Ibrahim.et.al DOI: 10.21608/adjalexu.2024.277755.

1487

EVALUATION OF TITANIUM PREPARED

PLATELET RICH FIBRIN IN BONE
REGENERATION IN LATERAL WINDOW
MAXILLARY SINUS AUGMENTATION WITH
DELAYED IMPLANT PLACEMENT
(RANDOMIZED CONTROLLED CLINICAL
TRIAL)

Radwa M. Kh. G. Ibrahim1* BDS, Adham A. El Ashwah2 PhD, Ahmed O.

Swedan3PhD, Nesma M. Khalil4 PhD, Dina M. N. Metawie5PhD,
ABSTRACT
INTRODUCTION: Titanium prepared platelet rich fibrin (T-PRF) has been applied as an alternative to the traditional bone graft
in sinus lifting approach.
OBJECTIVES: This trial aimed to evaluate the effect of the use of T-PRF alone on bone formation process as applied in maxillary
sinus floor elevation in comparison to traditional T-PRF/bone graft combination as indicated by implant stability as primary
objective.
MATERIALS AND METHODS: This clinical trial included 18 patients seeking implant placement in upper posterior maxilla
compromised with maxillary sinus pneumatization. All the patients underwent sinus lifting procedure through which a combination
of xenograft and T-PRF was used in the control group whereas; T-PRF alone was applied in the test group. Delayed implant
placement was applied. Therefore, the time frame of the whole trial is 7 months; 4 months following sinus filling and 3 months after
implant placement. The two groups were compared in clinical, radiographic and histological evaluation parameters including bone
height, density and volume along with implant stability.
RESULTS: Clinical results revealed that there was no significant difference between T-PRF/ xenograft group and T-PRF group in
terms of primary stability (p value=0.811). Radiologically, T-PRF/xenograft showed superior outcomes than T-PRF group in total
bone height gain and pre-implant bone density gain (p value=0.001, 0.002 respectively). Histomorphometric results indicated that
the difference between the control and test groups was not significant.
CONCLUSIONS: T-PRF alone can be used as an effective grafting material in two stage maxillary sinus augmentation as proven
by implant stability as the primary objective measured clinically. Acceleration of bone formation process can be achieved by means
of T-PRF whether alone or in combination of xenograft.
KEYWORDS: Sinus lifting, augmentation, platelet concentrate, platelet rich fibrin, PRP.
RUNNING TITLE: titanium prepared platelet rich fibrin for sinus lift.

* Corresponding author:
E-mail :[email protected]

INTRODUCTION
Implant placement in edentulous posterior maxilla bone grafts has been investigated to evaluate their
is considered one of the major dilemmas healing promotion efficiency and osteogenic
confronting oral and maxillofacial surgeon. That is ability.Apart from the classical bone grafts,
mainly related to poor bone quality and quantity in autologous platelet concentrate has attracted more
this particular area. A common scenario is attention in the past 2 decades. Some evidence has
represented in maxillary sinus pneumatization been provided regarding its osteogenic, angiogenic
following extraction of upper molars yet, and anti-inflammatory impact on both soft and hard
compromising residual bone height necessary for tissue regeneration. (1)
implantation procedure. (1) Considerable previous studies highlighted the
As a result, several techniques have been developed promising act of PRF in bone synthesis whether it
over the past few decades in order to elevate is applied as the only biomaterial or in combination
maxillary sinus floor without perforation of the with other components as bone grafts or even
schneiderian membrane to provoke osteogenic certain chemicals. (2, 3) In the literature, a debate
process with or without grafting material. On the about application of PRF in maxillary sinus lifting
other hand, a diversity of biomimetic materials and has risen. (4-6) On one hand, a number of scientists
1
Alexandria Dental Journal. Volume x Issue x
Ibrahim.et.al Titanium Prepared Platelet Rich Fibrin For Sinus Lift

