Abstract
Bone regeneration of oral and maxillofacial defects in situ remains a significant clinical challenge. This study investigates the synergistic effects of phosphorus (P) and zinc (Zn) co-doping in wollastonite bioceramics to enhance osteogenic activity and antibacterial potential for bone repair. Cylindrical bioceramic granules with varying P/Zn ratios (CSi-P8: CSi-Zn6 = 3:0, 2:1, 1:2 and 0:3) were fabricated via co-precipitation and evaluated for in-vitro bioactivity, cell proliferation, osteogenic differentiation, and antibacterial performance. The experimental results demonstrated that the co-doped groups (8P/6Zn-2:1 and 8P/6Zn-1:2) exhibited superior hydroxyapatite formation in simulated body fluid (SBF), sustained Ca²⁺/Si⁴⁺ ion release, and synergistic osteogenic effects, as evidenced by elevated RUNX2/β-catenin expression and BMSC proliferation. Zn doping conferred dose-dependent antibacterial activity against Staphylococcus aureus (93% inhibition for 8P/6Zn-0:3). In vivo cranial defect experiments in rabbits revealed that the 8P/6Zn-2:1 granules significantly promoted new bone trabeculae formation and defect closure within 16 weeks, outperforming single-doped and control groups. Histological and micro-CT analyses confirmed enhanced bone volume fraction (BV/TV%) and trabecular density (Tb.N) in the co-doped groups. These findings highlight the dual functionality of P/Zn co-doped wollastonite (e.g. 8P/6Zn-2:1), where P enhances osteogenesis via increasing the expression of RUNX2/β-catenin and apatite deposition, while Zn provides antibacterial protection, offering more promising implants for infected oral bone defects.
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Acknowledgements
We would like to thank Dr. Binji Cao for his technical assistance in manuscript writing.
Funding
This study received financial support from the Medical and Health Technology Project of Hangzhou (A20230968, Xiurong Ke), the Medical and Health Research Project of Zhejiang Province (2025KY174, Xiurong Ke), Key Laboratory of Oral Biomedical Research of Zhejiang Province Foundation (2021M001, Lingling Dong), and National Natural Science Foundation of China (82101649, Lijie Fan).
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Dong, L. & Li, Y.: material preparation, data analysis and writing-original draft; Dong, L. & Feng, Y.: *in vivo* experiments and harvest of femoral bone specimens; Feng, Y. & Wang, X: suggestions on the animal bone defect model; Liu, Y. & Ke, X.: XRD, EDS and X-ray analysis; Dong, L. & Wang X.: μ-CT investigation and statistic analysis; Ke, X. & Fan, L.: supervision and funding acquisition; Yu, Y. & Ke, K.: proofread the paper; Fan, L. & Ke, X: experimental guidance and writing-review & editing. All authors reviewed the manuscript.
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All of the animal experiments of this study were strictly performed in accordance with the ethical standards of the ARRIVE guidelines (PLoS Bio 8(6), e1000412,2010). The animal studies of this study were registered under ethical committee approval number ZJU21202 and ZJU20220475 by the Ethics Committee of Zhejiang University respectively. The anesthesia and euthanasia methods of this study were performed in accordance with the American Veterinary Medical Association (AVMA) Guidelines for the Euthanasia of Animals (2020). The sample size is calculated based on pre-experimental data (n = 6, using random grouping). All data were expressed as the mean ± SD and analyzed for variance using SPSS 26.0, with a significance level of p < 0.05.
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Dong, L., Li, Y., Feng, Y. et al. Co-incorporation of Phosphorus and zinc into wollastonite ceramic granules synergically facilitating thin-walled structures regeneration. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44387-7
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DOI: https://doi.org/10.1038/s41598-026-44387-7
