PRF: biology and mode of action, indications, clinical application: zm-online

2022-09-04 19:00:53 By : Ms. Chloe Zhou

Easy to use, little equipment and time required, but a high regeneration potential for soft tissue and bones - this makes the autologous platelet concentrate Platelet Rich Fibrin (PRF) interesting for dental practices without a surgical focus.Examples are the treatment of extraction sockets for socket preservation or recession coverage in periodontal surgery.Sebastian Blatt Hendrik Naujokat 08/16/2022 No comments Page 1 of 2Fig. 1: Alveolar ridge preservation after extraction 36 with two autologous PRF-Clot Sebastian Blatt inserted into the alveolus and secured with mattress suturesThe use of autologous platelet concentrates was first described in 1940, here for the reconstruction of peripheral nerves [Ghanaati et al., 2018].The use of an autologous, platelet-rich human plasma in surgery due to its hemostatic and adhesive properties was described by Kingsley in 1954 [Kingsley, 1954;Mozzati et al., 2010].From this, the concept of fibrin glue developed in the early 1970s and 1980s – a blood clot made of fibrinogen and thrombin that was used to cover defects, initially in animal experiments and later in clinical applications [Matras, 1982].Disadvantages of this early fibrin glue system were seen in the possible transmission of viruses due to the use of donor cryoprecipitates.As an alternative, fibrinogen was soon obtained from autologous plasma and mixed with bovine thrombin and calcium to finally form fibrin.Fibrin is used to regenerate diverse organ systems due to its high biocompatibility, which represents an excellent niche for stem or progenitor cells [Ahmed et al., 2008].Platelets were added to this concept later [Alsousou et al., 2009].Whitman et al.demonstrated a thrombocyte gel that could be prepared after autologous blood sampling in a two-stage centrifugation process with the addition of thrombin for thrombocyte activation [Whitman et al., 1997].Building on the work of Knighton et al., who first introduced the concept of wound healing of cutaneous ulcers using growth factor application from autologous platelet concentrates [Knighton et al., 1986], the first generation of autologous platelet concentrates developed [Marx et al., 1998].Platelet-rich plasma (PRP) is considered the most important representative of this class [Moraes et al., 2013].PRP can be defined as the volume fraction of the plasma in autologous whole blood that can have a platelet concentration that is up to five times higher than that in donor blood [Marx et al., 1998].After venous blood collection via a specific collection set with plastic tubes, the collected blood is mixed with an anticoagulant (mainly thrombin or calcium chloride) and separated into different phases using different gravitational forces with two centrifugations using a tabletop centrifugation system.The platelets can now be extracted from this as a so-called PRP clot [Alsousou et al., 2009].These procedures continue to be used successfully in much of regenerative medicine.Nevertheless, some disadvantages of these methods are discussed in the current literature: On the one hand, the time required for PRP production necessitates the use of an anticoagulant, which thwarts the concept of purely autologous application and seems to have a negative impact on growth factor expression.In addition, the two-pass centrifugation process is laborious and cells involved in wound healing, such as leukocytes, are largely excluded before use [Ghanaati et al., 2018].In addition, it is also important to take into account inter-individual differences in the donor/recipient system, which can vary greatly both in platelet concentration and in growth factor expression and appear to be mutually dependent [Weibrich et al., 2002].Different PRP concentrations therefore seem to have a variable effect on wound healing processes [Alsousou et al., 2009], which can be confirmed in in vitro analyzes [Dohan Ehrenfest et al., 2012].In order to remedy these disadvantages, the "second generation" of autologous platelet concentrates was developed, the most important representative of which is that of Choukroun et al.PRF presented for the first time in 2001 [Miron et al., 2017].PRF is characterized by a one-off centrifugation process, which runs in particular without the addition of an anticoagulant [Fujioka-Kobayashi et al., 2017].The platelets are activated and the fibrin polymerizes.Depending on the centrifugal force selected and the tube system (glass or plastic coating), three phases are formed: a red thrombus in contact with the base of the red blood cells, an acellular fibrin gel and a "buffy coat" as whitish lines that indicate accumulation of platelets within the PRF fibrin matrix [Dohan et al., 2006].Depending on the clinical indication, a solid or liquid PRF fibrin clot can be extracted for further use.In order to restore the integrity of the tissue after an injury, after a surgical intervention or after a foreign body implantation, tissue regeneration occurs through the interaction of immune cells, growth factors, extracellular matrix and the cells located in the wound bed.There are roughly two processes involved in healing: the inflammatory and the proliferative phase.In the inflammatory phase, the activity of peripheral monocytes in the blood cleanses the wound of pathogenic foreign bodies.In the proliferative phase, the wound is reclosed by de novo vascularization (angiogenesis), peripheral