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   Table of Contents    
Year : 2021  |  Volume : 25  |  Issue : 6  |  Page : 463-479  

Autologous Platelet Concentrate of 2nd and 3rd generations efficacy in the surgical treatment of gingival recession: an overview of systematic reviews

1 Faculty of Dental Medicine at Universidade Cato´lica Portuguesa; Center for Interdisciplinary Research in Health, Institute of Health Sciences, Universidade Católica Portuguesa, Viseu, Portugal; Department of Periodontics and Oral Medicine at the University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
2 Faculty of Dental Medicine at Universidade Cato´lica Portuguesa, Portugal
3 Department of Periodontics and Oral Medicine at the University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
4 Department of Stomatology, Santiago de Compostela University, Santiago De Compostela, Spain
5 Private Clinician, Portugal

Date of Submission17-Aug-2020
Date of Decision21-Mar-2021
Date of Acceptance21-Jul-2021
Date of Web Publication01-Nov-2021

Correspondence Address:
Gustavo Vicentis De Oliveira Fernandes
Quinta Da Alagoa Ave., 225 – 1 Dt., Viseu 3500-606

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jisp.jisp_515_20

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Background: Autologous platelet concentrate (APC)/platelet-rich fibrin (PRF) of second and third generations has increased use in periodontics to optimize wound healing. Few systematic reviews (SRs) have reported improved clinical outcomes, while other studies reported significantly better results for the connective tissue graft (CTG). There is still unclear clinical evidence about APC/PRF use to treat gingival recession (GR) defects. Then, the purpose of this SR was to evaluate the use of APC/PRF membranes (2nd and 3rd generations) in root coverage (RC) procedures and assess its efficacy as a substitute biomaterial. Materials and Methods: An electronic search was conducted in PubMed, Cochrane Central, Web of Science, Google Scholar, BookSC databases, and gray literature. The search strategy, without date restriction up to April 2020, included keywords as “platelet-rich fibrin,” “autologous platelet concentrates,” “blood,” “systematic review,” “periodontics,” “surgery,” “tissue,” “gingiva,” “gingival recession,” “connective tissue,” “graft,” and “root coverage.” The methodological quality was evaluated through the AMSTAR2, and a population, index test, comparator, outcome strategy was used to assess specific clinical parameters such as recession depth, clinical attachment levels, and RC outcomes. Results: Nine SRs were included. Only three articles described the technique of APC/PRF production. Three studies reported unfavorable outcomes using APC, while six reported favorable results and postoperative discomfort reduction. Articles included in this SRs that provided information about APC/PRF membranes (n = 13) showed no significant difference between APC/PRF and the control group for the parameters analyzed. Conclusions: This implies that APC/PRF may be considered a feasible substitute biomaterial for treating GR defects, although the CTG still provides superior outcomes. Further long-term and controlled studies are needed to verify this finding.

Keywords: Autologous platelet concentrate, gingival recession, periodontal surgery, root coverage, systematic review

How to cite this article:
Fernandes GV, Santos NB, Siqueira RA, Wang HL, Blanco-Carrion J, Fernandes JC. Autologous Platelet Concentrate of 2nd and 3rd generations efficacy in the surgical treatment of gingival recession: an overview of systematic reviews. J Indian Soc Periodontol 2021;25:463-79

How to cite this URL:
Fernandes GV, Santos NB, Siqueira RA, Wang HL, Blanco-Carrion J, Fernandes JC. Autologous Platelet Concentrate of 2nd and 3rd generations efficacy in the surgical treatment of gingival recession: an overview of systematic reviews. J Indian Soc Periodontol [serial online] 2021 [cited 2022 Aug 19];25:463-79. Available from:

   Introduction Top

Gingival recession (GR)[1],[2] is prevalent among all age groups.[3] It is defined as gingival migration to an apical point to the cementoenamel junction, exposing the root surface and involving loss of periodontal attachment apparatus. Many etiological factors are involved in the development of GR defects,[2],[4] such as the presence of muscle insertion close to the gingival margin,[2],[5] reduced thickness of the alveolar bone,[6] inadequate tooth alignment,[7] reduced width of attached keratinised tissue width (KTW),[8],[9] traumatic factors such as piercings[4] or incorrect toothbrushing procedures,[10] restorations invading supracrestal tissues attachment,[11] plaque-induced periodontal disease,[12] and viruses.[13] Moreover, GR defects are often associated with hypersensitivity,[9] root caries, and cervical abrasion.[14],[15]

GR defects are likely to progress with time if left untreated.[16],[17] This treatment is part of periodontal plastic surgery.[18] Many root coverage (RC) techniques have been developed to obtain predictable RC.[1],[16],[19],[20] The most common methods involve the adjuvant use of either a connective tissue graft (CTG) or de-epithelized free CTG,[21] which are considered to be the gold standard for RC treatment.[15]

Periodontal plastic surgery using CTG may increase the operative time, donor site morbidity, and pain. As a result, researchers have developed other biomaterials/biologic agents as substitutes, including but not limited to allogeneic grafts,[19] xenogeneic or synthetic collagen membranes,[22] enamel matrix derivative (EMD), or autologous platelet concentrate (APC)/platelet-rich fibrin (PRF) of second and third generation (membranes).

Among alternative biomaterials, APC/PRF has gained attention, mainly the second generation of membranes. It is a strong natural fibrin matrix enriched with platelets, cytokines, and growth factors, without risk of cross-infection.[23] APC/PRF is also easy to harvest and manipulate and presents a reduced production cost with good mechanical properties.[24] In addition, alkaline phosphatase activity is significantly upregulated by PRF.[24] This three-dimensional scaffold allows a continuous release of growth factors and cytokines over 10 days,[25] enhancing the early stages of tissue repair.

