Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review

YIJOM-3061; No of Pages 10

Int. J. Oral Maxillofac. Surg. 2015; xxx: xxx–xxx http://dx.doi.org/10.1016/j.ijom.2014.12.010, available online at http://www.sciencedirect.com

Systematic Review Paper Dental Implants

Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review

V. Moraschini, E. S. P. Barboza Department of Periodontology, School of Dentistry, Fluminense Federal University, Rio de Janeiro, Brazil

V. Moraschini, E. S. P. Barboza: Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review. Int. J. Oral Maxillofac. Surg. 2014; xxx: xxx–xxx. # 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Abstract. The current literature was reviewed to evaluate the effect of autologous plasma concentrates on the preservation of extraction sockets. A comprehensive literature search was performed from October 2013 to February 2014 in the MEDLINE/PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Four studies, published between the years 2010 and 2013, met the eligibility criteria and were included in the review. There were 102 extractions (55 tests, 47 controls) in 82 patients. There was considerable heterogeneity between studies with regard to the design, follow-up time, surgical techniques, and method of preparation of plasma concentrates, and therefore the data could not be analyzed quantitatively. The use of plasma concentrates seems to accelerate healing and soft tissue epithelialization in extraction sockets and reduce postoperative pain and discomfort. However, there is no evidence to date to confirm that plasma concentrates improve hard tissue regeneration.

Socket preservation procedures should be performed at the time of extraction to minimize resorption of external tissues and maximize bone formation inside the socket.1 The preservation of the ridge after tooth extraction is fundamental to the success and predictability of treatments that include dental implants. Tissue loss after extraction is physiological, progressive, and more marked during the first 3–6 months, and is followed by less intense resorption thereafter. Two recent systematic reviews on dimensional 0901-5027/000001+010

changes in soft and hard tissues showed that changes in thickness are usually greater than those in height. In addition, the buccal wall is usually more affected than the lingual wall, and the mandible tends to undergo greater resorption than the maxilla.2,3 Several grafting techniques and materials combined or not with biological barriers have been suggested to reduce ridge changes after extractions.4–9 Although several of these techniques and materials may limit or reduce resorption, the quality

Key words: alveolar socket preservation; growth factors; platelet concentrates; systematic review; tooth extraction. Accepted for publication 15 December 2014

of the newly formed tissue inside the extraction socket may vary widely.4 Recently, the use of plasma-rich growth factor (PRGF) has been recommended for tissue regeneration in oral surgeries.10–12 Some studies have described the potential of plasma concentrates rich in growth factors to stimulate soft and hard tissue repair and regeneration and to reduce inflammation and the consequent pain and discomfort.11–13 Important factors and cytokines, such as platelet-derived growth factor (PDGF), transforming growth factor beta

# 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Moraschini V, Barboza ESP. Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review, Int J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.ijom.2014.12.010

YIJOM-3061; No of Pages 10

2

Moraschini and Barboza

(TGF-b), vascular endothelial growth factor (VEGF), and platelet-derived endothelial growth factor (PDEGF), are released during the preparation of plasma concentrates. These factors, also found in tissues during natural healing, are responsible for the regulation of cell events, such as induction, proliferation, differentiation, chemotaxis, and the synthesis of the extracellular matrix,13 which accelerates mitosis, osteoblast proliferation, vascularization, and collagen synthesis.14,15 As plasma concentrates are autologous and easily obtained at a relatively affordable cost, they have been used increasingly for the preservation of extraction sockets. A systematic review of the literature on the effects of autologous platelet concentrates for alveolar socket preservation was conducted. Materials and methods

Focused question

The focused question was ‘What is the effect of autologous platelet concentrates for alveolar socket preservation using autologous plasma concentrates when compared with natural (spontaneous) socket healing?’ Search strategy

The search strategy was based on the PRISMA guidelines (http://www. prisma-statement.org). A broad electronic search was performed from October 2013 to February 2014 in the database of the National Library of Medicine, Washington, DC (MEDLINE/PubMed) and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant publications in indexed journals. The electronic search followed the strategy shown in Table 1.

Development of a protocol

The method used in this systematic review was adapted from the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA)16 and the guide prepared by Needleman.17 Clinical questions were formulated and organized according to the PICO framework for evidencebased practice.18,19

Screening and selection

Human studies (partially edentulous patients), published in English, including randomized clinical trials (RCTs), controlled clinical trials (CCTs), and prospective cohort studies with a control group, were included in this review. In addition,

studies that conducted quantitative or qualitative analysis of bone and soft tissue changes by means of clinical or radiographic follow-up for at least 2 months were also included in the present study. Studies in animals, case reports, case series, retrospective studies, technique descriptions, and narrative reviews, as well as studies that included the extraction of third molars or the immediate placement of implants, were excluded. The screening of titles and abstracts for potential inclusion in the review was undertaken by the two reviewers independently. Selected full studies were read carefully and analyzed for the eligibility criteria (inclusion/exclusion) and planned data extraction. Differences between reviewers were resolved by discussion and consensus.

Assessment of heterogeneity

The heterogeneity of the primary results of the studies included in this review was evaluated according to the following factors: study design, follow-up time, number, age, and gender of participants, extraction site, extraction method and intervention, evaluation method, and statistical analysis.

Table 1. Systematic search strategy. Focus question Search strategy Population Intervention

Outcomes

Search combination Database search Language Electronic databases Selection criteria Inclusion criteria

Exclusion criteria

What is the effect of autologous platelet concentrates for alveolar socket preservation using autologous plasma concentrates when compared with spontaneous socket healing? (1) MeSH terms: extraction socket OR tooth extraction socket OR post-extraction socket OR alveolar socket OR Text words: fresh extraction socket (2) MeSH terms: socket preservation OR extraction socket preservation OR platelet growth factors OR platelet rich plasma OR platelet rich fibrin OR Text words: PRP OR PRF OR L-PRP OR L-PRF OR PRGF (3) MeSH terms: extraction socket healing OR wound healing OR bone healing OR tissue healing OR dimensional change OR Text words: dimensional changes OR socket dimensional changes 1 AND 2 AND 3 English MEDLINE/PubMed and Cochrane Central Register of Controlled Trials (CENTRAL)  RCTs, CCTs, and prospective cohort studies with a control group  Studies that conducted quantitative or qualitative analysis of bone changes and soft tissues by means of clinical or radiographic follow-up for at least 2 months  Population: partially edentulous humans  No restriction on age or number of patients  Healthy individuals (no systemic diseases)  Intervention: treatment to preserve the extraction socket using autologous plasma concentrates (PRP or PRF)  Comparison: no biomaterial in the control group; only clot in the socket  Outcome: dimensional changes of soft and hard tissues Studies in animals, case reports, case series, retrospective studies, technique descriptions, and narrative reviews, as well as studies that included the extraction of third molars or the immediate placement of implants

MeSH, medical subject headings; PRP, platelet-rich plasma; PRF, platelet-rich fibrin; L-PRP, leucocyte- and platelet-rich plasma; L-PRF, leucocyte- and platelet-rich fibrin; PRGF, plasma-rich growth factor; RCT, randomized clinical trial; CCT, controlled clinical trial.

Please cite this article in press as: Moraschini V, Barboza ESP. Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review, Int J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.ijom.2014.12.010

YIJOM-3061; No of Pages 10

Medline/PubMed Records identified through database searching (n = 259)

Cochrane (CENTRAL) Records identified through database searching (n = 42)

Included

3

moderate risk of bias and the other study a high risk of bias.30 Study design and study population

Records excluded (n = 287)

Full-text articles assessed for eligibility (n = 14)

Eligibility

Screening

Identification

Platelet concentrates for socket preservation

Full-text articles excluded (n = 10)

Studies included in the present systematic review (n = 4)

Fig. 1. Flow diagram (PRISMA format) of the screening and selection process. Quality assessment

Results

The methodological quality of each study was assessed according to the criteria suggested by Van der Weijden et al.,2 which combine the criteria described in the PRISMA statement,16 the CONSORT statement,20 the MOOSE statement,21 and the STROBE statement,22 and those in the studies conducted by Moher et al.,23,24 Esposito et al.,25 and Needleman.26 The following criteria were used to define the risk of bias: (1) randomized distribution; (2) inclusion and exclusion criteria to select patients; (3) examiner and patient randomization; (4) balanced experimental groups; (5) identical treatment in all groups, except for the intervention; and (6) information about follow-up. When all criteria were met, the risk was classified as low, if any one of these criteria was not met, the risk was classified as moderate, and if two or more criteria were not met, the risk was classified as high.

Search results

Statistical analysis

After analysis of the selected studies, data on dimensional (vertical and horizontal) changes of the soft and hard tissues were collected. Mean results and their standard deviations were recorded when available in the studies. Other data, such as postoperative complications, healing, and analysis of newly formed tissues, were also collected. The analysis of the studies included revealed great heterogeneity in design. Therefore, a quantitative analysis followed by meta-analysis could not be conducted.17,27 A descriptive analysis was thus performed.

The initial search yielded 259 titles in MEDLINE/PubMed and 42 in the Cochrane Central Register of Controlled Trials (Fig. 1). After the first evaluation, 14 potential studies were selected. Of these 14 studies, 10 were excluded because they did not meet the eligibility criteria. Reasons for exclusion are shown in Table 2. Four prospective studies published between 2010 and 2013 were included in this systematic review.

Assessment of heterogeneity

Preliminary examination of the selected studies revealed considerable heterogeneity. The study characteristics are shown in Table 3.

Assessment of quality

The analysis of quality is shown in Table 4. Two studies had a high level of evidence and low risk of bias.13,28 One study29 had a

Two studies were RCTs13,28 and two were CCTs29,30; three were parallel-group studies,13,28,29 and one had a split-mouth design.30 The duration of follow-up was at least 2 months in all studies. The number of participants ranged from eight30 to 2829; their mean age was 38.8 years (range 20– 75 years), and 40.2% (n = 33) were male. There were 102 extractions (55 tests and 47 controls) in 82 subjects. Extraction and intervention type and reason

One study performed extractions with flaps.13 Another study performed two types of extraction, one with and one without a flap.28 For all studies, the authors reported that the sockets were debrided carefully after extraction to remove granulation tissue before closing or using plasma concentrates. All sockets corresponded to molars or premolars that had an indication for extraction. Antibiotics were not prescribed in any study. Two studies13,29 used plateletrich plasma (PRP) in the test group, and two used platelet-rich fibrin (PRF).28,30 Evaluation method and study outcome

The patients in the studies included in this review underwent clinical, histological, and radiographic tests. The evaluation methods used and results are shown in Table 5. Soft tissue healing

Soft tissue healing was evaluated in two studies.13,30 One study used the soft tissue healing index described by Landry et al.,31 which includes tissue colour, bleeding, alveolar ridge epithelialization, and the presence of granulation tissue or suppuration. A statistically significant difference

Table 2. Excluded studies. Reason for exclusion

Authors

Extraction of impacted mandibular third molars

Sammartino et al.33 Gu¨rbu¨zer et al.37 Gawande and Halli32 Vivek and Sripathi Rao34 Gu¨rbu¨zer et al.38 Mozzati et al.39 Rutkowski et al.36 Ce´lio-Mariano et al.35 Anitua61

Growth factors associated with autologous bone or others biomaterials No control group

Simon et al.15

Please cite this article in press as: Moraschini V, Barboza ESP. Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review, Int J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.ijom.2014.12.010

YIJOM-3061; No of Pages 10

4

Moraschini and Barboza

Table 3. Main characteristics of selected studies. Design and evaluation time

Authors, year

Title

Alissa et al.13, 2010

The influence of platelet-rich plasma on the healing of extraction sockets: an explorative randomised clinical trial

Farina et al.29, 2013

Plasma rich in growth factors in human extraction sockets: a radiographic and histomorphometric study on early bone deposition Influence of platelet-rich fibrin on alveolar ridge preservation

Suttapreyasri and Leepong30, 2013 Hauser et al.28, 2013

Pharmacological treatment

Clinical and histological evaluation of post-extraction platelet-rich fibrin socket filling: a prospective randomized controlled study

RCT Parallel Blinded 3 months CCT Parallel Not blinded 2 months CCT Split-mouth Not blinded 2 months RCT Parallel Blinded 2 months

Subjects (sites), gender, mean age (range)

Interventions (sites)

n = 23 (23) 8 M/15 F 30.5 (20–52) years

PRP-flap (12) NH (11)

n = 28 (36) 13 M/15 F 55.2 (34–74) years

PRP (18) NH (18)

n = 8 (20) 3 M/5 F 22.6 (20–27) years

PRF (10) NH (10)

n = 23 9 M/14 F 47 (22–75) years

PRF (9) PRF-flap (6) NH (8)

Measurement

Outcome

Conclusions

Anti-inflammatory as needed

Clinical and radiographic

This study suggested that PRP may have some additional benefits in reducing healing complications and improving healing of soft tissue of extraction sockets. It remains unclear whether the use of PRP in post-extraction sites can promote bone healing.

Chlorhexidine gluconate 0.12% for 7 days NR

Micro-CT and histological

Incidence of socket complications Post-operative quality of life Soft tissue healing Hard tissue healing Hard tissue healing

Clinical, model casts, and radiographic

Soft tissue healing Hard tissue healing

Anti-inflammatory (number of days not reported)

Micro-CT, nanoindentation test, clinical, and radiographic

Hard tissue healing

The plasma rich in growth factors (PRP) treated group did not show any enhancement in early (4 and 8 weeks) bone deposition compared to the control group. The preliminary results of this study demonstrated neither better alveolar ridge preservation nor enhanced bone formation of PRF in the extraction socket. The use of PRF revealed limited effectiveness by accelerated soft tissue healing in the first 4 weeks. The results of this study indicated that the use of PRF membranes to fill the socket after tooth extraction leads to improved alveolar bone healing with a better preservation of the alveolar crest width.

RCT, randomized clinical trial; M, male; F, female; PRP, platelet-rich plasma; NH, natural healing; CCT, controlled clinical trial; PRF, plateletrich fibrin; CT, computed tomography; PRGF, plasma rich in growth factors; NR, not reported.

favouring the use of PRP was found (P = 0.03).13 The other study30 evaluated soft tissue healing by measuring the width of the socket ridge mesiodistally (M–D) and buccolingually (B–L) using a periodontal probe. Immediately after extraction, mean measures in the PRF group were M–D 4.79  0.59 mm and B–L 7.38  1.12 mm, and in the control group were M–D 4.70  1.09 mm and B–L 7.61  1.12 mm. Eight weeks after extraction, ridge healing was slightly better in the PRF group (M–D 1.76  1.36 mm, B–L 3.31  0.9 mm) than in the control group (M–D 2.17  1.65 mm, B–L 3.92  0.64 mm), however this was not statistically significant.

tient perceptions of pain, oral function, general activities, and other symptoms. Pain was statistically less intense in the first 3 days in the PRP group. Moreover, the patients in the test group needed less analgesic medication than those in the control group in the first week. Patients treated with PRP also reported less bad taste in the mouth, less halitosis, and a lower accumulation of food in the operated region because there was a biological barrier in the socket. However, other events under analysis, such as speech, sleep, and daily activities, were not statistically different between the groups. Hard tissue healing

Postoperative health-related quality of life index

One study13 used a questionnaire in the first week after extraction to evaluate pa-

One study analyzed horizontal changes before and after 8 weeks of follow-up using a calliper clamp positioned in the oral region of the socket at about 4 mm

below the gingival margin.28 The PRFflapless group had less bone resorption (0.06 mm) than the PRF-flap group (0.42 mm) or the control group (0.43 mm; P < 0.05). The analysis of vertical changes using standardized periapical radiographs revealed that the control group had a greater bone loss (P < 0.05) in the mesial (M 0.77  0.17 mm) and distal (D 2.07  0.81 mm) regions 1.21  than the PRF-flapless (M 0.40 mm; D 0.76  0.25 mm) and 0.86  0.34 mm; D PRF-flap (M 2.15  1.05 mm) groups, which indicated that PRF prevented bone resorption. Alissa et al.13 evaluated standardized peri-apical radiographs using specialized software (Win TAS software, Steve Paxton, UK) and reported that there was more trabecular bone and greater bone volume in the test group (PRP) than in the control group at the 3-month follow-up, which

Please cite this article in press as: Moraschini V, Barboza ESP. Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review, Int J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.ijom.2014.12.010

YIJOM-3061; No of Pages 10

Platelet concentrates for socket preservation

5

Table 4. Quality assessment of included studies. Validity/quality criteria External Representative population group Eligibility criteria defined Internal Random allocation Allocation concealment Blinded to the patient Blinded to the examiner Blind during statistical analysis Reported loss to follow-up No. (%) of dropouts Treatment identical, except for intervention Statistical Sample size calculation and power Point estimates presented for primary outcome Measures of variability for the primary outcome Intention to treat analysis Clinical aspects Study design Validated measurement Calibration of examiner Reproducibility data shown Reason for extraction

Estimated potential risk of bias

Alissa et al.13

Farina et al.29

Suttapreyasri and Leepong30

Hauser et al.28

Yes Yes

Yes Yes

Yes Yes

Yes Yes

Yes ND ND Yes ND Yes 7 (30.4%) Yes

ND ND No Yes ND Yes 0 Yes

ND ND No ND ND ND 0 Yes

Yes ND ND Yes ND Yes 1 (4.34%) Yes

Yes Yes

ND Yes

ND Yes

ND Yes

Yes

Yes

Yes

Yes

ND

ND

ND

ND

RCT (parallel)

CCT (parallel)

RCT (parallel)

ND ND No Root fracture, caries, periodontal disease, endodontic failure, orthodontic reason Low

ND ND No Root fracture, caries, periodontal disease, endodontic failure

CCT (split-mouth) ND ND No Requiring extraction

Moderate

High

ND ND No Root fracture, caries, periodontal disease, endodontic failure Low

ND, not described; RCT, randomized clinical trial; CCT, controlled clinical trial.

indicated that PRP had a positive effect. Suttapreyasri and Leepong30 also evaluated vertical bone resorption in the mesial and distal regions using peri-apical radiographs, but did not find any statistical differences between the PRF (M 0.70 mm; D 1.23 mm) and the control (M 1.33 mm; D 1.14 mm) groups at 8 weeks of follow-up (P > 0.05). Horizontal changes of combined hard and soft tissues

One study30 assessed the horizontal changes in soft and hard tissues of the socket ridge by analyzing study models. In both groups evaluated, the contraction of buccal tissues started in the first week after extraction, whereas changes in lingual tissues started only in the second week. Buccal changes were more marked than lingual changes. Eight weeks after extraction, buccal (B) and lingual (L) tissues in the PRF group (B 1.96  1.10 mm; L 1.59  0.64 mm) had fewer dimensional changes than those in the control group (B 2.59  0.7 mm; L 1.78  0.47 mm).

Histomorphometric analysis 29

One study conducted an immunohistochemical analysis of vascular and endothelial cells (von Willebrand factor), osteoblast activity, and immunological cells. Although the test group had a greater number of CD68+ cells (giant multinucleated cells, macrophage fusion) and a higher von Willebrand factor, the difference between groups at 8 weeks was not statistically significant. The amount of osteocalcin, a protein associated with osteoblast activity, was similar in the test and control groups at all follow-up times.

Micro-CT analysis

The volume and amount of newly formed bone were analyzed using micro-CT in two studies.28,29 Farina et al.29 did not find any statistically significant differences in bone volume or the amount and density of mineral tissue between the test and control groups at 8 weeks. In contrast, Hauser et al.28 found significantly greater bone volume in the PRF-flapless group than in

the PRF-flap and the control groups. The authors also found that the PRF-flap group had lower bone volume than the other groups. Methods for platelet concentrate preparation

The studies used different methods to prepare plasma concentrates. Table 6 summarizes the methods used in the studies included in this review.

Discussion

A systematic review of the literature on the effects of autologous platelet concentrates for alveolar socket preservation was conducted. After database searches and the analysis of eligibility criteria used in this review, four studies were selected. There are few studies in the literature regarding the topic presented in this study. In addition, the low quality of studies is the main reason for the low number of articles included in this review. Of the potential candidates for inclusion (n = 14),

Please cite this article in press as: Moraschini V, Barboza ESP. Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review, Int J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.ijom.2014.12.010

YIJOM-3061; No of Pages 10

6

Moraschini and Barboza

Table 5. Clinical outcomes and results. Outcome

Authors 13

Alissa et al.

Measurement method

Incidence of socket complications Postoperative quality of life Soft tissue healing Hard tissue healing

Farina et al.29

Suttapreyasri and Leepong30

Hauser et al.28

62

Criteria of Cheung and Griffin Health-related quality of life questionnaire Healing index of Landry et al.31 Standardized peri-apical radiographs

Effect of PRP/PRFa

P-valueb

Sig. Non-sig.

0.06 0.22

Sig. Sig.

0.03 0.01

Bone volume Tissue mineral content Tissue mineral density Mean number of CD68+ stained cells Mean area of CD68+ staining Mean number of von Willebrand factor-positive stained cells Mean area of von Willebrand factor positive staining Mean osteocalcin staining score

Micro-CT Micro-CT Micro-CT Histomorphometric

Non-sig. Non-sig. Non-sig. Non-sig.

0.792 0.662 0.429 0.792

Histomorphometric Histomorphometric

Non-sig. Non-sig.

0.662 0.792

Histomorphometric

Non-sig.

0.792

Histomorphometric

Non-sig.

0.247

Dimensions of the socket orifice (M–D)/(B–L) Alveolar ridge contour change Radiographic resorption of marginal bone levels (M–D)

Periodontal probe

Non-sig.

>0.05

Model casts Standardized peri-apical radiographs

Sig. Non-sig.

0.031 >0.05

Bone volume to total volume

Micro-CT

NR

Trabecular number

Micro-CT

Trabecular thickness

Micro-CT

Trabecular separation

Micro-CT

Elastic modulus

Nano-indentation test

Working energy

Nano-indentation test

Tissue hardness

Nano-indentation test

Alveolar width at 4 mm apical to the crest Alveolar height (M–D)

Calliper

PRF-flapless Sig. PRF-flap Non-sig. PRF-flapless Sig. PRF-flap Non-sig. PRF-flapless Non-sig. PRF-flap Non-sig. PRF-flapless Sig. PRF-flap Non-sig. PRF-flapless Sig. PRF-flap Non-sig. PRF-flapless Sig. PRF-flap Non-sig. PRF-flapless Non-sig. PRF-flap Non-sig. PRF-flapless Sig. PRF-flap Non-sig. PRF-flapless Sig. PRF-flap Sig.

Standardized peri-apical radiographs

<0.05 NR <0.05 <0.05 <0.05 NR <0.05 <0.05

PRP, platelet-rich plasma; PRF, platelet-rich fibrin; CT, computed tomography; M–D, mesial–distal; B–L, buccal–lingual; NR, not reported. a Sig., statistically significant difference favouring the use of PRP/PRF; Non-sig., not statistically significant. b P-values of the statistical analysis of the change between baseline and the end of follow-up.

eight were excluded because they used the extraction socket of impacted third molars.32–39 The main reason for exclusion was the fact that osteotomy of the socket walls is routine for the extraction of third molars, which affects the pattern, extent, and time of healing. Heterogeneity assessment

A considerable heterogeneity between articles was identified, as there were differences in population, types of plasma concentrate, surgical protocol, follow-up time, and plasma concentrate preparation. These differences made the analysis of data difficult and complicated the compar-

ison of results between studies; therefore, a valid quantitative analysis and a subsequent meta-analysis could not be conducted. The method used to prepare plasma concentrates may affect plasma quality directly and study results indirectly. Different preparations will have different biological properties. In the case of PRP, centrifugation speed and time and the type of anti-clotting and activation agents used may affect the quality and quantity of cells. These factors are less critical in the preparation of PRF, because natural clotting occurs after centrifugation, and the addition of anti-clotting agents, thrombin, and calcium hydrochloride to change

the biochemical properties of blood is not necessary. This is the reason why PRF is the easiest plasma concentrate to prepare.40 Possible factors affecting dimensional changes after tooth extraction

Time of evaluation

The follow-up time may be a critical factor in studies evaluating dimensional changes after extraction. The mean follow-up time in the studies included in this review was 2.25 months, ranging from 2 to 3 months. A few other studies have investigated the healing sequence of extraction sockets

Please cite this article in press as: Moraschini V, Barboza ESP. Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review, Int J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.ijom.2014.12.010

YIJOM-3061; No of Pages 10

Platelet concentrates for socket preservation

7

Table 6. Methods for platelet concentrate preparation.

Authors Alissa et al.13

Farina et al.29

Suttapreyasri and Leepong30

Hauser et al.28

Type of platelet centrifugation system PRP PCCS II (3i Implants Innovations, Palm Beach Gardens, FL, USA) PRP PRGF System IV (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain) PRF EBA 20 (Andreas Hettich GmbH and Co., KG, Tuttlingen, Germany) PRF NR

Centrifugation parameters: No., speed, time

Volume of blood drawn, ml

Anticoagulant solution

27

Citrate dextrose

1 3200 rpm 12 min

Autologous thrombin

20

Trisodium citrate

1 580 g 8 min

Calcium chloride

10

None

1 3000 rpm 10 min

None

8

None

1 2700 rpm 12 min

None

Activator

PRP, platelet-rich plasma; PRF, platelet-rich fibrin; NR, not reported.

in humans.41–45 In a classical study, Amler42 found that the primary clot undergoes almost full remodelling during the first week after extraction, which initiates the formation of the osteoid matrix. After 38 days, the socket is filled with about twothirds of trabecular bone. Evian et al.44 found that the socket is completely filled with bone at 10 weeks after extraction. Trombelli et al.45 concluded that the healing time of extraction sockets varies significantly between individuals, and remodelling from woven bone to lamellar bone occurs slowly. Trials with animals to evaluate the phases of new bone formation in extraction sites have revealed that the woven bone, which is found in the bone defect area in the earliest phase, begins to be replaced with lamellar bone in 60– 90 days.46,47 In 120–180 days, the socket is filled with lamellar bone, and the new periosteum is already stable and in place.46 Two recent reviews have confirmed that dimensional changes of soft and hard tissues may be faster in the first 3–6 months after extraction, followed by gradual reductions in dimensions thereafter.2,3 In comparison with the biological time necessary for socket healing, the mean follow-up time (2.25 months) of the studies included in this review may be too short to provide evidence of the effect of platelet concentrates on the later phases of socket healing. According to Plachokova et al.,48 studies with a short follow-up (up to 3 months) using plasma concentrates for bone regeneration have better results than studies with longer follow-up times, which suggests that plasma may have a signifi-

cant effect only on the initial phases of healing. Pharmacological treatment

In the studies included in this systematic review, antibiotics were not prescribed. Although the prophylactic prescription of antibiotics remains a controversial issue in the literature,49,50 two of the studies included in this review actually reported postoperative complications, such as dental alveolitis and infection.13,28 Alissa et al.13 used a quality of life questionnaire in the first week after extraction and found that the patients in the test group (PRP) required less analgesia than those in the control group. In two studies,15,29 rinsing the surgical site with 0.12% chlorhexidine gluconate was recommended. This recommendation was based on the study conducted by Bragger et al.,51 who found that patients who rinsed their mouth with a placebo solution had up to 1 mm more bone resorption at 6 months after extraction than those patients who rinsed with chlorhexidine. Flap vs. flapless

Full-thickness flaps were raised in two of the studies reviewed.13,28 Despite the possible effect of a full-thickness flap on future bone resorption, one of the studies13 found positive results of the association of extractions with a flap and the use of autologous plasma concentrates. The other study,28 which compared groups with and without a flap, found better bone quality on micro-

CT analysis and less horizontal bone resorption in the flapless groups. This result is in agreement with the conclusion of an RCT that evaluated the effect of flaps in extractions sockets.9 The authors found less bone resorption and greater preservation of keratinized gingiva at 3 months after extraction in the group without a flap. Other studies have found similar results.52–54 Platelet-rich plasma (PRP) vs. plateletrich fibrin (PRF)

To fill the extraction sockets, two studies used PRP prepared by different methods.13,29 The other two others studies used PRF.28,30 No significant differences were found between the results of the studies included in this review, which used different types of plasma concentrate. To date, no split-mouth study has compared the performance of PRP and PRF in the preservation of extraction sockets. One of the disadvantages of PRP in comparison with PRF is the greater complexity of preparation. While PRP requires the addition of anti-clotting agents and chemical activators, the preparation of PRF, the second generation of plasma concentrates, is simpler and faster.55 The three-dimensional fibrin matrix is rich in adhesive glycoproteins. Growth factors found in plasma have greater expression and concentration according to some studies, and growth factors and protein matrix are released more slowly and for a longer time in the case of PRF, which makes its performance significantly better than that of its predecessor.56–58 Another advantage of

Please cite this article in press as: Moraschini V, Barboza ESP. Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review, Int J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.ijom.2014.12.010

YIJOM-3061; No of Pages 10

8

Moraschini and Barboza

PRF is the possibility of producing a dense fibrin-rich matrix, which has the ideal consistency for handling and suture,59 different from PRP, which is a gel. Soft tissue dimensional changes

Two studies included in this review found that plasma concentrates had a positive effect on the acceleration of the initial phases of healing and epithelialization of soft tissues.13,30 These conclusions are in agreement with those reported in other studies that have evaluated the effect of plasma concentrates on soft tissue healing.36,60–63 Plasma concentrate cells tend to be the first to populate the surgical wound, and growth factors, such as PDGF, TGF-b, and VEGF, topically placed inside the socket, tend to accelerate soft tissue healing by stimulating angiogenesis, granulation tissue formation, and epithelialization.60,64 Recent studies have found not only improved healing, but also positive gains in keratinized gingiva after soft tissue surgeries using PRF when compared with spontaneous healing control groups.65,66

explanation for this difference may lie in the fact that during all repair processes, PRF might have induced a greater gain in soft tissue thickness, and this gain might have made up for hard tissue losses. Moreover, the use of study casts is not a precise method to evaluate dimensional changes, as impression materials may undergo contraction or expansion. In conclusion, the analysis of the studies included in this review showed considerable heterogeneity in methods and results. The data described here suggest that plasma concentrates reduce pain and inflammation and, therefore, provide more comfort postoperatively. Findings indicate that they may also induce and accelerate soft tissue healing because of growth factors. However, in contrast to other study results, there is no evidence to date for the effect of plasma concentrates on bone regeneration, particularly in the later phases of socket healing. Further randomized studies should be conducted, and a protocol for plasma concentrate preparation should be developed. Moreover, study methods should be standardized so that future results are reliable and comparable.

3.

4.

5.

6.

7.

8.

Hard tissue dimensional changes

Regarding the hard tissue dimensional changes, two studies included in this review found better results in the groups that used autologous plasma concentrates for alveolar socket preservation in comparison to control groups.13,28 In the other two studies included in this review,29,30 there were no statistically significant differences. The mean follow-up time (2.25 months) may have affected results, because more marked dimensional changes may occur for up to 6 months.3,67 Moreover, a histological study found that contaminated sockets heal more slowly than sockets free of contamination.68 Therefore, to improve the reliability of results, extractions due to periodontal disease, abscesses, or other infections should be excluded from studies evaluating new bone formation in extraction sockets. Horizontal changes of combined hard and soft tissues

In sites with no socket preservation procedures, mean horizontal and vertical changes at 6 months are expected to be 3.8 mm and 1.24 mm, respectively.69,70 Suttapreyasri and Leepong30 analyzed horizontal changes of the alveolar ridge in soft and hard tissues using casts. Eight weeks after extraction, buccal and lingual tissues in the PRF group had less resorption than in the control group. A possible

Funding

None. 9.

Competing interests

The authors declare that there was no conflict of interest in the elaboration of this study. 10.

Ethical approval

Not required.

11.

Patient consent

12.

Not required. Acknowledgements. This paper was prepared as part of the obligation of the first author to fulfil the requirements of the doctoral program in dentistry of Fluminense Federal University.

References 1. Barone A, Ricci M, Tonelli P, Santini S, Covani U. Tissue changes of extraction sockets in humans: a comparison of spontaneous healing vs. ridge preservation with secondary soft tissue healing. Clin Oral Implants Res 2013;24:1231–7. 2. Van der Weijden F, Dell’Acqua F, Slot DE. Alveolar bone dimensional changes of

13.

14.

15.

post-extraction sockets in humans: a systematic review. J Clin Periodontol 2009;36: 1048–58. Tan WL, Wong TL, Wong MC, Lang NP. A systematic review of post-extractional alveolar hard and soft tissue dimensional changes in humans. Clin Oral Implants Res 2012;23:1–21. Becker W, Becker BE, Caffesse R. A comparison of demineralized freeze-dried bone and autologous bone to induce bone formation in human extraction sockets. J Periodontol 1994;65:1128–33. Wang HL, Kiyonobu K, Neiva RF. Socket argumentation: rationale and technique. Implant Dent 2004;13:286–96. Barone A, Aldini NN, Fini M, Giardino R, Calvo Guirado JL, Covani U. Xenograft versus extraction alone for ridge preservation after tooth removal: a clinical and histomorphometric study. J Periodontol 2008; 79:1370–7. Barboza ES, Stutz B, Ferreira VF, Carvalho W. Guided bone regeneration using nonexpanded polytetrafluoroethylene membranes in preparation for dental implants. A report of 420 cases. Implant Dent 2010; 19:2–7. Calasans-Maia M, Resende R, Fernandes G, Calasans-Mais J, Alves AT, Granjeiro JM. A randomized controlled clinical trial to evaluate a new xenograft for alveolar socket preservation. Clin Oral Implants Res 2014; 25:1125–30. Barone A, Toti P, Piatelli A, Lezzi G, Derchi G, Covani U. Extraction socket healing in humans after ridge preservation techniques: comparison between flapless and flapped procedures in a randomized clinical trial. J Periodontol 2014;85:14–23. Anitua E. The use of plasma-rich growth factors (PRGF) in oral surgery. Pract Proced Aesthet Dent 2001;13:487–93. Carlson NE, Roach Jr RB. Platelet-rich plasma: clinical applications in dentistry. J Am Dent Assoc 2002;133:1383–6. Gruber R, Varga F, Fischer MB, Watzek G. Platelets stimulate proliferation of bone cells: involvement of platelet-derived growth factors, microparticles and membranes. Clin Oral Implants Res 2002;13: 529–35. Alissa R, Esposito M, Horner K, Oliver R. The influence of platelet-rich plasma on the healing of extraction sockets: an explorative randomised clinical trial. Eur J Oral Implantol 2010;3:121–34. Lynch SE, Nixon JC, Colvin RB, Antoniades HN. Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. Proc Natl Acad Sci U S A 1987;84:7696–700. Simon BI, Gupta P, Tajbakhsh S. Quantitative evaluation of extraction socket healing following the use of autologous platelet-rich fibrin matrix in humans. Int J Periodontics Restorative Dent 2011;31:285–95.

Please cite this article in press as: Moraschini V, Barboza ESP. Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review, Int J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.ijom.2014.12.010

YIJOM-3061; No of Pages 10

Platelet concentrates for socket preservation 16. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Loannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med 2009;6:1–6. 17. Needleman IG. A guide to systematic reviews. J Clin Periodontol 2002;29 (Suppl. 3):6–9. 18. Schardt C, Adams MB, Owens T, Keitz S, Fontelo P. Utilization of the PICO framework to improve searching PubMed for clinical questions. BMC Med Inform Decis Mak 2007;15:7–16. 19. Stevens KR. Systematic reviews: the heart of evidence-based practice. AACN Clin Issues 2001;12:529–38. 20. Schulz KF, Altman DG, Moher D. Consort 2010 statement: updated guidelines for reporting parallel group randomized trials. Obstet Gynecol 2010;115:1063–70. 21. Stroup DF, Berlin JA, Morton SC, Olkin L, Williamson GD, Renie D, et al. Metaanalysis of observational studies in epidemiology: a proposal for reporting. Metaanalyses Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283:2008–12. 22. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007;370:1453–7. 23. Moher D, Schulz KF, Altman DG, CONSORT Group (Consolidated Standards of Reporting Trials). The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. J Am Podiatr Med Assoc 2001;91:437–42. 24. Moher D, Cook DJ, Eastwood S, Olkin L, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomized controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet 1999;354:1896–900. 25. Esposito M, Coulthard P, Worthington HV, Jokstad A. Quality assessment of randomized controlled trials of oral implants. Int J Oral Maxillofac Implants 2000;16: 783–92. 26. Needleman IG. CONSORT. Consolidated Standards of Reporting Trials. Br Dent J 1999;186:207. 27. Ten Heggeler JM, Slot DE, Van der Weijden GA. Effect of socket preservation therapies following tooth extraction in non-molar regions in humans: a systematic review. Clin Oral Implants Res 2011;22:779–88. 28. Hauser F, Gaydarov N, Badoud I, Vazquez L, Bernard JP, Ammann P. Clinical and histological evaluation of postextraction plateletrich fibrin socket filling: a prospective randomized controlled study. Implant Dent 2013;22:295–303.

29. Farina R, Bressan E, Taut A, Cucchi A, Trombelli L. Plasma rich in growth factors in human extraction sockets: a radiographic and histomorphometric study on early bone deposition. Clin Oral Implants Res 2013;24: 1360–8. 30. Suttapreyasri S, Leepong N. Influence of platelet-rich fibrin on alveolar ridge preservation. J Craniofac Surg 2013;24:1088–94. 31. Landry R, Turnbull R, Howley T. Effectiveness of benzydamine HCl in the treatment of periodontal post-surgical patients. Res Clin Forums 1998;10:105–18. 32. Gawande PD, Halli R. Efficacy of platelet rich plasma in bone regeneration after surgical removal of impacted bilateral mandibular third molars: pilot study. J Maxillofac Oral Surg 2009;8:301–7. 33. Sammartino G, Tia M, Marenzi G, Di Lauro AE, D’Agostino E, Claudio PP. Use of autologous platelet-rich plasma (PRP) in periodontal defect treatment after extraction of impacted mandibular third molars. J Oral Maxillofac Surg 2005;63:766–70. 34. Vivek GK, Sripathi Rao BH. Potential for osseous regeneration of platelet rich plasma: a comparative study in mandibular third molar sockets. J Maxillofac Oral Surg 2009;8:308–11. 35. Ce´lio-Mariano R, Melo WM, Carneiro-Avelino C. Comparative radiographic evaluation of alveolar bone healing associated with autologous platelet-rich plasma after impacted mandibular third molar surgery. J Oral Maxillofac Surg 2012;70:19–24. 36. Rutkowski JL, Johnson DA, Radio NM, Fennell JW. Platelet rich plasma to facilitate wound healing following tooth extraction. J Oral Implantol 2010;36:11–23. 37. Gu¨rbu¨zer B, Pikdoken L, Urhan M, Suer BT, Narin Y. Scintigraphic evaluation of early osteoblastic activity in extraction sockets treated with platelet-rich plasma. J Oral Maxillofac Surg 2008;66:2454–60. 38. Gu¨rbu¨zer B, Pikdoken L, Tunali M, Urhan M, Kucukodaci Z, Ercan F. Scintigraphic evaluation of osteoblastic activity in extraction sockets treated with platelet-rich fibrin. J Oral Maxillofac Surg 2010;68:980–9. 39. Mozzati M, Martinasso G, Pol R, Polastri C, Cristiano A, Muzio G, et al. The impact of plasma rich in growth factors on clinical and biological factors involved in healing processes after third molars extraction. J Biomed Mater Res 2010;95:741–6. 40. Weibrich G, Kleis WK. Curasan PRP vs. PCCS PRP system collection efficiency and platelet counts of two different methods for the preparation of platelet-rich plasma. Clin Oral Implants Res 2002;13:437–43. 41. Mangos JF. The healing of extraction wounds: an experimental study based on microscopic and radiographic investigations. N Z Dent J 1941:4–24. 42. Amler MH. The time sequence of tissue regeneration in human extraction wounds.

43.

44.

45.

46.

47.

48.

49.

50.

51.

52.

53.

54.

55.

