Impact of Advanced Platelet Rich Fibrin and Enamel Matrix Derivative on Clinical and Molecular Wound Healing Parameters After Surgical Removal of Mandibular Third Molars

NCT06190015 | Unknown Phase 4 DMC

• 1 other identifier: 1/36/20
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Surgical Wound, Healed; Post Operative Pain

Keywords

third molar; wound healing; postoperative pain, edema

Outcome Measures

Primary Outcomes (28)

• Evaluation of postoperative pain on visual analog scale

  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.

  24 hours after surgery

• Evaluation of postoperative pain on visual analog scale

  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.

  24-48 hours after surgery

• Evaluation of postoperative pain on visual analog scale

  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.

  48-72 hours after surgery

• Evaluation of postoperative pain on visual analog scale

  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.

  72 hours- 7 days after surgery

• Evaluation of postoperative pain on verbal rating scale

  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).

  24 hours after surgery

• Evaluation of postoperative pain on verbal rating scale

  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).

  24-48 hours after surgery

• Evaluation of postoperative pain on verbal rating scale

  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).

  48-72 hours after surgery

• Evaluation of postoperative pain on verbal rating scale

  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).

  72 hours- 7 days after surgery

• Evaluation of postoperative pain by marking the number of pain tablets and time of their consumption

  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.

  24 hours after surgery

• Evaluation of postoperative pain by marking the number of pain tablets and time of their consumption

  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.

  24-48 hours after surgery

• Evaluation of postoperative pain by marking the number of pain tablets and time of their consumption

  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.

  48-72 hours after surgery

• Evaluation of postoperative pain by marking the number of pain tablets and time of their consumption

  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.

  72 hours- 7 days after surgery

• Evaluation of preoperative tragus- oral commissure and outer eye canthus-angle of the mandible distances at the side of the extraction

  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.

  1 hour preoperatively

• Evaluation of postoperative swelling

  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.

  24 hours after surgery

• Evaluation of postoperative swelling

  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.

  48 hours after surgery

• Evaluation of postoperative swelling

  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.

  72 hours after surgery

• Evaluation of postoperative swelling

  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.

  7 days after surgery

• Evaluation of preoperative maximal inter-incisor distance

  Maximal inter-incisor distance at baseline will be measured by means of a soft tape, and expressed in millimeters (mm).

  1 hour preoperatively

• Evaluation of postoperative trismus

  Trismus will be measured through assessment of a maximal inter-incisor distance by means of a soft tape, expressed in millimeters (mm).

  24 hours postoperatively

• Evaluation of postoperative trismus

  Trismus will be measured through assessment of a maximal inter-incisor distance by means of a soft tape, expressed in millimeters (mm).

  48 hours postoperatively

• Evaluation of postoperative trismus

  Trismus will be measured through assessment of a maximal inter-incisor distance by means of a soft tape, expressed in millimeters (mm).

  7 days postoperatively

• Relative gene expression of inflammatory and wound healing mediators in gingival crevicular fluid of the distal sulcus of the second mandibular molar 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.

  1 hour preoperatively

• 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

  To measure the protein expression of Mar1 in samples of gingival crevicular fluid before surgical removal of impacted mandibular wisdom teeth

  1 hour preoperatively

• Relative gene expression of inflammatory and wound healing mediators in wound exudate after surgical removal of impacted mandibular wisdom teeth

  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.

  48 hours postoperatively

• Relative gene expression of inflammatory and wound healing mediators in wound exudate after surgical removal of impacted mandibular wisdom teeth

  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.

  7 days postoperatively

• Protein expression of specialized pro-resolving inflammation mediator maresin 1 (Mar1) in wound exudate after surgical removal of impacted mandibular wisdom teeth

  To measure the protein expression of Mar1 in samples of wound exudate after surgical removal of impacted mandibular wisdom teeth

  48 hours postoperatively

• Protein expression of specialized pro-resolving inflammation mediator maresin 1 (Mar1) in wound exudate after surgical removal of impacted mandibular wisdom teeth

  To measure the protein expression of Mar1 in samples of wound exudate after surgical removal of impacted mandibular wisdom teeth.

  7 days postoperatively

• Evaluation of soft tissue healing using Landry healing index

  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

  7 days after surgery

Secondary Outcomes (14)

• 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 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 clinical attachment level of mandibular second molar in six points

  1 hour preoperatively

Study Arms (4)

Advanced platelet rich fibrin (APRF) group;

ACTIVE COMPARATOR

After surgical removal of one of the impacted mandibular third molar, APRF clots will be placed in the alveolus

Biological: Advanced platelet rich fibrin (APRF) clots

Control group 1;

NO INTERVENTION

Standard surgical removal of the other impacted mandibular third molar will be performed without placing APRF in the wound

Enamel matrix derivative (EMD) group;

ACTIVE COMPARATOR

After surgical removal of one impacted mandibular third molar, EMD with collagen sponges will be placed in the extraction alveolus

Device: Enamel matrix derivative (EMD) group

Control group 2;

NO INTERVENTION

Standard surgical removal of the other impacted mandibular third molar will be performed without placing EMD in the wound

Interventions

Advanced platelet rich fibrin (APRF) clots BIOLOGICAL

15 minutes before surgery, phlebotomy will be performed and two vacutainers containing 10ml of blood will be placed in the centrifuge for 8 min and 200g. Acquired APRF clots will be placed in the extraction alveolus

Advanced platelet rich fibrin (APRF) group;

Enamel matrix derivative (EMD) group DEVICE

After third molar removal, Pref Gel (EDTA) will be placed on the root surface for 2 min and then removed. Emdogain (EMD) will be placed on the collagen sponge (Botiss, Collacone) and then applied in the wound so that the side of the sponge which is covered with Emdogain is in contact with the root surface.

Also known as: Emdogain, Straumann,

Enamel matrix derivative (EMD) group;

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Belgrade: lead

Study Sites (1)

School of dental medicine, University of Belgrade

Belgrade, 11000, Serbia

Location

Related Publications (2)

• Nasirzade J, Kargarpour Z, Hasannia S, Strauss FJ, Gruber R. Platelet-rich fibrin elicits an anti-inflammatory response in macrophages in vitro. J Periodontol. 2020 Feb;91(2):244-252. doi: 10.1002/JPER.19-0216. Epub 2019 Sep 14.

  PMID: 31376159 BACKGROUND

• Gupta N, Agarwal S. Advanced-PRF: Clinical evaluation in impacted mandibular third molar sockets. J Stomatol Oral Maxillofac Surg. 2021 Feb;122(1):43-49. doi: 10.1016/j.jormas.2020.04.008. Epub 2020 Apr 29.

  PMID: 32360489 RESULT

Related Links

• This study was conducted on patients who had bilateral impacted third molars. One quadrant received A-PRF while the opposing quadrant in same patient was taken as control.

MeSH Terms

Conditions

Surgical Wound; Pain, Postoperative; Edema

Condition Hierarchy (Ancestors)

Wounds and Injuries; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Snjezana Colic, professor of oral surgery

  School of dental medicine, University of Belgrade, Serbia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Study Record Dates

• First Submitted: December 16, 2023
• First Posted: January 5, 2024
• Study Start: May 23, 2022
• Primary Completion: January 20, 2024
• Study Completion: March 20, 2024
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)