Using APC, previous SRs have reported improvement in clinical attachment levels (CAL) and mean and complete RC (CRC) outcomes. However, a limited number of studies described the use of APC as a biomaterial of choice.[21],[26]

In summary, the current clinical evidence is still unclear for practitioners. There is great confusion in the literature regarding outcomes and indications on the use of APC to treat GR defects.[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39] Considering the controversial options, a SR is essential before making any precise clinical recommendations on the treatment of GR using APC. This review contributes to the current debate on the adoption of this biomaterial as a substitute for CTG.

Thus, the purpose of the present SR and meta-analysis was to evaluate published SRs on the use of APC/PRF, specifically concerning the membranes of 2nd and 3rd generation, in periodontal surgeries for RC.

   Materials and Methods Top

Protocol development

A detailed protocol was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement[40] to systematically review the literature regarding periodontal surgeries for the treatment of GR defects. The present manuscript investigated only the evidence of systematic reviews (SRs). The protocol was registered on PROSPERO (Centre for Reviews and Dissemination [CRD], University of York) (CRD42020168582). The clinical question established for the search strategy was organized using the population, index test, comparator, outcome (PICO) framework.[41]

Focused question

The PICO-focused question for the present review was as follows: “Can GR defects (single or multiple) (P) be surgically treated applying APC/PRF (membranes of 2nd and 3rd generations) as the sole filling material (I), as a substitute for the gold standard CTG (C), and exhibit significantly improved clinical outcomes (O)?”

Search strategy

An electronic search, with no date restriction and only in the English language, was conducted in the PubMed/MEDLINE, Cochrane Central, Web of Science, Google Scholar, and BookSC databases up to April 30, 2020. Furthermore, a hand search was performed, and the gray literature report and OpenGrey databases were examined to identify unpublished studies (gray literature). Searches in the reference lists of the included studies (cross-referencing) were also conducted.

Medical subject heading (MeSH) terms, keywords, and other free terms related to “platelet-rich fibrin,” “autologous platelet concentrates,” “blood,” “systematic review,” “periodontics,” “surgery,” “tissue,” “gingiva,” “gingival recession,” “connective tissue,” “graft,” and “root coverage” were used with Boolean operators (OR, AND) to combine searches. The search strategy included appropriate changes in the keywords and followed the syntactic rules of each database.

Inclusion and exclusion criteria

This SR selected studies by the following inclusion criteria: The paper must identify itself as a SR for the treatment of GR including human studies; it must be in English language; it must have included detailed information about the treatments performed and the results obtained; it must have applied platelet concentrates (membrane) as a test treatment modality, involving second and third generation of PRF. In addition, only the publication with the longest follow-up data was included, in case of an updated publication of the same group.

SRs that did not meet the entire inclusion criteria and did not achieve scoring between 8 and 16 points on the AMSTAR 2 checklist[42] were excluded, just as in vitro studies, animal studies, case reports, clinical studies, consensus, and review articles that were not systematically performed. Studies that included patients with a significant health problem (American Society of Anesthesiologists Physical Status 3 and above) or used only CTG or another APC of a nonmembrane type were also rejected.

Data extraction and method of analysis

The search and screening process was performed by two independent review authors (GVOF and JCHF), who extracted the data independently from the selected articles for further analysis, using data extraction tables, which included the following parameters: author(s) and year of publication, the focused question, the journal of publication and impact factor, the observation period, and the number of studies included; the number and characteristics of patients treated and whether for localized or multiple recession; type of interventions (flap, technique, biomaterials), outcome measures achieved for CAL, CRC, mean RC (MRC), and recession depth (RD); and whether the study contained meta-analysis, a conclusion, and occurrence of adverse effects or postoperative complications.

Selection of studies

Duplicates were excluded, and the remaining articles were screened by title and abstracts for eligibility. Further examination regarding inclusion and exclusion was subsequently made by full-text analysis. The full text of any title or abstract that did not provide enough information regarding the inclusion criteria was also obtained. The same authors (GVOF and JCHF) performed the selection and analysis, and any disagreement was discussed with a third author (NBMS). Cohen's kappa test was adopted to evaluate the reviewers' consensus.

Risk of bias and method of analysis

The same two review authors independently assessed the risk of bias and study quality of the included SRs. The methodological quality of each SR was evaluated using the AMSTAR 2 tool. The guidelines featured 16 items answered with one of four options: 1, yes; 2, no; 3, cannot answer; and 4, not applicable. Only items with option 1 generated the score. Therefore, each article could obtain a score of between 0 (no criteria fulfilled) and 16 (all criteria fulfilled).

The data collected using the AMSTAR 2 tool were rated as low quality if it scored 0–5 out of a total of 16 points, of moderate quality if it scored 6–10, or high quality if it scored between 11 and 16. The AMSTAR ratings were verified by a third reviewer (NBMS) and any discrepancy was resolved by discussion with another reviewer (RACS). Only studies scoring 8 or more were included in the present review.

The studies of interest included within the SRs were scrutinized according to the theme proposed after in-depth analysis and meta-analysis. Then, other characteristics were addressed, such as the randomization process, groups similar at baseline, blinded group allocation, random housing, blinded interventions, random and blinded outcome assessment, reporting of dropouts, and other biases (funding) domains. The mean and standard deviation values were found for final RD, final CAL, and RC and assessed. All analysis was performed using 5% of the significance level.

The heterogeneity across the studies was quantified using the Q (Chi-squared) statistic, and df was its degrees of freedom.[43] They described the percentage of the variability in effect estimates that was due to heterogeneity rather than to sampling error (chance). Tau was a measure of residual between dispersions expressed in the same units as the effect estimate, Tau2 was an estimate of the residual between variances expressed in squared units of the effect estimate, H2 estimated the ratio of the unaccounted variability relative to the sampling variability, and the Higgins index (I2) inconsistency test was also performed.

When the homogeneity between the studies was acceptable (P ≥ 0.10, I2 ≤ 50%), the fixed-effect model was used for meta-analysis. The random-effects models were applied when significant heterogeneity existed (P < 0.10, I2 > 50%). However, the percentage for I2 classified between 0% and 40% might not be significant, 30%–60% might represent moderate heterogeneity, 50%–80% might represent substantial heterogeneity, and 70%–100% might present considerable heterogeneity. I2 estimates how much of the unaccounted variability (residual heterogeneity + sampling error) is attributable to residual heterogeneity.

