platelet rich fibrin VS platelet rich plasma

Platelet-Rich Fibrin

Epithelial coverage for gingival recession treatment

Platelet concentrates have been utilized in regenerative
medicine as a means to concentrate growth factors from
blood via centrifugation. Their use extends to many fields of medicine for the management of various indications,including osteoarthritic knees, the repair of rotator cuffs, skin regeneration, treatment of burn victims, cancer therapy, and oral tissue regeneration. While autogenous PRP was developed as a first-generation platelet formulation in the 1970s and 1980s, drawbacks including its incorporation of anticoagulants such as bovine thrombin have been shown
to prevent optimal wound healing. Nevertheless, PRP
has been utilized in many fields of medicine to regenerate various tissue types by releasing bioactive growth factors that are known to speed soft and hard tissue regeneration to the surrounding microenvironment.
In the late 1990s, Professor Robert Marx pioneered the
use of platelet concentrates (PRP) for regenerative appli-
cations in oral and maxillofacial surgery. Today PRP
is still utilized by certain clinicians as a means to optimize tissue regeneration. Nevertheless, a group of researchers showed that anticoagulant removal could further optimize the clinical results observed with PRP. This work led to the development of a second generation of platelet concentrates termed platelet-rich fibrin (PRF), later renamed leukocyte platelet-rich fibrin (L-PRF), successfully accomplishing the goal of anticoagulant removal . This second-generation platelet concentrate differs significantly from previous versions in that a high concentration of leukocytes is found within the formulations, drastically improving not
only host–immune system defense against incoming patho-gens but also the secretion of growth factors and
cytokines responsible for tissue regeneration.
The most common growth factors found in platelet
concentrates are PDGF, TGF-β, and VEGF.

The final composition of PRP contains over 95% platelets, cells known to be responsible for the active secretion of growth factors involved in initiating wound healing of various cell types, including osteoblasts, epithelial cells, and connective tissue cells.
Following use of PRP, several limitations were observed.
The technique and the preparation required the additional use of bovine thrombin or calcium chloride in addition to coagulation factors, and it was found that these items reduced the healing process during the regenerative phase.
Furthermore, the entire protocol was technique sensitive, with several separation phases lasting sometimes upward of 1 hour, making it inefficient for everyday medical purposes.
In addition, because PRP is liquid in nature, it requires a
scaffold to be utilized, most notably a bone grafting material.
Interestingly, studies have shown that growth factor release from PRP occurs very rapidly, whereas an optimal prefer-ence would be to deliver growth factors over an extended period of time during the entire regenerative phase
These combined limitations led to the emergence of PRF,
which takes advantage of the fact that without anticoagu-
lants, a fibrin matrix that incorporates the full set of growth factors trapped within its matrix can slowly release these growth factors over time. Furthermore, PRF (or L-PRF) contains white blood cells, which have been shown to be key contributors to wound healing. These cells, in combination with neutrophils and platelets, are the main players in tissue wound healing and together are able to further enhance new blood vessel formation (angiogenesis) and tissue formation.
To date, numerous studies have investigated the regener-
ative potential of PRF in various medical situations. With
respect to tissue engineering, it has long been proposed that in order to maximize the regenerative potential of various bioactive scaffolds, three components are essential:
• A 3D matrix capable of supporting tissue ingrowth
• Locally harvested cells capable of influencing tissue
growth
• Bioactive growth factors capable of enhancing cell
recruitment and differentiation within the biomaterial
surface
PRF encompasses all three of these properties, whereby
fibrin serves as the scaffold surface material; cells
including leukocytes, macrophages, neutrophils, and platelets attract and recruit future regenerative cells to the defect sites; and fibrin serves as a reservoir of growth factors that may be released over 10 to 14 days . PRF
may therefore be utilized in many aspects of regenerative dentistry and is often combined with various other biomaterials to improve tissue vascularization.
L-PRF: A natural fibrin matrix and its biologic properties
The removal of anticoagulants from PRF allows for the
formation of a fibrin clot during the centrifugation process.
Because clotting occurs rapidly, centrifugation must take
place within seconds after blood harvesting. This technology therefore requires that the office is equipped with acentrifuge and a collection system.
The original PRF protocol was very simple: A blood
sample is taken without anticoagulant in 10-mL tubes,
which are then immediately centrifuged at 750 g for 12
minutes. The absence of anticoagulant implies that within a few minutes, most platelets of the blood sample in contact with the tube walls are activated to release coagulation cascades. Fibrinogen is initially concentrated in the upper layer of the tube, before the circulating thrombin transforms it into fibrin. A fibrin clot is then obtained in the upper-middle portion of the tube, just between the red corpuscles at the bottom of the tube and the acellular plasma at the top (platelet-poor plasma [PPP]).
As previously mentioned, the success of this technique
depends entirely on the speed of blood collection and
its subsequent transfer to the centrifuge. Indeed, without
anticoagulants, the blood samples start to coagulate almost immediately upon contact with the tube glass, and it takes a minimum of a few minutes of centrifugation to concentrate fibrinogen in the middle and upper part of the tube. Quick handling is the only way to obtain a clinically usable PRF matrix. If the duration required to collect blood and launch
centrifugation is overly long, failure will occur. By driving out the fluids trapped in the fibrin matrix, practitioners will obtain very resistant autologous fibrin membranes.
Major cell type in L-PRF: Leukocytes Platelets are the cornerstone for cells found in each of the platelet concentrates, including L-PRF. In L-PRF platelets
are theoretically trapped within the fibrin network, and their 3D mesh allows for their slow and gradual release as well as the release of associated growth factors over time. Leukocytes are also trapped within the L-PRF membranes, unlike
in PRP. Leukocytes play a prominent role in wound healing, and several studies have now pointed to their key role in immune regulation by acting as anti-infectious cells.
Studies from the basic sciences have revealed the potent and large impact of leukocytes on tissue regeneration around bone biomaterials. They additionally release growth factors and serve as key regulators controlling the ability for biomaterials to adapt to new environments. 

