Vol. 133 No.

2 February 2022

Autologous platelet concentrates in oral surgery:

protocols, properties, and clinical applications
Laura O'Sullivan, BDS, MFDS RCSEd, PDTLHE,a and
R
ıcheal N
ı R
ıord
ain, MBBS, BDS, MA (Higher Ed), PhD, MFD, FFD, FDS(OM)b,c

Autologous platelet concentrates (APCs) are a relatively new phenomenon, with initial reports of their regenerative potential pub-
lished as recently as 1998. Despite their relative infancy, a huge body of evidence exists in support of their capacity to promote
osseous and soft tissue regeneration through the physiologic processes of platelet activation and subsequent growth factor release.
APCs have transformed many areas of healthcare and are now considered an essential component of the surgical milieu. In this
narrative review, we explore the evolution of autologous platelet therapies with a particular emphasis on their contemporary
applications in oral surgery, which rather fittingly was the first specialty to report the regenerative potential of APCs. (Oral Surg
Oral Med Oral Pathol Oral Radiol 2022;133:156 164)

The last 20 years have seen huge advances in the devel- BACKGROUND
opment and understanding of the role of autologous plate- The use of autologous blood products in surgery was first
let concentrates (APCs) in many areas of healthcare. Such reported in 1954 by Kingsley, who used “platelet-rich
is the predictability of their regenerative properties that human plasma” for its hemostatic and adhesive
APCs are now widely considered a fundamental treatment properties.1,2 In 1970, Matras3 introduced the concept of
modality in oral and maxillofacial surgery, orthopedics, fibrin glue by demonstrating enhanced healing of skin
sports medicine, and ophthalmology. Their popularity is wounds in a rat model. She went on to describe the hemo-
enhanced by their wide availability, ease of use, and cost- static and tissue-healing properties of fibrin glue when
effectiveness. Despite a plethora of published literature on used in oral and maxillofacial surgery, and later reported
the topic, efforts to date to develop a simplified classifica- its applications in microvascular and microneural surgery.
tion of autologous platelet products have been unsuccess- In 1994, Tayapongsak et al.4 reported a 97% success rate
ful, instead generating a minefield of complex in overcoming separation of fragments of particulate can-
nomenclatures that are challenging to understand. cellous bone and marrow grafts by using autologous fibrin
With clinical interest in APCs continually growing, pro- adhesive as a surgical adjunct during mandibular recon-
curement of production systems has become increasingly struction surgery.
commercially driven, and there remains little guidance for One of the many disadvantages of the fibrin glue sys-
clinicians in deciding which system is best suited to their tem is the potential for blood-borne virus transmission
individual needs. In recognition of this, we present a com- due to the use of donor cryoprecipitate, with at least
prehensive review of the relevant literature in a succinct one case of human immunodeficiency virus transmis-
format for the interested clinician. This review provides a sion reported in the literature.5,6 Fibrinogen can alter-
summary of the evolution of autologous platelet therapies natively be sourced from autologous plasma, but this
through the years, describing their physiologic properties, requires donation of blood by patients up to 3 weeks
preparation protocols, and clinical applications in an oral before surgery. This concentrated fibrinogen is cleaved
surgery context. by exogenous bovine thrombin in the presence of cal-
cium to form fibrin in the final coagulation cascade
a (Figure 1). The fibrin strands are then cross-linked to
Specialty trainee, Oral Surgery, Cork University Dental School and
Hospital, University College Cork, Cork, Ireland. form a stable fibrin clot in the presence of factor XIII.
b
Consultant/Senior Lecturer, Oral Medicine, Cork University Dental In an effort to address the shortcomings of fibrin
School and Hospital, University College Cork, Cork, Ireland. glue, Whitman et al.5 later described platelet gel as a
c
Honorary Associate Professor, Oral Medicine, University College more favorable autologous alternative. Its advantages
London, London Eastman Dental Institute, London, United King-
dom.
Corresponding author: Laura O’Sullivan, BDS, MFDS, RCSEd,
PDTLHE, Department of Oral Surgery, Cork University Dental Statement of Clinical Relevance
School and Hospital, Wilton Cork, Republic of Ireland, T12 E8YV.
E-mail address: [email protected] Autologous platelet concentrates (APCs) have been
Received for publication Mar 14, 2021; returned for revision May 19, lauded by some as revolutionary in the field of
2021; accepted for publication May 27, 2021.
Ó 2021 The Author(s). Published by Elsevier Inc. This is an open
regenerative medicine, and knowledge of the prop-
access article under the CC BY-NC-ND license (http:// erties and applications of APCs should therefore be
creativecommons.org/licenses/by-nc-nd/4.0/) considered “essential” knowledge for the modern-
2212-4403/$-see front matter day clinician.
https://doi.org/10.1016/j.oooo.2021.05.013

