Titanium and zirconium release from titanium- and zirconia implants in mini pig maxillae and their toxicity in vitro

Dent Mater. 2020 Mar;36(3):402-412. doi: 10.1016/j.dental.2020.01.013. Epub 2020 Jan 25.


Objective: Titanium (Ti)- and Zirconia (ZrO2)-implants in mini pig maxillae were compared with respect to Ti/zirconium (Zr) release into the surrounding bone tissues, the resulting short term tissue responses and the potential toxicity.

Methods: Ti/Zr release from Ti- and ZrO2-implants in mini pig maxillae was determined with inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). The spatial distribution of Ti and Zr in maxilla tissues near the implant surface was assessed with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). A histological analysis was performed to investigate the tissue responses after 12 weeks of implantation. The cytotoxicity and DNA damage of Ti particles and ZrO2 particles were studied with XTT and Comet assay.

Results: The mean Ti content in the bone adjacent to Ti-implants was 1.67 mg/kg-bone weight. The highest Ti content detected was 2.17 mg/kg-bone weight. The mean Zr content in the bone adjected to ZrO2-implants was 0.59 mg/kg-bone weight. The highest Zr content was 0.75 mg/kg-bone weight. The spatial distribution of the Ti and Zr in bone showed mainly a higher intensity of Ti and Zr close to the screw thread outer tip rather. Histological analysis indicated that near both implant-types signs of bone marrow fibrosis were present. EC50 of commercially available ZrO2-nanoparticles (NPs, <100 nm) and ZrO2-microparticles (MPs, <5 μm) was 13.96 mg/ml and 80.99 mg/ml, respectively. ZrO2-NPs and ZrO2-MPs can induce DNA damage at 70 μg/ml and 810 μg/ml, respectively.

Significance: After 12-weeks of implantation, increased concentrations of Ti and Zr can be detected in bone/tissues near Ti- and ZrO2-implants in mini pig maxillae. Ti content released from Ti-implants is two times higher than the Zr content released from ZrO2-implants. ZrO2-NPs showed lower cytotoxicity and DNA damage compared to results reported for Ti-NPs in human cells.

Keywords: Bone tissue; DNA damage; ICP-MS; ICP-OES; LA-ICP-MS; Nanoparticles; PDL cells; SEM; SLA; XTT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dental Implants*
  • Humans
  • Maxilla
  • Surface Properties
  • Swine
  • Swine, Miniature
  • Titanium
  • Zirconium*


  • Dental Implants
  • Zirconium
  • Titanium
  • zirconium oxide