support the principal of applying PRF as a uncovering after 3months. Secondary objectives of
supplemental not as an essential component relying this trial is to compare the effect of application of T-
on its modest osteogenic potential.(7) On the other PRF alone versus conventional T-PRF/xenograft
hand, other researches provide evidence regarding composite as a grafting material in delayed lateral
effective addition of PRF as a main treatment for wall maxillary sinus lifting approach as detected by
bone regeneration either in sinus lifting or other minimum time required for adequate bone formation
procedures.(7) (healing time), implant survival following placement
As a result of this controversy, it has been of prosthesis all over the entire follow up period,
emphasized in the literature that preparation of PRF parameters of newly formed bone (volume, density,
is technique sensitive that implying the importance height) as shown in radiological images as well as
of standardization of centrifugation protocol and histological parameters regarding bone surface area
solving the problems observed due to usage of ratio and non-mineralized bone surface area ratio.
silica coated plastic tubes. Therefore, usage of
titanium tubes instead of traditional tubes was MATERIALS AND METHODS
suggested. (7, 8-10) As a result, numerous improved 2.1 Study design:
approaches and modified versions of PRF have been This study represents a randomized controlled
introduced in order to overcome its shortcomings. clinical trial design involving 18 participants
Titanium prepared platelet rich fibrin (T-PRF) was requiring sinus lift procedure for the purpose of
first established by Mustafa Tunalei (10, 11) in 2012 implant placement. Using coin flipping as a simple
by replacing glass tube or silica coated plastic tube randomization method, the patients were randomly
used in the production of classical PRF by titanium and equally divided into two groups each group
tube aiming to overcome the questionable health contains 9 patients; the control group received T-
hazards of silica particles separated during PRF/xenograft as a conventional sub-sinus filling
centrifugation of the blood. Tunalei (11) has component and the test group underwent maxillary
observed formation of stronger and thicker fibrin sinus augmentation using T-PRF only.
network in addition to release of growth factors over This study was conducted on patients selected
a longer period of time than in the typical PRF. from the outpatient clinics of Oral and
Moreover, Tunalei et al. suggested that titanium Maxillofacial Surgery Department of the Faculty of
may trigger platelets more efficiently than silica in Dentistry in Alexandria University, Egypt. Written
other types of tubes. This is in addition to the informed consents were obtained from all
biocompatibility of titanium that will prevent participants after detailed description of the whole
detrimental health issues reported with casual silica procedures to be performed including its aim. This
coated plastic tubes. study was approved from ethics committee and
Importantly, in 2018, a clinical trial of utilization of T- research committee in Faculty of Dentistry in
PRF as the only filling material following maxillary Alexandria, Egypt. Ethical approval number is IRB
sinus floor elevation exhibited promising results as it No. 00010556_IORG 0008839-0301_10/2021. This
accelerated bone formation in comparison to study followed CONSORT guidelines for
allografts. (12) This latter study was accompanied with conducting clinical trials (figure 1). In addition, it is
delayed implants which directed attention towards its conformed to the Helsinki declaration of 1975, as
possible effectiveness without association with tenting revised in 2000 along with the Good Dental
by means of immediate implant. As a result, it could Clinical Practice Guide Lines with Alexandria
be effective in severe bone resorption cases including University.
residual bone height less than 5 mm in maxillary sinus 2.2 Participants: Eligibility criteria
augmentation. In addition, according to Olgun et al. Regarding Inclusion criteria, patients were selected
(12) the application of T-PRF alone in maxillary sinus by being not less than 18years old, non-smokers,
augmentation has been proven to be clinically and systemically in a healthy condition along with good
histologically successful. However, another study oral hygiene as indicated by plaque and bleeding
disputed the improvement of the effect of PRF by scores. In addition, participants should have
centrifugation in titanium tube. (13) Therefore, further residual bone height not more than 5 mm in
well controlled clinical trials are still required to posterior maxilla as measured with CBCT. (12) On
illustrate the exact structure and effect of T-PRF. The the other hand, medically compromised condition
Null hypothesis indicates that there is no difference such as uncontrolled diabetics, uncontrolled
between the outcome of the two groups; a group of T- hypertensive patients and congestive heart failure
PRF alone versus another group of conventional T- patients were excluded to avoid infections or any
PRF/xenograft as a filling material in lateral window adverse reactions related to immunity suppression
maxillary sinus lifting procedure. The primary or any other problems that would compromise bone
objective is stability of the implant scored by implant healing or even surgical procedure. Moreover,
stability quotients (ISQ) measured using osstell device patients suffering from acute maxillary sinusitis and
(Osstell ISQ, Göteborg – Sweden) both immediately those administering any antibiotics or regular anti-
after implant placement and at the time of implant inflammatory drugs were also excluded. This was
2
Alexandria Dental Journal. Volume x Issue x
Ibrahim.et.al Titanium Prepared Platelet Rich Fibrin For Sinus Lift

to prevent the effect of confounding variables and device. Careful elevation of the antral mucosal
reduce bias. (12) lining was done with delicate manipulation to avoid
2.3 Sample size estimation: any perforations. The schneiderian membrane
The minimal sample size was calculated based on a lifting was initiated from the sinus floor toward the
previous study aimed to evaluate the analytical posterior wall then superior wall and finally to the
difference between the use of xenograft (control anterior wall. For optimal graft placement,
group) and graftless tenting (test group) technique elevation of the membrane from the medial wall of
after sinus lift procedure with simultaneous implant the sinus was accomplished as well.
placement. Fouad W, et al. (2018) (14) concluded A bellow effect (movement of the sinus membrane
that sinus lift procedures with simultaneous implant with respiratory rhythm) upon patient’s breathing
placement using xenograft as a filling material or was observed for all the patients during the
graftless technique are considered reliable operation indicating the sinus membrane was intact.
procedures, however, the use of xenograft provides Following sinus membrane elevation, the sub-sinus
better results in all aspects regarding (bone height cavity was filled with T-PRF/xenograft for control
gain, bone density, and implant stability). Based on group or T-PRF alone in test group. T-PRF was
their results, adopting a power of 80% to detect a prepared by specific technique established by
standardized effect size (non-inferiority limit,d) of Tunalei et al. (11) as follows (figure 2):
10 in stability of the implant scored by ISQ 20ml blood sample was drawn from the antecubital
measured using Ostell device (primary outcome), vein or dorsal metacarpal veins of each participant
and level of significance 95%(α=0.05), the right or left arm or back of the hand using 20ml
minimum required sample size was found to be 9 syringe. Collected blood was immediately
patients per group (number of groups =2) (Total transferred into a 10ml grade IV titanium tube
sample size=18 patients). Any withdrawal for any (Tunalei especially manufactured titanium tubes,
reason was supposed to be compensated by Turkey) without anticoagulant. Each sample was
replacement to control for attrition (withdrawal) quickly centrifuged using a specific table
bias. The sample size was calculated using Gpower centrifugation device (80-1 centrifuge, china) (878g
version 3.1.9.2. for 12 min) at room temperature. T-PRF clot was
removed from the tube with sterile tweezers then
2.4 Materials: separated from the base of the red blood cells
The conventional therapy used in this trial is the utilizing sterile scissors. The collected T-PRF was
traditional T-PRF mixed with half gram to 1 gram divided into 2 parts; one part was divided into
of xenograft (OneGraft, Corticocancellous Bovine minute pieces to be mixed with xenograft in case of
Powder<2mm, German).T-PRF was the material to control group or to be used solely for test group.
be tested in this study as an alternative to classical The other part was squeezed between 2 glass slabs
bone graft. T-PRF was prepared by specific to form membrane like structure to be used as a
technique established by Tunalei et al. (10, 11) In barrier against fibrosis between the bone graft and
addition, Sinus lateral window kit was used to the mucoperiosteal flap. This was followed by
perform sinus lift procedure (Dentis Save Lateral replacement of the mucoperiosteal flap and suturing
Kit & instruments, Korea). Trephine bur (Trephine by simple interrupted suture technique utilizing
drills, China) 3mm in diameter is utilized to take a black silk suture.
bone column sample before implant placement for The patients were instructed to apply cold
the purpose of histological analysis. fomentation and to avoid hot drinks and food for
Moreover, Suitable implant system (Neodent, Helix the first 24 hours. From the second day post-
GM, Brazilian contents, Germany) was used in operatively, patients were advised to commence hot
addition to oseodensification kit (Densah bur, fomentation for further 24 hours. In addition,
Pakistan) that was used to promote primary patients were directed to avoid eating on the side of
stability for both groups. Implant stability was the surgery. Oral hygiene recommendations were
measured by resonance frequency analysis. Primary provided.
stability was measured at the time of implant Post–operative medications were provided to the
placement. Secondary Implant stability was measured patient including (12): Amoxicillin 1gm, clavulanic
at the time of uncovering after 3 months. acid 125mg tablets (Augmentin 1 gm.) combined
2.5 Maxillary sinus augmentation (1st surgical with metronidazole (500mg tablets) were provided
intervention) twice daily for 5 to 7 days, Anti-inflammatory
Lateral window sinus floor lifting procedure was analgesics: Diclofenac potassium (Cataflam 50
operated under local anesthesia (modified Cald well- tablets) was taken three times a day for 7 to 10
Luc sinus augmentation). A paracrestal incision was days, Anti-edematous drug: chymotrypsin
cut with one or two vertical releasing incisions to (Alphintern) 2 tablets half an hour prior eating three
create full thickness mucoperiosteal flap. times a day for 5 days, Chlorhexidine mouth
Round or elliptical bony window was cut 5mm washes 0.12%: three times per day after 24 hours
away from the bone crest using piezoelectric
3
Alexandria Dental Journal. Volume x Issue x
Ibrahim.et.al Titanium Prepared Platelet Rich Fibrin For Sinus Lift

