Journal of Investigative and Clinical Dentistry (2014), 5, 1–14

REVIEW ARTICLE Priodontics

Additive effect of autologous platelet concentrates in treatment of intrabony defects: a systematic review and meta-analysis Saurav Panda1, Jayakumar Doraiswamy2, Sankari Malaiappan2, Sheeja Saji Varghese2 & Massimo Del Fabbro3 1 Department of Periodontia, Institute of Dental Sciences and SUM Hospital, Bhubaneswar, Odisha, India 2 Department of Periodontia, Saveetha Dental College and Hospitals, Saveetha University, Chennai, Tamil Nadu, India 3 Department of Biomedical, Surgical and Dental Sciences, Scientific Institute for Care and Clinical Research (IRCCS) Galeazzi Orthopedic Institute, Universit a degli Studi di Milano, Milan, Italy

Keywords intrabony defects, periodontal regeneration, platelet concentrates, platelet-rich fibrin, systematic review. Correspondence Dr. S. Panda, Department of Periodontia, Institute of Dental Science & SUM Hospital, Bhubaneswar 751003, Odisha, India. Tel: +918908218110 Fax: +91 674 238 6380 Email: [email protected] Received 27 November 2013; accepted 5 May 2014. doi: 10.1111/jicd.12117

Abstract The aim of the present review is to systematically evaluate the additive effect of autologous platelet concentrates (APCs) in treatment of intrabony defects when used along with other regenerative procedures and when used alone in terms of clinical and radiological outcomes. A search was performed in electronic databases (i.e., MEDLINE and the Cochrane Central Register of Controlled Trials) in order to identify randomized clinical trials (RCTs) assessing the additive efficacy of APCs for healing and regeneration of hard and soft tissues in patients undergoing regenerative surgical procedures for the treatment of intrabony defects, having a follow-up of at least 9 months. Included studies underwent risk of bias assessment and data extraction. The main variables evaluated for efficacy were: pocket depth (PD), clinical attachment level (CAL), radiographic bone filling, and postoperative pain. The effect of APCs adjunct was evaluated for the following procedures: open flap debridement (OFD) alone, OFD plus grafting of the defect with autogenous bone or bone substitutes, and grafting in combination with a covering membrane for guided tissue regeneration (GTR). Platelet-rich fibrin (PRF) has a significant additive effect when used along with OFD. Plateletrich plasma (PRP) has a significant additive effect when used along with bone grafts. Conversely, PRP was found to be ineffective when used in combination with GTR procedures. No study evaluated the effect of APCs on postoperative pain. Platelet-rich plasma may be used advantageously as an adjunct to grafting materials, but not in combination with GTR, for treatment of intrabony defects. Moreover, PRF can be effective as a sole regenerative material, in combination with OFD. There is still a lack of evidence regarding the effect of PRF in combination with grafting materials and GTR, the effect of other types of APCs such as plasma rich in growth factors, and the effect of APCs on postoperative pain.

Introduction Regeneration has been defined as the reconstitution of a lost or injured part to restore the architecture and function of the periodontium.1 The goal of periodontal therapy has always been the regeneration of lost attachment apparatus.

ª 2014 Wiley Publishing Asia Pty Ltd

The objective of the periodontal reconstructive therapy is to regenerate all the tissues of the periodontium, including a functional periodontal ligament, alveolar bone, and cementum. Currently, there are a variety of treatment modalities available for periodontal regenerative therapy, including bone grafts and substitutes, guided tissue regen-

1

S. Panda et al.

Treatment of intrabony defects

eration (GTR), the use of growth factors, applications of tissue engineering, or combinations of two or more of the above listed approaches. Despite advances in surgical procedures and materials, complete and predictable regeneration of the lost periodontium remains a therapeutic challenge. In recent years, the knowledge of wound healing has been greatly enhanced by the identification and understanding of the role of growth factors (GFs) in the healing process and the technological intricacies required for using them. Plateletderived growth factors are naturally synthesized polypeptides, functioning as potent biologic mediators stimulating various cellular activities during wound healing, like cell proliferation, differentiation, and matrix synthesis, and thereby facilitating periodontal regeneration. In recent years, there has been a growing interest in the use of platelet concentrates for the treatment of many intraoral clinical conditions, including periodontal defects. However, there has been no agreement about the advantages derived from the adjunct of platelet concentrates to periodontal surgical procedures and various regenerative materials, as evidenced in some literature reviews. The first systematic review by Plachokova et al. in 20082 that evaluated the effect of platelet-rich plasma (PRP) on clinical applications in dentistry reported its beneficial effects in treatment of periodontal defects. Another systematic review by Kotsovillis et al.3 that evaluated the effect of a PRP adjunct in treatment of intraosseous defects, underlined the limits and the heterogeneity of available data and cautiously concluded that the specific selection of the graft type and the surgical procedures combined with PRP may be important. A recent systematic review by Del Fabbro et al.4 also evaluated the effect of PRP in various regenerative procedures of periodontal defects and concluded that it may be used advantageously as an adjunct to grafting procedure treatment for intrabony defects. This review also suggested that the use of PRP is ineffective when a GTR procedure is used for treating intrabony defects. Autologous platelet concentrates (APCs) include different types of preparations, among which the most well known are PRP, platelet-rich fibrin (PRF), and plasma rich in growth factors (PRGF). Several commercial techniques for obtaining platelet concentrates are available, however, their applications have been confusing because each method leads to a different product with different biology and potential uses. PRP is considered as a first generation platelet concentrate, and shows the release of an array of growth factors for 7 days, with peak release on its first day of application.5 Platelet-rich fibrin is considered as a second generation APC, as its technique of preparation is simpler when compared to PRP. In addition, PRF shows a sustained release of GFs for a period of 21 days with a peak rise at 2

7 days, thereby inducing proliferation, differentiation, and migration of cells responsible for periodontal regeneration.6 Plasma rich in growth factors is also a second-generation platelet concentrate, for which main difference with respect to PRP is the absence of leucocytes and the small blood volume required. According to a recent proposal, platelet concentrates can be classified into four categories, depending on their leucocyte and fibrin content: P-PRP (pure PRP, without leucocytes, which includes PRGF), L-PRP (PRP with leucocytes included), P-PRF and L-PRF.5 The contribution of blood-derived platelets to the bone-healing process is thought to be based on the GFs stored in their granules and released upon activation. The main GFs released from platelet aggregates are the following: platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-B), vascular endothelial growth factor (VEGF), epithelial growth factor (EGF), insulin-like growth factor 1 (IGF1), and basic fibroblast growth factor (bFGF), as well as three blood proteins known to act as cell adhesion molecules for osteoconduction (fibrin, fibronectin, and vitronectin). The adjunctive use of platelet concentrates to surgical procedures is recent and its efficacy remains controversial. Autologous platelet concentrates have been investigated as a possible beneficial adjunct in various regenerative procedures for treating intraosseous defects. In the past few years there has been an increasing interest on the use of platelet concentrates (especially PRF) in the oral field for the surgical treatment of bone defects. In particular, researchers have started to investigate whether the different properties of different platelet concentrates (e.g. PRP, PRF) can lead to different clinical and radiological outcomes, and/or to variable effects on the patient’s postoperative quality of life, which could lead to the preference for the use of specific platelet concentrates for specific surgical applications. Therefore, we decided to perform an updated systematic review evaluating the effect of autologous platelet concentrates (APCs) in periodontal regeneration. Hence, the aim of this evidence based review was to systematically evaluate the additive effect of autologous platelet concentrates (APCs) in treatment of periodontal intrabony defects, both when used along with other regenerative procedures and when used alone, in terms of clinical and radiological outcomes. Structured questions (a) What is the adjunctive effect of APCs over open flap debridement (OFD) in the treatment of periodontal intraosseous defects? Pico Analysis Patients: patients with periodontal intrabony defects. ª 2014 Wiley Publishing Asia Pty Ltd

S. Panda et al.

Intervention: treated with application of APCs alone. Comparison: compared to those treated with OFD alone. Outcome: to be assessed in terms of pocket-depth reduction, gain in attachment level, and defect fill. (b) What is the adjunctive effect of APCs in the treatment of periodontal intraosseous defects when using graft materials? Pico Analysis Patients: patients with periodontal intrabony defects. Intervention: treated with addition of APCs with bone graft placement. Comparison: compared with those treated with bone graft alone. Outcome: to be assessed in terms of pocket-depth reduction, gain in attachment level, and defect fill. (c) What is the adjunctive effect of APCs in the treatment of periodontal intraosseous defects when using a combined graft/GTR protocol? Pico Analysis Patients: patients with periodontal intrabony defects. Intervention: treated with addition of APCs along with bone graft and barrier membrane. Comparison: compared with those treated with bone graft and barrier membrane. Outcome: to be assessed in terms of pocket-depth reduction, gain in attachment level, and defect fill.

Materials and methods Search strategy For the identification of randomized clinical trials (RCTs) to be considered for inclusion in this systematic review, MEDLINE (accessed through PUBMED interface) and COCHRANE CENTRAL were employed as electronic databases. A literature search was carried out on articles published up to and including June 2012. Articles available online in electronic form prior to their publication in printed form were considered eligible for inclusion in this systematic review. Last electronic search was carried out on June 30, 2012. The following search terms alone and in combination using Boolean operators were used by means of PUBMED search builder: “platelet rich plasma,” “autologous platelet concentrate,” “platelet rich fibrin,” “intrabony defects,” “infra-bony defects,” “two-walled defects,” and “threewalled defects.” No language restriction was applied during the electronic search to include all the possible clinical trials in the potential relevant article search phase of the systematic review. No publication date restriction was applied. Reference lists of the reviews and of the identified ª 2014 Wiley Publishing Asia Pty Ltd

Treatment of intrabony defects

randomized trials were also checked for possible additional studies. Two reviewers (S.P., M.D.F.) independently screened the titles and abstracts of all retrieved articles according to predefined selection criteria. Additionally, a hand search was also carried out in all relevant periodontal journals up to and including June 2012: International Journal of Periodontics and Restorative Dentistry, Journal of Periodontology, Journal of Clinical Periodontology, and Journal of Periodontal Research. Inclusion criteria The criteria for the articles to be included in this present systematic review were as follows: (a) clinical trials, either of a parallel group or of a splitmouth design; (b) presence of at least one experimental group in which APCs were clinically applied as an adjunct to surgical procedures alone or in combination with bone grafting materials or GTR procedures for the therapy of periodontal intrabony defects; (c) presence of an appropriate non-APC control group, in which the same therapeutic procedures as those employed in at least one experimental group were clinically applied for the therapy of periodontal intraosseous defects, without the adjunctive effect of APCs; (d) patients included in the RCT should present with intrabony defects (clinical attachment level (CAL) ≥ 4 mm and pocket depth (PD) ≥ 3mm); (e) patients included in the RCT should have no systemic diseases that could potentially influence the outcome of periodontal therapy; (f) report of clinical attachment level at baseline and at the end of the follow-up period as the primary outcome variable and PD or radiographic defect depth at baseline and at the end of follow-up period as the secondary outcome variable; (g) articles having follow-up period of at least 9 months. Exclusion criteria (a) RCT design, including both parallel group and splitmouth design; (b) periodontal intrabony defects extending into furcation areas of teeth; (c) intrabony defects extending apically with endodontic involvements. Two reviewers (S.P. and M.D.F.) independently screened the titles and the abstracts of the articles initially retrieved through the electronic search. In the case of disagreement a joint decision was taken by discussion. 3

S. Panda et al.

Treatment of intrabony defects

The same reviewers assessed the full texts of all studies of possible relevance independently in order to confirm whether they met all inclusion criteria, Table 1 lists the reason(s) for exclusion of articles at this stage. Data extraction Two reviewers (S.P. and M.D.F.) independently extracted the data. Cases of disagreement were discussed until an agreement was reached. The following variables were extracted from each included study: study design, sample size (patients and teeth treated), follow-up duration, type of APC used, data on PD, CAL, radiographic fill, grafting material, and use of a membrane. The following methodological parameters were also recorded: the random sequence generation method, allocation concealment, blinding of outcome assessment, dropout explanation, sample size calculation, baseline comparison, clear definition of inclusion/exclusion criteria, and errors in methodology. Methodological quality assessment The methodological quality of the selected studies was independently evaluated by two reviewers (S.P. and M.D.F.) according to the above methodological parameters. All the criteria were assessed as adequate (yes), inadequate (no) or unclear. The authors of the identified

Table 1. Characteristics of excluded studies Reference

Reason for exclusion

26 20 18 13 38 39 22 1 31 15 36 17 37 25 5 2 14 32 21 3 23 10

Postoperative evaluation done at 6 months Control and experimental group uses PRF Postoperative evaluation done at 6 months Study includes apico-marginal defects Comparison between PPP and PRP Comparison between smokers vs. nonsmokers Postoperative evaluation done at 6 months Postoperative evaluation done at 6 months Control and experimental group uses PRP Postoperative evaluation done at 6 months Control and experimental group uses PRP Control and experimental group uses PRP Mixed (parallel and split-mouth) design Mixed (parallel and split-mouth) design Not a clinical trial Postoperative evaluation done at 6 months Postoperative evaluation done at 6 months Control and experimental group uses PRP Postoperative evaluation done at 6 months Postoperative evaluation done at 6 months Full text not available Control and experimental group uses EMD

EMD, enamel matrix derivatives; PRF, platelet-rich fibrin; PRP, plateletrich plasma.

4

RCTs were contacted to request clarification or to provide missing information as needed. In order to summarize the validity of studies, they were grouped into the following categories: low risk of bias if at least five of the quality criteria were judged adequate; moderate risk of bias if three to four quality criteria were judged adequate; high risk of bias if no more than two quality criteria were judged adequate. Criteria for assessing the risk of bias of RCTs in the present review were adapted from the guidelines reported in the Cochrane Handbook.7 In case of discrepancy between the two reviewers, an agreement was reached through discussion. Data analysis A meta-analysis was performed for each of the main comparisons investigated, if there was sufficient homogeneity among studies. The main comparisons were: (i) APC and OFD versus OFD alone; (ii) APC and bone graft (BG) versus BG alone; (iii) APC, BG, and GTR versus BG and GTR alone. For meta-analysis as well as for assessment of the risk of bias the software Comprehensive Meta-Analysis (CMA) was used (Version 2.0, BiostatTM, Englewood, NJ, USA). Results After the full-text evaluation, 15 studies were included for data extraction and analysis. The flow-chart depicticting the sequence of article selection is depicted in Figure 1. The list of excluded articles,8–31 along with the main reason for exclusion is summarized in Table 1. The general information regarding the selected articles is provided in Table 2, and Tables 3–5 show the variable of interest, that is, PD reduction, CAL, and radiological bone fill, respectively, for all the selected articles in this review. Quality of studies The quality of most of the included studies was generally good with a risk of bias score of “low” to “moderate” (Table 6). All studies included are randomized clinical trials with a high level of evidence score of “2”.7 However, most of the studies lacked mentioning proper sample size calculation and any protocol deviation, which may lead to heterogeneity in results. Most studies also failed to reveal the baseline comparison of the defect characteristics. Platelet-rich fibrin along with OFD When evaluating the additive effect of platelet concentrates in the surgical treatment of periodontal intrabony defects and using CAL as the primary outcome variable and PD as well as radiological intra bony defect depth as ª 2014 Wiley Publishing Asia Pty Ltd

S. Panda et al.

Treatment of intrabony defects

Figure 1. Selection flow-chart for articles included.

the secondary outcome variable, an overall positive effect was detected. Four studies32–35 were included in this meta-analysis, which evaluated the effect of PRF when used along with OFD. All studies were designed with a 9-month follow-up duration. The initial CAL ranged from 6.20 to 7.69 mm and from 6.26 to 6.50 mm in the test and control group, respectively, being rather homogeneous among the different studies. Out of the four studies, two studies32,34 showed a significantly greater PD reduction and clinical attachment gain with the use of PRF in the test group, when compared to the control group, where only the OFD procedure was employed. The results of meta-analysis (Figure 2a) were consistent with this finding, where one study32 lies beyond the funnel-plot homogeneity intervals (Figure 2b). ª 2014 Wiley Publishing Asia Pty Ltd

Within-group comparison showed a statistically significant PD reduction and CAL gain at the end of the followup in both test and control group in all four studies.32–35 Radiologically, the use of PRF as an adjunct with OFD showed a significantly greater bone fill, as compared to OFD alone, in all four studies.32–35 Platelet-rich plasma along with OFD Only one study33 included in this review evaluated the additive effect of PRP along with OFD in the treatment of intrabony defects. Pocket-depth reduction as well as CAL gain were not statistically significant when the endline result of both control and test group were compared. However, there was a significant amount of PD reduction and CAL gain at the end of the follow-up in both groups, 5

S. Panda et al.

Treatment of intrabony defects

Table 2. General information of selected articles Reference

Study design

Sample size

Test group

Control group

Study duration

16 29

RCT/split-mouth RCT/parallel

24 sites (12) 90 sites

TMBC alone OFD alone

12 months 9 months

30

RCT/parallel

90 sites

35 33 34 27 8 28 9 7 11 12 4 24

RCT/parallel RCT/split-mouth RCT/parallel RCT/split-mouth RCT/parallel RCT/parallel RCT/parallel RCT/parallel RCT/parallel RCT/parallel RCT/split-mouth RCT/parallel

32 40 56 28 30 60 28 29 24 30 50 70

TMBC + PRP PRF + OFD PRF + HA + OFD PRF + OFD PRP + OFD PRF + OFD BTCP + PRP PRF + OFD BPBM + PRP ABBM + PRP DFDBA + PRP BTCP + GTR + PRP BG + PRP ABBM + GTR + PRP NBM + GTR + PRP BTCP + GTR + PRP HA + PRP

sites sites (20) sites sites (14) sites sites sites sites sites sites sites (25) sites

OFD alone OFD alone BTCP alone OFD alone BPBM alone ABBM alone DFDBA alone BTCP + GTR BG alone ABBM + GTR NBM + GTR BTCP + GTR HA + saline

9 months 9 9 9 9 1 12 1 9 1 1 12 12

months months (36 weeks) months months year (12 months) months year (12 months) months year (12 months) year (12 months) months months

ABBM, anorganic bovine bone mineral; BG, bone graft; BPBM, bovine porous bone mineral; BTCP, beta tri-calcium phosphate; DFDBA, demineralized freeze dried bone allograft; GTR, guided tissue regeneration; HA, hydroxyapatite; NBM, natural bone mineral; OFD, open flap debridement; PRF, platelet-rich fibrin; PRP, platelet-rich plasma; RCT, random control test.

compared to baseline. In radiological terms, a significantly greater bone fill was found in the PRP group when compared to OFD alone.

No eligible study investigating the effect of PRF or other APCs than PRP in combination with bone graft materials was found.

