AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025140124
RESEARCH ARTICLE
Early Access

Therapeutic effects of 3D bioprinted mesenchymal stem cell-based artificial lymph nodes in lymphedema treatment

Hyo Jin Kang1† Ju-Hee Lee2† Yong Xun Jin3 Yujin Myung3 Jae Hoon Jeong3*
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1 Department of Biomedical Laboratory Science, Honam University, Gwangju, 62399, Republic of Korea
2 College of Korean Medicine, Dongguk University, Goyang, Gyeonggi-do, 10326, Republic of Korea
3 Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Gyeonggi-do, 13620, Republic of Korea
†These authors contributed equally to this work.
Received: 5 April 2025 | Accepted: 15 May 2025 | Published online: 15 May 2025
© 2025 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/ )
Abstract

Lymphedema is a condition resulting from impaired lymphatic function, with limited effective treatment options available. This study investigates the potential of 3D bioprinted scaffolds, utilizing biomaterials and human adipose-derived stem cells (hADSCs), as a novel approach to promote lymphangiogenesis and improve treatment outcomes in lymphedema. Scaffolds were characterized for cell viability, mechanical properties through compressive strength testing, and structural integrity after printing. In vivo therapeutic effects were assessed in Sprague Dawley rats through fluorescence imaging, histopathological analysis and immunofluorescence staining. Additionally, protein and gene expression of lymphangiogenic markers (LYVE-1, VEGF-C, VEGF-A) were analyzed using Western blotting and quantitative PCR. The scaffolds demonstrated high cell viability, structural integrity, and mechanical stability, with enhanced cell distribution and extracellular matrix deposition over time. Scaffolds containing hADSCs showed the most lymph node-like characteristics, with a well-defined capsule and increased lymphocytic infiltration. Immunofluorescence analysis revealed enhanced expression of LYVE-1, Prox1, and CD31, indicating significant lymphatic and vascular remodeling. Additionally, upregulation of LYVE-1, VEGF-C, and VEGF-A protein and mRNA levels highlighted the scaffolds' potential in promoting lymphangiogenesis and angiogenesis. These findings highlight the significant potential of hADSCs-loaded scaffolds in enhancing tissue regeneration, particularly in restoring lymphatic function in lymphedema.

Keywords
Lymphedema
Lymph nodes
Lymphangiogenesis
Mesenchymal Stem Cells
Bioprinting
Tissue engineering.
Funding
This research was supported by a Seoul National University Bundang Hospital grant (No. 14-2019-0010). This study was supported by research fund from Honam University, 2023 (No. 2023-0151)
Conflict of interest
The authors declare they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing