Is Platelet Concentrate Advantageous forthe Surgical Treatment of PeriodontalDiseases? A Systematic Review andMeta-AnalysisMassimo Del Fabbro,* Monica Bortolin,* Silvio Taschieri,* and Roberto Weinstein*

Background: The aim of the present review is to systematicallyevaluate the effects of autogenous platelet concentrates on clinicaloutcomes of the surgical treatment of periodontal diseases.

Methods: MEDLINE, EMBASE, and the Cochrane Central Registerof Controlled Trials were searched using a combination of specificsearch terms. Furthermore, a hand search of relevant journals andbibliographies of reviews was performed. Only randomized clinicaltrials were included. For periodontal intrabony defects, the primaryoutcome variable was the clinical attachment level. For gingival re-cession, outcome variables were root coverage and keratinized tissueincrease. Data were adjusted for baseline values. The methodologicquality of the included studies was assessed. The results of studiesin which the only difference between test and control groups was theadjunct of platelet concentrates were aggregated using a meta-analysis. For intrabony defects, the influences of guided tissue regen-eration (GTR) and study type (split-mouth versus parallel studies)were also evaluated.

Results: The initial search yielded 424 studies. Of the 29 eligiblestudies, 24 studies were included. There were16 studies on the treat-ment of periodontal intrabony defects, all of which used platelet-richplasma (PRP); six studies on gingival recession treatment; and twostudies on the treatment of furcation defects. A significant positive ef-fect of the adjunct of PRP was found for intrabony defects. Such an ef-fect was magnified in studies in which GTR was not used, whereas instudies using GTR, the use of PRP had no adjunctive effect. No effectof the study type was found. No significant effect of platelet concen-trates was found for gingival recession treatment in which only studieswith a follow-up £6 months displayed positive results. No significantbenefit of PRP could be demonstrated for furcation treatment.

Conclusions: PRP may exert a positive adjunctive effect when usedin combination with graft materials, but not with GTR, for the treatmentof intrabony defects. No significant benefit of platelet concentrateswas found for the treatment of gingival recession. J Periodontol2011;82:1100-1111.

KEY WORDS

Gingival recession; meta-analysis; periodontal disease;platelet-rich plasma; randomized controlled trial.

There is substantial experi-mental and clinical evi-dence that growth factors

can modulate the wound-healingresponse in hard and soft tis-sues.1-5 Many studies5-8 demon-strated that specific growth factorscontained in the a-granules ofplatelets (such as platelet-derivedgrowth factor, transforming growthfactor-b1, epithelial growth factor,vascular endothelial growth factor,insulin-like growth factor-I, basicfibroblast growth factor, and hepa-tocyte growth factor) may promotethe bone regeneration of oral andmaxillofacial bone defects. Animproved esthetic outcome, short-ened duration of treatment, andreduction of postoperative symp-toms were frequently reported instudies9-11 that used platelet con-centrates. Platelet growth factorsmay initiate healing by attractingundifferentiated cells within the fi-brin matrix that is formed in thevery early stages of the healingprocess and by triggering cell di-vision. Locally delivered plateletconcentrates are supposed to in-crease the proliferation of connec-tive tissue progenitors to stimulatefibroblast and osteoblast activityand enhance angiogenesis, all ofwhich are fundamental to tissue

* Department of Health Technologies, Scientific Institute for Care and Clinical Research (IRCCS)Galeazzi Orthopedic Institute, University of Milan, Milan, Italy.

doi: 10.1902/jop.2010.100605

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healing and regeneration.7,8,12 Platelets also playa role in the host defense mechanism at the woundsite by delivering signaling peptides that attractmacrophage cells.13 In addition, platelet concen-trates may contain small amounts of leukocytes thatsynthesize interleukins involved in the non-specificimmune reaction.14,15 The antimicrobial activity ofplatelet concentrates against several bacterial spe-cies involved in oral infections was also reported.16,17

In recent years, there has been a growing interestin the use of platelet concentrates for the treat-ment of many intraoral clinical conditions, includingperiodontal defects. However, there has been noagreement about the advantages derived from the ad-junct of platelet concentrates to periodontal surgicalprocedures as suggested by some reviews. The firstsystematic review18 that evaluated the effect ofplatelet-rich plasma (PRP) on clinical applications indentistry reported beneficial effects of PRP in the treat-ment of periodontal defects, whereas a subsequent,but not systematic, review19 reported divergent re-sults that ranged from the significant enhancementof graft healing to a null effect in the treatment of intra-osseous and furcation defects. Another systematic re-view20 based on randomized trials concluded that PRPimproved the outcome of gingival recession treatmentbut not the clinical attachment level (CAL) in chronicperiodontitis.

