New In Vivo Study by Wang et al. (2025) Shows Zirconia Implants Minimize Inflammatory Immune Responses Compared to Titanium
Recent research has highlighted several limitations of titanium implants, particularly regarding their potential contribution to peri-implantitis, an inflammatory condition affecting the peri-implant soft tissues (Daubert et al. 2023; Rakasevic et al. 2022). The relatively high prevalence of peri-implantitis associated with titanium implants has been partly attributed to adverse immune responses to titanium oxide, which may contribute to biological complications (Stolzer et al., 2023).
Although previous studies have reported no significant differences between zirconia and titanium implants in peri-implant crevicular fluid levels of pro-inflammatory cytokines such as interleukin (IL)-1β and TNF-α (Cionca et al., 2016), or in histological outcomes (Fretwurst et al., 2021), gingival biopsy analyses indicate that zirconia implants are associated with lower expression levels of nitric oxide synthase (NOS1, NOS3), vascular endothelial growth factor (VEGF), TNF-α, and IL-6 in the surrounding tissues (Degidi et al., 2006; Nickenig et al., 2012).
Wang et al. (2025) from National Taiwan University and Taipei Medical University evaluated the biocompatibility of zirconia and titanium implants by assessing short-term biological responses in a murine model up to 7 days post-implantation.
The results of the study showed that zirconia implants were associated with markedly reduced inflammatory activity in peri-implant tissues. Specifically, transcriptomic and cellular analyses revealed that zirconia implants were associated with:
- Significantly less infiltration and attachment of myeloid immune cells, particularly neutrophils, compared to titanium implants.
- Lower activation of innate inflammatory pathways, including reduced signaling related to pathogen-associated immune responses.
- A more favorable macrophage response, with less polarization toward the pro-inflammatory M1 phenotype and a relative shift toward the regenerative M2 phenotype.
- A tissue environment more conducive to healing, suggesting improved biocompatibility of zirconia compared with titanium.
Collectively, the findings indicate that zirconia implants exhibit greater biocompatibility than titanium implants, may contribute to reduced inflammation and promote improved tissue healing.
The abstract of the article is available here (>).
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References
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Pro-inflammatory cytokines at zirconia implants and teeth: A cross-sectional assessment. Clinical Oral Investigations, 20(8), 2285–2291. https://doi.org/10.1007/s00784-016-1729-z
Daubert, D., Lee, E., Botto, A., Eftekhar, M., Palaiologou, A., & Kotsakis, G. A. (2023).
Assessment of titanium release following non-surgical peri-implantitis treatment: A randomized clinical trial. Journal of Periodontology, 94(9), 1122–1132. https://doi.org/10.1002/JPER.22-0716
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Inflammatory infiltrate, microvessel density, nitric oxide synthase expression, vascular endothelial growth factor expression, and proliferative activity in peri-implant soft tissues around titanium and zirconium oxide healing caps. Journal of Periodontology, 77(1), 73–80. https://doi.org/10.1902/jop.2006.77.1.73
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Immunohistological composition of peri-implantitis-affected tissue around ceramic implants—A pilot study. Journal of Periodontology, 92(4), 571–579. https://doi.org/10.1002/JPER.20-0169
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Expression of interleukin 6 and tumor necrosis factor alpha in soft tissue over ceramic and metal implant materials before uncovering: A clinical pilot study. International Journal of Oral & Maxillofacial Implants, 27(3), 671–676.
Rakasevic, D., Lazic, Z., Soldatovic, I., Scepanovic, M., & Gabric, D. (2022).
Influence of titanium implant macrodesign on peri-implantitis occurrence: A cross-sectional study. Clinical Oral Investigations, 26(8), 5237–5246. https://doi.org/10.1007/s00784-022-04492-z
Stolzer, C., M. Muller, M. Gosau, et al. 2023. “Do Titanium Dioxide Particles Stimulate Macrophages to Release Proinflammatory Cytokines and Increase the Risk for Peri-Implantitis?” Journal of Oral and Maxillofacial Surgery 81, no. 3: 308–317. https:// doi. org/ 10. 1016/j. joms. 2022. 10. 019.
Wang LT, Chang HH, Liao YT, Chen WA, Huang YW, Chen YW. Zirconia Minimizes Myeloid Innate Immunity as Dental Implants: An In Silico and In Vivo Study. Clin Oral Implants Res. 2025 Dec;36(12):1626-1639. doi: 10.1111/clr.70037. Epub 2025 Sep 25. PMID: 40999557.
