Platelet Rich Fibrin (PRF) Application in Oral Surgery

Abstract

Platelet rich fibrin (PRF) is an autologous biological product which becomes popular day by day and available in a wide variety of fields in medicine. Platelet concentrates which are introduced at the early 90s have evolved over the years. The use such autologous materials have become trendy in recent years to encounter demanding expectations of patients, improve treatment success and maximize patient comfort. Despite its increasing use in dentistry and oral surgery, the most indications and effects are still being discussed. PRF is easily accepted by patients because of its low cost, easy to receive, low donor morbidity, low postoperative complication and infection rate. This biomaterial may be a solution for patients who have strong negative beliefs about the use of allografts and xenografts or who are afraid of complications during the grafting procedure. The objectives of these technologies are to use their synergistic effect to improve the hard and soft tissue regeneration. PRF in oral surgery are used for alveolar bone reconstruction, dental implant surgery, sinus augmentation, socket preservation, osteonecrosis, oroantral fistula closure, struggling with oral ulcers, preventing swelling and edema constitution. This chapter aims to review the clinical applications of platelets in oral surgery and the role of molecular components in tissue healing.

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
Chapter
Platelet Rich Fibrin (PRF)
Application in Oral Surgery
AlperSaglanmak, CaglarCinar and AlperGultekin
Abstract
Platelet rich fibrin (PRF) is an autologous biological product which becomes
popular day by day and available in a wide variety of fields in medicine. Platelet
concentrates which are introduced at the early 90s have evolved over the years.
The use such autologous materials have become trendy in recent years to encounter
demanding expectations of patients, improve treatment success and maximize
patient comfort. Despite its increasing use in dentistry and oral surgery, the most
indications and effects are still being discussed. PRF is easily accepted by patients
because of its low cost, easy to receive, low donor morbidity, low postoperative
complication and infection rate. This biomaterial may be a solution for patients
who have strong negative beliefs about the use of allografts and xenografts or who
are afraid of complications during the grafting procedure. The objectives of these
technologies are to use their synergistic effect to improve the hard and soft tissue
regeneration. PRF in oral surgery are used for alveolar bone reconstruction, dental
implant surgery, sinus augmentation, socket preservation, osteonecrosis, oroan-
tral fistula closure, struggling with oral ulcers, preventing swelling and edema
constitution. This chapter aims to review the clinical applications of platelets in
oral surgery and the role of molecular components in tissue healing.
Keywords: platelet rich fibrin, oral surgery, tissue healing, dental implant
. Introduction
In recent years, the question how to increase patient comfort after surgical
interventions became the main topic of oral surgical applications. In addition to
minimally invasive surgical techniques, extra procedures performed during or
after surgery are aimed to reduce postoperative morbidity. As a result of various
researches in recent years, the use of platelet concentrates give rise to improve
patient comfort and enhance healing after the operation.
Surgical techniques to gain bone and soft tissue can be difficult and associated
with higher morbidity. Although they are technique delicate, they just considered
as gold-standard, because of their capacity in healing enhancement [1]. However,
alternative autologous blood derivatives such as platelet rich fibrin (PRF) are
becoming a current issue with its easy use and effectiveness.
PRF is an autologous product acquired from the patient’s own blood and
enters dental field as a second- generation platelet concentrate under the name
PRF [Platelet Rich Fibrin] by Choukroun. Although they are known by different
names according to the centrifugation time (A-PRF, L-PRF, I- PRF, P-PRF) their

