Platelet-Rich Fibrin: Choosing the Right Formulation for Optimal Results

The first-generation blood platelet concentrate, platelet-rich plasma (PRP), was initially reported used in oral surgery procedures in 1997.³ Following venous blood draw, whole blood is treated with an anticoagulant (usually sodium citrate or anticoagulant citrate dextrose solution A) and undergoes two centrifugation steps.⁴ The centrifuge separates the individual cell types found in whole blood between separate layers (platelet-poor plasma, PRP, red blood cell layer), which can then be used during treatment. A separate platelet activator/agonist (bovine thrombin and calcium chloride) must be applied just before clinical use.⁵ Although PRP is an autologous biomaterial, the anticoagulant has been shown to compromise wound healing,⁶ while the coagulant may trigger antibody development to factors V, XI, and thrombin, possibly leading to life-threatening coagulopathies.^7,8

In 2001 Choukroun introduced the second-generation blood platelet concentrate, platelet-rich fibrin (L-PRF).⁹ Because PRF is derived from a patient's own blood without the use of anticoagulants, there is no risk of immunologic rejection. After centrifugation, three layers are present: platelet-poor plasma, the PRF clot, and red blood cell layer. A "buffy coat" layer is located at the base of the PRF clot, just above the red corpuscle layer. While the terms "autologous blood concentrate" and "blood platelet concentrate" can be used to describe both PRP and PRF, PRF also contains concentrations of leukocytes (white blood cells), which are not present in PRP.¹⁰ White blood cells provide the additional benefits of increased immune response, angiogenesis, and promotion of hard-tissue formation at surgical sites.^11,12 PRF has been shown to contain CD34+ stem cells that are found in peripheral blood¹³ and which aid in the process of tissue regeneration.¹⁴ The fibrin matrix serves as a scaffold and contains rich concentrations of platelets, growth factors, and leukocytes. The solid PRF clot exists in a thick, gel-like state and can be compressed into a flat membrane or a plug as desired for optimal utilization during treatment. The fibrin matrix may act as a cell-occlusive barrier against soft-tissue invagination into surgical sites.^2,15

While PRP rapidly releases more than 90% of its growth factors within 10 minutes of coagulation and depletes the remainder within 90 minutes,¹⁶ PRF, conversely, has a prolonged release (beyond 7 days) of growth factors and, moreover, has been shown to release a higher overall number of growth factors.¹⁷ Prolonged release is beneficial, as the process of tissue repair and remodeling lasts for months.

PRF is often used in periodontology and oral and maxillofacial surgery for hard- and soft-tissue augmentation, bone grafting, sinus augmentation, and implantology. PRF has also been utilized in endodontics for regenerative endodontic therapy as well as endodontic surgery.¹⁸ While many clinicians are aware of PRF, the differences among PRF formulations can be perplexing. Furthermore, for commercial reasons the names of many PRF protocols have been trademarked and are associated with a particular centrifuge device.¹⁹ Since the introduction of PRF two decades ago, numerous fixed-angle centrifuges and alterations to the centrifugation protocols have produced varying forms of PRF, including leukocyte-rich PRF (L-PRF), advanced PRF (A-PRF), liquid injectable PRF (i-PRF), and advanced PRF Plus (A-PRF+).^9,10,20-22 A trend has been towards lower g-forces and/or shorter centrifugation time, resulting in higher concentrations of platelets, leukocytes, and growth factors.^21,22

Concentrated PRF (C-PRF) was recently developed by using the L-PRF protocol and extracting only liquid contents from within the small buffy coat layer.²³ C-PRF produces very high concentrations of leukocytes and platelets, and C-PRF has been shown to be superior to i-PRF in terms of platelet and leukocyte concentration and growth factor release.²⁴

In 2018 Lourenço et al introduced horizontal centrifugation as a method to produce PRF.²⁵ A commercial PRF produced via horizontal centrifugation is known as Bio-PRF.

Lowering the relative centrifugation force can produce a liquid PRF, consisting of liquid fibrinogen.²¹ Three different liquid PRF formulations are i-PRF (fixed-angle centrifuge), C-PRF (fixed-angle centrifuge), and Bio-PRF liquid (horizontal centrifuge). The liquid PRF coagulates over the course of several minutes, and when combined with graft particulate such as allograft it congeals into a solid mass that allows for improved handling, manipulation, and placement into a surgical site; this is referred to as "sticky bone."²⁶ Sticky bone combines the osteoconductive and scaffolding properties of the allograft with the high concentrations of platelets, leukocytes, and growth factors found in PRF. One direct study shows higher concentrations of bioactive cells and growth factors in C-PRF compared to i-PRF²⁴; to date C-PRF has not been compared to Bio-PRF liquid.

With so much variation among PRF names and centrifuges, it can be challenging for dentists to choose which centrifuge is ideal for their clinical practice. Centrifuge devices can usually be programmed to follow other protocols not associated with their particular trademarked PRF.

In 2019 Miron et al compared cell concentrations among liquid PRF and solid PRF produced on three different centrifuge devices and found that among the protocols tested, the highest concentrations of platelets and leukocytes were found in solid and liquid PRF made using horizontal centrifugation.²⁷ Liquid PRF produced via horizontal centrifugation, in particular, contained the highest overall concentrations of both leukocytes and platelets. These findings indicate that PRF produced using a horizontal centrifuge is superior to that made from a fixed-angle centrifuge. Additionally, the authors advised against the use of the solid L-PRF protocol for membrane fabrication due to an uneven distribution of cells, which are located only at the base of the PRF clot.²⁷ The authors also found that the liquid A-PRF protocol did not achieve adequate separation of cell types and failed to produce high quantities of platelets or leukocytes.

Finally, another PRF derivative, concentrated growth factor (CGF), was developed by Sacco using a fixed-angle centrifuge.²⁸ Despite different centrifuges and protocols, CGF is identical to PRF in terms of mechanical and degradable properties.²⁹ To date, no studies have compared cell or growth factor concentrations between CGF, C-PRF, and Bio-PRF.

The properties and uses of PRF, as well as their formulations that are available commercially, are wide-ranging in dentistry. Clinicians can benefit from knowing and understanding the differences among the many PRF products that may be used to promote bone and soft-tissue healing and regeneration.

Andrew T. Moshman, DMD
Private Practice, Brooklyn, New York

The author had no disclosures to report.