AccScience Publishing / IJB / Online First / DOI: 10.36922/IJB026050046
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RESEARCH ARTICLE

Hollow spherical mineralized scaffold integrated with a bone marrow mesenchymal stem cell-laden three-dimensional delivery system for regeneration of critical-sized bone defects

Xiao Liu1,2 ,  Zhengyang Chang1,2,3 ,  Zijian Li1,2,3 ,  Jianpeng Gao1,2 ,  Hufei Wang1,2 ,  Jie Wu1,2 ,  Jiazhi Yan1,2,3 ,  Jianheng Liu1,2 ,  Licheng Zhang1,2* ,  Daohong Liu1,2* ,  Wei Zhang1,2* ,  Ming Li1,2*
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1 Department of Orthopaedics, The Fourth Medical Center of the Chinese PLA General Hospital, Beijing, China
2 Department of Orthopaedics, National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Beijing, China
3 Department of Orthopaedics, Medical School of Chinese PLA, Beijing, China
IJB, 026050046 https://doi.org/10.36922/IJB026050046
Received: 1 February 2026 | Revised: 15 March 2026 | Accepted: 20 March 2026 | Published online: 23 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/ )
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Abstract

Treating critical-sized bone defects is a significant clinical challenge. Three-dimensional (3D) printing combined with bone tissue engineering (BTE) has emerged as a promising strategy for bone regeneration; however, key limitations persist, including a mismatch between scaffold degradation and osteogenesis, as well as insufficient bioactivity. In this study, we aimed to fabricate a hollow spherical mineralized biphasic calcium phosphate scaffold by 3D printing (photopolymerization via digital light processing) and incorporated within its cavity a 3D delivery system composed of methacryloyl-modified gelatin hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs). The composite scaffold was systematically evaluated using material characterization, in vitro cytocompatibility analysis, and in vivo rabbit bone defect models. Our findings demonstrated that the scaffold exhibited favorable mechanical properties, biocompatibility, and enhanced osteogenic differentiation, migration, and pro-osteogenic gene expression in BMSCs. Notably, the scaffold effectively repaired critical-sized bone defects in rabbit models within 12 weeks. This novel BTE composite scaffold provides a groundbreaking design philosophy and an innovative therapeutic strategy for complex bone defect repair.

Graphical abstract
Keywords
3D printing
Biphasic calcium phosphate
Mineralized modification
Spherical hollow structure
3D culture
Bone regeneration
Funding
This research was funded by the National Key Research and Development Program of China (grant number:2024YFC2418800), the National Natural Science Foundation of China (grant number: 82402814), the Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund (grant numbers: L222146, L256032), the Youth Autonomous Innovation Science Foundation of Chinese PLA General Hospital (grant number: 22QNFC009), the Youth Autonomous Innovation Science Foundation of Chinese PLA General Hospital (grant number: 22QNCZ030).
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
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