Impact of Cerium Doping on the Osteogenic Properties of a 3D Biomimetic Piezoelectric Scaffold with Sustained Mg2+ Release

Kai Kang, Xiyuan Qin, Jiaqi Pan, Tianyu Zhang, Xincong Li, Hai Zhuang, Shoushan Bu Department of Stomatology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Shoushan Bu, Email [email protected]: In the realm of bone tissue engineering, the role of biomimetic piezoelectric scaffolds made from whitlockite (WH) nanoparticles is increasingly recognized. WH, the second most abundant mineral in human bone, possesses piezoelectric properties and the capacity to release magnesium ions (Mg2+), both of which are vital for osteogenic differentiation. This study investigates the osteogenic effects of cerium (Ce) doping on three-dimensional biomimetic piezoelectric scaffolds composed of whitlockite (WH) nanoparticles.Methods: WH nanoparticles with varying Ce concentrations were synthesized and scaffolds were prepared using a freeze-drying process with sodium alginate as the matrix. In vitro experiments with human bone marrow mesenchymal stem cells (hBMSCs) assessed cell proliferation and differentiation, while animal studies employed a rat calvarial defect model to evaluate new bone formation and mineralization.Results: Our findings revealed that Ce doping modifies the crystallinity and electrical properties of WH nanoparticles, thereby affecting their osteogenic potential. In vitro studies indicated that scaffolds with a Ce/Ca ratio of 0.06 significantly boosted osteogenic marker expression. Furthermore, animal studies confirmed that Ce-doped WH scaffolds, especially those with the 0.06 ratio, markedly improved both new bone formation and mineralization.Conclusion: The study demonstrates that Ce doping can significantly enhance the osteogenic properties of WH-based scaffolds, with the optimal Ce/Ca ratio of 0.06 being particularly effective in promoting bone formation. This research provides a promising approach for the development of advanced materials in bone tissue engineering. Keywords: whitlockite, cerium, piezoelectric scaffolds, bone tissue engineering