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RESEARCH ARTICLE

 A 3D-bioprinted alginate-MgP scaffold for superior regeneration of calvarial bone defects in a rat model

Shaimaa ElShebiney1 ,  Sara A. M. El-Sayed2 ,  Mduduzi N. Sithole3 ,  Mashudu T. Mphaphuli3 ,  Hanan H. Beherei2 ,  Pradeep Kumar3 ,  Mostafa Mabrouk2* ,  Yahya E. Choonara3*
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1 Narcotics, Ergogenics, and Poisons Department, Medical Research and Clinical Studies Institute, National Research Centre (NRC), Giza, Egypt
2 Refractories, Ceramics and Building Materials Department, National Research Centre, Dokki, Cairo, Egypt
3 Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
IJB, 025190188 https://doi.org/10.36922/IJB025190188
Received: 9 May 2025 | Accepted: 2 July 2025 | Published online: 2 July 2025
(This article belongs to the Special Issue Multifunctional Bioprinting for Tissue/Organ Engineering)
© 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

While autologous transplants are the traditional standard intervention for non-healing bone defect regeneration, they carry many risks and limitations. Regenerative composite biomaterials are promising alternatives to conventional autograft and allograft implants. This study aimed to overcome these challenges by creating a novel biodegradable 3D biomaterial scaffold that mimics the structural and physiological properties of native bone. Scaffolds composed of magnesium phosphate (MgP) doped with copper oxide (CuO) in specific proportions (3, 5, or 7% [w/w]) were homogenously distributed in an alginate polymer matrix for the repair of calvarial bone defects in a rat model. The scaffolds were fabricated using a 3D bioprinting technique, and their physical properties were characterized through X-ray diffraction, Fourier transform infrared spectroscopy, and mechanical strength assessments. The bioactivity of the scaffolds was evaluated in vitro for biomineralization and cytotoxicity, revealing high biomineralization and cell viability. Female rats were used for the in vivo experiments, and the defects were examined using microscopic and histological analysis, computed tomography imaging, as well as serum markers including osteocalcin and procollagen III. The in vivo results demonstrated high efficacy of the scaffolds in promoting bone regeneration and enhanced healing in the calvarial defect model. The incorporation of CuO not only improved the scaffolds’ mechanical properties but also exhibited angiogenic effects, fostering an environment conducive to bone healing. Our results indicated that the Alg–MgP–CuO scaffolds have great promise for bone tissue engineering applications and repair, especially with 7% (w/w) CuO doping.  

Graphical abstract
Keywords
3D bioprinting
Alginate
Bone regeneration
Copper oxide doping
Magnesium phosphate.
Funding
This research was funded by the project “Composite Bioinks for 3D Bioprinting and Their Application in Bone Tissue Engineering,” supported by the Academy of Scientific Research and Technology (ASRT) in Egypt. The authors acknowledge the financial support of the National Research Foundation (NRF) of South Africa under the SARChI Chair program (grant no. PPNT230823145247) awarded to Prof. Yahya Choonara.
Conflict of interest
The authors declare no conflict of interest.
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