Journal of the International Clinical Dental Research Organization

REVIEW ARTICLE
Year
: 2018  |  Volume : 10  |  Issue : 2  |  Page : 49--58

Soft and hard-tissue changes after the placement of smart blood derivative platelet-rich fibrin into intrabony defects: A systematic review and meta-analysis with at least 9-month follow-up


Surekha Rathod1, Ishita Wanikar2, Ameya Paralikar3,  
1 Department of Periodontics and Implantology, VSPM Dental College and Research Centre, Nagpur, Maharashtra, India
2 Department of Periodontology and Implantology, VSPM Dental College and Research Centre, Nagpur, Maharashtra, India
3 Department of Conservative Dentistry and Endodontics, M. A. Rangoonwala College of Dental Sciences and Research Centre, Pune, Maharashtra, India

Correspondence Address:
Dr. Ishita Wanikar
104, Department of Periodontology and Implantology, VSPM Dental College and Research Centre, Nagpur - 440 019, Maharashtra
India

Abstract

The application of platelet-rich fibrin (PRF) is gaining popularity in the treatment of bony defects as an endogenous regenerative therapy. The fibrillar aggregation matrix is incorporated with cells, cytokines, and growth factors and is released with time when inserted into implant, oral and maxillofacial surgery, and periodontal surgeries to promote healing. This paper evaluates the wide application of PRF in the regeneration of intrabony defects. A literature search of PubMed, EBSCO, and Google Scholar databases was performed by two reviewers for articles, published from January 1, 2002, to December 31, 2016, followed by a manual search of several dental journals. Weighted mean differences (MDs) and 95% confidence intervals (CIs) were calculated for pocket probing depth (PPD), clinical attachment level (CAL), gingival margin level (GML), and defect fill evaluated from baseline to the end of follow-up. Nine randomized clinical trials were included showing overall standardized MD in two groups for CAL as 1.194 (93% CI: 0.919, 1.362, P = 0.0001); for PPD as 0.034 (95% CI: 0.820, 1.248, 0.0001); for GML as 0.244 (97% CI: −0.016, 0.472, P = 0.024); and for bone defect reduction as 1.789 (98% CI: 1.493, 2.084, P = 0.0001). The results of the meta-analysis seem to support the effectiveness of PRF in the treatment of intrabony defects. There was an overall reduction in PPD and gain in CAL and GML and defect resolution. This proves that the application of PRF in the regeneration of intrabony defects has a promising future but should be used with caution with the heterogeneity present in the studies for gingival margin level.



How to cite this article:
Rathod S, Wanikar I, Paralikar A. Soft and hard-tissue changes after the placement of smart blood derivative platelet-rich fibrin into intrabony defects: A systematic review and meta-analysis with at least 9-month follow-up.J Int Clin Dent Res Organ 2018;10:49-58


How to cite this URL:
Rathod S, Wanikar I, Paralikar A. Soft and hard-tissue changes after the placement of smart blood derivative platelet-rich fibrin into intrabony defects: A systematic review and meta-analysis with at least 9-month follow-up. J Int Clin Dent Res Organ [serial online] 2018 [cited 2019 Jul 19 ];10:49-58
Available from: http://www.jicdro.org/text.asp?2018/10/2/49/249131


Full Text



 Introduction



Regeneration of the periodontium is the restoration of its lost architecture and function with apposition of new cementum, insertion of periodontal ligament fibers, and resolution of the bony defects.[1]

Gingivitis can very well be treated by oral hygiene practices and supragingival plaque control; however, deepened periodontal pockets usually require surgical intervention.[2] The complete restoration of the diseased periodontium cannot be achieved even by various regenerative procedures employed along with conventional open-flap debridement (OFD).[3],[4] Various growth factors, such as platelet-derived growth factor and bone morphogenetic protein, basic fibroblast growth factor, and angiopoietin vascular endothelial growth factor, have been found to contribute in periodontal regeneration.[5] As compared to different types of platelet concentrates, platelet-rich fibrin (PRF) has achieved very predictable outcomes. van Hinsbergh et al. discussed the role of PRF in angiogenesis. He stated that the natural characteristic polymerization during centrifugation, along with physiologic thrombin action on collected autologous fibrinogen is crucial to determine the three-dimensional organization of the fibrin network. This gives elasticity and strength to the PRF membrane.[6]

Clinical data reveal that PRF affects biologic activities at the cellular level by modulating the immune node property, integrin expression, fibroblast proliferation, migration, and thus favors coherent healing without inflammatory excess.[7],[8]

Therefore, the meta-analysis was aimed to determine the soft-tissue and hard-tissue changes clinically and radiographically after the placement of smart blood derivative PRF into intrabony defects.

 Materials and Methods



Data sources and search

A systematic search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis and Cochrane Collaboration recommendations to obtain appropriate articles for critical appraisal. Population, intervention, comparison, outcome was formulated to appropriately determine the parameters to evaluate the efficacy of PRF in the treatment of intrabony defects. The search included articles from the various databases PubMed, EBSCO, and Google Scholar published only in English between January 16, 2004, and December 31, 2016. Hand searching of the reference list of archived articles was combined, and duplicate articles were subsequently removed. By examining the bibliographies of retrieved articles, additional articles were identified. On the basis of the inclusion and exclusion criteria applicable, the titles of the retrieved articles were read independently by two authors (SR and IW).

Study selection and intervention

To be eligible for inclusion, publication had to report soft-tissue and hard-tissue changes (1)In vivo human studies; (2) PRF in intrabony defects; (3) in English; (4) follow-up of more than 6 months with no limits on the number of patients; and (5) randomized controlled trials (RCTs) with intrabony defects having a test group of PRF or in combination and a control group with OFD alone.

Publications were excluded if (1) In vitro; (2) nonhuman studies, (3) in languages other than English, (4) systemically unhealthy adults, (5) suffering from aggressive periodontitis were excluded from the study, and (6) study designs such as case series, case reports, retrospective studies, technical studies, animal studies, and reviews. The search carried out was on keywords chronic periodontitis OR intrabony defects AND periodontal regeneration AND PRF (OR platelet derivatives OR platelet concentrates) NOT furcation NOT root coverage.

Data extraction and collection

A total of 318 articles were retrieved and further filtered with human studies in English and RCT, clinical trials, and controlled clinical trials. Data were tabulated for (1) author and year, (2) study type and randomization method; (3) treatment groups; (4) patient and defect sample size; and (5) clinical and radiographic soft-tissue and tissue parameters as clinical attachment level (CAL), pocket probing depth (PPD), gingival margin level (GML), and bone fill evaluated after a period of at least 6 months. If authors deemed it inappropriate for inclusion, they were eliminated.[9],[10],[11],[12],[13],[14],[15],[16],[17],[18] At title stage, studies that included PRF used other than in inflammatory bowel disease (IBD) were excluded from the study. Eighteen articles were retrieved of which the relevant articles found to be nine articles. At the full-text stage, two investigators read and assessed each of the articles based on the criteria used in previous stages. Thus, the total number of articles reviewed: 9[19],[20],[21],[22],[23],[24],[25] [Figure 1].{Figure 1}

The full text was extracted if the title did not provide sufficient information. After screening by reviewers, the studies that did not meet the inclusion criteria were further excluded from the study [Table 1]. Hence, the relevant parameters with the corresponding data were extracted, and nine articles were included in the review [Table 2].{Table 1}{Table 2}

Outcome variables

Periodontal regeneration was primarily evaluated for changes in CAL and depth of IBD while the secondary outcome variable included changes in GML and PPD at the baseline and the final follow-up.

Data synthesis and statistical methods

Data were tabulated and analyzed in a descriptive format while the studies were analyzed for similarities and their suitability for meta-analysis. A meta-analysis was performed using software “Open Meta Analyst.” A fixed-effects model to cope-up with differences in variance among studies was used. Nonsignificant heterogeneity of included studies was seen with the test for heterogeneity and I2 was obtained. As an alternative to weighted mean differences (MDs), a standardized MD was used to estimate differences among groups.

Quality assessment of included studies

The criteria for assessment were based on the similarity of groups recruited, method of randomization, follow-up and dropouts, and blinding of the examiner. All criteria were judged as adequate, unclear, or inadequate. The risk of bias was assessed using the assessment tool and available criteria. No study was excluded for its risk of bias [Table 3] and [Table 4].{Table 3}{Table 4}

 Results



Characteristics of the participants

The number of patients in studies ranged from 20 to 136 patients (20–120 sites) diagnosed with chronic periodontitis. The mean age of the participants included ranged from 30.36 years to 37.16 years.

Characteristics of the defects

A total of 366 sites were treated. The defects were radiographic evidence of an IBD ≥3 mm and interproximal PPD ≥5 mm and clinical attachment loss ≥5 mm were included in the study [Table 5].{Table 5}

Meta-analysis

Plaque score, gingival score, and modified sulcus bleeding index

Of the nine studies reviewed, all the clinical trials showed no statistically significant difference. These studies included only those participants who were able to maintain acceptable oral hygiene with plaque index (PI) and modified sulcus bleeding index values below acceptable range after Phase I therapy. Results of all clinical trials showed that both treatment groups presented with high hygiene index (HI) scores after surgeries (1st and 2nd postoperative weeks). The HI improved even further during the 3rd and 4th weeks after surgery, further supporting the potential positive effects of PRF in the healing process.

Characteristics of the intervention

All the included studies used PRF in comparison to the traditional OFD procedure.

PRF was prepared following the protocol developed by Choukroun et al. with no variations in the centrifugation method (3000 revolutions [equivalent 400 × g] per minute for 10 min). One part of the PRF of the required size was filled into the defect, while the other part was used as a membrane to cover the defect. The mucoperiosteal flaps were relocated and fixed using interrupted or sling 3-0 or 4-0 nonabsorbable silk surgical suture, followed by a periodontal dressing in all the studies. Suitable antibiotics (amoxicillin 500 mg) and analgesics (ibuprofen 400 mg/800 mg and paracetamol 500 mg) along with chlorhexidine rinses were prescribed in most of the studies. Patient's response to PRF and OFD treatment and the results showed that PRF resulted in slightly better results in the experimental group for pain and healing.

Clinical attachment level

Gain in CAL was reported across different studies. Gain in attachment observed in experimental group ranged from 1.80 ± 0.63 mm to 4.73 ± 0.88 mm and in the control group from 1.30 ± 0.68 mm to 3.03 ± 0.18 mm. Gain in CAL was significant in the experimental group as compared to control group in continuous fixed effect model in all nine studies. The overall standardized MD in two groups was 1.194 (93% confidence interval [CI]: 0.919, 1.362), which was significant with the corresponding P = 0.0001. The parameter showed significant heterogeneity across studies with I2 of 3% and P = 0.0001. A forest plot representation shows MD of parameter across the studies [Table 6] and [Figure 2].{Table 6}{Figure 2}

In [Table 7], all the nine studies had reported a reduction in PPD as clinical parameter to check the efficacy of PRF. Reduction in PPD reported in experimental group ranged from 1.90 ± 0.74 mm to 4.69 ± 1.45 mm and in the control group from 1.60 ± 0.84 mm to 3.56 ± 1.09 mm. Reduction in PPD was significant in experimental group treated with PRF as compared to control group using continuous fixed effect model with standardized MD of 1.034 (95% CI: 0.820, 1.248) and associated P = 0.0001 in all nine studies. The heterogeneity across studies was significant as indicated by I2 of 90% with P < 0.0001. A forest plot of MD of PPD is shown in [Figure 3].{Table 7}{Figure 3}

The differences in gingival marginal position were analyzed in nine studies. Difference observed in the experimental group ranged from −0.07 ± 0.26 mm to 0.27 ± 0.07 mm, while in control group, it ranged from −0.06 ± 0.04 mm to 1.13 ± 0.74 mm. The change in gingival marginal position was significant in the treatment group as compared to control group in continuous fixed effect model with standardized MD of 0.244 (95% CI: −0.016, 0.472) with associated P = 0.024. The I2 value obtained was 97% indicating significant heterogeneity across studies with a P < 0.0001. A graphical representation of heterogeneity has been shown through MDs of GML [Table 8] and [Figure 4].{Table 8}{Figure 4}

Bone defect reduction (BDR) was compared across different studies. The six studies also reported the bone defect fill. Reduction in bone defect in the experimental group was reported between −2.50 ± 0.78 mm and 2.80 ± 0.89 mm and in the control group from −0.09 ± 0.11 mm to 1.24 ± 0.69 mm. The overall difference of mean changes in two groups was significant with standardized MD of 1.789 (98% CI: 1.493, 2.084) and the corresponding P = 0.0001. The parameter showed significant heterogeneity across studies with I2 of 98% and P < 0.0001. A forest plot representation shows MD of parameter across the studies [Table 9] and [Figure 5].{Table 9}{Figure 5}

 Discussion



The purpose of the present paper is to clinically and radiographically evaluate the hard tissue and soft-tissue changes with the use of autologous PRF in IBD. Although the efficacy of PRF has been tested elsewhere in the treatment of chronic periodontitis with many systematic reviews and meta-analysis supporting evidence for PRFs regenerative potential, to our knowledge, this is the most recent update to the pool of literature that included articles until 2016.

The studies included had a moderate risk of bias, and no heterogeneity was observed regarding quality, design, PRF preparation, surgical procedure, outcome variables, and postoperative follow-ups.

Chronic periodontitis is initiated and sustained by microorganisms living in communities, which are present in supragingival and subgingival plaque in the form of uncalcified and calcified biofilms. Plaque is considered the most important factor in the initiation, progression, and severity of periodontal infection and also a major contributor to the failure of periodontal treatment procedures. PI is unique among the most widely used indices for the assessment of plaque because it ignores the coronal extent of plaque on the tooth surface area and assesses only the thickness of plaque at the gingival area of the tooth and thus demonstrated good validity and reliability. The gingival index and the modified sulcular bleeding index were designed to determine the severity of the diseased gingiva and thus establish the activity of the periodontal lesion with the gingival bleeding. Initial periodontal therapy involves the removal of both subgingival and supragingival plaques. A periodontal flap surgery is done in sites with deeper, nonhealing pockets and persistent inflammation. An extremely high density of fibrin fibers detected in PRF provides additional stability to the wound and promotes rapid neoangiogenesis. It has also been found that an elevated concentration of various polypeptide growth factors incorporated in the surgical wound for angiogenesis and matrix biosynthesis lead to improvements in HI.

There are three crucial factors for healing and soft-tissue maturation as follows: angiogenesis, growth factors, and mesenchymal stem cell activity.[7] Fibrin gel in PRF and the action of cytokines trapped in the mesh fibrin matrix promote neoangiogenesis. PRF induces a significant and continuous stimulation and proliferation of gingival fibroblasts, dermal prekeratinocytes, preadipocytes, and maxillofacial osteoblasts.[1]

In all the nine articles reviewed PPD and CAL reduction and gain in gingival margin, level was seen with the test groups where PRF has been used along with OFD compared to OFD alone. The test groups with PRF showed no significant changes in the percentage of defect fill with bone-like dense tissue. There appeared to be new bone healing in the bony defects.