nerve repair and tissue reorganization [Canedo-Dorantes and Canedo-Ayala, 2019].The PRF can significantly influence these processes, particularly through its outstanding pro-angiogenic potential.The PRF consists of platelets, leukocytes, cytokines, glycemic chains and glycoproteins mixed with a slowly polymerizing fibrin network.The various cell types are “trapped” in this “fibrin network”, through the interaction of which the proliferation and differentiation of other cell lines are promoted and thus the local regeneration can be initiated, orchestrated over time and shortened as described above [Miron et al., 2017].Fibrin is considered a natural angiogenesis initiator and, by attracting circulating stem cells, provides the breeding ground for epithelially optimized wound healing [Faot et al., 2017].As a result, the fibrin network has a special position: while there is a one-off "outburst" of growth factors in first-generation preparations, the fibrin network enables spatial cell-cell interaction and is decisive for the (compared to PRP) slower and continuous (more physiological) growth factor release from the alpha granules of the platelets [Miron et al., 2019].Cytokines contained in the PRF and important for angiogenesis are primarily TGFβ-1, VEGF, PDGF, IGF I and II, IL-1β, IL-4, IL-6 and TNF-α [Dohan et al., 2006a;2006b;Miron et al., 2017].In combination, the addition of PRF can optimize the complex process of soft-tissue wound healing.There are currently a variety of benchtop centrifuges and collection systems for the production of different PRF protocols on the market.Recent research shows that different centrifugation methods and times have a significant impact on growth factor expression [Miron et al., 2019].This could be because certain cell types are distributed differently depending on the cumulative centrifugal force.Also, different vibration protocols have been identified for each centrifuge, each resulting in different cell content and PRF membrane composition [Dohan Ehrenfest et al., 2009].The exact presentation and the justified selection from the various protocols of the production methods are therefore increasingly being placed at the center of the current literature discussion [Dohan Ehrenfest et al., 2018].The Frankfurt working group led by Ghanaati et al.compared the different protocols scientifically for the first time and showed immunohistochemically the effects of centrifugal force on the distribution of monocytes, T and B lymphocytes, neutrophilic granulocytes, CD34-positive stem cells and thrombocytes as cell populations relevant for wound healing and tissue regeneration within the PRF [Ghanaati et al., 2014].This led to the development of the "low speed centrifugation concept" (LSCC), which can lead to a significant and, above all, long-term increase in the number of leukocytes and thrombocytes as well as the concentration of growth factors in autologous PRF-based matrices [Choukroun and Ghanaati, 2018].It has been shown in animal models that the growth factors detected in in vitro experiments also lead to increased formation of new blood vessels and faster soft tissue regeneration in vivo [Miron et al., 2017].Clear evidence and scientifically based preclinical studies on the possible influence of PRF on osseous regeneration are currently lacking in the current literature discussion [Miron et al., 2017].Isolated in vitro studies show a positive influence on the differentiation, proliferation and vitality of osteoblasts and the inhibition of osteoclastogenesis [Strauss et al., 2019].However, this effect could not be confirmed in other in vivo studies [Faot et al., 2017].However, the controversial data situation does not reflect the currently very frequent clinical use of PRF in the context of "guided bone regeneration".Further (particularly clinical) studies should therefore be initiated as a matter of urgency in order to be able to scientifically substantiate the practical use of autologous platelet concentrates in this indication as well.In the field of dento-alveolar surgery, the use of autologous thrombocyte concentrates is of great importance in clinical use today (Table 1).PRF is used in the form of a clot, as a membrane or in liquid form in combination with different biomaterials such as membranes or particulate bone replacement materials.After centrifugation, the clot can be pressed into the shape of a membrane and trimmed to the required size and shape using sterile tweezers and scissors.To date, multiple studies have shown a pro-angiogenic effect of PRF, particularly on soft tissue regeneration, which is associated with an optimized wound healing rate [Ghanaati et al., 2018].PRF can be used in the treatment of extraction sockets for alveolar ridge preservation (Figure 1).Here it leads to faster regeneration and wound healing and can significantly reduce the postoperative complication rates.Its use in the surgical removal of wisdom teeth has also been described in this context and is associated with a reduced postoperative complication rate and less postoperative pain [Choukroun et al., 2006;Hoaglin and Lines, 2013;He et al., 2017;Pan et al., 2019].Furthermore, PRF is used in periodontal surgery for recession coverage [Lekovic et al., 2012], where it can significantly optimize the regeneration of periodontal defects [Miron et al., 2017, Shah et al., 2015].In implantology, PRF is used not only for ridge preservation and overlay osteoplasty but also for sinus lift procedures (Figure 2) [Damsaz