AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB025170162
RESEARCH ARTICLE
Early Access

3D printing hydroxyapatite/nanoclay/polycaprolactone composite scaffold for immune regulation and promoting bone defect healing

Xiang Li1,2† Zhenyu Wen1† Jiaxiang Song1 Hao Tang1 Wanshun Liu1 Xitao Linghu1 Shuai Huang3* Weikang Xu2,4* Qingde Wa1*
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1 Department of Orthopaedic Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Honghuagang District, Guizhou, China
2 Institute of biological and Medical Engineering, Guangdong Academy of Sciences, Haizhu District, Guangzhou, Guangdong, China
3 Department of Orthopaedic Surgery, the First People’s Hospital of Foshan, Chancheng District, Foshan, Guangdong, China
4 Guangdong Institute of Medical Instruments, National Engineering Research Center for Healthcare Devices, Guangdong Provincial Key Laboratory of Medical Electronic Instruments and Materials, Tianhe District, Guangzhou, Guangdong, China
†These authors contributed equally to this work.
Received: 20 February 2025 | Accepted: 13 May 2025 | Published online: 16 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

Excessive inflammation is one of the major causes of failure in the clinical repair of critical-sized bone defects, and the immune microenvironment plays a pivotal role in osteogenesis. An appropriate local immune response following biomaterial implantation is essential for successful bone tissue regeneration. In this study, a hydroxyapatite/montmorillonite nanoclay/polycaprolactone (HNP) composite scaffold was designed to modulate macrophage polarization and enhance bone regeneration and fabricated via 3D printing. The developed HNP scaffold maintained favorable mechanical strength while significantly promoting BMSC adhesion, proliferation, osteogenic cytokine secretion, and osteogenic differentiation. Moreover, the HNP scaffold modulated the bone immune microenvironment by suppressing M1 macrophage polarization and promoting a shift toward the M2 phenotype, thereby establishing a pro-osteogenic immune milieu. In vivo studies using a rat calvarial defect model demonstrated that, compared with other groups, the HNP scaffold markedly enhanced M2 macrophage polarization, promoted angiogenesis, and accelerated new bone formation. Overall, the 3D-printed HNP scaffold effectively regulated the immune microenvironment and facilitated bone regeneration and neovascularization, highlighting its great potential as a promising candidate for bone tissue engineering applications.

Keywords
3D Printing
Bone Repair
Hydroxyapatite
Macrophage Polarization
Nanoclay
Funding
This research was supported by the National Natural Science Foundation of China (82160577, 32000964), the Key Program for Science and Technology Project of Guizhou Province (ZK [2021] 007), the Zunyi City Innovation Team Fund (Zunyi Science Talent (2024) No. 4), Guangdong Province Science and Technology Plan Project (2024A1515012265), the Hainan Academician Innovation Center (Nanfan Medical Materials and Health Technology Innovation Center) (2022GDASZH-2022020402-01).
Conflict of interest
We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing