Impact of Advanced Platelet Rich Fibrin and Enamel Matrix Derivative on Clinical and Molecular Wound Healing Parameters After Surgical Removal of Mandibular Third Molars
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Evaluation of postoperative swelling
研究概览
简要总结
Brief summary
The goal of this study is to compare the effects of advanced platelet rich fibrin and enamel matrix derivative placed in the extraction alveoli of patients who had surgical removal of mandibular wisdom teeth. The questions it aims to answer/evaluate are:
- postoperative pain, swelling, trismus, early wound healing using soft tissue healing index
- level of early local inflammatory response by measuring levels of inflammatory mediators in wound exudate
- degree of wound healing by measuring levels of early wound healing mediators in wound exudate
- incidence of alveolar osteitis and delayed infection
- levels of probing depth, clinical attachment loss, gingival margin level, bleeding on probing, gingival index, plaque index of the second mandibular molar 3 months after surgery
Participants of the study will be asked:
- for their preoperative clinical measurements (swelling, trismus, periodontal parameters) to be taken by the principal investigator
- to provide 20 ml of venous blood if necessary
- to preoperatively provide gingival crevicular fluid in the region of distal surface of the second mandibular molar and postoperatively wound exudate
- to note the number of painkiller pills taken after surgery and pain levels in different time points
- to come to regular checkups in which clinical measuring of postoperative swelling, trismus levels and periodontal parameters will be performed
详细描述
Surgical removal of impacted mandibular wisdom teeth is often related to the occurrence of postoperative pain, swelling, trismus and sometimes to the development of complications such as alveolar osteitis, delayed infection and formation of periodontal pocket on the distal surface of the second molar. In order to reduce postoperative discomfort and complications, nonsteroidal anti-inflammatory drugs and antibiotics are being routinely prescribed.
Placement of autologous materials and commercially available products in the extraction alveoli, in order to minimize postoperative pain, swelling, trismus and complications, is a therapy option that is discussed in literature.
Platelet rich fibrin (PRF) is an autologous fibrin derived from patient's venous blood rich in platelets, leucocytes, growth factors and cytokines. Advanced PRF (APRF) is a variant of PRF which is produced by smaller centrifugation speed and smaller relative centrifugal force for a longer time period in comparison to the other types of PRF clots. APRF contains leucocytes, vascular endothelial growth factor (VEGF), transforming growth factor β (TGF-β), interleukin -1β (IL1β) and interleukin-6 (IL6).
Local application of APRF in the extraction alveolus after surgical removal of impacted mandibular wisdom teeth has shown positive effects such as lesser postoperative pain, better soft tissue healing and lower incidence of alveolar osteitis and delayed infection.
In vitro studies have shown that PRF contains significant amounts of VEGF, TGF-β, IL1β, IL6. In vitro study also showed that PRF induces polymerization of M1 proinflammatory macrophages to M2 anti-inflammatory macrophages. M2 macrophages produce specialized pro-resolving lipid mediators which are important for resolution phase of inflammatory process and wound healing. Maresin 1 (MaR1), specialized pro-resolving lipid mediator, has shown an important role in inducing faster soft tissue and bone healing and therefore the presence of this mediator may be relevant to indicate the course of postoperative wound healing. Taking into consideration the data from clinical and in vitro studies, it would be beneficial to determine on a clinical model such as surgical removal of impacted mandibular wisdom teeth levels of VEGF, TGF-β, IL1β, IL6 and MaR1 after placing APRF into the extraction alveolus in comparison to the standard surgical removal of impacted mandibular wisdom teeth and compare those levels with clinical parameters of postoperative course.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 30 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Systemically healthy individuals (ASA I by American Society of Anesthesiologists classification);
- •Age 18-30 years;
- •Patients who have bilaterally impacted mandibular wisdom teeth which are in contact with the distal surface of the second mandibular molar.
排除标准
- •Systemic disorders;
- •Patients who have difficulties when phlebotomy is performed
- •History of pericoronitis in the area of impacted mandibular wisdom tooth
- •History of NSAIDs, corticosteroids and antibiotics intake within 10 days before surgery
结局指标
主要结局
Evaluation of postoperative swelling
时间窗: 7 days after surgery
Postoperative swelling will be evaluated by measuring distances tragus- oral commissure and outer eye canthus-angle of the mandible at the side of the extraction by using soft tape, expressed in millimeters.
Evaluation of preoperative maximal inter-incisor distance
时间窗: 1 hour preoperatively
Maximal inter-incisor distance at baseline will be measured by means of a soft tape, and expressed in millimeters (mm).
Relative gene expression of inflammatory and wound healing mediators in gingival crevicular fluid of the distal sulcus of the second mandibular molar preoperatively
时间窗: 1 hour preoperatively
To measure the relative gene expression of VEGF, TGF-β1, IL-6, IL-1β in samples of gingival crevicular fluid before surgical removal of impacted mandibular wisdom teeth.