   Results Top

Description of enrolled studies

The initial electronic search provided 773 papers, and after the removal of duplicates (n = 12), 761 remained. After reviewing the titles and abstracts, 40 articles associated APC with GR, excluding 721 papers. Through a detailed analysis from the title and abstract, 16 more were removed, leaving 24 for full-text review.

From the 24 articles assessed for eligibility, 15 were excluded after full-text review [Table S1]. The reasons for exclusion were: The article included treatment of GR but did not include APC studies (n = 9), the article did not achieve a score of at least 8 with the AMSTAR 2 tool (n = 3) [Table 1], one was an overview of SRs (n = 1), one was not a SR, and the last was a previous version of an updated article.

Table 1: AMSTAR-2 rating after full-text articles analysis

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Finally, 9 SRs[26],[44],[45],[46],[47],[48],[49],[50],[51] were included for qualitative synthesis and quantitative analysis, providing data to perform the meta-analysis [Figure 1]. Only articles on APC in the membrane-shaped approach (n = 13) within the 9 SRs were included for statistical analysis. A detailed analysis was conducted for each SR and the original articles included in them. The k values of agreement between the two authors/reviewers for potential article inclusion were 0.90 and 0.85 for the selected articles, which showed excellent agreement.
Figure 1: PRISMA flow diagram of the screening and selection process; n - number

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Systematic reviews included

Two SRs[45],[49] presented a moderate-quality study and 5[44],[45],[46],[47],[48] high-quality qualifications with the AMSTAR 2 tool. In addition, 5 SRs[26],[47],[48],[49],[51] chose the PRISMA statement as the standard guideline for its development. Castro et al.[48] also used the guidelines of the Belgian Centre for Evidence-Based Medicine. Three studies[44],[45],[46],[50] did not report any standard applied. Beyond this, only one study[47] was registered in the International Prospective Register of SRs (PROSPERO) platform, and another study[50] did not describe the database used.

Three out of 9 articles described the APC technique of production.[45],[47],[48] However, the common protocols were 2700 revolutions per minute (RPM)/12 min or 3000 RPM/10 min, or still 400 g/10 min.[45]

Chambrone and Tatakis[26] and Chambrone et al.[50] did not offer conclusions about PRF, even after inserting data in the table. Furthermore, the authors reported that all RC procedures led to RD reduction and CAL gain.[50] However, SCTG + coronally advanced flap (CAF) was still the gold standard,[49],[50] with an incidence of adverse effects (discomfort with or without pain) related to donor sites of SCTG within the first postoperative week.[50]

Three authors[44],[47],[49] were not in favor of APC, and their results were contradictory:[49] a nonsignificant benefit to treating GR,[44] no improvement of RC or CAL,[47] and a lack of a standardized protocol for the preparation of PRF membranes.[47],[48],[49] Three other articles[45],[48],[51] reported favorable effects on soft-tissue healing and postoperative discomfort reduction with good biological effects, low cost, and ease of preparation.[48] Li et al.[51] considered that PRF “should be preferred” for the treatment of Miller's Class I and II GR, and Valenzuela and Oliva[45] concluded that the regeneration efficacy of PRF in periodontal surgery is effective. Another SR[46] suggested that the addition of APC might exert a positive adjunctive effect in the treatment of GR [Table 2].
Table 2: Details Characteristics of each SR included in this Study

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Randomized controlled trials from included systematic reviews

Only 13 randomized controlled trials (RCTs)[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39] were analyzed and included in the meta-analysis. The average follow-up period was 6 months, but 3[28],[36],[39] studies had a longer follow-up of 12-month. In general, the studies were split-mouth, not blinded,[27],[28],[30],[32],[33],[34],[37],[38],[39] or single-blinded.[29],[31],[35],[36] Thamaraiselvan et al.[35] and Gupta et al.[33] selected a parallel design. Kuka et al.[39] only selected Miller's Class I (currently RT1)[52] patients. All other studies included Miller's Class I and II (currently RT1).[52]

The quality assessment indicated 7 articles[28],[33],[34],[35],[36],[38],[39] that were classified as moderate risk (two criteria were not met or were unclear) and 6[27],[29],[30],[31],[32],[37] as high risk (three or four criteria were not met or were unclear) [Figure 2] and [Figure 3]. The weight of each study was calculated proportionally to the number of citations. Therefore, the most relevant articles were Aroca et al.,[27] Jankovic et al.,[28] Jankovic et al.,[29] and Padma et al.[30] In addition, 5 authors[28],[29],[30],[35],[38] did not describe the type of centrifuge (hardware) used.
Figure 2: Risk of bias of the randomized controlled trials

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Figure 3: Risk of bias color score. Green, low risk of bias; yellow, unclear bias; red, high risk of bias

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Only the technique of CAF[29],[30],[31],[32],[34],[35],[36],[38],[39] and its modification (MCAF)[27],[28],[33],[37] was surgically applied. Five articles chose[29],[31],[34],[36],[37] CTG as the control group, and 7 only raised the flap and repositioned it coronally.[27],[30],[32],[33],[35],[38],[39] One study used EMD as the control group[28]. The test group in all RCTs was the APC group.[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39] One study[32] used concentrated growth factor (CGF), which is considered third-generation APC.