for 10 day period, Ephedrine nasal drops: 3 to 5 post-operative bone gain radiologically, two
times per day for 5 days. imaging soft wares (OsiriX Lite DICOM Viewer,
2.6 Delayed implant placement (2nd surgical Swiss\ Horos DICOM Viewer GNU Lesser General
intervention) Public License, Version 3.0, (LGPL 3.0), UK) were
Delayed implant placement was performed after 4 used for analyzing bone volume in centimeter
months for both groups. Crestal incision with cubic. These soft wares allow determination of
reflection of a full mucoperiosteal flap was done bone image in circular slides. The application is
under local anesthesia. Small points were marked then used to collect and compute the bone volume
with the use of marker burs on the area where of these slides. In addition, three dimensional
implants were located. The number of implants for radiological softwares (OnDemand 3D°TM, Korea)
each patient ranged from 1-2 implants according to were utilized to measure bone height in millimeters
the prosthetic plan for the patient. However, only and density in Hounsfield Units. This was done to
one implant was selected to represent the results of allow comparison with the preoperative parameters
each patient. The selection was performed and opposing measures of the other group in
depending on the specific location and its relation addition to determining the location of the implant
to determined bone measures representing the to be placed along with implants’ length and
eligibility criteria. diameter. Three types of bone gain were calculated.
Bone samples were collected from these points by Firstly, subtraction of pre-implant bone
means of 3mm trephine burs to be located 2 to 3mm measurement (height, density or volume) from
shorter than the implant length. Preservation of preoperative bone measurement was done to
bone specimens were done at room temperature in determine amount of bone gain as a result of sinus
covered formaldehyde containers (10%). (15) The lifting only. Secondly, pre-implant bone
implant fixture of suitable length and diameter was measurement was subtracted from post-implant
placed by the typical technique followed by bone measures after 3 months to identify amount of
measuring primary implant stability using osstell bone gain resulted from implant placement solely.
device and then fixture was sealed with a cover Finally, total bone gain of the whole process was
screw. computed by subtraction of preoperative bone
The flap was repositioned and sutured with black measures form post-implant bone measures
silk suture. Immediate Post-operative instructions 2.9 Histological assessment:
and medications were provided to the patients and The bone specimens collected prior to implant
sutures were removed after one week. After 3 placements were fixed directly in 10% neutral
month of implant positioning, CBCT was buffered formalin, then, rinsed in distilled water,
performed to ensure proper implant placement and decalcified in 8% hydrochloric acid, dehydrated in
bone formation and to compute post-implant bone ascending grades of alcohol, cleared in xylene and
measurements. Clinically, implants were exposed finally embedded in paraffin wax. 5 µm thick serial
and healing abutments were installed to prepare for sections were prepared, cut and stained with
prosthetic phase. haematoxylin and eosin stain to evaluate the newly
2.7 Clinical assessment: formed bone (15) as well as Masson-Goldner
Clinical assessment of the participants was Trichrome stain using the conventional methods for
determined the day following surgery then after one detection of non-mineralized bone. (17)
week, two weeks for each surgery and 4 and 7 2.10 Histomorphometric assessment:
months post-operatively. The outcomes of the trial Specimens were inspected by means of Olympus
were estimated by measuring level of pain using light microscope (Olympus BX41 Phase Contrast &
numerical rating scale NRS from 0-10, where 0 Darkfield Microscope, Olympus Corporation,
reading indicates no pain, (1-3) indicates mild pain, Japan). From each specimen, three serial sections
(4-6) shows moderate pain and (7-10) reflects were selected and a digital microscopic camera
severe pain. (16) Additionally, edema and (Olympus DP20 digital microscope camera,
dehiscence of the wound were detected by Olympus Corporation, Japan) was used to obtain
inspection of the area to determine if they were images for these serial sections for both groups
present or not. Nasal congestion or bleeding was where histomorphometric measurements were
identified by direct questioning of the patient. obtained using Fiji image j software (National
Furthermore, Implant stability was measured by Institutes of Health, USA) followed by calculation
resonance frequency analysis. Primary stability was of the mean value. Two parameters were calculated (18):
measured at the time of implant placement. Secondary a) Bone surface area ratio:
implant stability was measured at the time of Photos of H&E stained slides magnified ×40 were
uncovering after 3 months. utilized for tracing the bone surface area on the
2.8 Radiological assessment: software and the percentage of bone is calculated in
Firstly, CBCT was performed preoperatively and relation to the whole surface area of the field.
after 4 months of sinus lifting and 3 months after b) non-mineralized bone ratio:
implant insertion for all participants. To evaluate
4
Alexandria Dental Journal. Volume x Issue x
Ibrahim.et.al Titanium Prepared Platelet Rich Fibrin For Sinus Lift

Images of Masson-Goldner Trichrome stained operatively. Mild degree of bleeding was observed
specimens with × 40 magnifications were adjusted during surgery in two patients and was controlled
in color deconvolution mode to differentiate shades successfully with pressure. Normal post-surgical
of the field. Red confined areas were measured to swelling was observed in all the patients. However,
compute the non-mineralized bone surface area it was completely resolved in 4- day- duration.
ratio in relation to the entire surface area of the Moderate degree of pain was recorded in all
field. (17) patients following maxillary sinus lifting operation
2.11 STATISTICAL ANALYSIS in both groups which was managed effectively by
Data were collected, summarized using the IBM medication and disappeared within 5-7 days. Few
SPSS statistics version 29 to be statistically drops of blood were reported to get from nostrils
analyzed and compared with the proper statistical following surgery in 3 patients in the first 24 hours
analysis methods. Normality of distribution for post-operatively. Final implant based restorations
different variables including age, sex, bone height, were fabricated to all the patients in suitable timing.
density and volume along with histomorphometric Primary and secondary implant stability was
variables were investigated with Shapiro-Wilk test. reported with resonance frequency analysis method.
(19, 20) Data were displayed as mean and standard Four different points surrounding each implant was
deviations. Paired student t-test was applied to measured to calculate their average to be the
estimate significance levels within each group to representative of implant stability quotient variable
compare pre and post-test values. On the other ISQ. Within each group, P value was recorded to be
hand, detection of statistical significance between 0.971 for control group and 0.861 for test group. As
the two groups was determined using both a result, there was no significant difference between
independent samples t-test and One-way ANOVA primary and secondary stability of implants
test. (21) regarding each group separately. At the same time,
Utilization of T-PRF as a supporting material in the
RESULTS control group or as a single filling material for sub-
3.1 Sample characteristics sinus cavity in the test group have successfully
This trial involved 18 participants requiring sinus resulted in acceptable primary stability in less time
lift procedure for the purpose of implant placement. frame than usual (4 months instead of 6 months). In
The patients were randomly and equally divided addition, for both implant stability values, the mean
into two groups each group contains 9 patients; ISQ is 63.9067 for control group and 62.9811 for
control group that received T-PRF/xenograft as a test group with no significant difference between
conventional sub-sinus filling component and test the two groups where P value was 0.811 for
group underwent maxillary sinus augmentation primary stability and 0.559 for secondary stability
using only T-PRF. (table 3).
A Shapiro-Wilk’s test (19,20) (p>.05) and a visual 3.3 Radiological results
inspection of their histograms, normal Q-Q plots Bone height, density and volume were statistically
and box plots revealed that all variables including analyzed within each group (figure 3): and between
age, pre and postoperative bone heights, width, groups (figure3, figure 4) as following:
density and volume in addition to histological 3.3.1Bone height:
results were approximately normally distributed for Regarding bone height, there was significant
both control and test groups. difference between preoperative bone height and
There was no significant difference between control pre-implant bone height after 4 month of first
and test groups regarding age (table 1) and gender surgery within each group separately (P value <
(table 2). This clinical trial contains 18 maxillary 0.001 for both groups). Whereas there was
sinus augmentation procedures including 35 significant difference between pre-implant bone
implant insertions. For each lifting operation, only height and post implant bone height after 3 months
one implant was selected to represent the bony for the test group only (P value =0.006 for test
measurements according to its specific location in group and =0.134 for control group).
relation to the sinus pre and post-operatively. The To compare between the two groups, it was found
patients were allocated both equally and blindly that there was significant difference between
between the two groups taking into account that control and test group regarding the amount of gain
each group consisted of 9 cases; 5 females and 4 in pre-implant bone height (P value=0.001). The
males. The mean age of the participants was height of the bone was increased in higher
41.33±4.743 in the T-PRF/Xenograft control group percentage in control group in comparison to test
and 42.89±7.607 in the T-PRF alone test group. group after 4 months. At the same time, there was
3.2 Clinical results: no significant difference in the amount of bone
The three stages of the trial were performed safely height gain after implant insertion by 3 months (p
in both groups with no serious complications value=0.216). According to total bone height gain,
including sinus membrane perforation, failure of it was found that there is significant difference
implant primary stability, infection post-
5
Alexandria Dental Journal. Volume x Issue x
Ibrahim.et.al Titanium Prepared Platelet Rich Fibrin For Sinus Lift

