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RESEARCH ARTICLE

3D-printed Mg-substituted hydroxyapatite/ gelatin methacryloyl hydrogels encapsulated with PDA@DOX particles for bone tumor therapy and bone tissue regeneration

Shangsi Chen1 ,  Yue Wang1,2 ,  Junzhi Li3 ,  Haoran Sun4* ,  Ming-Fung Francis Siu2* ,  Shenglong Tan5*
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1 Department of Mechanical Engineering, Faculty of Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong, China
2 Department of Building and Real Estate, Faculty of Construction and Environment, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
3 Department of Surgery, School of Clinical Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, China
4 Koln 3D Technology (Medical) Limited, Hong Kong Science Park, Shatin, Hong Kong, China
5 Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China
IJB 2024, 10(5), 3526 https://doi.org/10.36922/ijb.3526
Submitted: 29 April 2024 | Accepted: 14 May 2024 | Published: 17 July 2024
(This article belongs to the Special Issue Advanced Biomaterials for 3D Printing and Healthcare Application)
© 2024 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 development of bifunctional scaffolds for clinical applications, aimed at preventing tumor recurrence and promoting bone tissue regeneration simultaneously at the surgical site, is imperative in repairing bone tumor-related defects. In the current study, Mg-substituted hydroxyapatite (MgHAp) nanocomposites were synthesized via a biomineralization process. Doxorubicin hydrochloride (DOX), an anticancer drug, was incorporated in polydopamine (PDA) particles to synthesize PDA@DOX particles. MgHAp/gelatin methacryloyl (GelMA) hydrogels encapsulated with PDA@DOX particles were designed and fabricated to construct MgHAp/GelMA-PDA@DOX hydrogels via 3D printing. The 3D-printed MgHAp/GelMA-PDA@DOX hydrogels exhibited antitumor synergy by providing combined chemotherapy and phototherapy for bone tumor cell ablation. The hydrogels showed a good photothermal effect and could induce hyperthermia upon irradiation with an 808 nm near-infrared (NIR) laser. Moreover, MgHAp/GelMA-PDA@DOX hydrogels could release DOX sustainably and controllably. In vitro experiments demonstrated that 3D-printed MgHAp/GelMA-PDA@DOX hydrogels could effectively eradicate MG63 cells through the synergy of induced hyperthermia and DOX release. Furthermore, due to the sustained release of Mg2+, 3D-printed MgHAp/GelMA-PDA@DOX hydrogels could promote the proliferation of rat bone marrow-derived mesenchymal stem cells and facilitate alkaline phosphatase activity and the expression of osteogenic genes, such as osteocalcin (Ocn), type I collagen (Col1), runt-related transcription factor-2 (Runx2), and bone morphogenetic protein-2 (Bmp2), indicating their excellent osteogenic effect. As a result, 3D-printed MgHAp/GelMA-PDA@DOX hydrogels showed great potential in the treatment of bone tumor-related defects by effectively killing tumor cells and simultaneously promoting bone tissue regeneration.

Keywords
3D printing
Magnesium
Anti-tumor effect
Bone tissue regeneration
Controlled release
Funding
This work was financially supported by the National Nature Science Foundation of China (Grant No. 82201133) and Fong On Construction Ltd. in Hong Kong (Grant No. ZDBM, ZDCA). The research sponsored from Fong On Construction Ltd. (HK) has potential interest in exploring the potential application of extrusion-based 3D printing technology in automation within the construction industry
Conflict of interest
The authors declare no conflicts of interest.
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