Platelet-rich plasma along with bone grafts

Platelet-rich plasma along with bone graft and GTR

Seven studies36–42 were included to evaluate the additive effect of PRP when used along with bone graft in treatment of intrabony defects. The main characteristics of these studies are described in Tables 3–6. The baseline CAL ranged from 5.10 to 17.15 mm and from 4.50 to 16.12 mm in the test and control group, respectively, being rather variable among the different studies. Altogether, PRP demonstrated a consistent positive effect on radiological bone fill, when used along with bone substitutes. The forest plot in Figure 2c indicates a significant improvement in the CAL in the group using platelet concentrates in combination with graft materials over the group using graft materials alone. The funnel plot for CAL in Figure 2d showed that variability of each study was rather homogeneous except for one study, which showed the greatest positive effect of PRP adjunct, and also showed the lowest values of presurgical CAL.42 The two studies with the highest presurgical CAL36,39 showed the least favorable outcomes. In two studies in which PRP produced a significant positive effect on CAL gain, the benefit on PD reduction and radiographic bone filling did not achieve statistical significance.36,40 Long-term follow-up and a choice of proper study design could possibly improve the homogeneity of the results.

Four studies29,43–45 were included in this systematic review evaluating the additive effect of the use of PRP when used along with bone graft and GTR. All four studies showed no significant difference in clinical parameters, when compared to the group using bone graft and GTR membrane alone. However, these studies did not consider radiological parameters for their assessment. The initial CAL ranged from 10.1 to 11.1 mm and from 9.9 to 11.4 mm in the test and control group, respectively, being rather homogeneous among the different studies. Platelet-rich plasma showed no additive beneficial effect when combined with bone graft and GTR membrane for the treatment of intrabony defects. Moreover, results obtained by meta-analysis of PD reduction and clinical attachment gain in the experimental group over the control group was not significant, as shown in the forest plot for CAL in Figure 2e. The funnel plot in Figure 2f shows a similar standard error among each study but heterogeneity in outcomes, revealing both positive and negative effects of the adjunct of the PRP in the GTR procedures.

6

Discussion The present systematic review aimed to assess the effect of autologous platelet concentrates (APCs) in improving ª 2014 Wiley Publishing Asia Pty Ltd

S. Panda et al.

Table 3. General interpretation of pocket depth (PD) reduction for selected articles

Treatment of intrabony defects

Reference

Test group†

Control group

Interpretation

16

B–7.28  0.53 12–2.31  0.48

B–7.91  0.71 12–2.81  0.64

29

PRF B–8.17  9–4.27  PRF + HA B–8.37  9–4.10  PRF B–7.88  9–4.06  PRP B–7.90  9–4.13  B–7.88  9–3.19  B–6.30  9–3.50 

OFD B–8.03  1.13

Reduction in PD of 4.38 mm (60.9%) for control compared to 4.97 (68%) for test, P < 0.001 Significant decrease in PD when PRF vs. OFD and PRF + HA vs. OFD, P < 0.001

1.56 1.04 2.19 1.05 0.23 0.24

   

1.67 2.11 1.25 1.43

30

35 33

34 27

B–8.56 9–4.02 B–9.00 9–6.60

1.26 0.69 1.19 0.85 1.44 0.83

8

B–8.6  1.8 12–3.4  1.4

28

B–8.4 12–3.8 B–9.1 12–3.3

9

   

1.9 0.9 0.6 0.5

OFD 9–5.07  0.74 OFD B–7.76  1.22

No significant PD reduction when both PRF vs. OFD and PRP vs. OFD compared

OFD 9–4.80  0.66 B–6.75 9–3.19 B–6.35 9–3.30

   

1.69 1.52 0.23 0.29

B–8.08 9–4.87 B–8.70 9–6.20

   

2.56 1.79 1.57 1.40

B–8.5  2.0 12–3.2  1.3 B–8.0 12–4.5 B–9.0 12–3.6

   

1.5 2.7 0.8 0.9

7

B–7.80  0.28 9–4.20  0.49

B–8.36  0.53 9–5.07  0.45

11

B–8.6  1.7 12–3.1  1.7

B–8.8  1.7 12–3.1  1.0

12

B–8.9  2.3 12–3.4  2.0

B–8.9  2.5 12–3.4  2.3

4

B–9.9  1.4 12–3.6  1.0

B–9.9  1.3 12–3.0  0.9

24

B–7.7  1.5 12–3.0  0.8

B–7.9  1.8 12–4.2  1.9

No significant PD reduction between the groups Significant PD reduction within the group. No significance between the group, P = 0.036 Significant PD reduction both between and within group, P < 0.001 No significant PD reduction between the group, P = 0.43, but significant within the group No significant PD reduction between group, but significant at 12 months within group Significant PD reduction both between and within groups, P < 0.05 No significant PD reduction between the group, but significant at 12 months within the groups, P < 0.001 No significant PD reduction between the group, but significant at 12 months within the groups, P < 0.001 No significant PD reduction between the group, but significant at 12 months within the groups, P < 0.001 No significant PD reduction between the group, but significant at 12 months within the groups, P < 0.001 No significant PD reduction between the group, but significant at 12 months within the groups, P < 0.05 Significant PD reduction both between and within groups

HA, hydroxyapatite; OFD, open flap debridement; PRF, platelet-rich fibrin; PRP, platelet-rich plasma. †B, Baseline; 9, 9 months.

hard and soft tissue healing in the treatment of periodontal intrabony defects based on randomized clinical trials. The high level of evidence and the limited risk of bias for most studies would suggest that the outcomes obtained from these studies are likely to be reliable. However, some flaws regarding sample size calculation ª 2014 Wiley Publishing Asia Pty Ltd

and baseline comparison of the defect characteristics give rise to some doubts on the standardization of the studies. The APCs were found to have an overall beneficial effect when used as an adjunct with other regenerative surgical procedures, but not in combination with GTR. 7

S. Panda et al.

Treatment of intrabony defects

Table 4. General interpretation of gain in clinical attachment level (CAL) for selected articles Reference