between the two groups in favor of control group

(table 4).
3.3.2 Bone density:
Regarding bone density, there was significant
difference between preoperative bone density and
pre-implant bone density within control group only
(P value = 0.003 for control group and = 0.868 for
test group). However, there was significant
difference between pre-implant bone density and
post-implant bone density within both control and
test groups (P value = 0.004, 0.001 respectively).
To compare between the two groups, it was found
that there was significant difference between
control and test group regarding the amount of gain
in pre-implant bone density (P value=0.002). The
density of the bone was increased in higher
percentage in control group in comparison to test
group after 4 months. At the same time, there was
no significant difference in the amount of bone
density gain in both post-implant insertion by 3
months only (p value=0.220) and total bone density
gain for the whole procedure (p value=0.147) (table 5).
3.3.3. Bone volume:
In terms of bone volume, there is significant Figure 1: Consort 2010 flow diagram.
difference between preoperative bone volume and
pre-implant bone volume for test group only (P
value= 0.008 for test group and = 0.193 for control
group). Conversely, there was significant difference
between pre-implant bone volume and post-implant
bone volume within control group solely (P
value=0.002 for control group and= 0.286 for test
group).
To compare between the two groups, it was found Figure 2 a) 20ml blood sample was drawn from the
that there was no significant difference between antecubital vein or dorsal metacarpal veins of each
control and test group regarding the amount of gain participant right or left arm or back of the hand
in all three stages; pre-implant bone volume gain, using 20ml syringe and was immediately
post-implant bone volume alone gain and total bone transferred into a 10ml grade IV titanium tube
volume gain (P value=0.904, 0.445 and 0.506 without anticoagulant. b) The collected T-PRF was
respectively) (table 6). divided into 2 parts. c) One part of T-PRF was
3.4 Histological results: inserted in the sub-sinus cavity in test group.
In both control and test groups, histological
examination revealed formation of numerous bone
trabeculae surrounding bone marrow spaces.
However, thicker bone trabeculae were observed in
control group in comparison to test group (figure 5
a, d). Whereas upon higher magnification, newly
formed bone was observed including osteocytes and
numerous resting and reversal lines (figure 5 b, c, e,
and f). Figure 3 Cone beam computerized tomography
In both groups, Goldener Masson Trichrome stain CBCT for case 1(test group) showing a)
showed homogenously mineralized bone trabeculae preoperative bone measurements (bone height,
(stained green) with minute scattered areas of width and density). b) Pre-implant radiograph
unmineralized bone (stained red) (figure 6 a, b, c CBCT after 4 month of sinus lift showing bone
and d). height and density. c) CBCT after implant
placement by 3 month showing bone height,
density.

6
Alexandria Dental Journal. Volume x Issue x
Ibrahim.et.al Titanium Prepared Platelet Rich Fibrin For Sinus Lift

Figure 4 Cone beam computerized tomography

CBCT for case 2(control group) showing a)
preoperative bone measurements (bone height,
width and density). b) Pre-implant radiograph
CBCT after 4 month of sinus lift showing bone
height and density. c) CBCT after implant
placement by 3 month showing bone height, Figure 6 LM of bone samples of control group (a
density. and b) and test group (c and d) showing areas of
homogenously mineralized bone trabeculae (stained
green) and unmineralized bone (stained red) (b and
d) are higher magnification of (a and c)
respectively. Goldener masson trichrome stain (a
and c )× 40, (b and d) ×100.
3.5 Histomorphometric results:

Statistical analysis revealed that there was no

significant difference in bone surface area
percentage between control and test group (P value
= 0.884). In addition, the difference of non-
mineralized bone surface area ratio between T-
PRF/Xenograft control group and T-PRF test group
is not significant as well. (P value=0.625) (table 7).

Table 1 statistical description of patient age.

Group Test of significance
P value
T- T-PRF
Figure 5. Light micrograph (LM) of bone samples PRF/xenograft test group
control group n=9
of control group (a, b, and c) and test group (d, e, n*=9
and f). Control group a) bone sample consists of
thick bone trabeculae (arrows) surrounding bone Age
(years)
marrow tissues (arrow heads). b) A higher
magnification of previous micrograph inset Mean±SD† 41.33±4.743 42.89±7.607 P‡= 0.610 NS§
showing the structure of the newly formed bone
which contains osteocytes (short arrows), numerous Min. - 35-50 32-55
Max.¶
resting lines (long arrows) and reversal lines (arrow
*: Number of patients. †: Standard deviation. ‡:
heads). c) A higher magnification of previous Probability of error (chance). §: Statistically not
micrograph inset showing the regularly distributed significant (p≥0.05). ¶: Minimum to maximum. Tests of
osteocytes’ lacunae (arrows). Test group d) bone significance: to compare between the two groups are
sample consists of numerous cancellous bone independent T-Test and One way Anova.
trabeculae (arrows) surrounding bone marrow
tissues (arrow heads). e) A higher magnification of Table 2 statistical description of patient gender
the previous micrograph inset showing the structure Patient group T-PRF/Xenograft T-PRF (test group)
(control group) n=9
of the newly formed bone which contains n*= 9
irregularly distributed osteocytes ( short arrows) in Patient Female Male Female Male
gender
some areas and resting lines (long arrows). f) A
Patient 5 4 5 4
higher magnification of previous micrograph inset number
showing osteocytes’ lacunae (arrows) and reversal *: Number of patients
line (arrow heads). H&E (a and d) ×40, (b and e)
×100, (c and f) ×400.

