Cite this article
3
Download
37
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
ORIGINAL RESEARCH

3D-printed scaffolds co-doped with magnesium oxide and niobium for enhanced in vitro osteogenesis

Yongning Sheng1 Jie Pei2 Kai Chen3 Yanxin Liu4* Zeyu Liu1,5* Kun Fu1,6*
Show Less
1 Department of Joint Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
2 Department of Orthopedics, Haikou People’s Hospital, Haikou, Hainan, China
3 Department of Orthopedics, Wenchang People’s Hospital, Wenchang, Hainan, China
4 Department of Bioengineering, University of California, Los Angeles, California, United States of America
5 Center for Musculoskeletal Surgery, Charité–Universitätsmedizin Berlin, Berlin, Germany
6 Department of Joint Surgery, Hainan Sino-German Orthopedic Hospital, Haikou, Hainan, China
Submitted: 15 November 2025 | Revised: 13 January 2026 | Accepted: 12 February 2026 | Published: 31 March 2026
© 2026 by the Author(s). Licensee Biomaterials Translational, USA. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 (CC BY-NC-SA 4.0) (https://creativecommons.org/licenses/by-nc-sa/4.0/deed.en)
Abstract

Conventional three-dimensional (3D)-printed bone scaffolds often lack adequate mechanical strength and osteoinductive cues. Here, biphasic magnesium oxide/niobium (MgO/Nb) co-doped scaffolds were fabricated by fused deposition modeling using a poly(L-lactic acid)/calcium carbonate/hydroxyapatite matrix, and the MgO:Nb ratio was systematically optimized. MgO/Nb incorporation improved compressive strength relative to MgO/Nb-free controls while maintaining the printed porous architecture. In MC3T3-E1 cultures, scaffolds containing 5 wt% MgO–Nb elicited the most favorable osteogenic responses, including enhanced proliferation, increased alkaline phosphatase activity during early differentiation, and greater mineral deposition assessed by Alizarin Red S staining. Quantitative polymerase chain reaction at day 14 further showed upregulated Col1a1 (encoding type I collagen), Bglap (encoding osteocalcin), and Runx2 (encoding RUNX-2) expression, indicating promoted osteogenic differentiation. Collectively, these findings demonstrate that MgO/Nb biphasic co-doping provides a scalable route to enhance both mechanical performance and in vitro osteogenesis of 3D-printed composite scaffolds, supporting further in vivo validation for bone regeneration.

Keywords
Osteogenic scaffolds
Magnesium oxide
Niobium
Osteoblasts
Biocompatible materials
Funding
This work was supported by the Hainan Provincial Health Science and Technology Innovation Joint Project (grant number: WSJK2024MS228).
Conflict of interest
The authors declare that there is no conflict of interest for the present work.
References
  1. Xu H, Li H, Liu R, et al. Four-dimensional perspective on biomimetic design and fabrication of bone scaffolds for comprehensive bone regeneration. ACS Mater Lett. 2024;6(9):4262-4281. doi: 10.1021/acsmaterialslett.4c00889

 

  1. García-Gareta E, Coathup MJ, Blunn GW. Osteoinduction of bone grafting materials for bone repair and regeneration. Bone. 2015;81:112-121. doi: 10.1016/j.bone.2015.07.007

 

  1. Hurle K, Oliveira JM, Reis RL, Pina S, Goetz-Neunhoeffer F. Ion-doped brushite cements for bone regeneration. Acta Biomater. 2021;123:51-71. doi: 10.1016/j.actbio.2021.01.004

 

  1. Liu Z, Liu Y, Shi T, Fu K. Injectable antimicrobial quaternary chitosan salt/tannic acid as a delivery platform for enhanced cranial bone regeneration via the synergy of BMP-2 and VEGF. ACS Appl Bio Mater. 2025;8(9):7909-7924. doi: 10.1021/acsabm.5c00935

 

  1. Zhang L, Yang G, Johnson BN, Jia X. Three-dimensional (3D) printed scaffold and material selection for bone repair. Acta Biomater. 2019;84:16-33. doi: 10.1016/j.actbio.2018.11.039

 

  1. Zhu S, Sun H, Mu T, Richel A. Research progress in 3D printed biobased and biodegradable polyester/ceramic composite materials: Applications and challenges in bone tissue engineering. ACS Appl Mater Interfaces. 2025;17(2):2791-2813. doi: 10.1021/acsami.4c15719

 

