Immunological-Clinical Evaluation of the Etiopathogenesis of Peri-Implantitis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Blood testing, total blood count, and indices derived from it.
研究概览
简要总结
A total of 100 adult volunteers of both sexes will be enrolled in the project. The study will be conducted within an international consortium formed for the project, comprising the following institutions: Wroclaw Medical University (Poland), Sapienza University of Rome (Italy), University of Barcelona (Spain), University of Bern (Switzerland), and Egas Moniz University (Portugal). Each international partner institution will recruit 20 volunteers as participants in the experiment. Each of the participating institutions will submit an application to their respective local bioethics committee for approval to conduct the medical experiment. Each partner institution will conduct procedures at their respective clinical locations.
Eligibility Criteria participants must have undergone previous implant treatment that has resulted in active, advanced peri-implantitis. Exclusion Criteria: General and local contraindications for surgical procedures Pregnancy; Use of bisphosphonates or other antiresorptive medications in medical history Laboratory Analysis Procedures.
During the initial visit, patients will undergo a medical interview and a dental examination with regard to: Oral Hygiene Indices; Periodontal disease indices. For the implant site, the following parameters will be evaluated: Pocket Depth Bleeding on Probing Width and height of the attached gingiva Possible implant mobility, assessed using the Mobility Index Following the clinical examination, each participant will be referred for a Cone Beam Computed Tomography (CBCT) scan with measurements including: Bone loss percentage for each of the four implant surfaces, Bone density. Next, a 20ml venous blood sample will be collected from the antecubital vein of each participant and sent to a laboratory for further analysis, including: Hematological Inflammation Indices: Systemic Immune-Inflammation Index, Aggregate Index of Systemic Inflammation, Complete blood count, Lipid profile, APOA., APOBg, Inflammatory markers, albumin, total protein, total ferritin, fibrinogen, Cytokine profile, HOMA2 Parameters, Thyroid profile, Vitamin D level Next, each participant will undergo implant explantation surgery, during which tissue samples will be collected for further analysis. Implant surface will be analyzed using: light microscopy, scanning electron microscopy, corrosion testing.
Follow-Up will be scheduled four weeks later with following evaluation: Clinical assessment of the implantation site. A CBCT scan to assess bone structure in the post-implantation region, with measurements including percentage of bone loss. Moreover, 20ml of venous blood will be collected from the antecubital vein of each participant. The blood sample will be preserved and sent to an analytical laboratory for further testing, including for same as previously mentioned tests.
详细描述
The following research experiment project is part of the scientific section of a project funded under the Erasmus+ program (KA220-HED - Cooperation partnerships in higher education) entitled "Integrating Peri-Implantitis Research into Higher Education Curriculum - Developing and Integrating Evidence-Based Teaching Materials and Clinical Tools." According to the current state of knowledge, there are two main theories explaining the development of peri-implantitis. The first theory suggests that the primary etiological factor is the invasion of periopathogens along the gingival crevice surrounding the implant, resembling the pathogenic development seen in natural periodontal diseases such as gingivitis and periodontitis. In this scenario, bacterial invasion is facilitated by the distinct structure of the peri-implant soft tissues, which differ from natural gingival tissue in several ways: a more uniaxial, parallel orientation of collagen fibers relative to the implant's long axis, lower cellular density, and reduced mitotic potential of the surrounding soft tissue.
The second theory proposes that marginal bone loss around the implant is the result of an immuno-osteolytic reaction, with pathogenic bacteria appearing as a secondary phenomenon. According to this theory, the initiation of the pathological process is attributed to an immune response triggered by the presence of titanium ions and other metallic elements, such as vanadium, which is commonly found in titanium alloys. In vitro models have demonstrated that an increase in Ti concentration leads to macrophage activation and increased secretion of pro-inflammatory cytokines, particularly interleukin IL-1B and arachidonic acid derivatives. This macrophage activation is significantly higher in cases where prior bacterial lipopolysaccharide (LPS) exposure has occurred, suggesting an additive effect of bacterial factors in the overall disease process. Furthermore, vanadium appears to disrupt the balance of T/B lymphocytes, suppress the secretion of anti-inflammatory cytokines, and activate the innate immune response via Toll-like receptors and NF-κB signaling pathways.
Despite conceptual differences between these two theories, both agree on the fundamental premise that biological processes occurring on the implant surface and in its immediate vicinity play a critical role in the development of peri-implantitis. These processes are modulated by the physicochemical properties of the implant surface.
