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

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.

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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