Test group†

Control group

Interpretation

16

B–5.24  0.57 12–1.43  0.51 PRF B–6.40  1.33 9–3.37  0.56 PRF + HA B–6.63  1.10 9–2.97  0.93 PRF B–6.20  1.49 9–3.03  0.76 PRP B–6.16  1.53 9–3.23  1.22 B–7.69  1.82 9–3.56  2.06 B–5.10  0.36 9–3.30  0.26 B–6.87  2.34 9–3.56  1.84 B–17.15  1.58 9–12.45  1.25 B–9.9  1.7 12–5.3  1.8 B–8.4  1.9 12–4.8  2.3 B–10.1  1.3 12–5.7  1.1 B–8.53 + 0.42 9–5.40  0.50 B–10.3  1.4 12–5.7  1.6 B–10.9  2.2 12–6.4  1.8 B–11.1  1.9 012–6.1  1.7 B–8.4  1.8 12–5.0  1.8

B–5.14  0.77 12–2.20  0.79 B–6.57  1.17

No significant CAL gain between the group, P < 0.01, but significant at 12 months within the groups Significant CAL gain both within and between the groups, P < 0.001

29

30

35 33 34 27 8 28 9 7 11 12 4 24

9–3.90  0.76

B–6.26  1.17

No significant CAL gain in between the groups, but significant CAL gain within the group P < 0.001

9–3.43  0.89

B–6.50 9–4.38 B–4.50 9–3.40 B–6.23 9–3.46 B–16.12 9–11.96 B–9.6 12–4.9 B–8.1 12–5.9 B–9.9 12–5.9 B–9.07 9–6.21 B–10.4 12–5.9 B–11.1 12–6.5 B–11.4 12–6.2 B–8.8 12–4.2

 1.75  2.16  0.30  0.22  2.11  1.65  1.27  1.59  1.9  1.5  2.2  2.5  1.0  1.2 + 0.57  0.58  2.6  1.8  2.5  2.3  2.1  1.5  1.8  1.9

Significant CAL gain both within and between the groups, P < 0.01 No significant CAL gain in between the groups, but significant CAL gain within the group, P < 0.05 No significant CAL gain in between the groups, but significant CAL gain within the group, P < 0.001 No significant CAL gain in between the groups, but significant CAL gain within the group, P < 0.001 No significant CAL gain in between the groups, but significant CAL gain within the group, P < 0.001 Significant CAL gain both within and between the groups, P < 0.01 No significant CAL gain between the groups, but significant at 12 months within the groups, P < 0.001 No significant CAL gain between the group, but significant at 12 months within the groups, P < 0.001 No significant CAL gain between the group, but significant at 12 months within the groups No significant CAL gain between the group, but significant at 12 months within the groups, P < 0.001 No significant CAL gain between the group, but significant at 12 months within the groups Significant CAL gain both between and within groups, P < 0.001

PRF, platelet-rich fibrin; PRP, platelet-rich plasma. †B, baseline; 9, 9 months.

Briefly, PRP was found to be effective when used in adjunct to bone grafts in treatment of intrabony defects. Platelet-rich fibrin was found to have significantly better tissue healing ability when used in adjunct to OFD compared to OFD alone, in the treatment of such defects. The latter is a novel finding as compared to previous systematic reviews on the same topic. In fact, the most recent systematic review available highlighted the absence of a control group where patients were treated with only OFD.4 This is clearly a significant comparison, as clinical implications would be obvious if APCs did not deliver treatment outcomes superior to OFD. Interestingly, it was possible to perform a meta-analysis, which showed a 8

significant benefit only for PRF and not for other APCs. It is possible that the more robust and long-lasting fibrin mesh of PRF as compared, for example, to PRP, for which only one study investigating such a comparison was found, makes PRF more appealing than other APCs for being used as a regenerative material for intrabony defects treatment. In the study investigating PRP over OFD alone, a markedly higher bone fill was found, suggesting that the use of PRP may improve the radiological outcome, thereby enhancing the hard tissue regeneration, even though this was not clinically evident.33 In the metaanalysis on the above topic, one study showed a markedly positive outcome as compared to others, as shown by ª 2014 Wiley Publishing Asia Pty Ltd

S. Panda et al.

Treatment of intrabony defects

Table 5. General interpretation of radiological bone fill for selected articles Reference

Test group†

16

B–110.59 12–137.66 PRF B–5.63  9–2.43  PRF + HA B–6.03  9–2.17  PRF B–5.06  9–2.26  PRP B–4.90  9–2.20  B–4.52 9–2.39 B–4.90 9–1.70 B–5.18 9–2.68 B–8.48 9–4.44 NA B–9.2 12–5.9 NA B–9.07 9–5.93 NA NA NA B–5.0 12–1.4

29

30

35 33 34 27 8 28 9 7 11 12 4 24

 17.32  14.13

Control group

Interpretation

B–94.49  12.28 12–119.56  10.20 B–5.80  0.81

Radiodensity considered

1.16 0.68

Significant bone fill when PRF vs. OFD, and PRF + HA vs. OFD considered, P < 0.001

9–4.87  1.04 1.16 0.99 B–4.83  1.14 1.36 0.82

Significant bone fill in test group as compared to control

9–4.70  1.14 1.47 1.09  1.11  0.71  0.32  0.18  1.27  0.64  1.44  1.57

B–4.40 9–3.08 B–4.65 9–2.15 B–4.99 9–4.87 B–7.59 9–3.76

       

1.04 0.92 0.26 0.21 1.35 0.92 1.27 1.24

NA  1.4  1.6

B–9.0  1.7 12–6.4  1.9 NA

 0.47  0.56

B–9.64  0.61 9–6.50  1.57 NA NA NA

 1.6  1.3

B–4.8  1.7 12–2.1  1.7

Significant bone fill both within and between the group, P < 0.001 Significant bone fill both within and between the groups, P < 0.050 Significant bone fill in test group as compared to control Significant bone fill within both groups, P < 0.001. No significant difference between the group, P = 0.57 NA Significant bone fill within both groups, P < 0.001. No significant difference between the group NA Significant bone fill within both groups, P < 0.001. No significant difference between the group NA NA NA Significant bone fill in test group as compared to control

HA, hydroxyapatite; OFD, open flap debridement; PRF, platelet-rich fibrin; PRP, platelet-rich plasma. †B, baseline; 9, 9 months.

