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RESEARCH ARTICLE

Three-dimensional-printed bionic dual crosslinked drug-loaded hydrogel composite scaffolds for large bone defect repair  

Xulin Hu1,2†* ,  Zhen Zhang3† ,  Lijin Ning4† ,  Yixuan Lan1 ,  Wang Gong1 ,  Jiayu Liu1 ,  Shuhao Yang5 ,  Haoming Wu1 ,  Weiming Zhao1 ,  Jian He6 ,  Kainan Li1* ,  Weizong Weng7,8*
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1 Department of Orthopedics, Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, China
2 Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China
3 Department of Chemistry, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan, China
4 Department of Dentistry, School of Jinzhou Medical University, Jinzhou Medical University, Jinzhou, Liaoning, China.
5 Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
6 Department of Basic Medicine, Faculty of Medicine, Henan University of Science and Technology, Luoyang, Henan, China
7 Department of Orthopaedics, Chenggong Hospital, Xiamen University, Xiamen, Fujian, China
8 Department of Orthopedics, Institute of Translational Medicine, Shanghai University, Shanghai, China
†These authors contributed equally to this work.
IJB, 025380391 https://doi.org/10.36922/IJB025380391
Received: 21 September 2025 | Accepted: 12 November 2025 | Published online: 14 November 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

The structure, composition, and function of natural bone have long been the focus of bone tissue engineering. However, existing organic–inorganic three-dimensional (3D) printing systems are limited by the stability of hydrogels and the content of inorganic salts, hindering the fabrication of robust 3D scaffolds. In this study, we developed a hydrogel–inorganic particle bioink and implemented a multi-step crosslinking strategy. The organic phase, composed of sodium alginate, gelatin, and chitosan, was combined with β-tricalcium phosphate and crosslinked via ionic pre-crosslinking followed by a Schiff base reaction to form a dual-crosslinked network. The resulting scaffolds exhibited excellent mechanical properties and biomimetic microarchitecture while maintaining shape stability under physiological conditions. Furthermore, the tunable swelling behavior of the hydrogel enabled efficient loading and controlled release of the small molecule epigallocatechin gallate. This composite scaffold demonstrated adjustable swelling, controllable degradation, and significantly enhanced cellular compatibility, providing a novel, efficient, and scalable strategy for repairing complex bone defects and offering new insights for the design and application of 3D-printed bone scaffolds.

Graphical abstract
Keywords
β-tricalcium phosphate
Bionic tissue structure
Hydrogel base
Three-dimensional printing
Funding
This study was supported by the National Science Foundation of China (NSFC, #82402822, 82202674), the Central Government of Sichuan through the Special Project of Local Science and Technology Development (#2024ZYD0155), the Health Commission of Sichuan Province Medical Science and Technology Program (#24QNMP036), and the Natural Science Foundation of Xiamen, China (3502Z20227124).
Conflict of interest
Xulin Hu serves as the Editorial Board Member of the journal, but did not in any way involve in the editorial and peer-review process conducted for this paper, directly or indirectly. Other 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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