et al., 2020].A clinical study showed that the use of PRF as the sole filling material can lead to sufficient implant stability and ossification in the long-term follow-up [Simonpieri et al., 2011].Fig. 2: Top row from left: Insertion of the PRF membrane for sinus lift augmentation and simultaneous implantation, bottom row from left: Intraoperative findings after plastic wound closure, radiological control and prosthetic rehabilitation after six months |Sebastian BlattThe combination of PRF and bone replacement material for intraoral bone augmentation / guided bone regeneration procedures is widespread (Figure 3).However, as mentioned above, clear evidence must be discussed if the results are sometimes controversial [Liu et al., 2019;Pripatnanont et al., 2013;Yoon et al., 2014].A possible explanation for the different results of the studies could be the diversity of the analyzed materials and their specific biophysical properties as well as the different times of the investigation.In particular, the early scaffold/tissue reaction seems to be of outstanding importance, which initially requires stable osteointegration and subsequent healing [Khalil et al., 2011].Fig. 3: From top left to bottom right: Preoperative findings for a fibroodontoma in the lower jaw on the left, overlay plastic with PRF-biologized xenogeneic bone replacement material ("sticky bone") and biologized Goretex membrane, bottom right: postoperative findings |Sebastian BlattPRF is also used in a variety of ways in "major" maxillofacial and plastic surgery, for example in surgical facial scar and wrinkle correction [Sclafani, 2011;Hassan et al., 2020].The use of PRF can also be indicated for oncological issues and in particular for the therapy of drug-associated necrosis of the jaw [Ghanaati et al., 2018], but to date there has also been conflicting evidence on the influence on soft tissue healing and the reduction in occurrence of recurrences [Blatt et al., 2022].The existing evidence on the clinical indication and application of the PRF is currently being evaluated critically and published by the German Society for Implantology (DGI) under the auspices of the "Working Group of Scientific Medical Societies" (AWMF) in a consensus-based S3 guideline ("The use of Platelet Rich Fibrin in dental implantology”).Publication of the guideline is planned for the end of 2022.Autologous platelet concentrates such as PRF represent an important therapeutic additive in regenerative and reconstructive head and neck surgery. Due to their pro-angiogenic potential, they have a particular influence on soft-tissue-optimized regeneration with reliable evidence of a benefit in dento-alveolar surgery, in periodontal surgery and in (pre)implantological interventions.However, further studies are essential in order to be able to scientifically evaluate the possible influence of autologous platelet concentrates on procedures of bone regeneration.In particular, the regeneration of combined hard and soft tissue defects is a common clinical challenge in regenerative oral and facial surgery [Turnbull et al., 2018].If the gold standard of autologous tissue transfer is not possible or only possible to a limited extent, for example in the case of severe comorbidity of the patient, substitute materials of different origins are used [Tatullo et al., 2012].An initial sufficient vascular supply/connection of the introduced tissue/foreign material seems to be essential for the desired healing and regeneration [Rather et al., 2019].This can only be insufficiently achieved through the use of bone substitute materials - regardless of their origin - which often limits the use of the materials in the clinical indication [Bhatt and Rozental, 2012].A pre-vascularization with an increase in the pro-angiogenic properties of these materials could overcome this limitation, increase the regenerative potential and thus expand the clinical indication [Rather et al., 2019].Various methods have been used in this context to increase vascularization, in particular through the use of stem cell therapy and often in combination with novel 3D printing methods [Pirosa et al., 2018].However, the implementation of these procedures in clinical workflows has failed to date, not least because of the complex approval procedures and conditions.Autologous platelet concentrates could serve as a "clinical alternative" here, which increase the vascular supply and could thus be used for the biological functionalization of biomaterials [Blatt et al., 2021;2021a;2020].Autologous platelet concentrates such as PRF therefore represent a promising method in regenerative surgery that could initiate, control and optimize tissue regeneration in clinical translation directly or indirectly via tissue engineering methods.According to the current evaluation by the Federal Statistical Office, this is how many people were aiming for a doctorate in dentistry at the end of 2021.Corona virus: Dentists and doctors will find all relevant information and contact points for the practice regarding SARS-CoV-2 in an overview here - constantly updated!The information on this page is continuously updated.The security of your data is a key concern for us.In order to be able to protect this data even better in the future, your password must be at least 8 characters long and have at least three of the following four characteristics:If your password does not yet correspond to these characteristics, you will be asked to choose a new password the next time you log in.