolonged drug delivery. Biocompatibility assessments revealed that
            et al. 3D-bioprinted cell-laden blood   the nanoparticles were nontoxic even at high concentrations and over extended
            vessel with dual drug delivery
            nanoparticles for advancing    periods. Moreover, the incorporation of statin within the nanoparticles enhanced
            vascular regeneration. Int J Bioprint.   the proliferative capacity and functional abilities of endothelial progenitor cells,
            2024;10(2):1857.            thereby promoting angiogenesis and vascular repair. Co-administration of curcumin
            doi: 10.36922/ijb.1857
                                        with statin further augmented the therapeutic effects by reducing intracellular
            Received: September 18, 2023  reactive oxygen species levels and providing antioxidant protection against
            Accepted: November 17, 2023
            Published Online: January 12, 2024  oxidative stress. Furthermore,  we  successfully integrated these nanoparticles
                                        into artificial blood vessels (ABVs) using three-dimensional printing technology,
            Copyright: © 2024 Author(s).
            This is an Open Access article   creating customizable constructs capable of supporting vascular regeneration. The
            distributed under the terms of the   viability and proliferative capacity of cells within the ABVs were preserved, which
            Creative Commons Attribution   has  potential  for targeted  drug  delivery  and  localized  therapy.  In  in vivo  models
            License, permitting distribution,
            and reproduction in any medium,   of  hindlimb  ischemia,  transplantation  of  nanoparticle-loaded  ABVs  resulted  in
            provided the original work is   significant improvements in terms of recovery speed and blood flow. Histological
            properly cited.             analysis confirmed the enhanced expression of vascular-related markers, indicating
            Publisher’s Note: AccScience   improved angiogenesis. Collectively, our findings demonstrate the potential of
            Publishing remains neutral with   statin/curcumin-loaded nanoparticles as a promising approach for vascular tissue
            regard to jurisdictional claims in   engineering and regenerative medicine. These nanoparticles offer controlled drug
            published maps and institutional
            affiliations.               delivery, biocompatibility, and enhanced regenerative properties, suggesting that



            Volume 10 Issue 2 (2024)                       331                                doi: 10.36922/ijb.1857
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