AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025480495
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RESEARCH ARTICLE

Psoralen immunomodulation: In vitro macrophage reprogramming to enhance osseointegration of 3D-printed porous titanium scaffolds in osteoporosis

Jian Ji1† ,  Jijie Peng2,3† ,  Yilong Wu4† ,  Yue Meng5 ,  Di Che6 ,  Siyan Chen6 ,  Jingyang Chen6 ,  Xingmao Zhou6 ,  Junzhe Wu6* ,  Yufeng He2,3* ,  Yuzhu Wang6*
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1 Department of Breast Surgery, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China
2 State Key Laboratory of Mechanism and Quality of Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, Macao SAR, China
3 Department of Traditional Treatment Center, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, Guangdong, China
4 Department of Orthopaedic Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Miyazaki, Japan
5 Department of Orthopaedic Surgery, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China
6 Department of Orthopaedic Surgery, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, Guangdong, China
†These authors contributed equally to this work.
IJB, 025480495 https://doi.org/10.36922/IJB025480495
Received: 25 November 2025 | Accepted: 24 December 2025 | Published online: 8 January 2026
© 2026 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

Psoralen inhibits osteoclast activity and bone resorption while enhancing osteoblast activity and bone formation. However, its role in modulating macrophage polarization to enhance osteoblast function and scaffold osseointegration under osteoporotic conditions remains underexplored. We fabricated Voronoi-structured metal scaffolds by 3D printing and evaluated psoralen in vitro in a macrophage– bone marrow mesenchymal stem cell co-culture system using serum from psoralen-treated rats, and in vivo in an osteoporotic bone-defect model with oral psoralen administration. The results demonstrated that psoralen treatment promoted M2 macrophage polarization, increased the M2/M1 ratio, and upregulated osteogenic gene expression in vitro. Improved bone formation parameters—including bone volume fraction, trabecular thickness, and trabecular number—around the implanted scaffolds were observed in vivo. The findings suggest a synergistic effect between gradient scaffold structures and psoralen in enhancing M2-mediated osteogenesis. Taken together, these findings may provide novel strategies for improving bone repair and prosthesis integration in osteoporosis.  

Graphical abstract
Keywords
Macrophage polarization
Osseointegration
Osteoporosis
Psoralen
Funding
This work was supported by the Traditional Chinese Medicine Inheritance Innovation Development Research Project of Zhongshan City (No. 2024B3019) and China Postdoctoral Science Foundation (No. 2024M750668). The funders had no role in the design of the study, the collection, analysis, and interpretation of the data, or in writing the manuscript.
Conflict of interest
The authors declare that 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
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