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Factor V blood samples and the possibility that these resulting plate-
let concentrates might confer a physiologic advantage in
Prothrombin Thrombin the healing of hard and soft tissue defects. Thus was born
the era of autologous platelet-rich therapies.

PLATELETS
Fibrinogen Fibrin
Platelets are small anucleate cell fragments derived
from megakaryocytes7 with a lifespan of 9 to 10 days.8
XIII They are the smallest of the blood cells, with an aver-
age diameter of 2 to 5 mm, thickness of 0.5 mm, and
Cross-linked
fibrin clot numbering 150-400 £ 109 in the average individual.9
The role of platelets in hemostasis and thrombosis was
Fig. 1. Final common pathway of the coagulation cascade. recognized as far back as 1882 by Bizzozero, who
described the adherence of platelets to sites of blood
included a high concentration of platelets, native con- vessel injury and formation of platelet aggregates to
centration of fibrinogen, and collection of 1 unit of begin the repair process.10
whole blood (450 mL) immediately preoperatively, The internal structure of platelets has been studied at
negating the need for advance predonation of blood. length with the aid of electron microscopy, cell frac-
They documented a 2-stage centrifugation process, tionation, and platelet release studies.7 Platelets contain
which allows selective siphoning of erythrocytes and many of the cytoplasmic organelles common to most
platelet-poor plasma, leaving behind platelet-rich eukaryotic cells (Figure 2), but in contrast, these organ-
plasma. A disadvantage of this technique is the need elles are primarily secretory in function, releasing their
for exogenous bovine thrombin to activate the platelet contents readily in response to signals such as collagen,
gel mixture, as is the case with fibrin glue preparation. thrombin, and thromboxane A2. In the 1960s, two addi-
This initial inception of autologous blood products into tional platelet-specific secretory organelles were identi-
the surgical armamentarium sparked much further research fied as being central to the processes of hemostasis,
into the selective sequestration of platelets from autologous thrombosis, inflammation, angiogenesis, host defence,

Fig. 2. Internal platelet structure (http://www.platelet-research.org/).