The immuno-osteolytic concept of peri-implantitis, also known as the foreign body reaction theory, is largely based on physicochemical changes that occur on the implant surface over time due to its exposure to the oral tissue environment. These changes are associated with gradual degradation, corrosion, and aging of titanium alloys.
In biomedical applications, biphasic titanium alloys are most commonly used, particularly the Ti-6Al-4V alloy, which contains 6% aluminum and 4% vanadium. Aluminum stabilizes the α-phase, improving mechanical strength and reducing weight, while vanadium stabilizes the β-phase, enhancing alloy plasticity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •PD (Pocket Depth) at the implant site exceeds 6mm,
- •Positive BoP (Bleeding on Probing) index
- •Bone loss exceeding 66% on at least one implant surface
排除标准
- •General and local contraindications for surgical procedures
- •Pregnancy
- •Use of bisphosphonates or other antiresorptive medications in medical history
研究组 & 干预措施
Study group
Every participant will achieve same intervention when it comes to surgical treatment, clinical examination, radiology evaluation and defined parameters of blood serum.
干预措施: Blood testing (Diagnostic Test)
结局指标
主要结局
Blood testing, total blood count, and indices derived from it.
时间窗: On the day of implant removal (before implant removal) and 4 weeks after.
Hematological Inflammation Indices: Systemic Immune-Inflammation Index (SII) calculated as follows: SII=NEUxPLT/LYMPH
Blood testing, HOMA2 Parameters
时间窗: On the day of implant removal (before implant removal) and 4 weeks after.
HOMA2 Parameters - Glucose mg/dl, C-Peptide mg/dl,
Clinical examination - general, oral cavity
时间窗: On the day of implant removal (before implant removal) and 4 weeks after.
Oral Hygiene Index (OHI) %, Aproximal Plaque Index (API) %
Implant surface evaluation, light microscopy
时间窗: Within 48 hours after implant removal
Assessment of the implant surface, identifying areas with fatigue-related material degradation, such as microcracks.
Blood testing, Vitamin D3 level
时间窗: On the day of implant removal (before implant removal) and 4 weeks after.
25(OH)D, 1.25(OH)2 D3 ng/ml
Implant surface evaluation, Scanning electron microscopy
时间窗: Within 48 hours after implant removal
Assessment of the implant surface, identifying areas with fatigue-related material degradation, such as microcracks.
Radiology-based evaluation
时间窗: On the day of implant removal (before implant removal) and 4 weeks after.
Cone-Beam Computed Tomography: Bone density on the implant site (before and after implant removal), measured in Hounsfield units (HU)
Clinical examination - general, oral cavity, utilizing a UNC15 periodontal probe
时间窗: On the day of implant removal (before implant removal).
Community Index of Periodontal Treatment Needs (CPITN)
Implant surface evaluation - detection of other metals presented in the titanium alloy.
时间窗: Within 48 hours after implant removal
Energy-dispersive X-ray spectroscopy (EDS)
Titanium ions concentration in tissues attached to implant' surface
时间窗: Within 48 hours after implant removal
Inductively coupled plasma mass spectrometry (ICP-MS)
Blood testing, Thyroid profile
时间窗: On the day of implant removal (before implant removal) and 4 weeks after.
TSH μIU/ml
Clinical examination - implant site, utilizing a UNC15 periodontal probe
时间窗: On the day of implant removal (before implant removal).
Pocket Depth (PD) - measured on four surfaces around the implant in mm.
Blood testing, lipid profile.
时间窗: On the day of implant removal (before implant removal) and 4 weeks after.
CHOL mg/dl , HDL mg/dl, LDL mg/dl, TG mg/dl, APOA1 mg/dl, APOB mg/dl
Blood testing, Inflammatory markers.
时间窗: On the day of implant removal (before implant removal) and 4 weeks after.
Inflammatory markers: CRP mg/l, albumin (ALB) mg/dl, TP mg/dl,TF mg/dl, FIB mg/dl
Blood testing, Inflammatory marker.
时间窗: On the day of implant removal (before implant removal) and 4 weeks after.
ESR mm/h
Blood testing, Cytokine profile.
时间窗: On the day of implant removal (before implant removal) and 4 weeks after.
TNF- α pg/ml , IL- 1β pg/ml, IL-6 pg/ml, IL-8 pg/ml, IL-10 pg/ml
Radiology-based evaluation
时间窗: On the day of implant removal (before implant removal).
Cone-Beam Computed Tomography: Bone loss percentage on the implant site (%), calculated as the ratio of bone defect depth from the implant platform to the base of the defect, relative to the total implant length, assessed separately for each of the four implant surfaces (mesial, distal, buccal, and lingual/palatal)
次要结局
未报告次要终点