Platelets

main rationale is the same. They are increasing the healing capability of the tissue
by releasing growth factors from platelet granules. These factors are essential for
inflammation process and they have positive effect on healing enhancing. Since it is
an autologous product, it does not cause allergic reactions, it can be prepared rapidly
and easily, there is no risk of disease transfer and no risk of donor site morbidity.
The main advantages are controlling inflammation and suppressing infection by
leukocyte and cytokine secretion [2] (Figures  and ).
In order to get in depth information about the supportive effect of PRF
one should know about the healing pattern of injured tissue. There are four
sequential phases of wound healing: Hemostasis, inflammatory, proliferative
and remodeling phase [3]. At hemostasis phase, platelets are essential for blood
clot formation and PRF with rich platelet granules is promotive to accommodate
a strong fibrin network. This blood clot serves as a reservoir which allows cell
migration, adhesion and proliferation. The impact of this fibrin matrix pro-
ceeds throughout the whole healing process. Inflammatory phase starts with
the injury and takes 5–7days approximately. During this phase, platelets are
releasing various growth factors to the injured site that migrate inflammatory
cells (Lymphocytes, macrophages and neutrophils). These factors are PDGF
(Platelet-derived growth factor), VEGF (Vascular endothelial growth factor),
TGF B (Transforming growth factor) and pro-inflammatory cytokines such as
interleukins (IL-1, IL-6, IL-8) and tumor necrosis factor alpha (TNF-α), whose
roles are enhancing angiogenesis and tissue healing. Within the comprising of
new blood vessels with angiogenesis, acidic and hypoxic environment change.
In the proliferative phase, MSCs (Mesenchymal stem cells) releasing from newly
formed blood vessels, BMP’s (Bone morphogenic protein) and TGF-β are playing
an important role in MSCs organism. MSC’s role is inducing osteoblast differenti-
ation. The last but not the least, remodeling phase is characterized as maturation
process. Within this process, vascularity ratio and collagen deposition decreases
and mineral deposition increases with the replacement of woven bone into lamel-
lar one [4–6].
Fibrin forms a matrix for the migration of cells such as fibroblasts and endo-
thelial cells, which are crucial in angiogenesis and new tissue formation. PRF is a
strong fibrin matrix structure, platelets and leukocytes attach on it and activate
degranulated growth factors with the consequence of releasing cytokines. It has
been suggested that PRF, a natural fibrin network, can protect the growth factors
containing in its own structure from proteolysis. Thus growth factors may maintain
their activity for a long time and stimulate tissue regeneration [7].
Figure 1.
Bloodletting of a patient.


Platelet Rich Fibrin (PRF) Application in Oral Surgery
DOI: http://dx.doi.org/10.5772/intechopen.92602
. Types of PRF
The main purpose of using PRF is to release the rich content of alpha granules
of platelets into the environment for therapeutic purposes. In addition to the basic
functions of platelets, the contents of alpha and dense granules are very important
for different processes such as inflammation and angiogenesis [8]. The main differ-
ences between PRF types are their centrifuge speed.
• Advanced platelet rich fibrin (A-PRF): It is obtained with longer centrifuga-
tion time and lower rpm. Thus, more neutrophilic granulocytes are present in
the distal region of the clot. Neutrophilic granulocytes contribute to monocyte
differentiation in macrophages (Figure ).
• Pure platelet rich fibrin (P-PRF): After the first centrifuge (6min high
speed), transferring the buffy coat and PPP (Platelet poor plasma) to the sec-
ond tube, which contains CaCl2. After the second centrifuge starts and takes
15min long, stable platelet-fibrin takes place. The authenticity of this method
is the presence of separation gel at the first tube.
• Leukocyte and platelet rich fibrin (L-PRF): It is very simple and cheap
method. Blood samples are taken into glass tubes without any anticoagulant
and centrifuged immediately at low speed. It is formed three different layers
with acellular plasma, platelet-rich fibrin and erythrocyte layer at the bottom,
respectively. Thrombocyte rich fibrin matrix is very powerful and autologous
biomaterial can be used in different fields in oral surgery.
• Injectable platelet rich fibrin (I-PRF): Blood involves high number of leuko-
cytes. However coagulation occurs within few minutes after the centrifugation
has finished. The use of I-PRF [Injectable] is at an early stage. But the results
are very promising in terms of increasing vascularity and soft tissue healing.
• Liquid platelet rich fibrin (Liquid-PRF): Liquid-PRF was defined with low-
speed centrifugation (LSC), which allows forming of a liquid-PRF formula of
fibrinogen and thrombin rather than its conversion to fibrin [2].
Figure 2.
PRF membrane preparation.

Platelets

. PRF in post extraction
Tooth extraction has various adverse effects such as pain, bleeding, swelling,
infection etc. Wound healing in the tooth extraction is characterized by bone loss
as a natural process. Furthermore; extraction will result recession around adjacent
teeth and hinders the functional and esthetic prosthetic rehabilitation. PRF have
been shown to play an important role in tissue healing with the releasing growth
factors from alpha granules, regulate cellular events such as cell adhesion, migra-
tion, proliferation, differentiation and extracellular matrix deposition. Major
changes occurred within the first year following extraction, but a major part of
bone resorption takes place only within 3months [9, 10].
The rationale behind the enhancement of PRF in socket healing is very slowly
polymerizing, cell migration and fibrin network capable of proliferation. During
remodeling of the fibrin network many important growth factors from activated
platelets and the release of the matrix glycoproteins. This biochemical structure
gives rise to the tissue regeneration (Figures  and ).
Figure 4.
PRF membrane utilization in guided bone regeneration.
Figure 3.
A-PRF centrifuge device.


