AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB026060049
RESEARCH ARTICLE
Early Access

Immunomodulatory 3D-printed hydroxyapatite/tricalcium phosphate/polycaprolactone composite scaffolds promote bone regeneration via macrophage polarization

Hao Tang1 Guangquan Zhao1 Yuanhao Lv1 Qianyu Xie1 Jiaxiang Song1 Shuai Huang3* Weikang Xu2* Qingde Wa1*
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1 Department of Orthopedic Surgery, The Second Affiliate Hospital of Zunyi Medical University, Zunyi 563000, China
2 Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510632, China
3 Department of Orthopaedic Surgery, The First People's Hospital of Foshan, School of Medicine, Southern University of Science and Technology, Foshan, 528000, China; #81, North of Lingnan Ave, Foshan 528000, Guangdong, China
Received: 4 February 2026 | Revised: 22 March 2026 | Accepted: 30 March 2026 | Published online: 22 April 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/ )
Abstract

Excessive inflammation remains a significant impediment in the regeneration of critical-sized bone defects, where the local immune microenvironment plays a crucial role in osteogenesis. However, most bone scaffolds primarily emphasize mechanical support and osteoconductivity, while their immunomodulatory potential remains largely unexplored. In this study, we designed and fabricated three-dimensional (3D) printed Hydroxyapatite/β-Tricalcium Phosphate/Polycaprolactone (HA/TCP/PCL, HTP) composite scaffolds to regulate macrophage polarization and promote bone regeneration. The HTP scaffolds demonstrated exceptional structural integrity and mechanical strength, facilitating the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells. Notably, the HTP scaffolds effectively modulated the immune microenvironment by inhibiting the polarization of pro-inflammatory M1 macrophages and promoting their transition to the regenerative M2 phenotype. This immunomodulatory effect further enhanced osteogenic factor secretion, establishing a correlation between immunoregulation and osteogenesis. In a rat calvarial defect model, compared to other groups, the HTP scaffolds significantly increased M2 macrophage infiltration, promoted angiogenesis, and accelerated new bone formation. This study demonstrates that 3D-printed HTP composite scaffolds promote bone regeneration and angiogenesis by establishing a regenerative immune microenvironment, highlighting their potential as an advanced immunomodulatory platform for bone tissue engineering.

Keywords
Bone repair
Hydroxyapatite
Macrophage polarization
β-Tricalcium Phosphate
3D printing
Funding
This study was supported by the National Natural Science Foundation of China (32571583), the Guangdong Province Science and Technology Plan Project (2024A1515012265), the Zunyi City Science & Technology Innovation Talent Project (No. [2024] 04), and the GDAS Project of Science and Technology Development (2023GDASZH-2023010102).
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing