Systemic effect of alumina-coated titanium implants: histopathological analysis in rats

Abstract

The systemic biocompatibility of implant materials is crucial for ensuring their safety, since materials such as titanium (Ti), hydroxyapatite (HAp) and, in particular, alumina (Al₂O₃) can affect vital organs beyond the site of implantation. While alumina-based coatings are valued for their mechanical stability, experimental studies suggest that aluminium ion release can cause toxicity to the liver and immune system.

The aim of the study is to evaluate the organ-specific toxicity of Ti bone implants, both with and without functional-protective coatings, by conducting a histopathological analysis of the liver, kidney and spleen in an experimental model.

Materials and methods. Cylindrical Ti pins, either uncoated, alumina-coated (Al), or HAp-coated, were produced and characterized previously. Ninety-five female Wistar rats were divided into four groups (Ti-, Al-, HAp-groups, and sham control). Implants were inserted into the right femur following by postsurgical treatment and observation. Liver, kidney, and spleen tissues were collected at 1, 2, 4, and 8 weeks and processed for blinded histopathological evaluation using a semi-quantitative scale (based on ISO 10993-11:2017). Statistical analysis utilized Kruskal–Wallis tests, with p < 0.05 denoting significance.

Results. In the first week after implantation, all groups showed hepatocellular swelling, sinusoidal congestion and moderate portal mononuclear infiltration in the liver. They also showed tubular epithelial swelling and focal lymphocytic infiltration in the kidneys and follicular hyperplasia in the spleen. By the second week, these inflammatory alterations persisted but generally decreased, showing no significant difference from the sham-operated control group. By the fourth week, hepatocyte swelling and periportal infiltration were evident primarily in the Ti-group, while the Al₂O₃- and HAp-coated groups showed only mild reactions. Renal infiltration remained more pronounced in the Ti-group. By the eighth week, liver morphology was almost normal in all groups, with only minimal residual periportal infiltration. The kidneys showed only slight tubular swelling. While most splenic changes had resolved, some Ti-group specimens retained follicular hyperplasia, indicating a prolonged systemic response.

Conclusions. This study confirms that all tested Ti-based biomaterials are acceptable in terms of systemic biocompatibility. No necrosis or irreversible organ damage was observed, indicating an absence of toxicity induced by the materials. The initial, transient histological changes were nonspecific responses to surgical stress. Systemic responses indirectly correlated with the implant surface. HAp coatings demonstrated the most favourable systemic profile due to their robust osseointegration, whereas uncoated Ti resulted in prolonged immune activation. This highlights the importance of coatings that promote rapid and complete osseointegration in minimizing long-term systemic effects.