Platelet Rich Fibrin (PRF) Application in Oral Surgery
DOI: http://dx.doi.org/10.5772/intechopen.92602
On the other hand the role of PRF in soft tissue healing has been shown at
well-designed meta-analyses. In fact there are no significant differences in alveolar
osteitis, acute inflammation or alveolar infection following tooth extraction. New
bone gain and bone remodeling topic is also contradictory. However it was con-
cluded that PRF is good at decreasing swelling, edema, pain and trismus following
tooth extraction [9–11].
. PRF for maintaining swelling, edema and pain
Modern studies on clinical research showed that PRF aim to increase not only
the success of the treatments but also the patient comfort. In this sense, the use of
autologous products is advantageous such as high acceptability, low risk of disease
transfer, low morbidity and low cost. PRF plays a crucial role in tissue repair. Their
alpha granules include many substances, plenty of growth factors with significant
effects on the inflammatory and proliferative resident cells at the site of injury, like
mesenchymal stem cells, fibroblasts, chondrocytes and osteoblasts. This potential
may be increased by the concentration of the platelets. Certain in-vitro and in-vivo
studies have shown that the use of PRF is significantly advantageous in terms of cell
migration. Most of clinical studies found the use of PRF positive at wound healing.
According to the results of clinical studies, the use of PRF provides an advantage in
soft tissue healing, reducing swelling and trismus and increasing patient comfort.
However evidences on maintaining pain is scarce and pain usually adhere on early
formation of soft tissue healing [12].
. PRF in periodontal treatment
PRF can also be used in regenerative periodontal therapy to enhance hard and
soft tissue wound healing and promote periodontal tissue regeneration. Various
studies have shown the favorable benefit of using PRF as an adjunct to traditional
periodontal surgical techniques. These studies all exhibit improved clinical out-
comes regarding key clinical parameters such as clinical attachment level and
pocket depth with the use of PRF when compared to conventional techniques
applied alone.
The rationale behind this benefit is believed to lie in the differentiation and
proliferation inducing abilities of PRF.The rich source of bioactive cells within
PRF itself stimulate the local environment and regulate the inflammation process,
Figure 5.
PRF membrane application in immediate implantation for filling the buccal gap.

Platelets

thereby enhancing periodontal wound healing and reducing postoperative discom-
fort. In addition to these benefits the PRF sample also inherently supplies growth
factors, releasing them slowly into the wound for 7–14days. Other obvious benefits
include graft stabilization. Furthermore, a possible antimicrobial effect of L-PRF is
also present [13].
Another reason for PRF being favored in periodontal therapy is its multi-
purpose nature. The centrifuged buffy coat can be used alone in defects, combined
with particulate graft materials or as a thin membrane covering in regeneration
techniques. Studies also show that PRF can be used as an alternative to connective
tissue grafts (CTG) in periodontal plastic surgery owing to its cellular contents.
Additionally, the many benefits of PRF use in periodontal therapy also include its
graft stabilization, wound sealing and hemostatic abilities. Evidently, along with its
favorable biologic outcomes and low-cost PRF seems to be almost ideally suited for
various periodontal purposes [13, 14].
The performance of PRF in different periodontal surgery indications was mea-
sured and PRF was found to perform superiorly when compared to conventional
perio-plastic surgeries applied alone. Its use in intra-bony defects and furcation
defects have proved beneficial in reducing pocket depth values, clinical attachment
level gains and bone fill percentages. Improved outcomes in intrabony defects were
obtained when used alone or in conjunction with other biomaterials. In furcation
defects also, traditional flap surgeries tended to perform better when comple-
mented with PRF.Coronally Advanced Flap (CAF) procedures showed improved
results when accompanied with either CTGs or PRF membranes. Compared to each
other however, these two materials seemed to perform similarly. Therefore, it can
only be said that PRF can be considered a suitable alternative to CTGs in periodon-
tal plastic surgery [14, 15].
. PRF in sinus lifting
Implant rehabilitation success is highly related with sufficient bone volume
and density. The posterior maxilla represents a challenging and unique area for
successful dental implant rehabilitation because of its relatively deficient bone
volume and poor bone quality caused by alveolar bone resorption and maxillary
sinus pneumatization. Rehabilitation of posterior maxillary bone volume has been
successes by different procedures, such as Le Fort I osteotomies, onlay grafts and
sinus lifts [16, 17]. Maxillary sinus floor elevation is considered one of the most
successful procedures that can be performed using different grafting materials,
such as autogenous, xenograft, allograft, alloplast and PRF [18, 19].
Autogenous bone with osteogenic, osteoinductive and osteoconductive proper-
ties is still considered to be the gold standard. However, grafting with autogenous
bone is associated with donor site morbidity, extended duration of surgical proce-
dures and the volume of bone graft harvested may be insufficient for the require-
ments. Biomaterials, thus, are promising substitutes for autogenous bone grafts in
maxillary sinus augmentation. Osteoconductive properties of these biomaterials
have been shown in clinical studies with satisfactory clinical outcomes.
On the other hand, these bone graft materials demonstrate lack of osteogenic
and osteoinductive potential with distinct osteogenic capacity and bone formation.
Moreover, some disadvantages, mainly related to a limited availability, prolonged
healing time and impact on host responses can appear when using these bone sub-
stitutes. To overcome these problems, new substances with osteoinductive proper-
ties, such as platelet-rich fibrin (PRF) was recently introduced as replacement or
additional materials in sinus augmentation procedures [20].