Figure 2.32 This might be due to lack of baseline comparison and inclusion of defects with different characteristics and severity in this specific study. However, a long-term follow up would have possibly eliminated such heterogeneity and provided a result more in line with the other analogue studies. Clinical attachment level was considered to be the primary outcome variable for evaluating the effect of APCs in the treatment of periodontal intrabony defect. This parameter is commonly used for evaluating the efficacy of regenerative periodontal therapy and is reported by all included studies, unlike other parameters such as PD reduction and radiographic bone fill that are not systematically reported. However, in some studies not all of these parameters provided a concordant result, meaning that the statistically significant benefit of the adjunct of APCs to the surgical procedure was demonstrated by ª 2014 Wiley Publishing Asia Pty Ltd

some parameters (e.g., CAL) but not by others (e.g., PD and radiographic bone fill).36,40 This might simply depend on the relatively short observation period of these studies. In fact, due to slow bone metabolism, radiographic bone filling may require a longer observation period to detect a positive result. The included studies were grouped under various regenerative treatment procedures in adjunct to APCs, so as to attempt a meta-analysis. The result of the meta-analysis was substantially in accordance with previous systematic reviews,3,4 which found a beneficial effect of PRP alone and when combined with bone grafting materials in such defects. The use of bone grafts is considered to be the gold standard in treatment of intrabony defects. Different types of bone-graft materials have been used as a regenerative filler in treatment of intrabony defects, but in the present review it was not possible to analyze them separately because the information would 9

S. Panda et al.

Treatment of intrabony defects

Table 6. Risk of bias assessment – major criteria

Reference

Randomization

Allocation concealment

Assessor blinding

Drop outs

Sample size

Baseline comparison

Inclusion/Exclusion criteria

Error in methodology

Risk of bias

16 29 30 35 33 34 27 8 28 9 7 11 12 4 24

Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No

No Yes Yes No No Yes No No No No No No No Yes No

Yes Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes

No Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes No No No Yes

No Yes Yes Yes No Yes No No No No No No No No No

No No No No No No No Yes Yes Yes Yes Yes Yes Yes Yes

Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

No No No No No No No No No No No No No No No

Moderate Low Low Low Low Low Moderate Low Low Low Low Moderate Moderate Low Moderate

have been too fragmented. In addition, in the meta-analysis of studies evaluating the effect of PRP as an adjunct to bone grafting, one study displayed an extremely positive outcome, well beyond the confidence intervals (Figure 2). This, however, must be interpreted cautiously because it was not actually due to a wide difference in the efficacy of PRP but to an extremely low variability (standard deviation) in both groups of that specific study, which emphasized the beneficial result. This systematic review also investigated the effect of APCs when used in adjunct to GTR barrier membranes. In accordance to a previous systematic review4 it was concluded that PRP did not show any beneficial effect when used with barrier membranes. This insignificance may be due to the masking effect of GTR, which holds a proven efficacy in various regenerative periodontal procedures.46 Another critical point is the presurgical defect depth, which could influence both the choice of regenerative technique and treatment outcomes. In the meta-analysis regarding the effect of PRP in combination with bone grafts it was observed that in the studies with the highest baseline CAL value,37,40 PRP had the least favorable effect, while in the study with the most beneficial effect of PRP the baseline CAL values were the lowest.43 However, since several other differences existed in the protocol of the studies involved in this meta-analysis, such as the graft material, the device for PRP preparation, and the followup duration among others, it was not possible to draw conclusions on the true effect of the initial periodontal condition on the treatment outcome, which should be evaluated with more standardized studies. This systematic review showed positive effects of platelet concentrates that retain a leucocyte component, such 10

as PRP and PRF. However, the effect of leucocyte-poor platelet concentrates such as the PRGF could not be considered in this review as no randomized clinical studies exist in regard to treatment of intrabony defects with such a type of platelet concentrate. In recent in vitro studies, PRGF demonstrated a stimulating effect on both alveolar osteoblasts47 and gingival fibroblasts,48 suggesting a possible beneficial effect in regeneration of periodontal tissues. Of course this must be confirmed by welldesigned clinical studies. The quality of the included studies, as said, was generally good, with moderate to low risk of bias. However, the results of the present literature analysis showed a substantial heterogeneity among different studies with regard to experimental designs, surgical techniques, follow-up duration, and methods of preparation of platelet concentrates. Implications for future research In the present review, one-, two- and three-walled infrabony defects were considered together but it would be beneficial to look at each defect type separately, conducting a meta-analysis to see the effect of APCs on each type of periodontal infrabony defect. This would have been very difficult in the present review, as many of the selected studies did not provide this essential information. Future studies could explore this point. The effect of platelet concentrates other than PRP and PRF (e.g., PRGF) on periodontal intrabony defect treatment has not been investigated. There is also a lack of evidence concerning the effect of APCs on postoperative symptoms like pain and swelling that might enlighten awareness about a patient’s quality of life and preferences ª 2014 Wiley Publishing Asia Pty Ltd

S. Panda et al.

Treatment of intrabony defects

(a)

(b)

(c)

(d)

(e)

(f)

Figure 2. Meta-analysis results for comparison between treatment modalities for clinical attachment level. (a) Forest plot depicting the clinical attachment gain in test group (PRF/OFD) over control group (OFD). (b) Funnel plot depicting the clinical attachment gain in test group (PRF/OFD) over control group (OFD). (c) Forest plot depicting the clinical attachment gain in test group (PRP/BG) over control group (BG alone). (d) Funnel plot depicting the clinical attachment gain in test group (PRP/BG) over control group (BG alone). (e) Forest plot depicting the clinical attachment gain in test group (PRP/BG/GTR) over control group (BG/GTR alone). (f) Funnel plot depicting the clinical attachment gain in test group (PRP/BG/ GTR) over control group (BG/GTR alone). PRF, platelet-rich fibrin; OFD, open flap debridement; BG, BG, bone graft; PRP, platelet-rich plasma; GTR, guided tissue regeneration.

ª 2014 Wiley Publishing Asia Pty Ltd

11

S. Panda et al.

Treatment of intrabony defects

regarding use of APCs. As the existing studies exhibit methodological limitations, there is a need for further well-controlled clinical trials to provide accurate information on the effect of platelet concentrates for periodontal intrabony defect treatment. Conclusion Based on the results obtained from the present systematic review it can be concluded that the evidence on the beneficial additive effect of APCs in surgical treatment of

References 1 American Academy of Periodontology. Glossary of Periodontal Terms, 3rd edn. Chicago: American Academy of Periodontology, 1992. 2 Plachokova AS, Nikolidakis D, Mulder J, Jansen JA, Creugers NH. Effect of platelet-rich plasma on bone regeneration in dentistry: a systematic review. Clin Oral Implants Res 2008; 19: 539–45. 3 Kotsovilis S, Markou N, Pepelassi E, Nikolidakis D. The adjunctive use of platelet-rich plasma in the therapy of periodontal intraosseous defects: a systematic review. J Periodontal Res 2010; 45: 428–43. 4 Del Fabbro M, Bortolin M, Taschieri S, Weinstein R. Is platelet concentrate advantageous for the surgical treatment of periodontal diseases? A systematic review and meta-analysis. J Periodontol 2011; 82: 1100–11. 5 Dohan Ehrenfest DM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: from pure plateletrich plasma (P-PRP) to leucocyteand platelet-rich fibrin (L-PRF). Trends Biotechnol 2009; 27: 158–67. 6 Carroll RJ, Amoczky SP, Graham S, O’Connell SM. Characterization of Autologous Growth Factors in Cascade Platelet Rich Fibrin Matrix (PRFM). Edison, NJ: Musculoskeletal Transplant Foundation, 2005. 7 Higgins JPT, Green S. eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated September 2009] The Cochrane Collaboration, 2009. Available from: www. cochrane-handbook.org.

12

intrabony defects has been increasing in recent years. Platelet concentrates may be advantageously used as a cost-effective adjunct to surgical regenerative therapy, even in combination with bone grafts, although they did not show any advantage when used together with GTR. Moreover, platelet-rich fibrin proved to be effective as a sole regenerative material for treatment of intrabony defects, in combination with OFD. Further long-term, multicentre clinical trials are to be carried out to validate these treatment strategies in evidence-based clinical practice.

8 Ozdemir B, Okte E. Treatment of intrabony defects with beta-tricalciumphosphate alone and in combination with platelet-rich plasma. J Biomed Mater Res B Appl Biomater 2012; 100: 976–83. 9 Lekovic V, Milinkovic I, Aleksic Z et al. Platelet-rich fibrin and bovine porous bone mineral vs. platelet-rich fibrin in the treatment of intrabony periodontal defects. J Periodontal Res 2012; 47: 409–17. 10 Kaushick BT, Jayakumar ND, Padmalatha O, Varghese S. Treatment of human periodontal infrabony defects with hydroxyapatite + b tricalcium phosphate bone graft alone and in combination with platelet rich plasma: a randomized clinical trial. Indian J Dent Res 2011; 22: 505–10. 11 Goyal B, Tewari S, Duhan J, Sehgal PK. Comparative evaluation of platelet-rich plasma and guided tissue regeneration membrane in the healing of apicomarginal defects: a clinical study. J Endod 2011; 37: 773–80. 12 Yilmaz S, Kabadayi C, Ipci SD, Cakar G, Kuru B. Treatment of intrabony periodontal defects with platelet-rich plasma versus platelet-poor plasma combined with a bovine-derived xenograft: a controlled clinical trial. J Periodontol 2011; 82: 837–44. 13 Yilmaz S, Cakar G, Ipci SD, Kuru B, Yildirim B. Regenerative treatment with platelet-rich plasma combined with a bovine-derived xenograft in smokers and non-smokers: 12-month clinical and radiographic results. J Clin Periodontol 2010; 37: 80–7. 14 Markou N, Pepelassi E, Vavouraki H et al. Treatment of periodontal en-

15

16

17

18

19

dosseous defects with platelet-rich plasma alone or in combination with demineralized freeze-dried bone allograft: a comparative clinical trial. J Periodontol 2009; 80: 1911–19. Camargo PM, Lekovic V, Weinlaender M, Divnic-Resnik T, Pavlovic M, Kenney EB. A surgical reentry study on the influence of platelet-rich plasma in enhancing the regenerative effects of bovine porous bone mineral and guided tissue regeneration in the treatment of intrabony defects in humans. J Periodontol 2009; 80: 915–23. Pradeep AR, Shetty SK, Garg G, Pai S. Clinical effectiveness of autologous platelet-rich plasma and peptideenhanced bone graft in the treatment of intrabony defects. J Periodontol 2009; 80: 62–71. Harnack L, Boedeker RH, Kurtulus I, Boehm S, Gonzales J, Meyle J. Use of platelet-rich plasma in periodontal surgery – a prospective randomised double blind clinical trial. Clin Oral Investig 2009; 13: 179–87. Yamamiya K, Okuda K, Kawase T, Hata K, Wolff LF, Yoshie H. Tissueengineered cultured periosteum used with platelet-rich plasma and hydroxyapatite in treating human osseous defects. J Periodontol 2008; 79: 811–18. Ilgeneli T, Dundar N, Kal BL. Demineralized freeze dried bone allograft and platelet rich plasma vs platelet rich plasma alone in infrabony defects: a clinical and radiographic evaluation. Clin Oral Investig 2007; 11: 51–9.

ª 2014 Wiley Publishing Asia Pty Ltd

S. Panda et al.

20 Yassibag-Berkman Z, Tuncer O, Subasioglu T, Kantarci A. Combined use of platelet-rich plasma and bone grafting with or without guided tissue regeneration in the treatment of anterior interproximal defects. J Periodontol 2007; 78: 801–9. 21 Ouyang XY, Qiao J. Effect of plateletrich plasma in the treatment of periodontal intrabony defects in humans. Chin Med J (Engl) 2006; 119: 1511–21. 22 Czuryszkiewicz-Cyrana J, Banach J. Autogenous bone and platelet-rich plasma (PRP) in the treatment of intrabony defects. Adv Med Sci 2006; 51 (Suppl. 1): 26–30. 23 Camargo PM, Lekovic V, Weinlaender M, Vasilic N, Madzarevic M, Kenney EB. A reentry study on the use of bovine porous bone mineral, GTR, and platelet-rich plasma in the regenerative treatment of intrabony defects in humans. Int J Periodontics Restorative Dent 2005; 25: 49–59. 24 Hanna R, Trejo PM, Weltman RL. Treatment of intrabony defects with bovine-derived xenograft alone and in combination with platelet-rich plasma: a randomized clinical trial. J Periodontol 2004; 75: 1668–77. 25 Rodrigues SV, Acharya AB, Thakur SL. An evaluation of platelet-rich plasma without thrombin activation with or without anorganic bone mineral in the treatment of human periodontal intrabony defects. Platelets 2011; 22: 353–60. 26 Lekovic V, Camargo PM, Weinlaender M, Vasilic N, Kenney EB. Comparison of platelet-rich plasma, bovine porous bone mineral, and guided tissue regeneration versus platelet-rich plasma and bovine porous bone mineral in the treatment of intrabony defects: a reentry study. J Periodontol 2002; 73: 198–205. 27 Camargo PM, Lekovic V, Weinlaender M, Vasilic N, Madzarevic M, Kenney EB. Platelet-rich plasma and bovine porous bone mineral combined with guided tissue regeneration in the treatment of intrabony defects in humans. J Periodontal Res 2002; 37: 300–6.