  1. Dong J, Ding H, Wang Q, Wang L. A 3D-printed scaffold for repairing bone defects. Polymers (Basel). 2024;16(5):706. doi: 10.3390/polym16050706

 

  1. Liu Z, Pei J, Sheng Y, et al. Composite 3D-printed scaffold based on glucosamine-loaded hyaluronic Acid methacrylate for osteochondral regeneration. ACS Appl Bio Mater. 2026;9(3):1558-1568. doi: 10.1021/acsabm.5c02113

 

  1. Shaikh S, Mehrotra S, Van Bochove B, et al. Strontium-substituted nanohydroxyapatite containing biodegradable 3D printed composite scaffolds for bone regeneration. ACS Appl Mater Interfaces. 2024;16(47):65378-65393. doi: 10.1021/acsami.4c16195

 

  1. Morya S, Kumari J, Kumar D, Syed A, Awuchi CG. Three-dimensional (3D) printing technology: 3D printers, technologies, and application insights in the food diligence. Food Printing: 3D Printing in Food Industry. Singapore: Springer; 2022. p. 81-100. doi: 10.1007/978-981-16-8121-9_6

 

  1. Korpela J, Kokkari A, Korhonen H, Malin M, Närhi T, Seppälä J. Biodegradable and bioactive porous scaffold structures prepared using fused deposition modeling. J Biomed Mater Res B Appl Biomater. 2013;101B(4):610-619. doi: 10.1002/jbm.b.32863

 

  1. Bohner M, Santoni BLG, Döbelin N. β-tricalcium phosphate for bone substitution: Synthesis and properties. Acta Biomater. 2020;113:23-41. doi: 10.1016/j.actbio.2020.06.022

 

  1. Zhou X, Zhou G, Junka R, et al. Fabrication of polylactic acid (PLA)- based porous scaffold through the combination of traditional bio-fabrication and 3D printing technology for bone regeneration. Colloids Surface B. 2021;197:111420.doi: 10.1016/j.colsurfb.2020.111420

 

  1. Donate R, Paz R, Quintana Á, Bordón P, Monzón M. Calcium carbonate coating of 3D-printed PLA scaffolds intended for biomedical applications. Polymers. 2023;15(11):2506. doi: 10.3390/polym15112506

 

  1. Zhao C, Wu H, Ni J, Zhang S, Zhang X. Development of PLA/Mg composite for orthopedic implant: Tunable degradation and enhanced mineralization. Compos Sci Technol. 2017;147:8-15. doi: 10.1016/j.compscitech.2017.04.037

 

  1. Xu D, Xu Z, Cheng L, Gao X, Sun J, Chen L. Improvement of the mechanical properties and osteogenic activity of 3D-printed polylactic acid porous scaffolds by nano-hydroxyapatite and nano-magnesium oxide. Heliyon. 2022;8(6):e09748. doi: 10.1016/j.heliyon.2022.e09748

 

  1. Pádua AS, Graça MPF, Silva JC. Polycaprolactone/doped bioactive glass composite scaffolds for bone regeneration. J Funct Biomater. 2025;16(6):200. doi: 10.3390/jfb16060200

 

  1. Sun X, Xu X, Zhao X, et al. Three-dimensional bioprinted scaffolds loaded with multifunctional magnesium-based metal–organic frameworks improve the senescence microenvironment prompting aged bone defect repair. ACS Nano. 2025;19(24):22141-22162. doi: 10.1021/acsnano.5c03023

 

  1. Mukasheva F, Adilova L, Dyussenbinov A, Yernaimanova B, Abilev M, Akilbekova D. Optimizing scaffold pore size for tissue engineering: Insights across various tissue types. Front Bioeng Biotechnol. 2024;12:1444986. doi: 10.3389/fbioe.2024.1444986

 

  1. Chatterjee T, Maji M, Paul S, Ghosh M, Pradhan SK, Meikap AK. Microstructural, electrical and mechanical characterizations of green-synthesized biocompatible calcium phosphate nanocomposites with morphological hierarchy. Mater Chem Phys. 2023;296:127245. doi: 10.1016/j.matchemphys.2022.127245

 

  1. Huang Q, Liu Y, Ouyang Z, Feng Q. Comparing the regeneration potential between PLLA/Aragonite and PLLA/Vaterite pearl composite scaffolds in rabbit radius segmental bone. Bioact Mater. 2020;5(4):980-989. doi: 10.1016/j.bioactmat.2020.06.018

 