Summary of main results

The success of any regenerative periodontal therapy can be determined by the reduction in IBD and gain in CAL. Maintenance of oral hygiene is equally important/contributory necessary for bringing the soft-tissue and hard tissue changes during the follow-up period. The results of this meta-analysis showed standard mean deviation (SMD) for CAL as 1.194 (93% CI: 0.919, 1.362, P = 0.0001); for PPD as. 034 (95% CI: 0.820, 1.248, 0.0001); for GML as 0.244 (97% CI: −0.016, 0.472, P = 0.024); and for BDR as 1.789 (98% CI: 1.493, 2.084, P = 0.0001).

 Conclusion



The merits of smart blood derivative PRF over OFD alone have been proven in the meta-analysis with SMD of 1.141 mm in CAL and 1.789 mm for IBD after treatment of IBDs with PRF when compared to OFD. The hard tissue and soft-tissue healing and postoperative discomfort reduction were favorable when PRF was used. However, standardization of the procedure right from extracting blood to its formation is very essential when optimal effects are expected. The histologic evaluation of regenerated tissues is required to support the findings of these RCTs.

Clinical implications and future trends

Clinically, significant improvements in the periodontal parameters such as CAL, IBD, and reduction in PD when IBDs were treated with PRF alone compared to OFD. As PRF is easy to obtain autologous material, effective and user-friendly, can be more widely used in periodontal regeneration, does not necessitate the need for anticoagulant and antithrombin and thus has no antigenicity is an effective regenerative material and capable of improving the defect resolution of bone graft materials alone or in combination. Other indications for its use include gingival recession, socket preservation, and furcation involvement. It is a convenient and economic regenerative material whose long-term stability needs to be evaluated.

Limitations

The primary limitation is the inclusion of only RCTs published in the English.