A recent systematic review21 that evaluated the ef-fect of a PRP adjunct in the treatment of periodontalintraosseous defects underlined the limits and theheterogeneity of available data and cautiously con-cluded that the specific selection of bioactive agentsand procedures combined with PRP may be important.

A further issue is that different techniques wereadopted to obtain platelet concentrates. Several com-mercial methods are available in the market for thepreparation of different types of platelet concentratessuch as PRP, plasma rich in growth factors (PRGF),and platelet-rich fibrin (PRF), and each one has spe-cific features and effects.22 Taken together, the avail-able clinical evidence can be confounding for thepractitioner.

The aim of the present evidence-based systematicreview is to determine whether the use of autologousplatelet concentrates may affect the outcome of re-generative procedures for the treatment of peri-odontal defects and gingival recession.

MATERIALS AND METHODS

Literature SearchA search was performed in electronic databases (i.e.,MEDLINE, EMBASE, and the Cochrane Central Reg-ister of Controlled Trials) using the following searchterms alone and in combination by means of Booleanoperators: ‘‘platelet-rich plasma,’’ ‘‘autologous plate-

let concentrate,’’ ‘‘plasma-rich growth factors,’’ and‘‘platelet-rich fibrin.’’ The search was limited to clini-cal trials involving human subjects. No languageor time restriction was applied. The last electronicsearch was performed during September 2010.

An additional hand search was carried out in themajor international journals in the field of periodontol-ogy, implant dentistry, and oral and maxillofacial sur-gery (i.e., the British Dental Journal, British Journal ofOral and Maxillofacial Surgery, Clinical Implant Den-tistry and Related Research, Clinical Oral ImplantsResearch, Implant Dentistry, International Journal ofOral and Maxillofacial Implants, International Journalof Oral and Maxillofacial Surgery, International Jour-nal of Periodontics and Restorative Dentistry, Journalof Clinical Periodontology, Journal of Oral and Max-illofacial Surgery, Journal of Periodontal Research,Journal of Periodontology, and Oral Surgery OralMedicine Oral Pathology Oral Radiology and Endo-dontology). All issues of these journals from 1998to September 2010 were searched.

Reference lists of the reviews and of identified ran-domized trials were also checked for possible addi-tional studies. Finally, the manufacturing companiesproducing devices for concentrating platelets werecontacted to identify ongoing or unpublished studiespertinent to this review.

Inclusion and Exclusion CriteriaAll randomized clinical trials (RCTs) assessing the ef-ficacy of platelet concentrates for healing and regen-eration of hard and soft tissues in patients undergoingsurgical procedures for the treatment of periodon-tal defects and gingival recession were included. Allother types of study designs, like case series, case re-ports, retrospective studies, technical studies, animalstudies, and reviews, were excluded. Studies investi-gating the effect of platelet concentrates in surgicalprocedures involving implant therapy, like the maxil-lary sinus augmentation procedure, were also ex-cluded as were articles reporting on any other oralsurgical intervention like tooth extraction, inlay andonlay grafts for the treatment of jawbone defects,treatment of odontogenic cysts, and periapical sur-gery. No limitation was placed regarding the numberof patients treated. Studies were only included if a testgroup using platelet concentrates was compared toa control group in which platelet concentrates werenot used.

Data ExtractionThe titles and abstracts of retrieved articles werescreened independently by two reviewers (MDF andMB), and publications meeting the inclusion criteriawere identified. When the title and abstract of an arti-cle did not provide sufficient information to make adecision, the full text was obtained and examined.

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Publications that did not meet the inclusion criteriawere excluded. In case of a disagreement, a third re-viewer (ST) was consulted, and a joint decision wasachieved after discussion. The full text of all includedstudies was obtained. Characteristics of the includedstudies were examined by the reviewers, and relevantdata were extracted. Studies were grouped accordingto the type of surgical intervention performed.