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and mitogenesis: a-granules and dense (d) granules. Table I. Summary of growth factors released during
a-Granules are the most abundant of all platelet organ- platelet activation and their physiological
elles, with the average platelet boasting between 50 properties
and 80. They play a fundamental role in protein synthe-
Growth factor Function
sis, storage, and release; these proteins (growth factors,
PDGF  Initiates connective tissue healing
membrane proteins, chemokines, adhesion proteins,  Mitogenesis of connective tissue cells
immune mediators) are either suspended within the  Macrophage activation
a-granule or bound to its membrane. Dense granules TGF-b  Chemotaxis and mitogenesis of osteoprogeni-
are less populous, with an average of 3-8 per human tor cells
platelet. They are the primary source of adenosine  Stimulates collagen deposition by osteoblasts
diphosphate (ADP) during hemostasis, one of the main  Inhibits osteoclast formation and bone
deposition
drivers of platelet aggregation and activation.9
VEGF  Promotes angiogenesis through endothelial
cell proliferation and migration
Platelet activation
EGF  Promotes chemotaxis and angiogenesis of
Platelet activation is a typical physiologic response to endothelial cells
contact between platelet surface receptors and exposed  Promotes mesenchymal cell mitosis
collagen in injured tissue such as a blood vessel. The IGF  Regulates late-stage differentiation and activ-
process stimulates migration of a- and d-granules to ity of osteoblasts
release their contents either by fusion with the platelet  Regulates apoptosis
HGF  Potent inducer of angiogenesis
membrane or via the open canalicular system. The
 Antifibrotic properties
flood of local coagulation factors, particularly factor V,
FGF  Promotes endothelial cell chemotaxis and
promotes the production of thrombin (Figure 1). A con-
mitogenesis
comitant increase in intracellular Ca2+ concentration
promotes further granule secretion. This complex inter- EGF, epidermal growth factor; FGF, fibroblast growth factor; HGF,
play of platelet activation, fibrinogen release, thrombin hepatocyte growth factor; IGF, insulin-like growth factor; PDGF,
platelet-derived growth factor; TGF-b, transforming growth factor
production, and growth factor secretion culminates in b; VEGF, vascular endothelial growth factor.
the formation of a stable fibrin clot. Over 300 different
proteins have been identified during a-granule secre-
tion.9 At the same time, dense granules release a host 3. Slower centrifugation cycle of PRP at 2400 rpm to
of proteins, each with important effects: ADP enhances refine separation from erythrocytes
platelet platelet aggregation, serotonin enhances vas- 4. Return of PPP and erythrocytes to the patient via a
cular tone, and Ca2+ ions promote thrombin formation central venous catheter or peripheral venous access
and further granule secretion.
Growth factors are fundamental to the successes of
regenerative medicine, being hailed as a “biological Marx et al.12 reported accelerated and enhanced
solution to biological and medical problems.”11 A sum- bone deposition in their cohort of 88 patients who
mary of the fundamental growth factors released during underwent reconstruction of mandibular defects with
platelet activation is presented in Table I. adjunctive use of PRP at graft sites.
PRP deserves recognition for paving the way for fur-
AUTOLOGOUS PLATELET CONCENTRATES ther advances in autologous platelet therapies and for
TABLE II standardizing the preparation protocol in line with that
Platelet-rich plasma previously described by Whitman et al.5 The inconve-
Following the earlier work of Whitman et al.5 into the nience of patients having to attend several days or
standardization of autologous platelet gel preparation, weeks before surgery to donate a blood sample was
Marx et al.12 took things a step in further in 1998 by overcome by obtaining blood samples immediately
describing their protocol for platelet-rich plasma (PRP) preoperatively. Both platelet gel and PRP permit a
preparation in patients undergoing mandibular recon- “command gelification” by the manual addition of a
struction under general anesthesia: calcium-based activator to the platelet concentrate.
This allows surgeons to apply PRP/platelet gel as
required to the surgical site at the desired time.
1. Centrifugation at 5600 rpm generating 3 distinct Although the above advances cannot be disputed,
layers: 180 mL of erythrocytes, 70 mL of PRP with there were certain disadvantages to the original PRP
leukocytes (“buffy coat”), and 200 mL of platelet- technique that limited its accessibility for widespread
poor plasma (PPP) use: the need for a complex cell separator system such
2. Removal of PPP as the Electro Medics 500 (Medtronic)12 often
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Table II. Summary of properties of main autologous platelet concentrates

Properties PRP PRGF L-PRF
Category First generation First generation Second generation
Volume of blood 450 mL 36 mL 40 mL
Centrifuge system Electro Medics 500 (Medtronic) System V centrifuge (Endoret) Process tabletop PC-02 centrifuge
(Nice, France)
Centrifugation speed 5600 rpm 580g 2700 rpm
2400 rpm
Time 20-30 min 8 min 12 min
Volume of platelet-rich concentrate 70 mL 8 mL PRF “clot”
Leukocytes Yes No Yes
Protocols represent those originally reported in the literature and have likely been updated.
L-PRF, leukocyte and platelet-rich fibrin; PRGF, plasma rich in growth factors; PRP, platelet-rich plasma.

requiring help from a hematologist, the large quantity

of blood (400-450 mL) required to produce approxi-
mately 70 mL of PRP, additional material costs (cathe-
ters, central venous lines), 2 centrifugation cycles
making the process time-consuming, and the need for
bovine exogenous thrombin to activate the mixture.

