The Use of Platelet Rich Fibrin in Pulpal and Periodontal Regeneration in Mature Teeth

September 27, 2023 updated by: University of Nebraska
In cases of permanent tooth avulsion, it is widely accepted that some necrosis always occurs after avulsion injury. If the pulp tissue does not revascularize or if endodontic therapy is not performed, the pulp space can become infected. Platelet rich fibrin (PRF) is a second generation platelet concentrate that allows the clinician to obtain fibrin membranes enriched with platelets and growth factors from an anticoagulant-free blood harvest. Clinical relevance of PRF and revascularization has been demonstrated in several case studies of avulsion. To date no human clinical trials have been performed evaluating the effectiveness of PRF on pulpal revascularization after reimplantation and its benefits in limiting inflammation. The following study consists of two phases: Phase 1: An in vitro model evaluating the effects of PRF in limiting inflammatory response of pdl cell cultures in the presence of an inflammatory mediators. Phase 2: An in vivo model utilizing mature teeth previously treatment planned for extraction, treating with PRF, reimplanting teeth and following for three to four months before extracting and performing histological analysis. If PRF is capable of promoting revascularization in mature teeth the potential benefits extend to limiting the need for endodontic therapy following mature tooth avulsion, potential for mature tooth transplantation in situations of congenitally missing teeth, and utilization of PRF in endodontic revascularization therapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

When a tooth is avulsed, it is separated from its socket causing damage to the attachment apparatus. The periodontal ligament (pdl) is a group of specialized connective tissue fibers that attaches the cementum of the root (outer layer) to the alveolar bone. Avulsion can cause damage to the pdl and possible cemental tears. If the periodontal ligament is left attached to the root and minimal time lapse occurs damage to the tissues is usually limited. In these cases, reimplantation is a widely accepted treatment; however the long term success of an avulsed tooth is dependent on various factors. When excessive drying occurs prior to re-implantation, a severe inflammatory response is elicited directly on the root surface which may result in osseous replacement or replacement resorption. Some necrosis always occurs after avulsion injury, and while the necrotic pulp is of little consequence, this necrotic tissue is at high risk for bacterial contamination. If the pulp tissue does not revascularize or if endodontic therapy is not performed, the pulp space can become infected. It has been suggested that treatment strategies should attempt to limit peri-radicular inflammation therefore promoting favorable cemental healing and limiting unfavorable osseous replacement.

Platelet rich fibrin (PRF) is a second generation platelet concentrate that allows the clinician to obtain fibrin membranes enriched with platelets and growth factors from an anticoagulant-free blood harvest and without the addition of artificial biochemical modification. PRF has demonstrated clinical relevance through its ability to stimulate cell proliferation of osteoblasts, gingival fibroblasts, and periodontal ligament (PDL) cells. In addition, PRF has been shown to limit epithelial cell growth therefore promoting connective tissue and alveolar bone regeneration and inhibiting epithelial proliferation. These properties make it a favorable product for surgical procedures requiring micro vascularization.

In vitro studies with PRF and canine dental pulp cells demonstrate PRF's ability to promote chemotaxis and proliferation of the pulp cells and contributed to pulp repair. When PRF was combined with human dental pulp cells derived from extracted third molars it did not interfere with vitality and stimulated proliferation and differentiation. Additionally it upregulated the expression of osteoprotegerin and alkaline phosphatase.

Animal models evaluated PRF granules combined with human pdl stem cells and placed them on the root surface of freshly extracted canine teeth. The teeth were then reimplanted and evaluated histologically after a healing phase. A regeneration of the PDL-like tissue and reduction in ankylosis and inflammation were noted in animals with the PRF granules.

Clinical relevance of PRF and revascularization has been demonstrated in several case studies of avulsion. These case studies utilized a general protocol of minimally instrumenting the avulsed tooth. One study performed a 3 mm resection of the root apex followed by minimal instrumentation of the canal. Blood is then drawn from the patient and PRF is prepared via Choukroun's method. The PRF is then placed on the root surface and condensed into the canal. The tooth was then reimplanted, splinted, and the patient followed for up to 24 months. The tooth tested vital to thermal and percussion testing and radiographically did not show signs of replacement resorption or inflammation.