Primary Outcome VariablesFor studies evaluating the treatment of periodontal in-trabony defects, the change in CAL between baselineand the final follow-up was considered. For eachstudy, the CAL change was adjusted for the initial clin-ical condition in terms of defect severity by dividing bythe CAL value at baseline. This ratio was expressed inpercentages and used for the meta-analysis. The ef-fects of surgical techniques (in particular the use ofguided tissue regeneration [GTR]) and study design(i.e., parallel group versus split-mouth studies) onclinical outcomes were also evaluated. For studiesevaluating gingival recession treatment, the percent-age of root coverage and the keratinized tissue in-crease at the end of each study were considered forthe meta-analysis. For studies evaluating the effectof platelet concentrates on other types of periodontalsurgical procedures, such as furcation defect treat-ment, the outcome variables reported in each studywere examined before establishing the primary out-come variable to be used for the meta-analysis.

Secondary Outcome VariablesAny other clinical variable reported in the includedstudies was considered, such as the defect width,number of walls, changes in probing depths and gin-gival recession, and radiographic changes betweenbaseline and the final follow-up. Patient-based vari-ables such as esthetics, postoperative discomfort(i.e., pain, swelling, infection, and abscess), any typeof complication, and adverse events, when reported,were also considered.

Assessment of Risk of BiasThe risk of bias of included studies was evaluated in-dependently and in duplicate by two reviewers (MDFand MB) as part of the data extraction process. Crite-ria for assessing the risk of bias of RCTs in the presentreview were adapted from the guidelines reported inthe Cochrane Handbook.23 Included trials were as-sessed considering the following criteria: sequencegeneration (the randomization method), concealedallocation of treatment, blinding of evaluators for out-come assessment, completeness of outcome data,comparability of control and treatment groups at en-try, clear definitions of exclusion/inclusion criteria,and other sources of bias (clear definition of successcriteria, calibration of assessors, and sample size cal-

culation). All criteria were judged as adequate (yes),unclear, or non-adequate (no). The authors of iden-tified RCTs were contacted for clarification or to pro-vide missing information whenever possible.

To summarize the validity of studies, they weregrouped into the following categories: 1) a low riskof bias if none of the quality criteria were judged as in-adequate and no more than two of them were judgedas unclear; 2) moderate risk of bias if one to three cri-teria were judged as inadequate; and 3) a high risk ofbias if four or more criteria were judged as inadequate.In case of discrepancy between the two reviewers, anagreement was obtained by discussion. Otherwise,a third reviewer (ST) was consulted until a consensuswas achieved by discussion.

Data SynthesisFor each trial, the mean difference in the primary out-come variable, along with 95% confidence intervals(CIs), was calculated to estimate the effect of inter-ventions. Clinical heterogeneity was assessed by ex-amining the types of participants, interventions, andoutcomes in each study. A meta-analysis was at-tempted only if studies of similar comparisons (theonly difference between test and control groups wasthe adjunctive use of platelet concentrates in the for-mer) that reported the same outcome measures werefound. The primary outcome variables from each studywere combined for continuous data using a random-ef-fects model. In the case of a continuous variable, likeCAL and keratinized tissue, the mean difference wasadjusted for the baseline value. The analysis was per-formed using software,† and the results were graphi-cally presented by means of Forest plots. Funnelplots were also used to assess the publication bias.The risk of bias was synthesized by means of a graph.The patient was considered the unit of analysis.

RESULTS

The initial electronic search provided 424 studies.Figure 1 is a flowchart that summarizes the articleselection process. After screening the titles and ab-stracts, 29 studies investigating the effects of plateletconcentrates in periodontal procedures were iden-tified. No further study was identified by the hand-searching of journals and other search methods.After review of the full texts, five articles24-28 were ex-cluded because platelet concentrate was used in allstudy groups. Twenty-four RCTs9,10,29-50 fulfilled allinclusion criteria and were included in the presentanalysis. Finally, only 14 articles could be submittedto meta-analysis (10 for periodontal defects and fourfor gingival recession). Most of the RCTs had a split-mouth design. The included articles were published

† Review Manager (RevMan) Version 5.0, 2008, The Nordic CochraneCenter, The Cochrane Collaboration, Copenhagen, Denmark.

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in a period ranging from 2002 to 2009. They describeddifferent surgical procedures (i.e., the treatment ofperiodontal intrabony defects, furcation defects, andgingival recession) performed in a total of 628 patients.