According to the conclusions described in each study, 4[27],[28],[32],[34] considered that PRF offered no additional benefit in terms of MRC or short-term wound healing for the treatment of multiple GRs;[27] the findings were not sufficient to advocate the clinical effect of PRF,[34] and no relevant advantages or benefits compared to the controls were reported.[28],[32],[34] On the other hand, some authors[28],[29],[31],[36],[37] reported avoiding using a donor site and decreased discomfort postoperatively in the APC group. Moreover, APC helped in early healing[33],[35] in the first[28] and 2nd weeks,[29] due to the presence of growth factors,[34] which might have enhanced the results. APC provided additional benefits along with MRC in the treatment of RT1 GR when compared with CAF alone;[30] CAF + PRF was considered a superior choice for treatment over the control,[33] beyond interesting results in better soft-tissue healing[39] and a significant increase in the gingival thickness (GT), which might improve the predictability and long-term stability of the soft tissue in RC.[33],[38] Moreover, authors[34],[35] reported that PRF might have positive, albeit weak, but significant clinical results for RC.

Bias was more likely to exist in non-RCTs.[53] Only one study[27] included patients who smoked, despite the controversy in the literature about its negative influence of smoking on periodontal healing[54] or a high success rate after accomplished RC surgery (CAF)[55] [Table 3].
Table 3: Articles extracted from the SRs included in this study, which were included in the meta-analysis

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Publication bias and statistical analysis

The parameters RD, CAL, CRC, MRC, and RC (mm) were obtained to fill [Table 4]. Only the parameters RD, CAL, and RC were used in the meta-analysis, which combined only similar comparisons that reported the same outcome measures. Due to the extreme difference observed in the results of Öncü[37] for RC, due to be considered not well-conducted with very wide confidence interval and weak strength, it was excluded from the meta-analysis.
Table 4: Parameters obtained from randomized controlled trials included in Meta-analysis. recession depth, clinical attachment level, complete root coverage (%), mean root coverage (%), and root coverage (mm)

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The outcome variables from each study were combined for continuous data, using a random-effects model because of the high heterogeneity found (I2RD = 80.14%; I2CAL = 73.53%; I2RC = 67.7%), confirmed by Tau that represents the amount of true heterogeneity. The results were graphically presented by forest plots [Figure 4]. Funnel plots [Figure S1] and normal Q-Q plots [Figure S2] assessed the publication bias. The patient was considered the unit of analysis.
Figure 4: Forest plot. (a) Recession depth; (b) Clinical attachment level; (c) Root coverage; MD - Mean deviation; CI - Confidence interval; RE - Random-effects

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The forest plots [Figure 4]a, [Figure 4]b, [Figure 4]c evaluated RD, CAL, and RC, and there was no significant statistical significance among the groups (P = 0.179, 0.922, and 0.652, respectively). In RD, the result was slightly favorable to PRF treatment (0.27 [−0.13–0.68]), increasing the heterogeneity caused mainly by Padma et al.[30] CAL remained practically neutral. The RC favored the control group (−0.55 [−0.88–0.22]).

The funnel plots showed asymmetry, represented by points outside the triangular area of the 95% CI region, which indicated a possibility of publication bias. Three studies of CAL and RC, and 5 of RD, increased the RC heterogeneity (I2) significantly, contributing to the asymmetry [Figure S1]. The Q-Q plot presented a similar result only for RC, with 4 studies outside the line [Figure S2] and [Table 4].

   Discussion Top

Autologous platelet concentrate/platelet-rich fibrin generations, protocol, and number of membranes surgically applied

There are three generations of APCs/PRFs. The first generation is mainly represented by the platelet-rich plasma.[48] The second generation is represented by PRF, which is a superior scaffold[56] and induces a significant release of cytokines[57],[56] from a three-dimensional fibrin matrix, creating an enhanced process of healing when gradually released after the fibrin matrices resorb.[58],[59] Since then, PRF has been extensively applied.[25],[48],[60],[57] For the third-generation, a modification was proposed, which is the CGF,[61] alternating the centrifugation speed from 2400 rpm (547 g) to 3000 rpm (855 g) with different times. This last generation is characterized by containing abundant CGF in its rigid fibrin,[61] yielding results in speeding tissue proliferation and differentiation up.[62]

The present study did not accept investigations[26],[44],[46],[50],[51] that included the first generation of APC because of the lack of membrane structure, which is viscous and difficult to keep entirely on the surgical site, creating bias concerning the efficiency and outcomes. Therefore, the second[27],[28],[29],[30],[31],[33],[34],[35],[36],[37],[38],[39] and third[32] generations were included, with no significant differences between them, contradicting the literature.[50] The studies relied on the superiority of continuously releasing many growth factors and molecules, accelerating cell proliferation and migration, stimulating the synthesis of Type I collagen, and neoangiogenesis.[63] In addition, second- and third-generation APC is easier to handle, insert, and keep in position, during periodontal surgeries. Moreover, it has increased anti-inflammatory and antibacterial effects, and the membrane remained solid after 1 week, compared to the first generation, which after 3 days completely dissolved, releasing the growth factors only in the 1st h.[64]

A limitation of this review was that none of included articles conducted an APC/PRF qualification or quantification of the levels of the cells, growth factors, cytokines, or other molecular components.[65] This step is important because it plays a significant role in the self-regulation of inflammatory and infectious phenomena.[55] Moreover, there is a lack of standardized protocol for preparing[47],[48],[49] and handling of APC/PRF (e.g., how many membranes should be placed per surgical site), limiting the data interpretation.[48] Only 3 out of 9 SRs described the protocol applied, 2700 RPM/12 min, 3000 RPM/10 min,[47],[48] or still 400 g/10 min.[45] Of the initially enrolled studies, five[28],[29],[30],[35],[38] did not report the hardware used, limiting the equipment details and likely resulting in different structured APC membranes. In addition, Castro et al.[48] discussed the handle and number of APC membranes, with one membrane elected as the treatment standard for all RCTs in that study. Only Aroca et al.[27] prepared 4 membranes, and it is unclear whether they applied all in situ. No study standard gave a minimum thickness and/or the number of membranes to treat GR. Subsequently, it might be suggested that 4 unfolded or at least 2 folded membranes to be used to achieve a significant substantivity in the long-term.

