Platelet-rich Fibrin: A Paradigm in Periodontal Therapy - A Systematic Review.

Periodontal tissue regeneration has always been a challenge for the periodontists owing to its structural complexity. Although with tissue engineering as a growing multidisciplinary field, this aim has partially been fulfilled. In recent years, platelet-rich fibrin (PRF) has gained wide attention for its utilization as a biocompatible regenerative material not only in dental but also in medical fields. The following systematic review has gathered all the currently available in vitro, animal, and clinical studies utilizing PubMed electronic database from January 2006 to August 2016 highlighting PRF for soft and hard tissue regeneration and/or wound healing. Although results are encouraging but require further validation from clinical studies to justify the potential role of PRF in periodontal regeneration so that this relatively inexpensive autologous biomaterial can be utilized at a wider scale.

INTRODUCTION

Primary objective of day-to-day ongoing researches is to optimize healing and the biggest challenges that the researchers are facing is the development of a regenerative biomaterial to regulate inflammation and accelerate wound healing.[1]

Healing is a complex process that involves organization of cells, biochemical triggers, and extracellular matrix synthesis for repair of the tissue.[2] Role of platelets in hemostasis and wound healing is well established, but the exact mechanism of healing in depth is still unclear.[3]

Role of platelets in regeneration was proven way back in the 1970s,[4] owing to the fact that it is a reservoir of growth factors that are responsible for neovascularization, collagen synthesis, cell division, cell differentiation, induction, and migration of other cells to the injured site.[5]

Postperiodontal surgery, wound healing occurs through a complex interaction between gingival fibroblasts, periodontal ligament cells, osteoblasts, and epithelial cell. Damage of blood vessels results in fibrin formation followed by platelet aggregation and elaboration of growth factors in the tissues.[6] This cellular interaction is under molecular control of biochemical mediators, i.e., cytokines and growth factors.

The crucial role of platelets in inflammation and wound healing is due to the presence of several growth factors and cytokines.[7] Furthermore, they contain fibrin, fibronectin, and vitronectin that provide connective tissue, a matrix and create an efficient network for cell migration.[1] This has led to the idea of using platelets as therapeutic tools to improve tissue repair, particularly in wound healing.

SEARCH STRATEGY FOR THE IDENTIFICATION OF STUDIES

The PubMed database of the US National Library of Medicine was utilized as the electronic databases, and a literature search was accomplished on articles using combination of various MeSH and free text words “Platelet rich fibrin or PRF and Periodontal therapy,” “Platelet rich fibrin or PRF and clinical applications,” “Platelet rich fibrin or PRF and Periodontology” from January 2006 to August 2016. A total of 49 scientific papers (14 in vitro, 2 animal, and 33 clinical studies) meeting the criteria were scrutinized. There was no restriction on the language and publication status imposed on the articles. Further additional studies were sought by searching the reference lists of identified trials and reviews.

CLASSIFICATION OF PLATELET-RICH CONCENTRATES

Following the debates about the various components of these platelet-rich concentrate preparations, a first classification was proposed by Dohan Ehrenfest et al., 2009,[8] which is now widely accepted. The classification is simple and is based on the presence or absence of leukocytes and the density of fibrin architecture in platelet concentrates. Depending on the difference in these parameters, it can be divided into the following four main types, i.e., pure platelet-rich plasma, pure platelet-rich fibrin (PRF), leukocyte and platelet-rich plasma, and leukocyte and PRF which are described here forth in Figure 1.

Figure 1

Description of different types of platelet rich concentrates

PROPOSED MECHANISM OF ACTION

Properties of platelet concentrates depends on the techniques used as Choukroun's PRF is based on mechanical concentration process.[910] PRF is a condensation of suspended growth factors within platelets [Figure 2].[11121314] These growth factors are considered as tissue regenerative boosters and are ramified in wound healing. Based on elaborated growth factors from PRF, optimization of clinical usage of PRF can be done.[1516]

Figure 2

Role of platelet-rich fibrin growth factors and cytokines in tissue regeneration and wound healing. Transforming growth factor ß1, insulin-like growth factor 1 and 2, platelet-derived growth factor, cytokine vascular endothelial growth factor, and interleukin 1, 4, and 6

APPLICATION OF PLATELET-RICH FIBRIN IN CLINICAL PERIODONTOLOGY

A convincing healing bioregenerative material, PRF, shows compelling data in various in vitro and clinical studies. It can be utilized in various procedures such as management of intrabony defects, gingival recession, furcation defects, extraction socket preservation, and accelerated healing of wound. The following are some of the important studies highlighting its regenerative potential in the field of Periodontology [Table 1].

Table 1

The studies implicating the role of platelet-rich fibrin in clinical periodontology

DISCUSSION

The regeneration of the lost periodontal structures is the ultimate aim of the periodontal therapy to restore the health, function, and esthetics of periodontium. From periodontal point of view, the experimental and in vitro studies emphasizing the role of PRF on periodontal regeneration and periodontal wound healing are important and hereby discussed.

The breakthrough in vitro study that introduced PRF in medical field was conducted by Choukroun et al. It highlighted improved neovascularization, wound closing with accelerated tissue remodeling in the absence of infectious events.[16]

PRF used either in combination with bone grafts (bovine porous bone mineral, nanocrystalline hydroxyapatite, and demineralized freeze-dried bone allograft [DFDBA]) or pharmacologic agents such as metformin gel was found to be more effective in terms of improvements in clinical parameters and radiographic defect depth reduction compared to when bone grafts or metformin used alone.[1718192024] Furthermore, the clinical and radiographic results of PRF used alone were comparable to DFDBA for periodontal regeneration.[19]

Although the efficacy of PRF as compared to Emdogain was found to be inferior in terms of defect resolution.[21]

Studies have shown similar probing depth reduction, clinical attachment level gain, bone fill at sites treated with PRF, or PRF with open flap debridement. However, due to the fact that PRF is less technique sensitive, it may be considered as a better treatment option than PRF.[23]

PRF being a reservoir of soluble growth factors and cytokines (transforming growth factor beta-1, insulin-like growth factor 1 and 2, platelet-derived growth factor, cytokine vascular endothelial growth factor, and interleukin 1, 4, and 6) that not only help in tissue regeneration but also accelerate wound healing. Studies have shown that PRF, when used with coronally advanced flap for recession coverage, has shown to decrease matrix metalloproteinase-8 (MMP-8) and interleukin beta levels but increase in tissue inhibitor of MMP-1 levels at 10 days, thereby promoting periodontal wound healing in the earlier phase of the process.[2627]

A systematic meta-analysis by Moraschini and Barboza Edos[28] and clinical studies by Keceli et al.[29] and Gupta et al.[32] have highlighted the inconsistent results of PRF in covering Miller Class I and Class II gingival recessions with no improvement in terms of root coverage, keratinized mucosa width, or clinical attachment level, but it was shown to have increased the gingival thickness.

Further, Padma et al.[37] in a randomized controlled trial proved predictable treatment for isolated Miller class I and II recession defects when used with coronally advanced flap. It provided superior root coverage with added benefit in gain in clinical attachment level and width of keratinized gingiva after 6 months postoperatively.

On comparing with PRF and connective tissue graft (CTG) in gingival recession procedures, it was found that there was a greater gain in keratinized tissue width in CTG group but better wound healing in PRF group.[39]

Similar to the management of infrabony defects, the use of PRF in furcation defects when combined with bone grafts (hydroxyapatite) and rosuvastatin has shown better results emphasizing its role in periodontal regeneration.

Various in vitro studies have shown a positive biological effect in human gingival fibroblast which can have a potential role in the management of gingival recession and periodontal tissue engineering.[47]

It is well established that PRF contains soluble growth factors that not only stimulate tissue healing but also bone regeneration.[48] For guided tissue regeneration procedures, PRF has proved to be superior scaffold as compared to collagen membrane when used for in vitro cultivation of periosteal cells.[49]

PRF has also shown remarkable positive healing effects when used for the preservation of extraction socket and in sinus lift procedures during simultaneous dental implantation (Jeong et al., 2014).[52]

The studies show outstanding results with PRF in regenerating periodontal osseous defects and preserving extraction healing socket. Although there were conflicting data when PRF was used for managing gingival recession defects for root coverage.

CONCLUSION

Studies have confirmed that PRF is a therapeutic regenerative biomaterial with immense potentiality that has widespread clinical applications in medical as well as dental perspectives. The use of PRF alone or in combination with other biomaterials (such as bone grafts, soft tissue grafts, and pharmacologic agents) provided safe and promising results in the form of improvements in clinical and radiographic parameters in the management of periodontal osseous defects and hard tissue preservation of extraction socket. Although in denuded root coverage procedures in cases of gingival recessions, PRF showed some contradictory findings, and the results were not that favorable, but still, it provided an added advantage in terms of increment in gingival tissue width and thickness (gingival biotype). Tissue biotype is an important factor because it narrates the way a tissue will respond to inflammation, trauma, and surgical insult. Hence PRF does result in thick gingival biotype which shows greater dimensional stability during remodeling and enhancing collateral blood supply to the underlying osseous structure as compared to thin biotype which may compromise it.

Although the potentiality of this nonexpensive, autologous biomaterial is encouraging, preparation and storage after preparation form the loop holes that need attention. The time interval between the speed of handling and ultimately its usage is highly crucial for its structural integrity and leukocyte viability. Hence, these limitations should be focused and worked upon by the researchers. Further validation is needed in the form of long-term randomized control studies with larger sample sizes to affirm the benefits and identifying the hidden potential of PRF as a biomaterial in the field of clinical periodontology.55

FINANCIAL SUPPORT AND SPONSORSHIP

Nil.

CONFLICTS OF INTEREST

There are no conflicts of interest.