Treatment of Periodontal Intrabony DefectsSixteen articles29-44 reported the treatment of peri-odontal intrabony defects (Table 1). Overall, 602 de-fects (307 test and 295 control defects) were treatedin 446 patients. In all studies, PRP was used. No studyevaluated the effect of PRP alone versus open-flapdebridement alone. Various bone substitutes wereused as grafting materials: anorganic bovine bone,b-tricalcium phosphate, demineralized freeze-driedbovine bone, bioactive glass, and hydroxyapatite. Inone study,40 enamel matrix derivative was also used.Eight studies29,31,34-38,41,44 performed additional GTRusing various kinds of membranes: porcine-derivedcollagen membranes, polylactic acid membranes,synthetic bioabsorbable membranes, and expandedpolytetrafluoroethylene membranes. Follow-up pe-riods ranged from 6 to 12 months. Healing was as-sessed through the measurement of different clinicalparameters and, in some studies, through ra-diographic evaluation. Fourstudies30,32,33,42 reported apositive effect of plateletconcentrates. Six studies wereexcluded from the meta-analysis because either PRPwas not the only adjunc-tive treatment in the testgroup,29,31 the platelet con-centrate was compared to abone substitute,35 the meanvalues for CAL changewere not provided,37,43 orthe baseline CAL was not re-ported.44 From the meta-analysis of the 10 remainingstudies,30,32-34,36,38-42 a sig-nificantly greater CAL gainwas observed in the cases inwhich PRP was used com-pared to control sites (meanadjusted percentage differ-ence: 5.50%; 95% CI: 1.32%to 9.67%; P = 0.01) as shownin Figure 2. In terms of milli-meters, the mean weightedCAL-gain difference was0.50 mm (95% CI: 0.12 to0.88 mm). The Funnel plotdid not show asymmetry, in-dicating an absence of publi-cation bias (Fig. 3).

PRP and GTR. A further meta-analysis was per-formed by separately considering the studies that usedGTR in both test and control groups and those in whichmembranes were not used at all. In the four stud-ies34,36,38,41 that used GTR, the effect of PRP was neg-ligible (mean adjusted percentage difference: 0.56%;95% CI: -2.92% to 4.04%; P = 0.75) as shown in Figure4. Conversely, in the six studies30,32,33,39,40,42 in whichGTR was not used, PRP demonstrated a significant pos-itive effect on periodontal intrabony defects treatment(mean adjusted percentage difference: 9.70%; 95% CI:3.16% to 16.24%; P = 0.004) as shown in Figure 5. Interms of millimeters, the mean weighted CAL-gain dif-ference in favorof the PRP group was 0.04mm(95%CI:-0.33 to 0.41 mm) and 0.84 mm (95% CI: 0.27 to 1.42mm) for studies using and not using GTR, respectively.

Effect of experimental design. No significant effectof the experimental design was found. In the sevenparallel group studies,32,36,38-42 the mean adjustedpercentage difference in CAL change between testand control groups was 4.46% (95% CI: -0.19% to9.10%), which corresponded to a mean weighted dif-ference of 0.39 mm (95% CI: -0.01 to 0.79 mm),

Figure 1.Flowchart summarizing the article selection process.

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and in the three split-mouth studies,30,33,34 it was9.16% (95% CI: -2.40% to 20.72%), which corre-sponded to a mean weighted difference of 0.80mm (95% CI: 0.10 to 1.50 mm).

Treatment of Gingival RecessionSix studies9,10,45-48 reported the treatment of gingivalrecession (Table 2). Overall, 217 defects (106 testand 111 control defects) were treated in 136 patients.Different surgical procedures were performed to ob-tain root coverage (coronally advanced flap, modifiedcoronally advanced flap, and coronally positioned tun-nel). In some cases, grafting materials (connective tis-sue grafts harvested from the palate or acellular dermalmatrix allograft) were added. In two studies,9,10 a colla-gen sponge was used as a carrier for platelet concen-trates. Follow-up periods ranged from 6 weeks to

12 months. Various clinical parameters were evaluatedtoassess healing.Onlyone study10 reported significantdifferences, in terms of clinical parameters, in favor ofthe platelet-concentrate group. This study10 had theshortest follow-up among included studies (6 weeks).In this study,10 the authors also presented a histologicevaluation of the connective tissue donor-site showingmore inflammatory cells and less collagen in controlsamples. In the studies by Cheung and Griffin9 andYen et al.10 the pain level was assessed through a visualanalog scale (VAS) at 1 week and at 1 and 3 weeksafter surgery, respectively. No differences were foundat 1 week, whereas a significant reduction of pain wasobserved at 3 weeks in the test group.10

Root coverage. Two studies10,46 were excludedfrom the meta-analysis because mean values for root

Table 1.