A possible substitute for connective tissue graft

The primary reason to substitute CTG is based on the incidence of adverse effects such as discomfort with or without pain related to donor sites within the first postoperative week.[44] Although 4 out of 7 SRs[45],[46],[48],[51] described favorable adjunctive effects from APC on soft-tissue healing, postoperative discomfort reduction, and positive results in RD and CAL, another 3[44],[47],[49] reported contradictory results with nonsignificant benefit,[66] still recommending CTG as the gold-standard procedure for RC and CAL to treat RT1 GR defects.

The literature remains controversial on the clinical outcomes of APC/PRF in GR defects. Superior results for CTG with improved long-term tissue stability[67] compared to APC/PRF were previously reported. On the other hand, Li et al.[51] considered that PRF “should be preferred,” and Valenzuela and Oliva[45] concluded that the regeneration efficacy of PRF is effective. Only one SR[46] suggested that the addition of APC/PRF might exert a positive adjunctive effect. Nevertheless, the current study verified a divided opinion on APC/PRF application on GR coverage, but with more SRs in favor of using APC during RC procedures.

Some interesting findings can give greater support to the use of PRF, which has the potential to shorten the treatment period;[29] in addition, it induces a decrease of matrix metalloproteinase-8 (MMP-8) and interleukin-1 beta, and an increase in a tissue inhibitor of MMP-1 levels within 10 days, promoting periodontal wound healing in the earlier phase of the process.[68]

Surgical technique used in the included studies

The only surgical technique used for all studies was the CAF and MCAF, considered the gold-standard procedure. Both techniques require periosteal incisions, eliminating the muscle tension.[1],[69] The MCAF precludes the need for vertical incisions and sutures, thus achieving better and stable RC.

A difference in preference was observed among the studies between CAF and MCAF. Moraschini et al.[47] considered CAF instead of MCAF that was used by Aroca et al.,[27] while another study[50] stated CAF and MCAF as the “same procedure.” However, current knowledge shows that CAF yields an inferior result compared to MCAF,[70] and outcomes showed a significant correlation between long-term stability and regular maintenance. The MCAF results after one year for CRC and MRC were, respectively, 88% and 97%,[71] and after 5 years, 85% and 94.6%.[70] CAF and MCAF, when compared, achieved a respective CRC of 77.7% versus 89.3%,[72] with MCAF presenting a higher success rate. MCAF had a favorable result beyond a better postoperative course, with less scar tissue formation.

Periodontal parameters assessed

The mean percentage of RC among the studies may range between 9% and 100%[73] and is influenced by different prognostic factors, categorization, and professional experience.[50] This SR observed that MRC ranged between 65% and 100%, indicating agreement with the literature.

The maintenance of long-term success for GR treatment remains unclear since most of the studies had a limited period of follow-up, 6–12-month.[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39] In addition, factors such as KTW and GT that influenced the outcomes of RC were not included in the analyses.[74] However, GT and KTW were not the aims of this study, and as previously stressed in a SR by Tavelli and coworkers,[75] scarce information regarding the effect of GT on RC on published studies impedes a deeper look into this aspect. If applied APC/PRF as a substitute, promising results have been found,[31] which may be explained by the biology of APC/PRF (contains several growth factors influencing tissue proliferation).[31],[37] Nonetheless, this statement needs to be confirmed with further studies.

The main outcomes set were RD, CAL, and RC, appropriate for assessing GR treatment. Of all RCTs, only one[30] achieved 100% success in the test group to reduce RD, providing superior RC (almost 1 mm more), and CAL gained more than 1 mm. Furthermore, less morbidity, enhanced healing,[29] and fewer clinical difficulties occurred with donor-site surgery.[31],[36],[37] Twelve studies[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39] provided no additional advantage of APC for RC.

The results between APC/PRF and controls had similar success rates, as previously reported.[76] RD reduction results were more promising in the APC/PRF group[28],[32],[33],[34],[35],[38],[39] as in the literature.[58] Twelve RCTs assessed CAL and showed no significant benefit of APC/PRF in CAL gain. RCTs were evaluated for RC percentage, and the results showed that APC/PRF with CAF exerted a slightly less satisfactory outcome than the control (CAF/MCAF alone or associated with CTG). To add to the controversy, another SR reported favorable outcomes highlighted in the APC group.[58] There was no statistical significance in any parameters. Nonetheless, neither RCTs followed up longer than 12 months nor reported adherence to the CONSORT statement.[77] Longer follow-up studies are warranted to confirm conclusions, and adherence to the PROSPERO, PRISMA, and CONSORT statements[78] is essential to increase the quality and transparency of studies.[54]

There is an enthusiasm for the use of APC/PRF to cover the exposed root. However, it is primarily necessary to define a standard reproducible technique to obtain an optimal effect of the APC/PRF. Nevertheless, a divided opinion was kept for the treatment of RT1 (Miller's Class I and II). On the one hand, vast confusion was caused by the RCTs regarding the lack of recommendations for APCs/PRFs. In contrast, considering the superiority of the SRs studies, a majority recommended the use of APC/PRF as a feasible substitute biomaterial for GR treatment. Therefore, the main result found in this SR to treat GR with RC procedures showed better overall response for the control groups.

