The Power of Platelet-Rich Fibrin

The phenomenon of wound healing has intrigued clinicians and researchers for decades. Various bioactive surgical additives have been developed and explored for inflammation regulation and enhanced wound healing.¹ Platelet contains a high concentration of essential growth factors that stimulate cell migration and proliferation, which support wound healing.² Due to this favorable property, autologous platelet concentrates were introduced as a therapeutic modality for expedited healing. The autologous platelet principle revolves around accumulating platelets from the patient’s whole blood in a fibrin clot, and utilizing it for hard and soft tissue healing.^1,3 Platelet-rich fibrin is an autologous leucocyte platelet-rich fibrin matrix containing cytokines, platelets and numerous growth factors.⁴ It is a biodegradable scaffold that promotes wound healing, guides epithelial cell migration, and is used as an adjunct for bone and soft tissue regeneration.⁴

Platelet-rich fibrin protocol requires single centrifugation without the addition of an anticoagulant; 10 ml of venous blood is taken and added to sterile glass tubes and immediately centrifuged at 3000 rpm for 10 minutes. The fibrin clot is formed in the middle layer, in which most of the platelets and leucocytes are concentrated. The topmost layer consists of cellular plasma, and the base is formed by the red blood cells (Figure 1).⁵

AUTOLOGOUS PLATELET CONCENTRATE GENERATIONS

The protocol of platelet-rich fibrin formation has evolved over time. The first generation of platelet concentrate from autologous blood used for tissue regeneration was platelet-rich plasma (PRP). This process involves adding an anticoagulant to the venous blood and two centrifugations (soft and hard spins) to obtain the concentrated PRP.¹ However, the clinical protocol was cumbersome, and the addition of anticoagulants and bovine serum poses a risk of cross contamination.⁶

To combat these limitations, a second-generation platelet concentrate, platelet-rich fibrin, was developed.^2,6 The second generation, called leukocyte-PRF (L-PRF) or Choukroun’s PRF, was made using 10 ml of autologous blood, centrifuged once (3000 rpm for 10 minutes) without added anticoagulants or bovine serum.^3,6 The fibrin aspect allows for better scaffolding that mirrors a natural blood clot. Choukroun’s PRF is well studied and involves autologous blood that contains platelets, lymphocytes, monocytes, stem cells, granulocytes and growth factors.⁶ More processing techniques were introduced for newer preparations. These techniques use lower centrifugation forces (1500 rpm for 10 minutes), and the formulations are called advanced platelet-rich fibrin, which demonstrated an increase in platelets and neutrophilic granules.⁷ Recently, an injectable platelet-rich fibrin was developed, with one centrifugation cycle for 700 rpm for three minutes. It contains a larger quantity of leucocytes and plasma proteins due to the low centrifugation speed.⁷

WHAT MAKES IT UNIQUE?

Platelet-rich fibrin is created from autogenous blood and is unique to the patient. It can connect elements in tissue for a better clinical outcome. For example, mixing bone graft with platelet-rich fibrin can help the grafted tissues heal more efficiently. The added matrix components, such as fibrin, glycosaminoglycans, fibronectin and others, aid this process.⁸ Growth factors released from the platelet-rich fibrin clot in vitro after five to 10 minutes of the initial clotting process, and continue to be released for three to five hours.^7–9 The architecture of the clot functions as a scaffold for tissue regeneration.⁷ It can carry mesenchymal cells and allow them to differentiate and proliferate. He et al⁹ studied the release of TGF-β, platelet-derived growth factor-AB, and alkaline phosphatase from L-PRF, and found that all three were released at a slow, constant rate. Platelet-derived growth factor, which is naturally found in platelets and other cells, is actively involved in wound healing and has shown improved bone regeneration potential.¹⁰ Ghanaati et al⁶ noted that T-lymphocytes, B-lymphocytes, stem cells and monocytes were in the first 25% to 30% proximal part of the platelet-rich fibrin clot. The investigators also found that using different settings for centrifugation could alter the clot’s specific cell types. These other centrifugation protocols created either standard platelet-rich fibrin or advanced platelet-rich fibrin, based on rpm and centrifugation time.⁶

APPLICATIONS

Platelet-rich fibrin is commonly used in oral and maxillofacial surgery to aid healing. It is taken as an autologous blood sample, centrifuged, and placed into the surgical site as a clot. The architecture of the fibrin in trapping cytokines and growth factors, along with the leukocyte content, play an essential role in its ability to accelerate healing. The most common oral and maxillofacial surgery preparations are L-PRF. These autologous fibrin clots and platelet concentrates mirror the effects of proper bleeding from a surgical site — that is, they allow the site to form a good fibrin clot, stimulate neoangiogenesis, and provide the architecture for leukocytes to protect the area from infection and clean debris. This circumnavigates issues with lack of clotting or controlled bleeding from the surgical site.