Platelet Rich Fibrin (PRF) Application in Oral Surgery
DOI: http://dx.doi.org/10.5772/intechopen.92602
The biologic mediators have osteoinductive properties and they are considered
to accelerate the formation of new bone and to reduce the time interval. The
strengths of PRF comes from promoting the vascularization of bone tissue, reduc-
ing tissue inflammation, improving scaffold mechanics and accelerating new bone
formation [20]. Newly, researchers have paid greater attention to the success of
PRF application in maxillary sinus lifting procedures, but no consensus has been
reached. Some researchers have reported positive effects of PRF application in sinus
augmentation procedures.
Platelet concentrates have been used to accelerate bone generation and improve
healing by releasing growth factors such as transforming growth factor β1 and β2,
platelet-derived growth factor and vascular endothelial growth factor, which are
able to induce angiogenesis and activate cell proliferation.
In the literature there are some different application techniques for PRF in the
sinus augmentation such as PRF as a sole grafting material, PRF with allografts or
PRF with xenografts. All of these techniques have variable clinical, radiographic
and histologic and histomorphometric outcomes.
Mazor etal. [21] and Simonpieri etal. [22] performed sinus lift by using lateral
approach and PRF was used as a sole grafting material and implants were applied
immediately to serve as tent pegs. During the healing period there were no com-
plications. A 100% survival rate was observed in total of 57 sinus lift procedures
and 110 implants during the follow-up period (2years). Radiographic examination
was performed by CT scan or panoramic radiographs about 6months after the
sinus augmentation to examine the bone volume, where the average bone gain was
9.8mm. Histologic and histomorphometric examination accomplished by Mazor
etal. showed that dense collagen matrix, easily identified osteocytes and osteoblasts
in the lacunae and well-organized and vital bone with structured trabeculae with
more than %30 bone matrix.
Choukroun etal. [23] performed sinus augmentation with PRF in combination
with demineralized freeze-dried bone allograft (DFDBA). They found the rate of
vital bone/inert bone%20 both in test and control group but with a reduced healing
time at PRF group.
Zhang etal. [24] applied the PRF/xenograft mixture for the test group and
xenograft as a sole graft material for the control group. They found no statistically
significant difference between the two groups.
In light of this information, although there is not a consensus statement about
the effect of PRF as a grafting material at sinus lifting procedure, still it is a good
alternative material with its osteoinductive properties to enhance hard tissue
healing.
. PRF for preserving bone around implants
Marginal bone loss is an inevitable process which starts immediately follow-
ing implant placement. There have been done plenty of studies since decades
to minimize it. Previous studies about preserving bone around implants, has
focused on soft tissue thickness and it was hypothesized, adequate soft tissue
volume around implants has a positive effect in preserving marginal bone and
PRF is perfect material to augment soft tissue. We know PRF is a good autologous
material to enhance soft tissue healing with its growth factors including VEGF,
PRGF, etc. However researches about PRF usage to augment hard tissue have
contradictory results and there is need to do further detailed randomized con-
trolled clinical studies to know about the effect of PRF preserving marginal bone
[25] (Figures  and ).

Platelets

. PRF in rare clinical scenarios
PRF could also be beneficial with growth factors including in rare clinical
scenarios such as cyst treatment, sinus membrane perforations, oroantral fistulae
closure and osteonecrosis.
Figure 8.
Large sinus membrane perforation.
Figure 6.
Liquid PRF combined with MPM (Mineralized Plasmatic Matrix) and B-TCP graft material for sinus lifting.
Figure 7.
PRF pieces combined with xenograft in guided bone regeneration.


