Effects of platelet-rich fibrin in the surgical extraction of mandibular third molar: A systematic review and meta-analysis

A F M Shakilur Rahman

doi:10.4103/srmjrds.srmjrds_46_22

REVIEW ARTICLE

Year : 2022 | Volume : 13 | Issue : 3 | Page : 101-108

Effects of platelet-rich fibrin in the surgical extraction of mandibular third molar: A systematic review and meta-analysis

A F M Shakilur Rahman
Department of Oral and Maxillofacial Surgery, Rajshahi Medical College, Rajshahi, Bangladesh

Date of Submission	25-Mar-2022
Date of Decision	08-Jun-2022
Date of Acceptance	09-Jun-2022
Date of Web Publication	09-Sep-2022

Correspondence Address:
Dr. A F M Shakilur Rahman
Department of Oral and Maxillofacial Surgery, Rajshahi Medical College, Rajshahi
Bangladesh

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/srmjrds.srmjrds_46_22

Abstract

Background: Platelet-rich fibrin (PRF) has a wide variety of applications in the field of oral surgery due to its biological potential to accelerate the wound-healing process and tissue regeneration. Aim: The objective of this review was to find out whether the role of PRF had been reported to be efficient in the surgical extraction of mandibular third molar (M3). Methods: An electronic search of the English-language literature in the PubMed (Medline) database was performed for the period from January 2015 to September 2021. Only randomized controlled trials (RCTs) comparing the impact of PRF application were included in this review. According to the Cochrane Collaboration's standards, the reviewer assessed the risk of bias. Review Manager (version 5.4) Windows software was used for the meta-analysis. Results: A total of 39 papers were found in the computerized search, with 13 RCTs meeting the qualitative analysis requirements and 10 trials included in the meta-analysis. The results of a meta-analysis for M3 surgery showed that PRF reduces the incidence of alveolar osteitis (AO) (P = 0.005) and pain on the first (P = 0.05), third (P = 0.002), fourth (P = 0.01), and seventh (P = 0.0003) postoperative days. The meta-analysis also revealed that there was no substantial improvement (P = 0.44) in soft tissue healing with the application of PRF following M3 surgery. Conclusions: The application of PRF after M3 extraction decreased the incidence of AO and postextraction pain.

Keywords: Alveolar osteitis, extraction, fibrin, mandibular third molar, platelet-rich fibrin.

How to cite this article:
Rahman A F. Effects of platelet-rich fibrin in the surgical extraction of mandibular third molar: A systematic review and meta-analysis. SRM J Res Dent Sci 2022;13:101-8

How to cite this URL:
Rahman A F. Effects of platelet-rich fibrin in the surgical extraction of mandibular third molar: A systematic review and meta-analysis. SRM J Res Dent Sci [serial online] 2022 [cited 2023 May 28];13:101-8. Available from: https://www.srmjrds.in/text.asp?2022/13/3/101/355826

Introduction

One of the most common treatments in oral surgery is mandibular third molar (M3) extraction. The M3 extraction can be challenging in cases when the teeth are impacted and buried by a substantial amount of bone, resulting in more tissue handling, a prolonged duration of surgery, and therefore more postoperative consequences.^[1] Various postoperative consequences are possible, such as pain, trismus, edema, and alveolar osteitis (AO).^[2] Oral and maxillofacial surgeons are constantly striving to enhance their surgical procedures in order to reduce postoperative consequences.

In 2000, Choukroun pioneered the employment of platelet-rich fibrin (PRF) in France.^[3] In oral and maxillofacial surgery, PRF has been shown to be a beneficial surgical addition. Over 500 research papers have been published on this topic to date.^[4] PRF is regarded as a second-generation platelet concentrate because it is processed naturally without the inclusion of anticoagulants.^[5] It is processed in a straightforward, low-cost manner that does not necessitate the use of biochemical blood.^[6] It comprises three major specifications: first, during the natural polymerization process, platelets and their efficient growth factors become trapped in the fibrin matrix.^[6] Second, the involvement of leucocytes and their cytokines in the healing procedure, which contributes to anti-infective responses and immune modulation.^[7] Finally, the fibrin matrix architecture's consistency and complexity are provided by normal polymerization without the need for any anticoagulant or gelling product.^[8]

The PRF has an extensive variety of employment in oral surgical procedures due to its biological prospective to speed up the wound healing procedure. The purpose of this systematic review and meta-analysis was to find out if there was a difference in postoperative complications (pain, swelling, AO, trismus, soft tissue healing, and bone healing impairment) when PRF was applied in the tooth socket following M3 extraction.

Methods

Search strategy and information sources

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram was employed to design this systematic review [Figure 1]. The Cochrane Handbook for Systematic Reviews of Interventions was used as a guideline to conduct this review. The review objectives were constructed using the PICOS method [Table 1]. In the last 6 years, an electronic search of the English-language literature in the PubMed (Medline) database was performed for the period from January 2015 to September 2021 on PRF research on the extraction of M3. The author searched the electronic database using the keywords: “platelet rich fibrin,” “mandibular third molar,” and “extraction.”

Figure 1: Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram for screening and selection process of eligible articles

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Table 1: Population, intervention, comparison, outcomes, and study research question strategy

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Inclusion criteria

The articles that were included had to fulfill the inclusion requirements as well as the PICOS criteria [Table 1]. Only randomized controlled trials (RCTs) comparing the impact of PRF treatment on M3 extraction were included in this analysis. The English language-based articles and human studies were only included in the review.

Exclusion criteria

Exclusions included controlled clinical trials, retrospective studies, case studies, case reports, case series, experimental studies, in vitro studies, cohort, observational studies, conference abstracts, and review articles. The articles were excluded where the complete text could not be retrieved or, in the case of inadequate information.

Record screening

The reviewer reviewed the titles and abstracts found in the electronic database. Following the initial filtering, full-text articles, including all qualifying publications, were retrieved and thoroughly reviewed.

Data extraction

The first author's name, year of publication, country of origin, design of the study, study population, age, PRF centrifugation process, and outcome variables were all collected from the included papers.

Study risk of bias assessment

The Cochrane Collaboration's tool was employed to evaluate the risk of bias in the RCTs that were included. The authors' judgment was classified as low risk (green), high risk (red), and unclear risk of bias (white) according to the following criteria: (a) randomization, (b) allocation concealment, (c) blinding of participants and personnel, (d) blinding of outcome assessment, (e) incomplete outcome data, (f) selective reporting, and (g) other bias.

Meta-analysis

When the outcome parameters were adequately homogeneous, qualitative and quantitative analyses were conducted, and the meta-analysis was performed. For the meta-analysis of pain, trismus, and soft tissue healing, the mean difference (MD) or standardized MD (SMD) and associated 95% confidence interval (CI) were applied. To assess the occurrence of AO in dichotomous variables, the relative risk and 95% CI were computed. A fixed-effects model was implemented in the absence of statistical heterogeneity, Chi-square test (χ²) >0.10 and I-squared (I²) <50%. When statistical heterogeneity (I² >50%) was evident, the random-effects model was utilized to account for it and generate a more conservatively pooled intervention result. The meta-analysis calculations were performed using Review Manager (version 5.4) windows software (Cochrane's software for writing reviews and meta-analysis, UK). A meta-analysis was not possible for the variables with significant methodological and statistical heterogeneity; hence, just a qualitative analysis was undertaken.

Results

Study selection

The computerized scans identified a total of 39 papers. By reading the titles and abstracts, we excluded a total of 15 articles. For the final selection, 24 full-text papers were assessed. Eleven full-text articles were excluded for specific reasons. Finally, a total of 13 RCTs^{[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21]} were found in the PubMed (Medline) database and met the inclusion criteria to be reviewed for qualitative analysis [Table 2].

Table 2: Features of included studies

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Study characteristics

[Table 2] summarizes the features of the included articles as well as the retrieved data. In this review, ten studies^{[10],[12],[13],[14],[15],[17],[18],[19],[29],[21]} were included in the meta-analysis. Split-mouth RCTs accounted for nine of the trials,^{[10],[11],[12],[13],[14],[16],[17],[18],[21]} while parallel-group RCTs accounted for four.^{[9],[15],[19],[20]} The studies included were conducted in five different countries: Turkey,^{[10],[11],[12],[13],[17],[19],[20]} India,^{[9],[16],[21]} Brazil,^[14] Egypt,^[15] and Lithuania^[18] [Table 2].

Risk of bias in studies

[Figure 2] depicts the findings of the risk of bias evaluation. For all of the fields, none of the studies included in this evaluation were rated as having a low risk of bias [Figure 2].

Figure 2: Risk of bias summary: Review authors' judgments about each risk of bias item for each included study

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Results of postoperative outcome variables

Alveolar osteitis

Four studies reported AO as an outcome variable.^{[12],[15],[17],[18]} The PRF proved effective in lowering the incidence of AO.^{[12],[15],[18]} Unsal et al. reported that, except in smokers, the PRF had no influence (P < 0.018) on the incidence of AO.^[15] There was no significant clinical heterogeneity (I² = 0%, P = 0.69) among these trials.^{[12],[15],[17],[18]} The quantitative analysis revealed a reduction in the incidence of AO following the application of PRF (risk ratio = 0.29, 95% CI = 0.12, 0.68; Z = 2.81, P = 0.005) [Figure 3].

Figure 3: Forest plot comparing PRF versus control in the prevention of alveolar osteitis. CI: Confidence interval; PRF: Platelet-rich fibrin; M-H: Mantel–Haenszel

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Pain

With the exception of two trials,^[11],[16] the level of pain following M3 extraction was reported in 11 articles.^{[9],[10],[12],[13],[14],[15],[17],[18],[19],[20],[21]} The PRF showed a significant (P < 0.05) effect on reducing postoperative pain in five RCTs.^{[9],[15],[18],[20],[21]} On the other hand, the remaining studies reported that the statistical difference was not meaningful (P > 0.05) in terms of pain.^{[10],[12],[13],[14],[17],[19]} For the first, second, third, fourth, fifth, sixth, and seventh days, a meta-analysis on postoperative pain was conducted. On the first (SMD = −0.83, 95% CI = −1.65 to-0.01, Z = 1.98, P = 0.05), third (SMD = −1.46, 95% CI = −2.37 to-0.56, Z = 3.17, P = 0.002), fourth (SMD = −1.02, 95% CI = −1.82 to-0.21, Z = 2.46, P = 0.01), and seventh (SMD = −2.26, 95% CI = −3.49 to-1.04, Z = 3.63, P = 0.0003) postoperative days, the PRF had a significantly (P < 0.05) lower VAS score. Whereas, on the second (SMD = −0.16, 95% CI = −0.52–0.19, Z = 0.91, P = 0.36), fifth (SMD = −1.83, 95% CI = −4.09–0.43, Z = 1.59, P = 0.11), and sixth days (SMD = −0.65, 95% CI = −1.36–0.06, Z = 1.81, P = 0.07), there was no difference between the PRF and the control group. For the first to seventh days of analysis, the Chi-squared test (χ²) and I-squared (I²) results revealed a high level of heterogeneity (P < 0.1, I² >50%) among these trials.^{[10],[12],[13],[14],[18],[19],[20],[21]}

Swelling

There were seven RCTs that studied postoperative swelling.^{[9],[10],[12],[13],[18],[19],[21]} Except for two trials,^[12],[13] PRF improved the outcomes in terms of postoperative swelling. Gülşen and Şentürk concluded that PRF was equally efficient as the control group in alleviating postoperative swelling (P > 0.05) following M3 extraction.^[13] Asutay et al.^[12] found no significant differences in postoperative edema between the PRF and control groups. In the PRF-treated group, postoperative swelling was significantly (P < 0.05) reduced on the first,^{[9],[10],[18],[21]} second,^[19] third,^{[10],[18],[21]} and seventh POD.^[19],[21] The quantitative analysis was not performed due to the significant methodological heterogeneity in the assessment of swelling.

Bone healing

Six studies^{[9],[11],[14],[16],[20],[21]} reported PRF's effect on bone healing. The PRF was found to be considerably better (P < 0.05) at enhancing bone formation following M3 extraction in four studies.^{[14],[16],[20],[21]} A meta-analysis of these trials was not conducted due to the considerable methodological diversity.

Soft tissue healing

Five RCTs^{[14],[15],[16],[18],[20]} reported PRF's effect on soft tissue healing. Ritto et al.^[14] reported that the application of PRF had no effect (P > 0.05) on soft tissue healing following M3 extraction, but the results were not given. The PRF was considerably better (P < 0.05) at improving soft tissue healing following M3 extraction in three studies.^{[16],[18],[20]} In a meta-analysis, three trials^{[15],[18],[20]} were included, and the results revealed no significant soft tissue healing when PRF was administered into the M3 extracted socket (SMD = 0.68, 95% CI = −1.06, 2.42; Z = 0.77, P = 0.44; heterogeneity: I² = 96%, P < 0.00001) [Figure 4].

