Key points

Platelet-rich plasma and platelet-rich fibrin

Platelet-rich fibrin (PRF) is actually a second-generation technology. It is anteceded by platelet-rich plasma (PRP), which is whole blood centrifuged to remove red blood cells, leaving behind a suspension rich in white blood cells and plasma components that are thought to be important in promoting wound healing. Both PRF and PRP use autologous blood. Both PRF and PRP aim to use blood growth factors to promote the body’s own healing process. PRF builds on PRP by preserving the growth factors in a fibrin matrix and can exert its effects days or weeks after the surgery. As opposed to PRP, PRF is prepared without the use of anticoagulation factors, which are known to inhibit wound healing. In comparison to PRP, PRF preparations tend to have higher leukocyte count because of centrifuge technique improvements, a fibrin matrix that promotes healing and allows growth factors to be slowly released over time, and comes in moldable forms that improve workability.

A brief history of platelet-rich fibrin

As early as the 1950s, Kingsley used the term PRP to describe a thrombocyte concentrate used for patients with thrombocytopenia. Hematologists started to widely use the term in the 1970s.

The study of PRP took off in varying directions in the following decades with varying investigators proposing different protocols and different applications in medicine. These early ways to prepare PRP were sometimes lengthy, and anticoagulants such as bovine thrombin or CaCl ₂ were part of the preparation to prevent clotting and to keep the concentrate in a liquid form.

In the 1970s, Matras studied skin healing in rats. He proposed the use of what he called “fibrin glue” in various preparations to enhance healing in rats. The stickier fibrin glue had less anticoagulant effects, and he was unable to achieve consistent results. After that, there was a growing number of reports of platelet concentrates in “glue” or “gelatin” in general surgery, neurosurgery, and ophthalmology.

Interest in use of platelet concentrates in oral and maxillofacial surgery was elevated when in 1998 Marx showed that bone grafts grew more (74% vs 55% control) when infused with supraconcentrated platelet solution.

In 2000, Choukroun ^, finally coined the term PRF by using a form of platelet-rich concentrate that was firmer in consistency. This form of platelet concentration is widely accepted as the second-generation platelet concentration and is the focus of this article. In the 2 decades that followed, the original preparation was built upon to produce the PRF variants available today, including sticky bone (autologous fibrin glue mixed with bone graft) by Sohn, advanced PRF (A-PRF) by Choukroun, and injectable PRF (I-PRF) by Muorao. ^,

Mechanism of action

When the body tries to repair itself, it will undergo 3 phases: inflammatory phase, proliferative phase, and the remodeling phase. The first, inflammatory phase, is an acute inflammation reaction to injury. Blood is the vector that brings these inflammatory cells to the site of the injury. In addition to phagocytes that clean the wound, white blood cells and platelets release important cellular mediators that begin the healing process. Important growth factors that are released include TGFB1, PDGF, VEGF, IGF1, which mediate cell migration, proliferation, and differentiation. Platelets also secrete coagulation factors that ensure initial hemostasis. After 24 to 48 hours, the proliferative phase takes over by virtue of the presence of the inflammatory mixture of cellular signals created during the inflammatory phase. There can now be proliferation of fibroblasts, leukocytes, macrophages, and mesenchymal stem cells, which begin to lay the first foundations of the new tissue. Depending on the extent of the defect along with the immune capabilities of the body, the site will transition to the remodeling phase of healing when there is stability in the first tissues laid.

PRF is formed by dividing autologous blood into components that promote the wound-healing process and components that do not. Components that promote wound healing are suspended in a fibrin matrix for preservation and slow release as the wound heals. The red blood cells ideally are spun out during the centrifuge process, and what are kept are the white blood cells, platelets, and fibrin. Per volume, these ingredients for wound healing are found at much higher than physiologic levels. Refinement of PRF preparation techniques aims to preserve as much of the white blood cells and platelets and exclude as much of the red blood cells as possible.

The fibrin matrix is the main advantage PRF has over PRP. It acts as a 3-dimensional scaffold for the leukocytes and platelets and their release products. The matrix allows for delayed release of its contents so that the beneficial wound-healing effects are present for a longer time period. The matrix is also thought to trap more leukocytes within its network, although this is hard to prove because the slow centrifuge preparations can also have this effect. The mass effect of the fibrin clot is also advantageous in that it can take up space where PRP cannot. Peripherally proliferating cells can use the scaffold to penetrate the wounded site, which is not possible with the pure liquid preparation of PRP. The scaffold nature of PRF is especially true because the fibrin clot is workable and can be adapted to many tissue defect forms.

Types of platelet-rich fibrin

Broadly speaking, there are 2 types of PRF: a solid and a liquid. The solid PRF is the initial form of PRF made by Choukroun and colleagues. ^, As previously discussed, it improves on PRP by preparing the platelet concentrate without anticoagulation, thus producing a solid medium capable of allowing for a slow release of growth factors. Choukroun used a high centrifugal force (708 g ) in glass tubes to separate his blood products. This type of PRF had a dense fibrin structure. He would improve his technique in 2014 with Ghanaati by using a reduced centrifugal force (208 g ) and plastic tubes that are less likely to activate a clotting cascade to produce with he called A-PRF. This dense nature of the clot is the main form of solid PRF used today. A-PRF has a higher concentration of retained leukocytes because of its slow centrifugation and a more porous fibrin matrix, allowing for greater release of its contents. The greater porosity also allows for more blood vessel penetration during angiogenesis. These solid forms of PRF are malleable and can be shaped into pellets or cut into smaller pieces for bone grafting or pressed flat and be used as a membrane. I-PRF builds on this slow centrifugal force concept by being prepared at 60 g centrifugation force (at higher rpm but for less time) ( Fig. 1 ). The result is a suspension without anticoagulation that can be manipulated like PRP but retains the ability to form a slow release matrix once applied to tissue. ^{, ,} This form of PRF can be injected into deep tissue spaces, onto open wounds, and mixed with other graft materials, such as bone-grafting particles, to produce “sticky bone,” which has a puttylike consistency.

Solid PRF after centrifugation. The bottom layer is predominantly red blood cells and is discarded. The solid middle layer is clotted solid PRF. The top layer is unclotted plasma. Both the middle and the top layers have useable growth factors. In I-PRF, the clotting is not allowed during centrifugation, resulting in a liquid top and middle layer that is indistinguishable. PPP, Platelet Poor Plasma.

Platelet-rich fibrin preparation