To date no human studies have been performed evaluating the effectiveness of PRF on pulpal revascularization after reimplantation and its benefits in limiting inflammation. Additionally, only histological evidence of the benefits of PRF has been demonstrated in animal models. If PRF is capable of promoting revascularization in mature teeth the potential benefits extend to limiting the need for endodontic therapy following mature tooth avulsion, potential for mature tooth transplantation in situations of congenitally missing teeth, and utilization of PRF in endodontic revascularization therapy.

The following research would consist of two phases: Phase 1. An in vitro model evaluating the effects of PRF in limiting inflammatory response of pulp and pdl cell cultures in the presence of an inflammatory mediators. Phase 2. An in vivo model utilizing mature teeth previously treatment planned for extraction, treating in accordance to the procedure documented by one group, reimplanting teeth and following for three to four months before extracting and performing histological analysis.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Nebraska
      • Lincoln, Nebraska, United States, 68505
        • University of Nebraska, College of Dentistry

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • any adult with single rooted vital teeth previously treatment planned for extraction to meet their prosthetic or orthodontic needs.

Exclusion Criteria:

  • exclusion criteria will include: individuals with systemic illnesses that could compromise vascularity or healing,
  • patients who are pregnant,
  • or bisphosphonates.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PRF Treated
Subjects will be randomized to either receive either left tooth platelet rich fibrin; right tooth implant alone, OR right tooth platelet rich fibrin; left tooth implant alone. Following treatment each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically.
Procedure: Left Tooth Platelet Rich Fibrin; Right Tooth Implant Alone
All study participants will have two teeth extracted and 2 mm of root removed. Half of the subjects will have platelet rich fibrin endodontic revascularization therapy will be applied to the left tooth socket only. The right tooth is implanted alone. Each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically.
Procedure: Right Tooth Platelet Rich Fibrin; Left Tooth Implant Alone
All study participants will have two teeth extracted and 2 mm of root removed. Half of the subjects will have platelet rich fibrin endodontic revascularization therapy to the right tooth socket only. The left tooth is implanted alone. Each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically.
No Intervention: Control
Subjects will be randomized to either receive either left tooth platelet rich fibrin; right tooth implant alone, OR right tooth platelet rich fibrin; left tooth implant alone. Following treatment each tooth is replaced and splinted to the adjacent teeth. Teeth are followed for 3 months and then tested for vitality before extracting and examining histologically.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Vitality of Teeth (Units) Using Thermal and Percussion Sensitivity Trend Observed During Study Duration (3-11 Months)
Time Frame: 3-11 months. Each participant was measured for as long as it took to complete their prosthesis. The minimum study duration was 3 months and the maximum duration was 11 months in one subject.
Teeth (units) measuring vital via the following tests: thermal, percussion. Thermal was utilized with endo cold spray and percussion from tapping on teeth with mouth mirror.
3-11 months. Each participant was measured for as long as it took to complete their prosthesis. The minimum study duration was 3 months and the maximum duration was 11 months in one subject.
Vitality of Teeth Using Electronic Pulp Test (EPT Units) Trend Observed During Study Duration (3-11 Months)
Time Frame: 3-11 months. Each participant was measured for as long as it took to complete their prosthesis. The minimum study duration was 3 months and the maximum duration was 11 months in one subject.
Teeth (units) measuring vital via the following tests: EPT utilizing EPT units (0-80). There is no specific number that suggests vital vs un-vital but rather it is a trend towards un-vital which is determined as 80.
3-11 months. Each participant was measured for as long as it took to complete their prosthesis. The minimum study duration was 3 months and the maximum duration was 11 months in one subject.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Nebraska

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Elisabeth L Easley, DMD, University of Nebraska

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 29, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 26, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 19, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 22, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 4, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 27, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0443-14-FB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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