Leuko-cytes also play a large role in host defense to incoming pathogens. A study conducted following extraction of third molars showed that the placement of PRF scaffolds into extraction sockets resulted in a 10-fold decrease in third molar osteomyelitis infections.150 Furthermore, in a separate study, patients receiving PRF reported less pain and less need for analgesics when compared to controls, most notably due to the defense of immune cells that prevent infection, promote wound closure, and naturally reduce swelling and associated pain felt by these patients.

It is now known that the most important factor for tissue
regeneration is not necessarily the amount of growth factor released but the maintenance of a low and constant gradient over time. As the use of L-PRF has seen a continuous and steady increase in regenerative medicine, there has also been great interest in utilizing this technology for a wide variety of procedures to increase angiogenesis of tissues, an important scenario for tissue regeneration. Prior to initiating any blood collection, it is important that all centrifuges be prepared, open, and ready for use at the appropriate settings.
Because no anticoagulants are being utilized, blood collec-tion and centrifugation must occur rapidly to maximize the regenerative potential of L-PRF. After centrifugation, L-PRF membranes are removed, separated from the red clot, and transported to the L-PRF box to create barrier membranes.
Additionally, L-PRF clots can be utilized to fabricate plugs
(1 cm in diameter) for extraction sockets, or they can be cut into small fragments and mixed with bone grafting materials to improve their potential for angiogenesis .
More recently, it was proposed that a liquid PRF that clots after mixing with a bone grafting material could be fabricated by centrifuging for less time. This liquid plasma layer (which remains liquid for approximately 15 minutes) is mixed with bone grafting materials to create sticky bone . This liquid version of PRF contains an even higher concentration of leukocytes and growth factors and can be utilized to improve bone grafting material angiogenesis, handling, and stability.