AccScience Publishing / IJB / Volume 11 / Issue 3 / DOI: 10.36922/IJB025170162
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RESEARCH ARTICLE

Three-dimensional-printed hydroxyapatite/nanoclay/polycaprolactone composite scaffold for immunomodulation and bone defect repair

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 Orthopedic Surgery, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
2 Medical Materials and Engineering Research Laboratory, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou, Guangdong, China
3 Department of Orthopedic Surgery, The First People’s Hospital of Foshan, Foshan, Guangdong, China
4 Guangdong Provincial Key Laboratory of Medical Electronic Instruments and Materials, Guangdong Institute of Medical Instruments, National Engineering Research Center for Healthcare Devices, Guangzhou, Guangdong, China
†These authors contributed equally to this work.
IJB 2025, 11(3), 434–456; https://doi.org/10.36922/IJB025170162
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/ )
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Abstract

Excessive inflammation remains a major impediment to the clinical repair of critical-sized bone defects, with the immune micro-environment playing 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 and subsequently fabricated using three-dimensional (3D) printing, with the aim of modulating macrophage polarization and promoting bone regeneration. The resulting HNP scaffold exhibited favorable mechanical strength and significantly promoted bone marrow mesenchymal stem cell adhesion, proliferation, secretion of osteogenic cytokines, and osteogenic differentiation. Moreover, it modulated the bone immune micro-environment 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 micro-environment and facilitated both bone regeneration and neovascularization, highlighting its strong potential as a candidate for bone tissue engineering applications.

Graphical abstract
Keywords
Bone repair
Hydroxyapatite
Macrophage polarization
Nanoclay
Three-dimensional printing
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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