Platelet-rich fibrin has been used in periodontal surgery as a barrier between tissues to prevent healing by a long junctional epithelium. It has also been used to avoid damage of gingival tissues during surgery with bone grafting and accelerate soft tissue healing. In guided tissue regeneration (GTR), L-PRF can be used as a filling material and membrane. The platelet-rich fibrin acts as a blood clot and barrier membrane, where the blood clot must first be stabilized, and a barrier must be created. The L-PRF membrane is compatible with the host tissue and does not interfere with the natural healing process.

More robust than a natural blood clot, L-PRF can be used as a filling material when regenerating hard tissue in intrabony defects.⁸ The increased strength of the platelet-rich fibrin compared to PRP gel makes it easier to manipulate into the desired sites. The release of growth factor allows for quicker remodeling of soft tissues when L-PRF is used as a protective membrane. Since the L-PRF membrane boosts the periosteum’s healing properties, it augments the periosteum in protecting intrabony defects as they heal.⁸ In a randomized controlled trial, the adjunctive use of platelet-rich fibrin with open flap debridement showed significant improvement compared to the control group (open flap debridement only) for bone fill, reduction in probing depths, and soft tissue healing.¹¹

Platelet-rich fibrin can also be used as an adjunct to palatal wound healing after harvesting a palatal graft or along with root coverage procedures to aid accelerated soft tissue healing and achieve root coverage.^4,12 It is also widely utilized in implantology; for example, as an adjunct in socket grafting procedures — with or without the use of bone grafts — to maintain alveolar ridge dimensions and enhance healing.^13,14 Better clinical and histological results were seen in groups treated with platelet-rich fibrin in comparison to non-grafted control sites; similar improvements were seen in the preservation of alveolar ridge dimensions and patient comfort.^13,14

Due to its favorable healing properties, platelet-rich fibrin is also utilized as a grafting material in sinus augmentation procedures, in combination with bone grafts, or as a membrane to cover the graft material, or for the repair of a perforated Schneiderian membrane.^15–17

In endodontics, platelet-rich fibrin has been used as a successful scaffold for pulp revascularization procedures of the immature necrotic tooth by upregulating cellular proliferation, differentiation, and angiogenesis.¹⁸

ADVANTAGES AND DISADVANTAGES

As noted, the primary advantage of platelet-rich fibrin is its ability to promote wound healing. There are four phases to healing: hemostasis, inflammation, proliferation and maturation. Each phase encompasses various cell types that must interact with a three-dimensional (3D) extracellular matrix and growth factors to obtain successful results. The platelet-rich fibrin element is host cells’ presence (i.e., platelets, leukocytes and red blood cells); in particular, leukocytes play a vital role in the formation of new blood vessels and tissue. The second component that promotes healing is the 3D fibrin matrix. Unlike PRP, this matrix is obtainable due to acquiring platelet-rich fibrin without anticoagulants (which delay wound healing). The last component is its ability to serve as a reservoir of natural growth factors released for 10 to 14 days.⁷

The major disadvantage of platelet-rich fibrin is the requirement of an autologous blood source that contains various immune cells and highly antigenic plasmatic molecules in the fibrin matrix. These cells’ presence makes platelet-rich fibrin donor-specific, therefore limiting its use as an allogenic graft tissue.¹⁹ Additionally, the required use of autologous blood restricts the amount of platelet-rich fibrin available, as a low quantity is produced; thus, it can only be used in limited amounts.¹⁹ The protocol for platelet-rich fibrin preparation is also not standardized, which could also pose potential limitations.⁵

CONCLUSION

In vitro and in vivo evidence confirm that platelet-rich fibrin is a potential healing biomaterial with various applications in dentistry. It has demonstrated promising results, with better healing outcomes and decreased postoperative discomfort for patients. Platelet-rich fibrin can be utilized for many periodontal, implant, oral surgical and endodontic procedures, maximizing its benefits as an autologous source, and enhancing healing and regeneration potential. Ultimately, this approach offers a less time consuming and less expensive alternative to commercially available materials.

REFERENCES

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2. Ehrenfest DM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte-and platelet-rich fibrin (L-PRF). Trends Biotechnol. 2009;27:158–167.
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8. Del Corso M, Vervelle A, Simonpieri A, 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;13:1207–1230.
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15. Choukroun J, Diss A, Simonpieri A, et al. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part V: histologic evaluations of PRF effects on bone allograft maturation in sinus lift. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:299–303.
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17. Tajima N, Ohba S, Sawase T, Asahina I. Evaluation of sinus floor augmentation with simultaneous implant placement using platelet-rich fibrin as sole grafting material. Int J Oral Maxillofac Implants.2013;28:77–83.
18. Keswani D, Pandey RK. Revascularization of an immature tooth with a necrotic pulp using platelet‐rich fibrin: a case report.Int Endod J. 2013;46:1096–1104.
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This information originally appeared in Goel A, Villanueva JJ, Batra C, Satpathy B, Thompson T. Applications for platelet-rich fibrin in dentistry. Decisions in Dentistry. 2021;7(4):26–31.