Plasma rich in growth factors

Completing the complement of first-generation platelet
concentrates is a preparation known as plasma rich in
growth factors (PRGF), which is produced commer-
cially by Biotechnology Institute (BTI) under the trade-
mark EndoretÒ and differs from other APCs by
Fig. 3. EndoretÒ centrifuge loaded with blood bottles before
selectively excluding leukocytes from the product dur-
spinning (photograph taken by Laura O’Sullivan October 30,
ing preparation. The commercial EndoretÒ system is 2020).
suitable for use in a primary care setting and consists
of a system V centrifuge, PLASMATERM H, work
rack, activation containers, and digital timer unit, all of with an ink pen as shown in Figure 4 to demarcate the
which are reusable (Figure 3). Single-use KMU15 kits hematocrit, buffy coat (leukocytes), fraction 2 (plate-
containing the necessary materials for venipuncture let-rich component), and fraction 1 (plasma-poor com-
and fractionation are available to purchase. A 4-stage ponent). Fractionation is carried out using a plasma
preparation protocol is described for EndoretÒ : transfer device to collect all fraction 1 volumes from
each tube. This is repeated for the fraction 2 compo-
1. Blood collection: Four 9-mL tubes of venous blood nent in each tube. Fractionation should be carried out
are collected from the patient. Blood tubes are avail- immediately after centrifugation to prevent delay-
able with and without sodium citrate anticoagulant. related overlap of the various fractions. The protocol
2. Centrifugation: Blood is spun at 580g for 8 minutes. produces a consistent 2-mL volume of platelet-rich
This slow speed results in fractionation of the various fraction 2 immediately above the buffy coat following
blood cell constituents mainly by their specific gravi- centrifugation14,15 (Figure 4).
ties,13 the order of layers or “fractions” from the bottom 4. Activation: This step is only necessary when tubes con-
of the tube to the top being the red cell fraction, white taining anticoagulant have been used and involves the
cell fraction, and platelet fraction, respectively. This addition of 10% calcium chloride activator to fraction 1
single-step centrifugation process results in better- and fraction 2. The amount of activator is dependent on
defined fractions with less crossover, optimizing the the volume of plasma in each fraction, with 1 unit of
separation of the leukocyte-rich “buffy coat” (distinct activator added per 0.5 mL of plasma; assuming a total
from the buffy coat described in PRP) from the plate- volume of 8 mL of fraction 2 is collected during prepa-
let-rich “fraction 2” component immediately above. ration, then 16 units of calcium chloride are added to
This near-total elimination of leukocytes from the prod- the tube to activate it. Each fraction is then transferred
uct is the hallmark of EndoretÒ . to a separate “activation dish” and heated in the PLAS-
3. Fractionation: Tubes are transferred to the work MATERM H device at body temperature for 10 to 15
rack, and all caps are removed. Markings are placed minutes until they assume a jelly-like consistency.
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tweezers and compressed with gauze or similar mate-

rial for ease of application to the surgical site. The suc-
cess of this protocol relies on quick handling of the
blood samples; any delay between venipuncture and
centrifugation will result in failure of the technique.17