Relative gene expression of inflammatory and wound healing mediators in wound exudate after surgical removal of impacted mandibular wisdom teeth
时间窗: 7 days postoperatively
To measure the relative gene expression of VEGF, TGF-β1, IL-6, IL-1β in samples of wound exudate after surgical removal of impacted mandibular wisdom teeth.
Evaluation of soft tissue healing using Landry healing index
时间窗: 7 days after surgery
Independent researcher will evaluate soft tissue healing by marking the number in front of the given description: 1. Very poor- tissue color: more than 50% of gingivae red Response to palpation: bleeding Granulation tissue: present Incision margin: not epithelialised, with loss of epithelium beyond margins Suppuration: present; 2. Poor- Tissue color: more than 50% of gingivae red Response to palpation: bleeding Granulation tissue: present Incision margin: not epitheliased with connective tissue exposed. 3. Good- Tissue color: less than 50% of gingivae red Response to palpation: no bleeding Granulation tissue: none Incision margin: no connective tissue exposed 4. Very good- Tissue color: less than 25% of gingivae red Response to palpation: no bleeding Granulation tissue: none Incision margin: no connective tissue exposed 5. Excellent-Tissue color: all gingivae pink Response to palpation:no bleeding Granulation tissue:none; Incision margin:no connective tissue exposed
Evaluation of postoperative pain on visual analog scale
时间窗: 72 hours- 7 days after surgery
Pain will be measured on a 10-cm long visual analog scale (VAS), where 0 means no pain at all, and 10 represent the greatest pain patients have ever felt. Higher scores on a scale mean worse outcome.
Evaluation of postoperative pain on verbal rating scale
时间窗: 72 hours- 7 days after surgery
Pain will be measured on a 6-point verbal rating pain scale (VRS) where higher scores mean worse outcome (1-no pain; 2-mild pain; 3-moderate pain; 4-severe pain; 5-very severe pain; 6-the worst possible pain).
Evaluation of postoperative pain by marking the number of pain tablets and time of their consumption
时间窗: 72 hours- 7 days after surgery
After measuring their pain level on VAS and VRS, patients will be writing the number of Paracetamol tablets (500mg) that were taken and exact time of their consumption.
Protein expression of specialized pro-resolving inflammation mediator maresin 1 (Mar1) in gingival crevicular fluid of the distal sulcus of the second mandibular molar preoperatively
时间窗: 1 hour preoperatively
To measure the protein expression of Mar1 in samples of gingival crevicular fluid before surgical removal of impacted mandibular wisdom teeth
Evaluation of preoperative tragus- oral commissure and outer eye canthus-angle of the mandible distances at the side of the extraction
时间窗: 1 hour preoperatively
Postoperative swelling will be evaluated by measuring distances tragus- oral commissure and outer eye canthus-angle of the mandible at the side of the extraction by using soft tape, expressed in millimeters.
Evaluation of postoperative trismus
时间窗: 7 days postoperatively
Trismus will be measured through assessment of a maximal inter-incisor distance by means of a soft tape, expressed in millimeters (mm).
Protein expression of specialized pro-resolving inflammation mediator maresin 1 (Mar1) in wound exudate after surgical removal of impacted mandibular wisdom teeth
时间窗: 7 days postoperatively
To measure the protein expression of Mar1 in samples of wound exudate after surgical removal of impacted mandibular wisdom teeth.
次要结局
- Evaluation of preoperative probing depth of mandibular second molar in six points(1 hour preoperatively)
- Evaluation of postoperative probing depth of mandibular second molar in six points(3 months after surgery)
- Evaluation of preoperative clinical attachment level of mandibular second molar in six points(1 hour preoperatively)
- Evaluation of postoperative clinical attachment level of mandibular second molar in six points(3 months after surgery)
- Evaluation of postoperative bleeding on probing of mandibular second molar in six points(3 months after surgery)
- Evaluation of preoperative plaque index score of mandibular second molar(1 hour preoperatively)
- Incidence of postoperative alveolar osteitis(Within 7 days after surgery)
- Evaluation of preoperative gingival margin level of mandibular second molar in six points(1 hour preoperatively)
- Evaluation of postoperative gingival margin level of mandibular second molar in six points(3 month after surgery)
- Evaluation of preoperative bleeding on probing of mandibular second molar in six points(1 hour preoperatively)
- Evaluation of postoperative plaque index score of mandibular second molar(3 months postoperatively)
- Evaluation of preoperative gingival index score of mandibular second molar(1 hour preoperatively)
- Evaluation of postoperative gingival index score of mandibular second molar(3 months after surgery)
- Incidence of postoperative infection(Within 3 months after surgery)
研究者
Ruzica Brajovic
principal investigator
University of Belgrade