Platelet Rich Fibrin (PRF) Application in Oral Surgery
DOI: http://dx.doi.org/10.5772/intechopen.92602
Oroantral fistula (OAF) constitution is defined a pathological way between
maxillary sinus and oral cavity. It is an unnatural epithelial connection filled with
granulation tissue or polypoid extension of sinus membrane. It can either come into
existence spontaneously following a large maxillary cyst or tumor or as iatrogenic
after tooth extraction or dental implant surgery [26]. An OAF is highly iatrogenic
and depending on the perforation of sinus membrane during surgical interventions
at maxilla. Either this or that way the treatment of perforated sinus membrane is
bringing the tissue free from infection, cleaning the epithelium and repairing the
membrane (Figure ).
There are plenty of methods maintaining with OAF.PRF is one of them which is
recently introduced. The technique is as following; PRF clots obtained by centrifu-
gation should be isolated from PPP (Platelet Poor Plasma) and red blood cells, pre-
pared as thin membranes and applied perforated area layer by layer. The researches
about PRF in OAF closure conclude that, wound healing is faster and there was an
increase in soft tissue thickness during healing. Due to its natural ingredients, there
are no need to use additional materials, thus less donor site morbidity occurs.
Osteonecrosis is another rare clinical scenario which is defined as avascular
bone area surrounding soft tissue on occasion. Various clinical and medical consid-
erations can cause osteonecrosis. It can occur in consequence of bisphosphonates
(including denosumab), medications or iatrogenic dental malpraxis (In proper use
of NaOH2, formaldehyde, devitalizing agents). Either this or that way the healing
of necrotic bone takes 8weeks at least in appropriate circumstances. Osteonecrosis
can conclude either with a demarcation line or heal just as avascular necrosis.
Clinician should choose the treatment modality according to the clinical situation.
The main factor of osteonecrosis is the disturbance of vascular blood supply. The
management of patient with compromised healing in bone is controversial. Despite
the conventional treatment modalities, curettage of necrotic bone, antibiotic usage,
chlorhexidine glukonate; with more complex treatment modalities hyperbaric oxy-
gen therapy, ozone and low dose laser; PRF utilization alone or with these treatment
modalities takes place in recent years (Figure ) [27].
The use of PRF in cyst depends on the same rationale with the enhancement of
soft and hard tissue healing. Researches related to this topic conclude that using
PRF as a graft material is beneficial for shortening healing time and increasing bone
mineral density (Figures –).
Since it has been discovered the synergetic effect of PRF in healing enhancement
of covering oral mucosa, these platelet derivatives became even more important. PRF
Figure 9.
Sinus membrane perforation closure with PRF membrane.

Platelets

involves cytokines, chemokines, and antimicrobial derivatives with growth factors such
as VEGF, which are crucial to support hard and soft tissue in order to heal (Figure ).
. Conclusion and future perspectives
PRF with its strong fibrin matrix, including growth factors and slow release,
has a positive effect on wound healing. The most important factor for success in
oral surgical procedures is early wound healing. This improvement will decrease
the healing time and enhance relatively the healing of underlying bone. PRF’s
effect on decreasing pain, swelling and edema is evidenced based. Thus it is very
promising material in applications mostly associated with soft tissue healing such as
third molar extractions, oroantral fistula closure and alveolar cleft reconstructions.
Figure 11.
Radicular cyst enucleation.
Figure 10.
2 weeks follow up after PRF application of avascular necrosis area in mandible.


Platelet Rich Fibrin (PRF) Application in Oral Surgery
DOI: http://dx.doi.org/10.5772/intechopen.92602
However studies have sparsely mentioned about the positive effect of new bone
formation at sinus lifting, periodontal and peri-implant bone preservation and
alveolar bone augmentation. For future perspectives, with the use of new genera-
tions of PRF with increased growth factor capacity, combined with graft materials,
PRF will appear in more areas in oral surgery applications.
Acknowledgements
Dt. Ali İsik from Istanbul University Dentistry Faculty Department of Oral
Implantology, Istanbul, Turkey has valuable contributions to this book chapter.
Conflict of interest
The authors declare no conflict of interest.
Figure 12.
PRF utilization after cyst enucleation.
Figure 13.
Healing 2 months follow up after PRF augmentation.

Platelets

Author details
AlperSaglanmak*, CaglarCinar and AlperGultekin
Dentistry Faculty, Department of Oral Implantology, Istanbul University, Istanbul,
Turkey
*Address all correspondence to: alper.saglanmak@istanbul.edu.tr
© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms
of the Creative Commons Attribution License (http://creativecommons.org/licenses/
by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.


Platelet Rich Fibrin (PRF) Application in Oral Surgery
DOI: http://dx.doi.org/10.5772/intechopen.92602
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