PROPERTIES OF APCS
Leukocyte exclusion during APC preparation remains a
contentious issue, with no agreed consensus on the sub-
ject. One argument in favor of exclusion is the produc-
tion of a more homogeneous and reproducible platelet
product.18 One in vitro study investigating the activity
of human fibroblasts and osteoblasts treated with PRP
and PRGF, under both normal and inflammatory condi-
tions, showed consistently elevated release of proin-
flammatory cytokines such as interleukin (IL)-6, IL-8,
tumor necrosis factor-a, and IL-1b in the PRP-treated
cell groups. Although cytokines have a role to play in
the inflammatory process and in fighting infection,
excessive production can be destructive to surrounding
tissues.19 Concerns have also been raised about the
Fig. 4. Fractionation using plasma transfer device (PTD)
(photograph taken by Laura O’Sullivan October 30, 2020). potential for extracellular matrix destruction by neutro-
phils due to the release of matrix-degrading enzymes
as well as reactive oxygen species that destroy healthy
and injured tissues.18
The fraction 2 “clot” is rich in platelets, whereas the Nishiyama et al.13 investigated the composition of
fraction 1 “membrane” is a condensed fibrin structure PRGF fraction 2 versus PRP by collecting venous
with far less cellular entrapment. In their study con- blood from 7 healthy volunteers. Using an automated
ducted to investigate the effects of anticoagulant and hematology analyzer, they were able to show near total
antiplatelet drugs on the preparation of PRGF, Anitua elimination of erythrocytes and leukocytes from PRGF
et al.14 found that for patients taking warfarin, the time preparations, whereas the leukocyte count was
to clot formation was significantly longer than for non- increased 5.5-fold in the case of PRP. Platelets were
warfarinized patients. concentrated by a factor of 2.84 in PRGF and 8.79 in
PRP, whereas actual numbers of platelets per prepara-
Leukocyte and platelet-rich fibrin tion were slightly higher in the former.
This second-generation platelet concentrate was devel- The regenerative properties of APCs, via growth factor
oped in an effort to simplify the preparation process of release, are effected through migration and proliferation
APCs, negating the need for manual fractionation and of native osteoblasts and fibroblasts, which are concen-
activation. Its first clinical application was in the man- trated at the site of APC application through the forma-
agement of a patient with persistent Lyell syndrome tion of a biological 3-dimensional fibrin scaffold during
(toxic epidermal necrolysis) affecting the lower leg. platelet activation, which localizes these cellular compo-
Marked improvement in healing was observed 30 days nents and growth factors at the site. Optimization of cellu-
after initial leukocyte and platelet-rich fibrin (L-PRF) lar proliferation has been the focus of much research, with
treatment.16 one in vitro study demonstrating optimum proliferation of
Choukroun’s single-step preparation protocol fibroblasts and osteoblasts at a platelet concentration
involves obtaining a venous blood sample in 9- or 10- 2.5 times that seen in whole blood. Concentrations of pla-
mL tubes with no anticoagulant. These samples are telets above this level showed a negative effect on cellular
centrifuged immediately for 12 minutes at 750g using proliferation and impairment of osteoblast function.20
a Process tabletop PC-02 centrifuge (Nice, France) or a Nishiyama et al.’s13 findings confirm that platelet concen-
similar setup. The absence of anticoagulant means trations in PRGF are in the optimum range for maximum
platelet activation and fibrin polymerization commence regenerative potential.
almost immediately.17 Centrifugation produces a 3-lay- The potential antibacterial effects of PRGF against
ered suspension: erythrocytes at the base of the tube, methicillin-sensitive and methicillin-resistant strains of
acellular plasma at the top, and a dense fibrin clot sus- Staphylococcus aureus and methicillin-sensitive and
pended in the middle. The clot is removed with methicillin-resistant strains of Staphylococcus
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epidermidis have been studied in vitro.21 Although APPLICATIONS IN DIFFERENT MEDICAL

wound infections are typically polymicrobial in nature, FIELDS
staphylococci are believed to be major players in the Vascular surgery
etiology of delayed healing and infection in both acute Successful treatment of refractory leg ulcers with APCs
and chronic wounds.22 Using blood samples from 5 has been widely reported in the literature. In one small-
healthy volunteers, Anitua et al.21 demonstrated a scale study, superior healing of leg ulcers treated with
strong bacteriostatic effect of PRGF preparations dur- PRGF fraction 2 clots was reported compared to
ing the first 4 hours after incubation, with staphylococ- debridement with 0.9% normal saline alone. Mean
cal populations tending to recover once again after healed skin surface area, the primary outcome measure,
8 hours. Similar results have been reported for in vitro at 8 weeks was 72.94% (standard deviation [SD],
studies of PRP, which showed antibacterial activity 22.25) in the PRGF group (n = 5) and 21.48% (SD,
against S. aureus and Escherichia coli.23 Although the 33.56) in the control group (n = 4).24
antibacterial effect of PRGF has yet to be fully evalu- Similarly, a prospective cohort study of 44 patients
ated in vivo, it is reasonable to extrapolate the role that undergoing refractory leg ulcer debridement as
PRGF preparations might play in prophylaxis against described above, with placement of L-PRF clots over
surgical site infection. the entire surface area, showed excellent success rates
in achieving total wound closure of small ulcers
FORMULATIONS (10cm diameter) at 8 weeks and significant wound
The versatility of APCs stems from the many permuta- reduction in larger ulcers (10cm) at up to 15 weeks.25
tions of preparations that can be produced from a single
blood sample. Using PRGF as an example, the 4 differ- Sports medicine and orthopedic surgery
ent formulations are as follows: APCs have clinically proven benefits in functional
1. Liquid PRGF: nonactivated PRP recovery following tendon and ligament repairs.11 In
Indications one cohort study of patients undergoing surgical Achil-
les tendon repair with and without autologous PRGF
 Facial rejuvenation/wrinkle reduction (mesotherapy) treatment before wound closure, the authors were able
 Implant surface coating to promote “bioactivation” to demonstrate significant differences in the time to
and enhance osseointegration training activity resumption and the rate at which range
 Combination with autogenous or exogenous bone of motion was recovered, favoring PRGF-treated
graft material to improve handling cases.26 Improvements in overall tendon strength and
regeneration have also been demonstrated by injection
of PRP at surgical sites 1 week postoperatively in simi-
2. Supernatant: the “leftover” fluid after PRGF lar cases.27 Ultrasound-guided intratendinous injection
activation of PRGF has been applied successfully in the manage-
Indications ment of elbow tendinosis.28 PRGF has also been used
in patellar tendon repair surgery and has been pio-
 Mouth ulcers neered by the BTI research group for the arthroscopic
 Eye drops management of articular cartilage avulsion injuries in
knee joints.29

