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RESEARCH ARTICLE

3D-bioprinted cell-laden blood vessel with dual drug delivery nanoparticles for advancing vascular regeneration

Eun Ji Lee1,2† ,  Jaewoo Choi1,2† ,  Hye Ji Lim1,2 ,  Deokhyeon Yoon1,2 ,  Dong Myoung Lee1,2 ,  Donggu Kang3 ,  Jeong-Seok Lee3 ,  Hojun Jeon3 ,  Kyeong Hyeon Lee4 ,  Yong-Il Shin4,5 ,  Sang-Cheol Han6 ,  Woong Bi Jang1,2* ,  Sang-Mo Kwon1,2*
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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
IJB 2024, 10(2), 1857 https://doi.org/10.36922/ijb.1857
Submitted: 18 September 2023 | Accepted: 17 November 2023 | Published: 12 January 2024
(This article belongs to the Special Issue Nano-enabled 3D bioprinting for various tissue engineering)
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Vascular regeneration plays a critical role in the treatment of cardiovascular diseases and in tissue engineering applications. In this study, we fabricated and characterized statin/curcumin-loaded nanoparticles for potential applications in vascular regeneration. The nanoparticles exhibited consistent spherical shape and sizes, indicating reproducibility and stability of the fabrication process. The sustained release of the loaded drugs from the nanoparticles indicated their suitability for controlled and prolonged drug delivery. Biocompatibility assessments revealed that the nanoparticles were nontoxic even at high concentrations and over extended periods. Moreover, the incorporation of statin within the nanoparticles enhanced the proliferative capacity and functional abilities of endothelial progenitor cells, thereby promoting angiogenesis and vascular repair. Co-administration of curcumin with statin further augmented the therapeutic effects by reducing intracellular reactive oxygen species levels and providing antioxidant protection against oxidative stress. Furthermore, we successfully integrated these nanoparticles into artificial blood vessels (ABVs) using three-dimensional printing technology, creating customizable constructs capable of supporting vascular regeneration. The viability and proliferative capacity of cells within the ABVs were preserved, which has potential for targeted drug delivery and localized therapy. In in vivo models of hindlimb ischemia, transplantation of nanoparticle-loaded ABVs resulted in significant improvements in terms of recovery speed and blood flow. Histological analysis confirmed the enhanced expression of vascular-related markers, indicating improved angiogenesis. Collectively, our findings demonstrate the potential of statin/curcumin-loaded nanoparticles as a promising approach for vascular tissue engineering and regenerative medicine. These nanoparticles offer controlled drug delivery, biocompatibility, and enhanced regenerative properties, suggesting that they are valuable tools for promoting vascular regeneration and advancing therapeutic interventions for cardiovascular diseases. Further research is required to fully elucidate the mechanisms of action and optimize their clinical applications.

Keywords
3D Bioprinting
Nanoparticles
Artificial blood vessels
Atorvastatin
Curcumin
Funding
This work was supported by a grant from the National Research Foundation (NRF2020R1A2C2101297 and 2022R1A5A2027161) funded by the Korean government.
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Conflict of interest
The authors declare no conflicts of interest.
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