Randomized Trials Reporting Treatment of Periodontal Intrabony Defects

Authors,

Publication Year

Patients

(n)

Number of

Units (patients) Intervention

Membrane

Follow-up

(Months)

Effect

of PCTest Control Test Control

Camargo et al., 200229* 18 18 18 ABB + GTR + PRP GTR Yes† 6 ND

Hanna et al., 200430* 13 13 13 ABB + PRP ABB No 6 Positive

Okuda et al., 200532 70 35 35 HA + PRP HA No 12 Positive

Camargo et al., 200531* 28 28 28 ABB + GTR + PRP None Yes‡ 6 ND

Keles et al., 200635* 15 15 15 GTR + PRP BG + GTR Yes† 6 None

Christgau et al., 200634* 25 25 25 b-TCP + GTR + PRP b-TCP + GTR Yes§ 12 None

Ouyang and Qiao,200633i

10 9 8 ABB + PRP ABB No 12 Positive

Demir et al., 200739 29 15 14 BG + PRP BG No 9 None

Dori et al., 200738 24 12 12 ABB + GTR + PRP ABB + GTR Yes¶ 12 None

Yassibag-Berkmanet al., 200737

25 20 10 b-TCP + PRP/b-TCP +GTR + PRP

b-TCP Yes‡ 12 None

Dori et al., 200736 30 15 15 ABB + GTR + PRP ABB + GTR Yes‡ 12 None

Piemontese et al., 200842 60 30 30 DFDBA + PRP DFDBA No 12 Positive

Dori et al., 200841 28 14 14 b-TCP + GTR + PRP b-TCP + GTR Yes¶ 12 None

Dori et al., 200840 26 13 13 ABB + EMD + PRP ABB + EMD No 12 None

Camargo et al., 200944* 23 23 23 ABB + GTR + PRP ABB + GTR Yes‡ 6 None

Harnack et al., 200943* 22 22 22 b-TCP + PRP b-TCP No 6 None

Test = platelet-concentrate group; PC = platelet concentrate; ABB = anorganic bovine bone; ND = not determined; HA = hydroxyapatite; b-TCP = b-tricalciumphosphate; BG = bioactive glass; DFDBA = demineralized freeze-dried bone allograft; EMD = enamel matrix derivative.* Split-mouth study.† Polylactic acid membrane, Atrisorb�, Atrix Laboratories, Fort Collins, CO.‡ Porcine-derived collagen membrane, Bio-Gide, Geistlich Pharma AG, Wolhusen, Switzerland.§ Synthetic bioabsorbable membrane, Resolut XT, W.L. Gore & Associates, Flagstaff, AZ.i Split mouth was performed only when patients had matched pairs of defects.¶ Non-bioabsorbable e-PTFE (expanded polytetrafluoroethylene) membrane, W.L. Gore & Associates.

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coverage were not available. From the meta-analysisof the remaining four studies,9,45,47,48 no significanteffect of platelet concentrates was observed (meanweighted percentage difference: -4.22%; 95% CI:-14.30% to 5.86%; P = 0.41) as shown in Figure 6.

Keratinized tissue. The meta-analysis performedon four studies9,45,47,48 for keratinized tissue increaseshowed no significant effect of platelet concentrates(mean weighted difference: 0.18 mm; 95% CI: -0.19to 0.54 mm; P = 0.34) as shown in Figure 7.

Treatment of Furcation DefectsTwo split-mouth studies49,50 reported the treatmentof mandibular Class II furcation defects. In both stud-ies,49,50 the control group was treated by open-flap

debridement alone. The study by Pradeep et al.50 re-ported a favorable effect of PRP in the treatment ofClass II furcation defects in 20 patients, even whenno complete closure of the defect was observed after6 months. The study by Lekovic et al.49 also reporteda positive effect of the experimental group againstthe control group in 26 patients 6 months after sur-gery. However, because PRP was used in combina-tion with anorganic bovine bone and GTR, it was notpossible to determine the contribution of each factorto the positive outcome observed in the study.49

Assessment of Risk of BiasOf the randomized trials dealing with the treat-ment of intrabony defects, six trials30,36,38,40-42 wereclassified as having a low risk of bias, and 10trials29,31-35,37,39,43,44 were classified as having amoderate risk of bias. All RCTs dealing with gingivalrecession were classified as having a moderate riskof bias. One50 of the RCTs dealing with furcationdefect was judged as having a low risk of bias, andanother RCT49 was judged as having a moderaterisk of bias. Figure 8 summarizes the results of riskof bias for each item assessed.