Figure 4: Forest plot and meta-analysis of soft tissue healing (seventh day). CI: Confidence interval; IV: Inverse variance; PRF; Platelet-rich fibrin; SD: Standard deviation

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Trismus

Three studies showed trismus in their outcomes.^{[9],[12],[19]} Kumar et al.^[9] reported that on the 1^st POD, the interincisal distance was less in the PRF group than in the control group (P = 0.04). Asutay et al.^[12] found no statistically meaningful difference in trismus (P > 0.05) in their study. In trismus assessments, Afat et al.^[19] found no meaningful differences (P > 0.05) between groups. A meta-analysis of these trials was not performed due to the diversity in the measurement of trismus.

Discussion

Platelet-rich plasma (PRP) contains the growth factor and is generated chemically by applying a coagulant to blood. It has many drawbacks, including the need for two centrifugation rounds and the timely discharge of growth factors.^[26] There are certain unfavorable factors for PRP that resulted in the development of PRF, a new variety of platelet concentrate that overwhelms most of those negative aspects of PRP.^[5] Choukroun's PRF is a biomaterial composed of leukocytes and platelets with a unique structure and three-dimensional design.^[27] PRF is a fibrin mesh structure that stores a variety of growth factors and cytokines and gradually releases them during remodeling.^[6] By acting as a growth factor reservoir, PRF promotes vascularization and osteoblastic differentiation. PRF is an effective autologous tissue regeneration substance that has a wide array of therapeutic exercises in oral surgical procedure.

In this review, the study design of included RCTs was either a split-mouth^{[9],[11],[12],[13],[14],[16],[15],[16],[17],[18],[21]} or a parallel design.^{[10],[15],[19],[20]} Within the first 7 days, the PRF showed effectiveness in reducing the incidence of AO following M3 surgery.^{[15],[17],[18]} Two studies found a lower incidence of AO following the application of PRF into the M3 extracted socket.^[15],[18] Four RCTs^{[12],[15],[17],[18]} were included in this meta-analysis, and the result showed that PRF can be applied to reduce the occurrence of AO in the 1^st week following M3 extraction. The application of PRF in M3 extraction has been extensively researched, and previously published systematic reviews^{[4],[28],[29]} found that PRF had a favorable effect in reducing AO during the first 7 days. The PRF's unique 3D structure assures a continuous source of platelets, leukocytes, and cytokines, all of which can promote cell migration and speed wound healing.^[27] Furthermore, structured fibrin matrix of PRF aids clot creation and inhibits mechanical dislodgement.^[17]

The findings of this meta-analysis revealed that PRF has a favorable effect on postoperative pain, correlating with the findings of other published systematic reviews.^[4],[28] The meta-analysis showed a significant effect of PRF on postoperative pain on the 1^st, 3^rd, 4^th, and 7^th days, and no difference between groups on the 2^nd, 5^th, and 6^th days. Canellas et al.^[4] reported that the PRF has a favorable effect on pain in the 3^rd and 7^th days following M3 extraction. On days 1, 3, and 7 following extraction, Zhu et al.^[28] found that the VAS score in the PRF group was considerably lower than in the control group. The meta-analysis of the present review differs from the previous published report regarding soft tissue healing.^[28] We did not find statistical significance in terms of soft tissue healing after M3 extraction. In a meta-analysis, Zhu et al.^[28] showed that utilizing PRF resulted in significant soft tissue healing. However, more RCTs with homogeneous research methodology will be required in the future to conduct meta-analysis and draw a comprehensive conclusion.

Conclusion

In this review study, the meta-analysis shows that the employment of PRF limits the occurrence of AO as well as postextraction complications like pain and swelling following M3 surgery. However, the results also demonstrate that the PRF does not improve soft tissue healing following the extraction of M3. More RCTs are required to validate the data due to a scarcity of studies with low risk of bias and homogeneous research methodology that would allow for a more comprehensive meta-analysis and to permit the widespread use of this relatively affordable autologous biocompatible material.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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