7
Alexandria Dental Journal. Volume x Issue x
Ibrahim.et.al Titanium Prepared Platelet Rich Fibrin For Sinus Lift

Table 2 T-PRF/Xenograft vs. T-PRF in implant results of using of T-PRF alone versus allograft in
stability. maxillary sinus lifting after 4 month and 6 month
Implant stability Test of respectively. The present study goes in line with
(ISQ) Group significance P
T- Sole T-PRF value Olgun trial in presenting beneficial effect of T-PRF.
PRF/xeno test group That is, time required for bone regeneration has
graft been reduced from 6 to 4 month by application of
control
group T-PRF alone or even by addition of T-PRF to
P*=0.811 NS†
Xenograft with more rapid implant placement as
Primary stability ISQb shown in both groups.
According to the outcomes of both groups in the
Mean± SD‡ 63.9067± 62.9811±8.19
7.96526 001
present study, T-PRF, as an advanced generation of
Min.-Max.§ 54.50- 48.00-71.50 PRF, succeeded to form bone in less time in
75.29 comparison to other grafting materials. This comes
Secondary stability( after 3months) ISQc
P=0.559 NS
in agreement with two studies (23, 24) reported that
Mean± SD 64.0133± 62.5589±5.07 addition of PRF to freeze dried bone allograft
5.25541 044 reduced the time required for bone regeneration
Min.-Max. 55.00- 56.75-72.25
69.25
from 8 to 4 months in addition to a trial conducted
Paired sample significance ( within each group) in 2019 (25) suggested that use of L- PRF in
p value addition to deproteinized bovine bone mineral
Primary P=0.971 P=0.861 NS accelerated and enhanced bone formation process in
stability/Second NS
ary stability maxillary sinus lifting approach.
ISQb/ISQc Depending on the results obtained by the present
*: Probability of error (chance). †: Statistically not study, addition of T-PRF to corticocancellous
significant (p≥0.05). ‡: Standard deviation. §: bovine bone xenograft hastened regeneration of
Minimum-Maximum. Tests of significance: to bone sufficient to provide suitable primary stability
compare between the two groups are independent for implants placed earlier than conventional
T-Test and One way Anova. timing. This comes in contrary to a systematic
review presented by Ali, S. and his colleges (26), in
2015, which concluded from 5 studies (23, 24, 27-
29) that addition of PRF to demineralized freeze-
DISCUSSION dried bone allograft DFDBA has accelerated bone
Platelet-Rich Fibrin has been found to have regeneration process and reduced the healing time.
superior quality than other grafting alternatives due However, it has no significant influence when
to its high content of platelets which are applied with deproteinized bovine bone xenograft.
fundamental component in the healing process of The contradicting results could be explained by the
both soft and hard tissues. (22) An innovative superior quality of T-PRF as compared to
modification of PRF namely T-PRF have dragged traditional PRF.
attention due to its higher qualities than traditional In terms of implant stability measured clinically,
PRF. (11, 12) the results of the present study revealed comparable
In the present study, maxillary sinus lift with implant stability in both groups. This goes in line
delayed implant was done due to severe bony with conclusion of a systematic review done by
deficiency with residual bone height ranging from Inchingolo et al. (30) in which inclusion of PRP in
3.64 to 4.97mm in both groups along with low bone bone graft used in sinus lift procedure has been
density vary from 28 to 410.22 HU in control shown to promote primary stability of the implants
group and from 42.70 to 560.50 HU in test group. in comparison to using bone graft alone taking into
This was most likely expected to compromise consideration that T-PRF in the present study was
immediate implant fixation and reliable primary included in both groups.
stability. In the present clinical trial, application of However, in the present study, it has been found
T-PRF alone as a filling material for sub-sinus that T-PRF/xenograft group showed higher pre-
cavity with residual bone height (less than 5mm) implant radiographic bone height gain and total
with delayed implant placement was evaluated bone height gain compared to T-PRF group. These
clinically, radiologically and histologically in results are in agreement with the results of kempraj
comparison to conventional T-PRF/Xenograft. et al. (31), in 2020, which re-evaluated
In this clinical trial, it has been shown that T-PRF Choukroun’s PRF as the only filling material for
alone has the ability to provide the same results the sub-sinus cavity in delayed implant protocol of
produced by mixture of T-PRF and xenograft when lateral window technique as compared to Xenograft
used to fill the sub-sinus cavity with delayed used alone. They reported significant difference
implant fixation relying on clinical and histological between control and study group in the
analysis. These are approximately the same results radiologically measured bone height in the favor of
of Olgun trial (13), in 2018, which compared the the Xenograft group. (31) These results could be
8
Alexandria Dental Journal. Volume x Issue x
Ibrahim.et.al Titanium Prepared Platelet Rich Fibrin For Sinus Lift

