Correlation Between the Risk of Peri-Implantitis and Increased Levels of Proinflammatory Cytokines following an interaction between Titanium dioxide and Macrophages

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

DRKS

Registry ID

DRKS00028653

Enrollment

Registered

2022-04-12

Start date

2014-12-15

Completion date

Unknown

Last updated

2025-04-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Peri-implantitis

Interventions

Group 1: 10 ml venous blood from patients without dental implant to perform titanium dioxide stimulation test. Group 2: 10 ml venous blood from patients with at least one dental implant without signs

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Inclusion criteria

Inclusion criteria: - 20 patients without titanium implants in the jawbone - 20 patients with at least one titanium implant in the jawbone without peri-implantitis - 20 patients with at least one titanium implant in the jawbone with peri-implantitis or implant loss

Exclusion criteria

Exclusion criteria: Patients with titanium implants outside the jawbone and risk or high risk factors according to ITI-consensus-conference: Risk factors: - Radiated bone - Inadequately controlled Diabetes mellitus (HbA1c > 7,5%) - Hemorrhagic diathesis - Antiresorptive therapies (bisphosphonates, denosumab) - Smokers - Poor oral hygiene (from grad 3 according to Sillness and Löe) High-risk factors - Serious systemic diseases (e.g. leukemia, TBC) - Immunocompromised patients (e.g. HIV) - Drug abuse - Mental altered patients - Uncooperative patients

Design outcomes

Primary

Measure	Time frame
To measure the cytokine response of macrophages/monocytes after exposure with TiO2 particles, the TiO2-stimulation assay has been done. Accordingly, after individual informed consent, 10 milliliters of venous blood were taken from each patient, heparinized, anonymized, and sent for analysis within 24 hours to a laboratory medicine institute accredited according to DIN EN ISO 15189: 2014. Subsequently, macrophages in whole blood were stimulated with standardized TiO2 particles for 4 hours and then the cytokines TNFa and IL -1ß were measured in cell culture supernatant. TNF-a and IL-1ß levels were determined using the MILLIPLEX® Human Cytokine/Chemokine Magnetic Bead Panel multiplex assay (Merck, Germany) and the Luminex® 200™ System (Merck, Germany) [40]. For both cytokines, the lower detection limit was 3.2 pg/ml and the upper detection limit was 10.000 pg/ml. The test result is considered positive if the TNFa level exceeds 40 pg/ml of blood or the IL -1ß level exceeds 30/per ml of blood. Lower values are considered physiological for the respective cytokine. TNFa and IL -1ß are both highly active acute phase cytokines that can trigger an aseptic inflammatory response [41]. Thus, if only one of the two cytokines is positive, this is evaluated as a pathophysiological co-factor of possible peri-implantitis. Collection of patient data Individual patient data, medical history, and examination findings were recorded on a standardized Case Report Form (CRF). For implant recipients, the year of implant placement was also noted, the topographic position of the implants was documented according to the Fédération Dentaire Internationale (FDI) system [42] and the plaque index was classified according to Silness and Löe [38]. In patients with multiple implants, the maximum wearing time of the first placed implant was determined as the time interval between the date of placement and date of current diagnosis. Pocket depths were assessed with a HawePerioProbe © plastic probe (®	—

Measure

Time frame

To measure the cytokine response of macrophages/monocytes after exposure with TiO2 particles, the TiO2-stimulation assay has been done. Accordingly, after individual informed consent, 10 milliliters of venous blood were taken from each patient, heparinized, anonymized, and sent for analysis within 24 hours to a laboratory medicine institute accredited according to DIN EN ISO 15189: 2014. Subsequently, macrophages in whole blood were stimulated with standardized TiO2 particles for 4 hours and then the cytokines TNFa and IL -1ß were measured in cell culture supernatant. TNF-a and IL-1ß levels were determined using the MILLIPLEX® Human Cytokine/Chemokine Magnetic Bead Panel multiplex assay (Merck, Germany) and the Luminex® 200™ System (Merck, Germany) [40]. For both cytokines, the lower detection limit was 3.2 pg/ml and the upper detection limit was 10.000 pg/ml. The test result is considered positive if the TNFa level exceeds 40 pg/ml of blood or the IL -1ß level exceeds 30/per ml of blood. Lower values are considered physiological for the respective cytokine. TNFa and IL -1ß are both highly active acute phase cytokines that can trigger an aseptic inflammatory response [41]. Thus, if only one of the two cytokines is positive, this is evaluated as a pathophysiological co-factor of possible peri-implantitis. Collection of patient data Individual patient data, medical history, and examination findings were recorded on a standardized Case Report Form (CRF). For implant recipients, the year of implant placement was also noted, the topographic position of the implants was documented according to the Fédération Dentaire Internationale (FDI) system [42] and the plaque index was classified according to Silness and Löe [38]. In patients with multiple implants, the maximum wearing time of the first placed implant was determined as the time interval between the date of placement and date of current diagnosis. Pocket depths were assessed with a HawePerioProbe © plastic probe (®

—

Secondary

Measure	Time frame
The study was considered complete when all results of the TiO2 stimulation tests of the 60 patients were available and statistically analyzed.	—

Countries

Germany

Contacts

Public ContactMatthias Müller

Zahnarztpraxis

kontakt@zahnmueller.de08772 408

Outcome results

None listed

Source: DRKS (via WHO ICTRP) · Data processed: Feb 4, 2026