DISCUSSION

The present systematic review aimed to assess thevalue of platelet concentrates in enhancing hard-and soft-tissue healing in periodontal regenerativesurgical procedures based on randomized trials.Although the quality of the studies was consideredgenerally good, the results of the present literatureanalysis demonstrated a substantial heterogeneityamong different studies with regard to experimentaldesigns, study aims, surgical techniques, outcomeassessment variables, patient populations, follow-up

Figure 2.Forest plot of studies that evaluated CAL gain in the treatment of periodontal intrabony defects. Data are expressed as mean CAL changes adjustedfor baseline values in percentages. For each study the size of treatment effect (squares) together with 95% confidence interval (CI, horizontal bars)is indicated. The diamond indicates the overall estimate of treatment effect and its width indicates the overall 95% CI. The vertical line representsabsence of treatment effect. IV = inverse variance; df = degrees of freedom; I = index for assessing heterogeneity in a meta-analysis.

Figure 3.Funnel plot of studies that evaluated CAL gain in the treatment ofperiodontal intrabony defects. Data are expressed as mean CAL changesadjusted for baseline values in percentages. The lateral dotted linesrepresent CIs, and the central one represents the mean value. MD =mean difference (%).

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durations, and types and methods ofpreparation of theplatelet concentrate. Grouping of the included stud-ies according to the type of periodontal defect treatedallowed us to reduce variability among studies, so asto attempt a meta-analysis.

Periodontal Intrabony DefectsWhen evaluating the effect of platelet concentrates inthe surgical treatment of periodontal intrabony de-fects and using CAL as the primary outcome variable,an overall positive effect was detected (Fig. 2). De-spite the slightly different study-selection criteria, thepresent meta-analysis substantially confirmed theoutcomes of another systematic review19 that foundevidence for a beneficial effect of PRP in the treatmentof periodontal defects. This confirmation indicatedthat, independent of the clinical approach, the use ofplatelet concentrates may improve the CAL in theseprocedures.

PRP and GTR. An additional analysis showed that,when platelet concentrates are used in combinationwith GTR, no adjunctive effect can be detected after12 months (Fig. 4). Among the studies using GTRonly, the one with the shortest follow-up (6 months)reported a significant positive adjunctive effect ofPRP.44 This suggested that the proven efficacy ofGTR in regenerative periodontal procedures51 could

mask the effect of the platelet concentrate. This waseven more evident when prolonging the follow-up to12 months. Conversely, in those studies in whichGTR was not used, PRP showed a marked positive ef-fect on the CAL (Fig. 5). It is possible that the densefibrin network that is formed after platelet activationmay act as a barrier and prevent infiltration of epithe-lial tissue into the defect. Because of the high cost ofthe membranes used for GTR, and the competence re-quired for performing this technique, the adoption ofautologous platelet concentrates instead of barriermembranes would allow a reduction of the overalltreatment cost and a simplification of the procedure.Furthermore, as reported by some authors,52 it is pos-sible to flatten the platelet concentrate after activationand obtain autologous platelet-rich membranes,which can be placed over the defect, similar to con-ventional membranes.

PRP and other reconstructive materials. The trueeffect of platelet concentrates on periodontal regen-eration could not be evaluated in the present reviewbecause no study compared open-flap debridementalone versus open-flap debridement plus platelet con-centrates for the treatment of intrabony defects. Inall studies except one,31 a periodontal reconstructivetechnique (grafting or GTR or a combination of both)was used in control and test groups, with PRP used as

Figure 4.Forest plot of studies that evaluated CAL gain in the treatment of periodontal intrabony defects. Only studies that evaluated the use of PRP in association withGTR are reported. Significance of symbols is the same as those in Figure 2. IV = inverse variance; df = degrees of freedom; I = index for assessing heterogeneityin a meta-analysis.

Figure 5.Forest plot of studies that evaluated CAL gain in the treatment of periodontal intrabony defects. Only studies that evaluated the use of PRP withoutconcomitant use of GTR are reported. Significance of symbols is the same as those in Figure 2. IV = inverse variance; df = degrees of freedom; I = index forassessing heterogeneity in a meta-analysis.