Within the limitations of this SR, the utilization of the APC/PRF membranes, although a valid alternative to the traditional CTG, showed inferior results in terms of RC. Prospective investigations, including analysis of GT and KTW, are required since they have been demonstrated as significant prognostic factors for long-term outcomes.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Wennström JL. Mucogingival therapy. Ann Periodontol 1996;1:671-701.  Back to cited text no. 1
Camargo PM, Melnick PR, Kenney EB. The use of free gingival grafts for aesthetic purposes. Periodontol 2000 2001;27:72-96.  Back to cited text no. 2
O'leary TJ, Drake RB, Jividen G, Allen MF. The incidence of gingival recession in young males: Relationship to gingival and plaque score. Periodontics 1968;6:109-11.  Back to cited text no. 3
Chambrone L, Chambrone LA. Gingival recessions caused by lip piercing: Case report. J Can Dent Assoc 2003;69:505-8.  Back to cited text no. 4
Priyanka M, Sruthi R, Ramakrishnan T, Emmadi P, Ambalavanan N. An overview of frenal attachments. J Indian Soc Periodontol 2013;17:12-5.  Back to cited text no. 5
[PUBMED]  [Full text]  
Wennström JL, Lindhe J, Sinclair F, Thilander B. Some periodontal tissue reactions to orthodontic tooth movement in monkeys. J Clin Periodontol 1987;14:121-9.  Back to cited text no. 6
Stoner JE, Mazdyasna S. Gingival recession in the lower incisor region of 15-year-old subjects. J Periodontol 1980;51:74-6.  Back to cited text no. 7
De Rouck T, Eghbali R, Collys K, De Bruyn H, Cosyn J. The gingival biotype revisited: Transparency of the periodontal probe through the gingival margin as a method to discriminate thin from thick gingiva. J Clin Periodontol 2009;36:428-33.  Back to cited text no. 8
Chambrone L, Tatakis DN. Long-term outcomes of untreated buccal gingival recessions: A systematic review and meta-analysis. J Periodontol 2016;87:796-808.  Back to cited text no. 9
Khocht A, Simon G, Person P, Denepitiya JL. Gingival recession in relation to history of hard toothbrush use. J Periodontol 1993;64:900-5.  Back to cited text no. 10
Parma-Benfenati S, Frigazzato PA, Ruben MP. The effect of restorative margins on the postsurgical development and nature of the periodontium. Part I. Int J Periodontics Restorative Dent 1985;5:30-51.  Back to cited text no. 11
Löe H, Anerud A, Boysen H. The natural history of periodontal disease in man: Prevalence, severity, and extent of gingival recession. J Periodontol 1992;63:489-95.  Back to cited text no. 12
Prato GP, Rotundo R, Magnani C, Ficarra G. Viral etiology of gingival recession. A case report. J Periodontol 2002;73:110-4.  Back to cited text no. 13
Chambrone L, Pannuti CM, Tu YK, Chambrone LA. Evidence-based periodontal plastic surgery. II. An individual data meta-analysis for evaluating factors in achieving complete root coverage. J Periodontol 2012;83:477-90.  Back to cited text no. 14
Buti J, Baccini M, Nieri M, La Marca M, Pini-Prato GP. Bayesian network meta-analysis of root coverage procedures: Ranking efficacy and identification of best treatment. J Clin Periodontol 2013;40:372-86.  Back to cited text no. 15
Löst C. Depth of alveolar bone dehiscences in relation to gingival recessions. J Clin Periodontol 1984;11:583-9.  Back to cited text no. 16
Agudio G, Cortellini P, Buti J, Pini Prato G. Periodontal conditions of sites treated with gingival augmentation surgery compared with untreated contralateral homologous sites: An 18- to 35-year long-term study. J Periodontol 2016;87:1371-8.  Back to cited text no. 17
Miller PD Jr. Regenerative and reconstructive periodontal plastic surgery. Mucogingival surgery. Dent Clin North Am 1988;32:287-306.  Back to cited text no. 18
Gapski R, Parks CA, Wang HL. Acellular dermal matrix for mucogingival surgery: A meta-analysis. J Periodontol 2005;76:1814-22.  Back to cited text no. 19
Mahajan A, Bharadwaj A, Mahajan P. Comparison of periosteal pedicle graft and subepithelial connective tissue graft for the treatment of gingival recession defects. Aust Dent J 2012;57:51-7.  Back to cited text no. 20
Pini-Prato G, Nieri M, Pagliaro U, Giorgi TS, La Marca M, Franceschi D, et al. Surgical treatment of single gingival recessions: Clinical guidelines. Eur J Oral Implantol 2014;7:9-43.  Back to cited text no. 21
Dai A, Huang JP, Ding PH, Chen LL. Long-term stability of root coverage procedures for single gingival recessions: A systematic review and meta-analysis. J Clin Periodontol 2019;46:572-85.  Back to cited text no. 22
Saluja H, Dehane V, Mahindra U. Platelet-rich fibrin: A second generation platelet concentrate and a new friend of oral and maxillofacial surgeons. Ann Maxillofac Surg 2011;1:53-7.  Back to cited text no. 23
Chang YC, Zhao JH. Effects of platelet-rich fibrin on human periodontal ligament fibroblasts and application for periodontal infrabony defects. Aust Dent J 2011;56:365-71.  Back to cited text no. 24
Miron RJ, Zucchelli G, Pikos MA, Salama M, Lee S, Guillemette V, et al. Use of platelet-rich fibrin in regenerative dentistry: A systematic review. Clin Oral Investig 2017;21:1913-27.  Back to cited text no. 25
Chambrone L, Tatakis DN. Periodontal soft tissue root coverage procedures: A systematic review from the AAP Regeneration Workshop. J Periodontol 2015;86:S8-51.  Back to cited text no. 26
Aroca S, Keglevich T, Barbieri B, Gera I, Etienne D. Clinical evaluation of a modified coronally advanced flap alone or in combination with a platelet-rich fibrin membrane for the treatment of adjacent multiple gingival recessions: A 6-month study. J Periodontol 2009;80:244-52.  Back to cited text no. 27
Jankovic S, Aleksic Z, Milinkovic I, Dimitrijevic B. The coronally advanced flap in combination with platelet-rich fibrin (PRF) and enamel matrix derivative in the treatment of gingival recession: A comparative study. Eur J Esthet Dent 2010;5:260-73.  Back to cited text no. 28