attributed to the resilience of fibrin matrix of PRF greater percentage of radiographic bone volume
impeding its ability to perform the role of well- gain in favor of the allograft control group. This
structured scaffold against the schneiderian difference in the results could be explained by using
membrane which compress the plug of PRF. (32) T-PRF as a supporting material to xenograft in the
At the same time, in the current trial, it was control group of the present study which provides
observed that the difference between pre-implant comparable results in both groups. At the same
bone height and post-implant bone height was time, it was reported that allograft is capable of
significant only in the test group which could be accelerating bone remodeling in comparison to
explained by the tent pegs' effect of inserted traditional xenograft. (33) This indicates the
implant and its ability to compensate the less pre- importance of applying other trial that compare T-
implant bone height in the test group and enhance PRF alone and T-PRF/ allograft composite.
the prognosis of the test group. The present study emphasized, histologically, the
Despite the fact that bone height gain before ability of T-PRF to enhance both bone deposition
implantation was higher in control group than test and healing process whether used alone or in
group, the primary stability of both groups was not combination with other bone graft with no
significantly different. This entails that the amount significant difference between both groups. This
of bone formed by T-PRF alone was sufficient to goes in line with a recent systematic review (30)
achieve the main goal of the whole process which is conducted on 22 studies aiming to analyze the
obtaining a suitable primary stability to allow results of most recent studies for better
success of implantation procedure as shown in the identification of the capabilities of the autologous
present study. platelet concentrates displayed as platelet-rich
Regarding bone density, in the present study, it has plasma PRP, platelet-rich fibrin PRF and
been found that T-PRF/xenograft group showed concentrated growth factors CGF. In that
higher radiographic pre-implant bone density gain systematic review (30), it has been mentioned that
compared to T-PRF group. These results go in line there is histological evidence regarding the ability
with the results of kempraj et al. (31), in 2020, of growth factors to promote blood supply in
which reported significant difference between addition to acceleration of new bone generation. In
control and study group in the radiologically addition, introduction of PRF into the bone graft
measured bone density in the favor of the Xenograft have been proven to enhance bone deposition
group as well which are most likely due to the less depending upon natural healing process of human
resilience of xenograft scaffold in comparison to body due to the angiogenic capacity of PRF that
fibrin mesh in general. (32) At the same time, in the provokes healing process in the surgical area. This
present clinical trial, total bone density gain was is highly noticeable in surgical wounds with
reported to be not significantly different between deficient blood supply including sinus floor
the two groups which in the contrary to Kempraj et elevation.
al. results. This could be explained in favor of In the present study, histomorphometric analysis
superior quality of T-PRF compared to the has shown that mean of bone surface area ratio was
Choukroun’s PRF used by kempraj et al. (31) 36.42 in control group and 35.43 in the test group
In the current trial, although the increased value of which are not significantly different. Moreover,
radiographic bone density gain before implant average value of non-mineralized bone appeared by
placement was significantly different between both trichrome stain was detected to be 8.41 and 8.1 in
groups in favor of control group, this did not control and test group respectively which showed
negatively influence the primary stability of the no statistical significant difference between the two
implants. Additionally, it has been remarkably groups as well. At the same time, Systematic
compensated by the implant insertion to the extent review of Inchingolo et al. (30) for 5 work papers
made there is no significant difference between (34-38) conversely concluded that newly formed
both groups in post-implant bone density gain and bone ratio measured histologically is greater in the
total bone density gain. By another meaning, any case of application of CGF alone, another
advantage presented by the traditional T- derivative of PRF, as compared to Xenograft in the
PRF/Xenograft could be compensated for the test delayed sinus-lift procedure. (37) This could be
group after implant placement taking into justified by stiffer fibrin matrix of CGF than PRP,
consideration the achievement of the primary PRF. (39) These contradicting results between the
implant stability in the first place for both groups current study and the previous studies (30) could be
similarly. clarified by using T-PRF in both groups in the
In terms of bone volume, it has been reported in the present study that led to similar histomorphometric
present clinical trial that there is no significant results between both groups that did not applied in
difference between radiographic pre-implant, post- case of CGF study which was used only in one
implant and total bone volume gain in both groups. group. (37)
This is in the contrary to the outcomes obtained On the other hand, in the current trial, histological
from Olgun et al. clinical trial (13) which revealed indications of new bone formation detected by
9
Alexandria Dental Journal. Volume x Issue x
Ibrahim.et.al Titanium Prepared Platelet Rich Fibrin For Sinus Lift

multiple resting and reversal lines along with less

ratio of non-mineralized bone than mineralized CONCLUSION
bone in both groups support the potential of T-PRF This clinical trial supports the effectiveness of T-
to reduce required bone formation period from 6 to PRF in bone formation capacity as advanced
4 months group which allow earlier implant generation of traditional PRF which was used in
placement than in the conventional techniques. every day practice as a supplemental not as a main
Another point that was observed from histological grafting material in maxillary sinus augmentation
analysis is that despite of the difference in graft particularly with delayed implant placement.
volume clinically between both groups which was Finally, T-PRF alone is effective grafting material
higher in the control group; this did not impede the in two stage maxillary sinus augmentation as
maturation process of newly formed bone. indicated by implant stability as the primary
However, thicker bone trabeculae were observed in objective measured clinically. This has been
the control group which could be attributed to supported by histmorhometric measurements as
remnants of resorped bone graft. well. In addition, acceleration of bone formation
These histological outcomes of the present study process can be achieved by means of T-PRF to
along with other results in the literature emphasize reduce healing time from 6 to 4 months.
the role of the T-PRF in guidance healing of hard Ethical approval: This study was approved from
tissues. These results come in agreement with the ethics committee and research committee in Faculty
histological outcomes stated by Choukroun et al. of Dentistry in Alexandria, Egypt. Ethical approval
(23), in 2006. number is IRB No. 00010556_IORG 0008839-
In the present study, although radiological analysis 0301_10/2021.
revealed better bone height and density in case of Patient consent: Written informed consents were
applying T-PRF/Xenograft than in T-PRF alone. obtained from all participants after detailed
This is actually expected as xenograft is appearing description of the whole procedures to be
radiopaque in x-rays. In addition, microscopic performed including its aim.
results are more significant in relation to bone Funding: This research did not receive any specific
regeneration. Therefore, both clinical and grant from funding agencies in the public,
histological outcomes have been taking mainly into commercial, not-for-profit sectors.
consideration. However, the radiological results are Conflict of interest: The authors declare that they
implying that T-PRF doesn't completely fulfill the have no conflict of interest.
scaffold structure requirements needed for typical
bone deposition necessary for implant fixation. But REFERENCES
the clinical and histological results are still 1. Aimen E K, Magued H F, Adham A A.
satisfactory and emphasize the favorable role that EVALUATION OF COMBINATION OF
could be obtained from application of T-PRF by its BIPHASIC CALCIUM PHOSPHATE AND
ability to replace classic grafting material or by PLATELET-RICH FIBRIN AS GRAFTING
reduction of healing time to 4 month. MATERIAL FOR SINUS LIFT
To summarize, this study introduces more evidence AUGMENTATION. Alexandria Dental Journal.
to support the claim of reliable effect of T-PRF 2015 Dec 1;40(2):140-7.
whether it has been used alone or in combination 2. Gassling V, Hedderich J, Açil Y, Purcz N,
with other bone graft which has been predicted by Wiltfang J, Douglas T. Comparison of platelet
Simonpieri (40) via emerging superior modified rich fibrin and collagen as osteoblast‐seeded
generation of PRF. Eventually, the successful scaffolds for bone tissue engineering
results in both groups, in the present study, promote applications. Clinical oral implants research.
two significant hypotheses; firstly, the capability of 2013 Mar;24(3):320-8.
T-PRF to be used alone in maxillary sinus 3. Li Q, Pan S, Dangaria SJ, Gopinathan G,
augmentation even in delayed implant protocol and Kolokythas A, Chu S, et al. Platelet-rich fibrin
secondly, the reinforcing effect of T-PRF to promotes periodontal regeneration and enhances
xenograft and its ability to reduce normal healing alveolar bone augmentation. BioMed research
time. international. 2013 Mar 26;2013.
Drawbacks of this study involve small sample size, 4. Karunakar P, Prasanna JS, Jayadev M, Shravani
absence of split mouth technique to overcome GS. Platelet-rich fibrin,“a faster healing aid” in
differential effects. Finally, it has to be mentioned the treatment of combined lesions: A report of
that gender dimensions in this research could not be two cases. Journal of Indian Society of
addressed and is considered as a limitation of this Periodontology. 2014 Sep 1;18(5):651-5.
trial s' generalizability. Other well controlled 5. Zhao JH, Tsai CH, Chang YC. Clinical
clinical trials with larger sample size and re- application of platelet-rich fibrin as the sole
evaluation of T-PRF with introduction of suitable grafting material in maxillary sinus
scaffold are recommended. augmentation. Journal of the Formosan Medical
Association. 2015 Aug 1; 114(8):779-80.
10
Alexandria Dental Journal. Volume x Issue x
Ibrahim.et.al Titanium Prepared Platelet Rich Fibrin For Sinus Lift