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an adjunctive agent in the test group. The combineduse of a regenerative technique like GTR, whose effi-cacy is well known, and PRP can mask the true regen-erative effect of the latter. The type of biologic agentused in combination with platelet concentrates couldalso have an influence on the action of the growth fac-tors contained within the preparation, as suggestedby a recent systematic review.22 Other possible con-founding factors could be the number of defect wallsand the width of the defect. These factors were not sta-tistically evaluated in the present review because theywere not systematically reported, and such an inves-tigation would have implied a considerable fragmen-tation of data and reduced the power of the analysis.

Another systematic review20 reported that the useof PRP in association with graft biomaterials for thetreatment of periodontal defects led to a statisticallysignificant improvement of defect-associated clinicalparameters. However, when the additional effect ofPRP over the graft was evaluated, contrasting resultsemerged.

Excluded studies. Some studies were excludedfrom the present meta-analysis evaluating the spe-

cific effect of PRP in the treatment of intraosseousdefects even if they were judged of a good qualitylevel. In two studies,29,31 a test group consisting ofthe treatment of intrabony defects with anorganicbovine bone, GTR, and platelet concentrates wascompared to a control group consisting of the treat-ment with GTR alone29 or open flap debridementalone.31 These studies showed better outcomes forthe test group, suggesting that a combination ofmultiple agents like anorganic bovine bone, GTR,and platelet concentrates was effective in treatingintrabony defects. However, similar to what wasreported by a previous review,20 no conclusionabout the contribution of platelet concentratescould be drawn because the role played by eachagent in the regenerative process could not be distin-guished.

In another study,35 platelet concentrates were usedas alternative graft material compared to bioactiveglass, both in association with GTR. No differencesin terms of clinical parameters were found betweenthe two groups after 6 months, which suggested thatplatelet concentrates may be as effective as bioactive

Table 2.

Randomized Trials Reporting Treatment of Gingival Recession

Author, Publication Year Patients (n)

Number of Units (patients) Intervention

Histology Follow-up Effect of PCTest Control Test Control

Cheung and Griffin 20049* 15 15 15 PCG CTG No 8 months None

Huang et al., 200545 23 11 12 PRP No PRP No 6 months None

Yen et al., 200710* 20 20 20 CTG + PCG CTG Yes 6 weeks Positive

Keceli et al., 200846 40 20 20 CTG + PRP CTG No 12 months None

Aroca et al., 200948* 20 20 20 PRF No PRF No 6 months None

Shepherd et al., 200947 18 9 9 ADM + PRP ADM No 4 months None

PC = platelet concentrate; Test = platelet-concentrate group; PCG = PRP + collagen sponge; CTG = connective tissue graft; PRF = platelet-rich fibrin; ADM =acellular dermal matrix allograft.* Split-mouth study.

Figure 6.Forest plot of studies that evaluated root coverage (%) in the treatment of gingival recession. Significance of symbols is the same as those in Figure 2. IV =inverse variance; df = degrees of freedom; I = index for assessing heterogeneity in a meta-analysis.

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glass and may be used as graft material for treatingintrabony defects.

Study design. No significant differences in out-comes were found between studies adopting a split-mouth protocol and those studies with a parallel-groupdesign. This suggested that both study designs wereequally effective in assessing the influence of PRPon the outcomes of the surgical procedures. Funnelplots were performed for all comparisons, and no pub-lication bias was detected.

Gingival RecessionPlatelet concentrates showed no significant effect onthe improvement of root coverage and keratinized tis-sue when used as an adjunctive treatment for gingivalrecession. This result was in contrast with a recent re-view53 that reported accelerated wound healing andenhancement of root coverage procedures. However,in the latter review,53 studies of low-evidence levelsuch as case reports were also considered. This mighthave influenced the reliability of the conclusions, eventhough the authors correctly recognized the inade-quate available clinical evidence. In the present meta-

analysis, the only study47 thatshowed a positive effect ofplatelet concentrates in thetreatment of gingival reces-sions was the one withthe shortest follow-up (4months). Of the two exclu-ded studies, one study46 re-ported no effect of PRP after12 months of follow-up,whereas the other study10

found a positive effect after6 weeks, which was also val-idated by histologic analy-sis. Unfortunately, no meanvalues and SDs for root cov-erage were available forthese studies. Their inclusionwould have increased thepower of the meta-analysis,

but it is unknown if and how its outcome would havebeen modified. Because of the short half-life ofplatelet-derived growth factors, platelet concen-trates are supposed to have an effect on the very earlystages of bone and soft tissue healing. This triggereffect could induce an acceleration of the healingprocess, which implies an increase of the tissue re-generation in the first weeks after surgery. Such an ef-fect probably tends to disappear over the long term.Therefore, it can be speculated that studies withshorter follow-up time are more likely to producepositive outcomes than those with a longer follow-up duration. This was another reason for the exclu-sion of the study by Yen et al.10 (which had onlya 6-week follow-up) from the meta-analysis.