Jankovic S, Aleksic Z, Klokkevold P, Lekovic V, Dimitrijevic B, Kenney EB, et al. Use of platelet-rich fibrin membrane following treatment of gingival recession: A randomized clinical trial. Int J Periodontics Restorative Dent 2012;32:e41-50.  Back to cited text no. 29
Padma R, Shilpa A, Kumar PA, Nagasri M, Kumar C, Sreedhar A. A split mouth randomized controlled study to evaluate the adjunctive effect of platelet-rich fibrin to coronally advanced flap in Miller's class-I and II recession defects. J Ind Soc Periodontol 2013;17:631-6.  Back to cited text no. 30
Eren G, Atilla G. Platelet-rich fibrin in the treatment of localized gingival recessions: A split-mouth randomized clinical trial. Clin Oral Investig 2014;18:1941-8.  Back to cited text no. 31
Bozkurt Doğan Ş, Öngöz Dede F, Ballı U, Atalay EN, Durmuğlar MC. Concentrated growth factor in the treatment of adjacent multiple gingival recessions: A split-mouth randomized clinical trial. J Clin Periodontol 2015;42:868-75.  Back to cited text no. 32
Gupta S, Banthia R, Singh P, Banthia P, Raje S, Aggarwal N. Clinical evaluation and comparison of the efficacy of coronally advanced flap alone and in combination with platelet rich fibrin membrane in the treatment of Miller Class I and II gingival recessions. Contemp Clin Dent 2015;6:153-60.  Back to cited text no. 33
[PUBMED]  [Full text]  
Keceli HG, Kamak G, Erdemir EO, Evginer MS, Dolgun A. The adjunctive effect of platelet-rich fibrin to connective tissue graft in the treatment of buccal recession defects: Results of a randomized, parallel-group controlled trial. J Periodontol 2015;86:1221-30.  Back to cited text no. 34
Thamaraiselvan M, Elavarasu S, Thangakumaran S, Gadagi JS, Arthie T. Comparative clinical evaluation of coronally advanced flap with or without platelet rich fibrin membrane in the treatment of isolated gingival recession. J Indian Soc Periodontol 2015;19:66-71.  Back to cited text no. 35
[PUBMED]  [Full text]  
Tunalι M, Özdemir H, Arabacι T, Gürbüzer B, Pikdöken L, Firatli E. Clinical evaluation of autologous platelet-rich fibrin in the treatment of multiple adjacent gingival recession defects: A 12-month study. Int J Periodontics Restorative Dent 2015;35:105-14.  Back to cited text no. 36
Öncü E. The use of platelet-rich fibrin versus subepithelial connective tissue graft in treatment of multiple gingival recessions: A randomized clinical trial. Int J Periodontics Restorative Dent 2017;37:265-71.  Back to cited text no. 37
Dixit N, Lamba AK, Faraz F, Tandon S, Aggarwal K, Ahad A. Root coverage by modified coronally advanced flap with and without platelet-rich fibrin: A clinical study. Indian J Dent Res 2018;29:600-4.  Back to cited text no. 38
Kuka S, Ipci SD, Cakar G, Yılmaz S. Clinical evaluation of coronally advanced flap with or without platelet-rich fibrin for the treatment of multiple gingival recessions. Clin Oral Investig 2018;22:1551-8.  Back to cited text no. 39
Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009;6:e1000097.  Back to cited text no. 40
Methley AM, Campbell S, Chew-Graham C, McNally R, Cheraghi-Sohi S. PICO, PICOS and SPIDER: A comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv Res 2014;14:579.  Back to cited text no. 41
Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: A critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ 2017;358:j4008.  Back to cited text no. 42
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.  Back to cited text no. 43
Del Fabbro M, Bortolin M, Taschieri S, Weinstein R. Is platelet concentrate advantageous for the surgical treatment of periodontal diseases? A systematic review and meta-analysis. J Periodontol 2011;82:1100-11.  Back to cited text no. 44
Valenzuela HM, Oliva MP. Regeneration efficacy of platelet-rich fibrin in patients undergoing periodontal surgery: A systematic review and meta-analysis. Int J Odontostomatol 2014;8:21-8.  Back to cited text no. 45
Luo HY, Li RM, Wang CL, Peng L, Ye L. The adjunctive use of platelet concentrates in the therapy of gingival recessions: A systematic review and meta-analysis. J Oral Rehabil 2015;42:552-61.  Back to cited text no. 46
Moraschini V, Barboza Edos S. Use of platelet-rich fibrin membrane in the treatment of gingival recession: A systematic review and meta-analysis. J Periodontol 2016;87:281-90.  Back to cited text no. 47
Castro AB, Meschi N, Temmerman A, Pinto N, Lambrechts P, Teughels W, et al. Regenerative potential of leucocyte- and platelet-rich fibrin. Part A: Intra-bony defects, furcation defects and periodontal plastic surgery. A systematic review and meta-analysis. J Clin Periodontol 2017;44:67-82.  Back to cited text no. 48
Amine K, El Amrani Y, Chemlali S, Kissa J. Alternatives to connective tissue graft in the treatment of localized gingival recessions: A systematic review. J Stomatol Oral Maxillofac Surg 2018;119:25-32.  Back to cited text no. 49
Chambrone L, Ortega MA, Sukekava F, Rotundo R, Kalemaj Z, Buti J, et al. Root coverage procedures for treating single and multiple recession-type defects: An updated Cochrane systematic review. J Periodontol 2019;90:1399-422.  Back to cited text no. 50
Li R, Liu Y, Xu T, Zhao H, Hou J, Wu Y, et al. The additional effect of autologous platelet concentrates to coronally advanced flap in the treatment of gingival recessions: A systematic review and meta-analysis. Biomed Res Int 2019;2019:2587245.  Back to cited text no. 51
Kobayashi E, Flückiger L, Fujioka-Kobayashi M, Sawada K, Sculean A, Schaller B, et al. Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig 2016;20:2353-60.  Back to cited text no. 52