3. Fraction 2 clot: the platelet-rich scaffold (PRP/ Ophthalmology

PRGF) Alio et al.30 investigated the role of PRP in the man-
Indications agement of dry eye symptoms in a case series of 386
patients, a condition estimated to affect 4% to 30% of
 Extraction socket healing the population. Treatment consisted of autologous PRP
 Treatment of medication-related osteonecrosis of the eye drops applied at a dose of 1 drop 6 times per day
jaw (MRONJ) for 6 weeks, with 87.5% of patients reporting improve-
ment in their symptoms.

4. Fraction 1 membrane: PPP

APPLICATIONS IN ORAL SURGERY
Extraction socket healing
 Dental implant membrane A Cochrane review published in 2020 looked for the
 Sinus lift surgery membrane first time at adjunctive use of APCs in mandibular third
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molar sockets, citing reduced incidence of dry socket MRONJ

7 days postoperatively at APC-treated sites. No differ- MRONJ is a relatively new phenomenon, having first
ence in facial swelling or postoperative pain experience been described by Marx in 2003,38 and is a condition
were detected between groups. Authors of the review that is unique to patients with a history of bisphospho-
included 4 studies in their analysis and graded the nate or antiresorptive/antiangiogenic therapy. A discus-
available evidence as being at high or unclear risk of sion of the pathophysiology of MRONJ is beyond the
bias.31 Other systematic reviews in the literature appear scope of this review. Currently, no universally agreed
to support improvement in clinical outcomes such as protocol exists for the prevention and therapeutic man-
trismus, soft tissue healing, and facial swelling at APC- agement of MRONJ in at-risk patients. Scoletta et al.39
treated extraction sites.32-34 Conclusions appear to dif- reported favorable results for the prevention of
fer with regard to postoperative pain and inflammation. MRONJ in patients receiving intravenous bisphospho-
A further systematic review looking specifically at the nates, with prophylactic placement of PRGF in extrac-
effects of PRGF in postextraction sockets presented a tion sockets and avoiding mucoperiosteal flaps where
qualitative analysis of 8 studies, reporting reduced possible. In a retrospective case series of 32 patients
postoperative pain and incidence of postoperative com- undergoing treatment with intravenous bisphospho-
plications at PRGF-treated sites.35 nates, Mozzati et al.40 reported total mucosal coverage
with absence of exposed bone in all cases of surgical
Dental implantology debridement and placement of PRGF, with a minimum
More rapid and enhanced bone healing is observed follow-up of 48 months. A case series of 12 sites of
with use of PRGF at implant osteotomy sites, with the MRONJ and osteoradionecrosis investigated the effect
technique also producing superior soft tissue healing.36 of piezoelectric agitation of necrotic sites before
Recent advances have also led to clinicians combining L-PRF placement with unconvincing results (67% sites
PRGF with exogenous bone-grafting material such as demonstrating complete mucosal healing at 12
Bio-OssÒ (Geistlich Pharma) to improve the handling months), possibly influenced by the small sample
and adaptation at donor sites.18 One of the major chal- size.41
lenges in dental implantology is the atrophic maxilla,
and a retrospective case series published by Anitua Other
et al. suggested a promising role of PRGF in the aug- APCs have also demonstrated success in the manage-
mentation of vertical bone height at this site.37 Their ment of recurrent aphthous stomatitis and refractory
cohort of 26 patients underwent transcrestal sinus ele- oral lichen planus, in the promotion of apexification
vation and PRGF plug insertion at the base of each (root end closure) in immature teeth requiring end-
osteotomy site before placement of a total of 41 odontic treatment, and in the management of gingival
implants. They observed a sustained increase in verti- recession defects, leading to restoration of keratinized
cal bone height 3 years postoperatively.37 mucosa across exposed root surfaces.42

Fig. 5. Flowchart presentation of timeline of autologous platelet concentrate evolution.