In one study,9 the treatment with platelet concen-trates embedded in a collagen sponge was comparedto the treatment with connective tissue graft. No dif-ferences in clinical parameters were seen betweenthe two groups after 8 months of healing; moreover,the treatment with platelet concentrates resulted ina better esthetic appearance, suggesting that it may

Figure 7.Forest plot of studies that evaluated keratinized tissue increase (mm) in the treatment of gingival recession. Significance of symbols is the same as those inFigure 2. IV = inverse variance; df = degrees of freedom; I = index for assessing heterogeneity in a meta-analysis.

Figure 8.Risk-of-bias graph: judgments of review authors about each risk-of-bias item presented as percentages acrossall included studies.

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be an alternative to a connective tissue graft and re-duce the patient’s discomfort.

Furcation DefectsThe two selected studies reported a significantly bet-ter outcome in the group using PRP versus the controlgroup. However, because of differences between theexperimental treatment groups, no meta-analysis wasperformed. Therefore, no consistent evidence waspresent regarding the effect of PRP in the treatmentof furcation defects. This result was in line with thefindings of Trombelli and Farina.19

Methods for Preparation of Platelet ConcentratesDifferent protocols were used for platelet-concentrateproduction.Someof the includedstudies29-31,34,35,37,42,43

did not provide a detailed description of the protocolfor platelet-concentrate production (e.g., the use ofa cell separator, centrifugation steps, the amount ofblood collected preoperatively, the baseline plateletconcentration in the collected blood, the amount ofplatelet concentrate obtained, the final platelet con-centration, the type of blood anticoagulant, and theuse of a platelet activator). Any of these variablesmight have played a role in the platelet viability andactivity. Furthermore, different platelet concentratesmay have different biologic properties. For example,the technology for obtaining PRGF produces a leuko-cyte-free preparation with the aim of reducing thecontent of proinflammatory cytokines.

Further Effects of Platelet ConcentratesSome studies9-11,52,54-58 on various oral surgical pro-cedures highlighted the advantages of platelet con-centrates on the very early stages of soft tissuehealing and suggested that they might reduce post-operative inflammation and pain, with positive effectson the quality of life. However, these effects were notproperly assessed across the studies included in thepresent review. Only two studies9,10 evaluated painlevels after surgery and reported a beneficial effectof platelet concentrates in controlling postoperativesymptoms.

Indications for Future ResearchSome aspects emerged from this review that deservedfurther investigation. The effect of platelet concen-trates other than PRP (e.g., PRGF and PRF) on peri-odontal intrabony-defect treatment has not beeninvestigated. Evidence is lacking concerning the ef-fect of platelet concentrates on common postopera-tive symptoms like pain and swelling that might berelevant for patients’ quality of life and preferences re-garding the use of such adjunctive agents. Furtherrandomized studies are needed to investigate if theadjunctive use of platelet concentrates may havebenefits for the treatment of furcation defects. Future

studies should report with greater detail the protocolused for the preparation of platelet concentrates aswell as the baseline and final platelet concentrationfor each patient. Clinical evidence regarding the trueeffect of platelet concentrates over open-flap debride-ment alone, without other confounding factors like re-constructive techniques, is needed. Because of themethodologic limitations of the existing studies, thereis a need for further well-designed studies to providemore insight in the precise role of platelet concen-trates for periodontal tissue regeneration.

CONCLUSION

The evidence available in the literature for beneficialeffects of platelet concentrates in periodontal surgicalprocedures has been increasing in the recent years.Platelet-rich plasma may be advantageously used asan adjunct to grafting procedures, but not in combina-tion with GTR, for the treatment of intrabony defects,whereas no significant benefit of platelet concentrateswas found for gingival recession.

ACKNOWLEDGMENT

The authors report no conflicts of interest related tothis study.

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Correspondence: Dr. Massimo Del Fabbro, Galeazzi Ortho-pedic Institute, University of Milan, Via Riccardo Galeazzi 4,20161 Milan, Italy. Fax: 39-02-50319960; e-mail: massimo.delfabbro@unimi.it.

Submitted October 5, 2010; accepted for publicationDecember 1, 2010.

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