  1. Wei J, Guo-Wang P, Han Q, Ding J, Chen X. Preparation of antibacterial silver nanoparticle-coated PLLA grafted hydroxyapatite/PLLA composite electrospun fiber. J Control Release. 2015;213:e62-e63. doi: 10.1016/j.jconrel.2015.05.103

 

  1. Yao H, Wang J, Deng Y, Li Z, Wei J. Osteogenic and antibacterial PLLA membrane for bone tissue engineering. Int J Biol Macromol. 2023;247:125671. doi: 10.1016/j.ijbiomac.2023.125671

 

  1. Zhou Q, Su X, Wu J, et al. Additive manufacturing of bioceramic implants for restoration bone engineering: Technologies, advances, and future perspectives. ACS Biomater Sci Eng. 2023;9(3):1164-1189. doi: 10.1021/acsbiomaterials.2c01164

 

  1. Xia X, Huang J, Wei J, et al. Magnesium oxide regulates the degradation behaviors and improves the osteogenesis of poly(lactide-co-glycolide) composite scaffolds. Compos Sci Technol. 2022;222:109368. doi: 10.1016/j.compscitech.2022.109368

 

  1. Wang W, Wang L, Zhang B, et al. 3D printing of personalized magnesium composite bone tissue engineering scaffold for bone and angiogenesis regeneration. Chem Eng J. 2024;484:149444. doi: 10.1016/j.cej.2024.149444

 

  1. Liang H, Zhao D, Feng X, et al. 3D-printed porous titanium scaffolds incorporating niobium for high bone regeneration capacity. Mater Design. 2020;194:108890. doi: 10.1016/j.matdes.2020.108890

 

  1. Guo W, Feng S, Li B, et al. Niobium carbide-functionalized polylactic acid bone scaffold with near-infrared light-mediated shape memory and photothermal therapy for complex bone defects. Int J Biol Macromol. 2025;322:146578. doi: 10.1016/j.ijbiomac.2025.146578

 

  1. Obata A, Takahashi Y, Miyajima T, Ueda K, Narushima T, Kasuga T. Effects of niobium ions released from calcium phosphate invert glasses containing Nb₂O₅ on osteoblast-like cell functions. ACS Appl Mater Interfaces. 2012;4(10):5684-5690. doi: 10.1021/am301614a

 

  1. Lopes JH, Souza LP, Domingues JA, et al. In vitro and in vivo osteogenic potential of niobium-doped 45S5 bioactive glass: A comparative study. J Biomed Mater Res B Appl Biomater. 2020;108B(4):1372-1387. doi: 10.1002/jbm.b.34486

 

  1. Shanmugavadivu A, Lekhavadhani S, Babu S, Suresh N, Selvamurugan N. Magnesium-incorporated biocomposite scaffolds: A novel frontier in bone tissue engineering. J Magnes Alloys. 2024;12:2231-2248. doi: 10.1016/j.jma.2024.06.001

 

  1. Nie X, Zhang X, Lei B, Shi Y, Yang J. Regulation of magnesium matrix composites materials on bone immune microenvironment and osteogenic mechanism. Front Bioeng Biotechnol. 2022;10:842706. doi: 10.3389/fbioe.2022.842706

 

  1. De Souza Balbinot G, Leitune VCB, Da Cunha Bahlis EA, Ponzoni D, Visioli F, Collares FM. Niobium-containing bioactive glasses modulate alkaline phosphatase activity during bone repair. J Biomed Mater Res B Appl Biomater. 2023;111(6):1224-1231. doi: 10.1002/jbm.b.35227

 

  1. Ulbrich LM, Balbinot GDS, Brotto GL, et al. 3D printing of poly(butylene adipate-co-terephthalate) (PBAT)/niobium containing bioactive glasses (BAGNb) scaffolds: Characterization of composites, in vitro bioactivity, and in vivo bone repair. J Tissue Eng Regen Med. 2022;16(3):267-278. doi: 10.1002/term.3276

 

  1. Tao M, Cui Y, Sun S, et al. Versatile application of magnesium-related bone implants in the treatment of bone defects. Mater Today Bio. 2025;31:101635. doi: 10.1016/j.mtbio.2025.101635

 

  1. Cerqueira A, García-Arnáez I, Romero-Gavilán F, et al. Complex effects of Mg-biomaterials on the osteoblast cell machinery: A proteomic study. Biomater Adv. 2022;137:212826. doi: 10.1016/j.bioadv.2022.212826
Share
Back to top