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CONCLUSIONS mandibular third molars? J Oral Maxillofac Surg.

Previous efforts to categorize APCs according to leu- 2011;69:2305-2310.
kocyte content and fibrin matrix structure have yet to 9. Gremmel T, Frelinger AL 3rd, Michelson AD. Platelet physiol-
ogy. Semin Thromb Hemost. 2016;42:191-204.
garner universal acclaim.43 The terminologies arising 10. de Gaetano G, Cerletti C. Platelet adhesion and aggregation and
from this proposed classification (P-PRP, L-PRP, L- fibrin formation in flowing blood: a historical contribution by
PRF, L-PRP) have been superseded by yet more subca- Giulio Bizzozero. Platelets. 2002;13:85-89.
tegories, including iPRF44 (injectable PRF), aPRF45 11. Anitua E, S
anchez M, Orive G, And
ıa I. The potential impact of
(advanced PRF), and cPRP17 (concentrated PRP). the preparation rich in growth factors (PRGF) in different medi-
cal fields. Biomaterials. 2007;28:4551-4560.
These subcategories represent the range of formula- 12. Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss
tions produced by altering centrifugation protocols, JE, Georgeff KR. Platelet-rich plasma: growth factor enhance-
with up to 24 protocols described in the literature for ment for bone grafts. Oral Surg Oral Med Oral Pathol Oral
PRF alone.46 Radiol Endod. 1998;85:638-646.
The superfluous terminologies have been described 13. Nishiyama K, Okudera T, Watanabe T, et al. Basic characteris-
tics of plasma rich in growth factors (PRGF): blood cell compo-
as “disingenuous” by some experts who claim “PRP is nents and biological effects. Clin Exp Dent Res. 2016;2:96-103.
PRP, whatever way you look at it.”47 There is concern 14. Anitua E, Troya M, Zalduendo M, Orive G. Effects of anti-
in the scientific community that underlying commercial aggregant, anti-inflammatory and anti-coagulant drug consump-
interests may lead to a cycle of reinventing the wheel. tion on the preparation and therapeutic potential of plasma rich
in growth factors (PRGF). Growth Factors. 2015;33:57-64.
Ultimately, all APCs achieve the same end goal of
15. Anitua E, Murias-Freijo A, Alkhraisat MH, Orive G. Clinical,
regeneration, with relatively minor differences in prep- radiographical, and histological outcomes of plasma rich in
aration protocols and composition. Although original growth factors in extraction socket: a randomized controlled
protocols have been discussed here as far as possible clinical trial. Clin Oral Investig. 2015;19:589-600.
for their historical interest (Figure 5), we emphasize 16. Miron RJ, Choukroun J, eds. Platelet Rich Fibrin in Regenera-
that companies continue to update and refine their pro- tive Dentistry: Biological Background and Clinical Indications,
Hoboken, NJ: Wiley-Blackwell; 2017.
tocols in line with latest advances and technology. 17. Dohan DM, Choukroun J, Diss A, et al. Platelet-rich fibrin
This narrative review has demonstrated the signifi- (PRF): a second-generation platelet concentrate. Part I: Techno-
cant contribution of APCs to the field of regenerative logical concepts and evolution. Oral Surg Oral Med Oral Pathol
medicine in recent years. It is clear that APCs will con- Oral Radiol Endod. 2006;101:e37-e44.
tinue to play an increasingly pivotal role in improving 18. Anitua E, S
anchez M, Nurden AT, Nurden P, Orive G, And
ıa I.
New insights into and novel applications for platelet-rich fibrin
patient outcomes following surgical intervention. Fur- therapies. Trends Biotechnol. 2006;24:227-234.
ther research exploring clinical and patient-centered 19. Anitua E, Zalduendo M, Troya M, Padilla S, Orive G. Leukocyte
outcomes in this patient cohort would be most wel- inclusion within a platelet rich plasma-derived fibrin scaffold
come. stimulates a more pro-inflammatory environment and alters
fibrin properties. PLoS One. 2015;10:e0121713.
20. Graziani F, Ivanovski S, Cei S, Ducci F, Tonetti M, Gabriele M.
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