ª 2014 Wiley Publishing Asia Pty Ltd

Treatment of intrabony defects

28 Menezes LM, Rao J. Long-term clinical evaluation of platelet-rich plasma in the treatment of human periodontal intraosseous defects: a comparative clinical trial. Quintessence Int 2012; 43: 571–82. 29 D€ ori F, Nikolidakis D, H uszar T, Arweiler NB, Gera I, Sculean A. Effect of platelet-rich plasma on the healing of intrabony defects treated with an enamel matrix protein derivative and a natural bone mineral. J Clin Periodontol 2008; 35: 44–50. 30 Kang J, Sha YQ, Ou-yang XY. Combination therapy of periodontal intrabony defcts with demineralized freeze-dried bone powde and plateletrich plasma. Beijing Da Xue Xue Bao 2010; 42: 24–7. (In Chinese). 31 Dori F. Effect of combined therapeutic methods on healing of periodontal vertical bone defects in regenerative surgery. Orv Hetil 2009; 150: 517–22. doi:10.1556/OH.2009.28500. (In Hungarian). 32 Pradeep AR, Bajaj P, Rao NS, Agarwal E, Naik SB. Platelet-rich fibrin combined with a porous hydroxyapatite graft for the treatment of threewall intrabony defects in chronic periodontitis: a randomized controlled clinical trial. J Periodontol 2012. doi: 10.1902/jop.2012.110722. 33 Pradeep AR, Rao NS, Agarwal E, Bajaj P. Comparative evaluation of autologous platelet-rich fibrin and platelet-rich plasma in the treatment of three-wall intrabony defects in chronic periodontitis: a randomized controlled clinical trial. J Periodontol 2012; 83: 1499–507. 34 Sharma A, Pradeep AR. Autologous platelet-rich fibrin in the treatment of mandibular degree II furcation defects: a randomized clinical trial. J Periodontol 2011; 82: 1396– 403. 35 Thorat M, Pradeep AR, Pallavi B. Clinical effect of autologous plateletrich fibrin in the treatment of intrabony defects: a controlled clinical trial. J Clin Periodontol 2011; 38: 925–32. 36 Demir B, Seng€ un D, Berberoglu A. Clinical evaluation of platelet-rich

37

38

39

40

41

42

43

44

plasma and bioactive glass in the treatment of intra-bony defects. J Clin Periodontol 2007; 34: 709–15. D€ ori F, Kovacs V, Arweiler NB et al. Effect of platelet-rich plasma on the healing of intrabony defects treated with an anorganic bovine bone mineral: a pilot study. J Periodontol 2009; 80: 1599–605. Hassan KS, Alagl AS, Abdel-Hady A. Torus mandibularis bone chips combined with platelet rich plasma gel for treatment of intrabony osseous defects: clinical and radiographic evaluation. Int J Oral Maxillofac Surg 2012; 41: 1519–26. Okuda K, Tai H, Tanabe K et al. Platelet-rich plasma combined with a porous hydroxyapatite graft for the treatment of intrabony periodontal defects in humans: a comparative controlled clinical study. J Periodontol 2005; 76: 890–8. Parimala M, Mehta DS. Comparative evaluation of bovine porous bone mineral. J Indian Soc Periodontol 2010; 14: 126–31. Piemontese M, Aspriello SD, Rubini C, Ferrante L, Procaccini M. Treatment of periodontal intrabony defects with demineralized freeze-dried bone allograft in combination with platelet-rich plasma: a comparative clinical trial. J Periodontol 2008; 79: 802–10. Saini N, Sikri P, Gupta H. Evaluation of the relative efficacy of autologous platelet-rich plasma in combination with b-tricalcium phosphate alloplast versus an alloplast alone in the treatment of human periodontal infrabony defects: a clinical and radiological study. Indian J Dent Res 2011; 22: 107–15. Christgau M, Moder D, Wagner J et al. Influence of autologous platelet concentrate on healing in intra-bony defects following guided tissue regeneration therapy: a randomized prospective clinical split-mouth study. J Clin Periodontol 2006; 33: 908–21. D€ ori F, Huszar T, Nikolidakis D, Arweiler NB, Gera I, Sculean A. Effect of platelet-rich plasma on the healing of intra-bony defects treated with a

13

S. Panda et al.

Treatment of intrabony defects

natural bone mineral and a collagen membrane. J Clin Periodontol 2007; 34: 254–61. 45 D€ ori F, Huszar T, Nikolidakis D, Arweiler NB, Gera I, Sculean A. Effect of platelet-rich plasma on the healing of intrabony defects treated with an anorganic bovine bone mineral and expanded polytetrafluoroethylene membranes. J Periodontol 2007; 78: 983–90. 46 Sculean A, Nikolidakis D, Schwarz F. Regeneration of periodontal tis-

14

sues: combinations of barrier membranes and grafting materials – biological foundation and preclinical evidence: a systematic review. J Clin Periodontol 2008; 35(Suppl. 8): 106– 116. 47 Anitua E, Tejero R, Zalduendo MM, Orive G. Plasma rich in growth factors promotes bone tissue regeneration by stimulating proliferation, migration, and autocrine secretion in primary human osteoblasts.

J Periodontol 2013; 84: 1180–90. doi:10.1902/jop.2012.120292. 48 Anitua E, Troya M, Orive G. Plasma rich in growth factors promote gingival tissue regeneration by stimulating fibroblast proliferation and migration and by blocking transforming growth factor-b1-induced myodifferentiation. J Periodontol 2012; 83: 1028–37. doi:10.1902/jop. 2011.110505.

ª 2014 Wiley Publishing Asia Pty Ltd

Additive effect of autologous platelet concentrates in treatment of intrabony defects: a systematic review and meta-analysis.

The aim of the present review is to systematically evaluate the additive effect of autologous platelet concentrates (APCs) in treatment of intrabony d...
347KB Sizes 0 Downloads 3 Views