Rodella LF, Favero G, Boninsegna R, Buffoli B, Labanca M, Scarì G, et al. Growth factors, CD34 positive cells, and fibrin network analysis in concentrated growth factors fraction. Microsc Res Tech 2011;74:772-7.  Back to cited text no. 53
Anitua E, Sánchez M, Nurden AT, Nurden P, Orive G, Andía I. New insights into and novel applications for platelet-rich fibrin therapies. Trends Biotechnol 2006;24:227-34.  Back to cited text no. 54
Dohan Ehrenfest DM, de Peppo GM, Doglioli P, Sammartino G. Slow release of growth factors and thrombospondin-1 in Choukroun's platelet-rich fibrin (PRF): A gold standard to achieve for all surgical platelet concentrates technologies. Growth Factors 2009;27:63-9.  Back to cited text no. 55
Takeda Y, Katsutoshi K, Matsuzaka K, Inoue T. The effect of concentrated growth factor on rat bone marrow cells in vitro and on calvarial bone healing in vivo. Int J Oral Maxillofac Implants 2015;30:1187-96.  Back to cited text no. 56
Dohan Ehrenfest DM, Bielecki T, Jimbo R, Barbé G, Del Corso M, Inchingolo F, et al. Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates? An evidence-based answer comparing a pure platelet-rich plasma (P-PRP) gel and a leukocyte- and platelet-rich fibrin (L-PRF). Curr Pharm Biotechnol 2012;13:1145-52.  Back to cited text no. 57
Bae JH, Kim YK, Myung SK. Effects of platelet-rich plasma on sinus bone graft: Meta-analysis. J Periodontol 2011;82:660-7.  Back to cited text no. 58
Hofmänner P, Alessandri R, Laugisch O, Aroca S, Salvi GE, Stavropoulos A, et al. Predictability of surgical techniques used for coverage of multiple adjacent gingival recessions – A systematic review. Quintessence Int 2012;43:545-54.  Back to cited text no. 59
Eren G, Tervahartiala T, Sorsa T, Atilla G. Cytokine (interleukin-1beta) and MMP levels in gingival crevicular fluid after use of platelet-rich fibrin or connective tissue graft in the treatment of localized gingival recessions. J Periodontal Res 2016;51:481-8.  Back to cited text no. 60
de Sanctis M, Zucchelli G. Coronally advanced flap: A modified surgical approach for isolated recession-type defects: Three-year results. J Clin Periodontol 2007;34:262-8.  Back to cited text no. 61
Zucchelli G, De Sanctis M. Long-term outcome following treatment of multiple Miller class I and II recession defects in esthetic areas of the mouth. J Periodontol 2005;76:2286-92.  Back to cited text no. 62
Zucchelli G, De Sanctis M. Treatment of multiple recession-type defects in patients with esthetic demands. J Periodontol 2000;71:1506-14.  Back to cited text no. 63
Cairo F, Nieri M, Cincinelli S, Mervelt J, Pagliaro U. The interproximal clinical attachment level to classify gingival recessions and predict root coverage outcomes: An explorative and reliability study. J Clin Periodontol 2011;38:661-6.  Back to cited text no. 64
Fleming PS, Lynch CD, Pandis N. Randomized controlled trials in dentistry: Common pitfalls and how to avoid them. J Dent 2014;42:908-14.  Back to cited text no. 65
Chambrone L, Chambrone D, Pustiglioni FE, Chambrone LA, Lima LA. The influence of tobacco smoking on the outcomes achieved by root-coverage procedures: A systematic review. J Am Dent Assoc 2009;140:294-306.  Back to cited text no. 66
Kaval B, Renaud DE, Scott DA, Buduneli N. The role of smoking and gingival crevicular fluid markers on coronally advanced flap outcomes. J Periodontol 2014;85:395-405.  Back to cited text no. 67
Ghanaati S, Booms P, Orlowska A, Kubesch A, Lorenz J, Rutkowski J, et al. Advanced platelet-rich fibrin: A new concept for cell-based tissue engineering by means of inflammatory cells. J Oral Implantol 2014;40:679-89.  Back to cited text no. 68
Simonpieri A, Del Corso M, Sammartino G, Dohan Ehrenfest DM. The relevance of Choukroun's platelet-rich fibrin and metronidazole during complex maxillary rehabilitations using bone allograft. Part I: A new grafting protocol. Implant Dent 2009;18:102-11.  Back to cited text no. 69
Choukroun J. An opportunity in paroimplantology: PRF. Implantodontie 2001;42:55-62.  Back to cited text no. 70
Verma UP, Yadav RK, Dixit M, Gupta A. Platelet-rich fibrin: A paradigm in periodontal therapy –A systematic review. J Int Soc Prev Community Dent 2017;7:227-33.  Back to cited text no. 71
Zucchelli G, Mele M, Mazzotti C, Marzadori M, Montebugnoli L, De Sanctis M. Coronally advanced flap with and without vertical releasing incisions for the treatment of multiple gingival recessions: A comparative controlled randomized clinical trial. J Periodontol 2009;80:1083-94.  Back to cited text no. 72
Pini-Prato G. The Miller classification of gingival recession: Limits and drawbacks. J Clin Periodontol 2011;38:243-5.  Back to cited text no. 73
Cairo F, Cortellini P, Pilloni A, Nieri M, Cincinelli S, Amunni F, et al. Clinical efficacy of coronally advanced flap with or without connective tissue graft for the treatment of multiple adjacent gingival recessions in the aesthetic area: A randomized controlled clinical trial. J Clin Periodontol 2016;43:849-56.  Back to cited text no. 74
Tavelli L, Barootchi S, Cairo F, Rasperini G, Shedden K, Wang HL. The effect of time on root coverage outcomes: A network meta-analysis. J Dent Res 2019;98:1195-203.  Back to cited text no. 75
Sculean A, Gruber R, Bosshardt DD. Soft tissue wound healing around teeth and dental implants. J Clin Periodontol 2014;41 Suppl 15:S6-22.  Back to cited text no. 76
Schulz KF, Altman DG, Moher D, CONSORT Group. CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomised trials. BMC Med 2010;8:18.  Back to cited text no. 77
Sarkis-Onofre R, Cenci MS, Demarco FF, Lynch CD, Fleming PS, Pereira-Cenci T, et al. Use of guidelines to improve the quality and transparency of reporting oral health research. J Dent 2015;43:397-404.  Back to cited text no. 78


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4]

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