9

Oral Surg Oral Med Oral Pathol 1969;27: 309–18. Boyne PJ. Osseous repair of the postextraction alveolus in man. Oral Surg Oral Med Oral Pathol 1969;21:805–13. Evian CI, Rosenberg ES, Coslet JG, Corn H. The osteogenic activity of bone removed from healing extraction sockets in humans. J Periodontol 1982;53:81–5. Trombelli L, Farina R, Marzola A, Bozzi L, Liljenberg B, Lindhe J. Modeling and remodeling of human extraction sockets. J Clin Periodontol 2008;35:630–9. Cardaropoli G, Arau´jo M, Lindhe J. Dynamics of bone tissue formation in tooth extraction sites: an experimental study in dogs. J Clin Periodontol 2003;30:809–18. Scala A, Lang NP, Schweikert MT, de Oliveira JA, Rangel-Garcia Jr I, Botticelli D. Sequential healing of open extraction sockets. An experimental study in monkeys. Clin Oral Implants Res 2014;25:288–95. Plachokova AS, Nikolidakis D, Mulder J, Jansen JA, Creugers NH. Effect of plateletrich plasma on bone regeneration in dentistry: a systematic review. Clin Oral Implants Res 2008;19:539–45. Ahmad N, Saad N. Effects of antibiotics on dental implants: a review. J Clin Med Res 2012;4:1–6. Ata-Ali J, Ata-Ali F, Ata-Ali F. Do antibiotics decrease implant failure and postoperative infections? A systematic review and meta-analysis. Int J Oral Maxillofac Surg 2014;43:68–74. Bragger U, Schild U, Lang NP. Effect of chlorhexidine (0.12%) rinses on periodontal tissue healing after tooth extraction. (II). Radiographic parameters. J Clin Periodontol 1994;21:422–30. Fickl S, Zuhr O, Wachtel H, Bolz W, Huerzeler M. Tissue alterations after tooth extraction with and without surgical trauma: a volumetric study in the beagle dog. J Clin Periodontol 2008;35:356–63. Blanco J, Nun˜ez V, Aracil L, Mun˜oz F, Ramos I. Ridge alterations following immediate implant placement in the dog: flap versus flapless surgery. J Clin Periodontol 2008;35:640–8. Lazic´ C, Golubovic´ M, Markovic´ A, Sc´epanovic´ M, Misˇic´ T, Vlahovic´ Z. Immunohistochemical analysis of blood vessels in periimplant mucosa: a comparison between mini-incision flapless and flap surgeries in domestic pigs. Clin Oral Implants Res 2014. http://dx.doi.org/10.1111/clr.12337. [Epub ahead of print]. Del Corso M, Vervelle A, Simonpieri A, Jimbo R, Inchingolo F, Sammartino G, et al. Current knowledge and perspectives for the use of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in oral and maxillofacial surgery. Part 1: Periodontal and dentoalveolar surgery. Curr Pharm Biotechnol 2012;13:1207–30.

Please cite this article in press as: Moraschini V, Barboza ESP. Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review, Int J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.ijom.2014.12.010

YIJOM-3061; No of Pages 10

10

Moraschini and Barboza

56. Jeong KL, Kim SG, Oh JS, Lee SY, Cho YS, Yang SS, et al. Effect of platelet-rich plasma and platelet rich-fibrin on peri-implant bone defects in dogs. J Biomed Nanotechnol 2013; 9:535–7. 57. He L, Lin Y, Hu X, Zhang Y, Wu H. A comparative study of platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) on the effect of proliferation and differentiation of rat osteoblasts in vitro. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108:707–13. 58. Dohan Ehrenfest DM. How to optimize the preparation of leukocyte- and platelet-rich fibrin (L-PRF, Choukroun’s technique) clots and membranes: introducing the PRF box. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:275–8. 59. Dohan Ehrenfest DM, Del Corso M, Diss A, Mouhyi J, Charrier JB. Three-dimensional architecture and cell composition of a Choukroun’s platelet-rich fibrin clot and membrane. J Periodontol 2010;81:546–55. 60. Lindeboom JA, Mathura KR, Aartman IH, Kroon FH, Milstein DM, Ince C. Influence of the application of platelet-enriched plasma in oral mucosal wound healing. Clin Oral Implants Res 2007;18:133–9. 61. Anitua E. Plasma rich in growth factors: preliminary results of use in the preparation of future sites for implants. Int J Oral Maxillofac Implants 1999;14:529–35. 62. Cheung WS, Griffin TJ. A comparative study of root coverage with connective tissue and

63.

64.

65.

66.

67.

68.

platelet concentrate grafts: 8-month results. J Periodontol 2004;75:1678–87. El-Sharkawy H, Kantarci A, Deady J, Hasturk H, Liu H, Alshahat M, et al. Platelet-rich plasma: growth factors and pro- and anti-inflammatory properties. J Periodontol 2007;78:661–9. Fennis JP, Stoelinga PJ, Jansen JA. Mandibular reconstruction: a histological and histomorphometric study on the use of autogenous scaffolds, particulate corticocancellous bone grafts and platelet rich plasma in goats. Int J Oral Maxillofac Implants 2004;33:48–55. 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;32:41–50. 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 treatment of adjacent multiple gingival recessions: a 6-month study. J Periodontol 2009;80:244–52. Schropp L, Wenzel A, Kostopoulos L, Karring T. Bone healing and soft tissue contour changes following single-tooth extraction: a clinical and radiographic 12month prospective study. Int J Periodontics Restorative Dent 2003;23:313–23. Ahn JJ, Shin HI. Bone tissue formation in extraction sockets from sites with advanced

periodontal disease: a histomorphometric study in humans. Int J Oral Maxillofac Implants 2008;23:1133–8. 69. Lang NP, Pun BL, Lau IK, Li KY, Wong MC. A systematic review on survival and success rates of implants placed immediately into fresh extraction sockets after at least one year. Clin Oral Implants Res 2012;23 (Suppl. 5):39–66. 70. Ha¨mmerle CH, Araujo MG, Simion M. Osteology Consensus Report: evidence-based knowledge on the biology and treatment of extraction sockets. Clin Oral Implants Res 2012;23(Suppl. 5):80–2.

Address: Vittorio Moraschini Department of Periodontology School of Dentistry Fluminense Federal University Rua Mario dos Santos Braga 30 Centro Nitero´i Cep. 24020-140 Rio de Janeiro Brazil Tel: +55 2130268190 E-mail: [email protected]

Please cite this article in press as: Moraschini V, Barboza ESP. Effect of autologous platelet concentrates for alveolar socket preservation: a systematic review, Int J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.ijom.2014.12.010