Acknowledgment

The authors are highly obliged to seek support from Dr. Pradeep A.R., HOD and Professor, Government Dental College and Hospital, Bangalore, and Mr. Dhananjay Raje for performing statistical analysis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Zander HA, Polson AM, Heijl LC. Goals of periodontal therapy. J Periodontol 1976;47:261-6.
2Shah M, Patel J, Dave D, Shah S. Comparative evaluation of platelet-rich fibrin with demineralized freeze-dried bone allograft in periodontal infrabony defects: A randomized controlled clinical study. J Indian Soc Periodontol 2015;19:56-60.
3Sander L, Karring T. Healing of periodontal lesions in monkeys following the guided tissue regeneration procedure. A histological study. J Clin Periodontol 1995;22:332-7.
4Siciliano VI, Andreuccetti G, Siciliano AI, Blasi A, Sculean A, Salvi GE, et al. Clinical outcomes after treatment of non-contained intrabony defects with enamel matrix derivative or guided tissue regeneration: A 12-month randomized controlled clinical trial. J Periodontol 2011;82:62-71.
5Gassling V, Douglas T, Warnke PH, Açil Y, Wiltfang J, Becker ST, et al. Platelet-rich fibrin membranes as scaffolds for periosteal tissue engineering. Clin Oral Implants Res 2010;21:543-9.
6van Hinsbergh VW, Collen A, Koolwijk P. Role of fibrin matrix in angiogenesis. Ann N Y Acad Sci 2001;936:426-37.
7Choukroun J, Diss A, Simonpieri A, Girard MO, Schoeffler C, Dohan SL, et al. Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part IV: Clinical effects on tissue healing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:e56-60.
8Dohan DM, Choukroun J, Diss A, Dohan SL, Dohan AJ, Mouhyi J, et al. Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part I: Technological concepts and evolution. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:e37-44.
9Chang YC, Zhao JH. Effects of platelet-rich fibrin on human periodontal ligament fibroblasts and application for periodontal infrabony defects. Aust Dent J 2011;56:365-71.
10Lekovic V, Milinkovic I, Aleksic Z, Jankovic S, Stankovic P, Kenney EB, 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.
11Pradeep AR, Bajaj P, Rao NS, Agarwal E, Naik SB. Platelet-rich fibrin combined with a porous hydroxyapatite graft for the treatment of 3-wall intrabony defects in chronic periodontitis: A Randomized controlled clinical trial. J Periodontol 2017;88:1288-96.
12Bansal C, Bharti V. Evaluation of efficacy of autologous platelet-rich fibrin with demineralized-freeze dried bone allograft in the treatment of periodontal intrabony defects. J Indian Soc Periodontol 2013;17:361-6.
13Agarwal A, Gupta ND, Jain A. Platelet rich fibrin combined with decalcified freeze-dried bone allograft for the treatment of human intrabony periodontal defects: A randomized split mouth clinical trail. Acta Odontol Scand 2016;74:36-43.
14Elgendy EA, Abo Shady TE. Clinical and radiographic evaluation of nanocrystalline hydroxyapatite with or without platelet-rich fibrin membrane in the treatment of periodontal intrabony defects. J Indian Soc Periodontol 2015;19:61-5.
15Pradeep AR, Garg V, Kanoriya D, Singhal S. Platelet-rich fibrin with 1.2% rosuvastatin for treatment of intrabony defects in chronic periodontitis: A Randomized controlled clinical trial. J Periodontol 2016;87:1468-73.
16Aydemir Turkal H, Demirer S, Dolgun A, Keceli HG. Evaluation of the adjunctive effect of platelet-rich fibrin to enamel matrix derivative in the treatment of intrabony defects. Six-month results of a randomized, split-mouth, controlled clinical study. J Clin Periodontol 2016;43:955-64.
17Thorat M, Pradeep AR, Pallavi B. Clinical effect of autologous platelet-rich fibrin in the treatment of intra-bony defects: A controlled clinical trial. J Clin Periodontol 2011;38:925-32.
18Sharma A, Pradeep AR. Treatment of 3-wall intrabony defects in patients with chronic periodontitis with autologous platelet-rich fibrin: A randomized controlled clinical trial. J Periodontol 2011;82:1705-12.
19Pradeep AR, Rao NS, Agarwal E, Bajaj P, Kumari M, Naik SB, et al. Comparative evaluation of autologous platelet-rich fibrin and platelet-rich plasma in the treatment of 3-wall intrabony defects in chronic periodontitis: A randomized controlled clinical trial. J Periodontol 2012;83:1499-507.
20Rosamma Joseph V, Raghunath A, Sharma N. Clinical effectiveness of autologous platelet rich fibrin in the management of infrabony periodontal defects. Singapore Dent J 2012;33:5-12.
21Pradeep AR, Nagpal K, Karvekar S, Patnaik K, Naik SB, Guruprasad CN, et al. Platelet-rich fibrin with 1% metformin for the treatment of intrabony defects in chronic periodontitis: A randomized controlled clinical trial. J Periodontol 2015;86:729-37.
22Ajwani H, Shetty S, Gopalakrishnan D, Kathariya R, Kulloli A, Dolas RS, et al. Comparative evaluation of platelet-rich fibrin biomaterial and open flap debridement in the treatment of two and three wall intrabony defects. J Int Oral Health 2015;7:32-7.
23Chandradas ND, Ravindra S, Rangaraju VM, Jain S, Dasappa S. Efficacy of platelet rich fibrin in the treatment of human intrabony defects with or without bone graft: A randomized controlled trial. J Int Soc Prev Community Dent 2016;6:S153-9.
24Martande SS, Kumari M, Pradeep AR, Singh SP, Suke DK, Guruprasad CN, et al. Platelet-rich fibrin combined with 1.2% atorvastatin for treatment of intrabony defects in chronic periodontitis: A Randomized controlled clinical trial. J Periodontol 2016;87:1039-46.
25Kanoriya D, Pradeep AR, Singhal S, Garg V, Guruprasad CN. Synergistic approach using platelet-rich fibrin and 1% alendronate for intrabony defect treatment in chronic periodontitis: A Randomized clinical trial. J Periodontol 2016;87:1427-35.