6. Meshram VS, Lambade PN, Meshram PV, 17. Shi Z, Zhong Q, Chen Y, Gao J, Pan X, Lian Q,
Kadu A, Tiwari MS. The autologous platelet et al. Nanohydroxyapatite, nanosilicate-
rich fibrin: A novel approach in osseous reinforced injectable, and biomimetic gelatin-
regeneration after cystic enucleation: A pilot methacryloyl hydrogel for bone tissue
study. Indian Journal of Dental Research. 2015 engineering. International Journal of
Nov 1; 26(6):560-4. Nanomedicine. 2021 Aug 16:5603-19.
7. Duan X, Lin Z, Lin X, Wang Z, Wu Y, Ji M, et 18. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V,
al. Study of platelet‐rich fibrin combined with Longair M, Pietzsch T, et al. Fiji: an open-source
rat periodontal ligament stem cells in platform for biological-image analysis. Nature
methods. 2012 Jul; 9(7):676-82.
periodontal tissue regeneration. Journal of
cellular and molecular medicine. 2018 Feb; 19. Shapiro SS, Wilk MB. An analysis of variance
22(2):1047-55. test for normality (complete samples).
8. O'Connell SM. Safety issues associated with Biometrika. 1965 Dec 1; 52(3-4):591-611.
platelet-rich fibrin method. Oral Surgery Oral 20. Razali NM, Wah YB. Power comparisons of
Medicine Oral Pathology OralRadiology and shapiro-wilk, kolmogorov-smirnov, lilliefors
Endodontology. 2007 May 1; 103(5):587. and anderson-darling tests. Journal of statistical
9. Miron RJ, Pinto NR, Quirynen M, Ghanaati S. modeling and analytics. 2011 Jan 1; 2(1):21-33.
Standardization of relative centrifugal forces in 21. Cramer D. Fundamental statistics for social
studies related to platelet‐rich fibrin. Journal of research: step-by-step calculations and
computer techniques using SPSS for Windows.
periodontology. 2019 Aug; 90(8):817-20.
10. Tunalı M, Özdemir H, Küçükodacı Z, Akman S, Routledge; 2003 Sep 2.
Fıratlı E. In vivo evaluation of titanium-prepared 22. Carlson NE, Roach Jr RB. Platelet-rich plasma:
platelet-rich fibrin (T-PRF): a new platelet clinical applications in dentistry. The Journal of
concentrate. British Journal of Oral and Maxillofacial the American Dental Association. 2002 Oct 1;
Surgery. 2013 Jul 1; 51(5):438-43. 133(10):1383-6.
11. Tunalı M, Özdemir H, Küçükodacı Z, Akman S, 23. Choukroun J, Diss A, Simonpieri A, Girard
Yaprak E, Toker H, et al. A novel platelet MO, Schoeffler C, Dohan SL, et al. Platelet-rich
concentrate: titanium-prepared platelet-rich fibrin (PRF): a second-generation platelet
fibrin. BioMed research international. 2014 Jan concentrate. Part V: histologic evaluations of
21; 2014. PRF effects on bone allograft maturation in
12. Olgun E, Ozkan SY, Atmaca HT, Yalim M, sinus lift. Oral Surgery, Oral Medicine, Oral
Hendek MK. Comparison of the clinical, Pathology, Oral Radiology, and Endodontology.
radiographic, and histological effects of 2006 Mar 1; 101(3):299-303.
titanium‐prepared platelet rich fibrin to allograft 24. Tatullo M, Marrelli M, Cassetta M, Pacifici A,
materials in sinus‐lifting procedures. Journal of Stefanelli LV, Scacco S, et al. Platelet Rich
investigative and clinical dentistry. 2018 Nov; Fibrin (PRF) in reconstructive surgery of
9(4):e12347. atrophied maxillary bones: clinical and
13. Chatterjee A, Pradeep AR, Garg V, Yajamanya histological evaluations. International journal of
S, Ali MM, Priya VS. Treatment of periodontal medical sciences. 2012; 9(10):872.
intrabony defects using autologous platelet‐rich 25. Pichotano EC, de Molon RS, de Souza RV,
fibrin and titanium platelet‐rich fibrin: a Austin RS, Marcantonio E, Zandim‐Barcelos
randomized, clinical, comparative study. Journal DL. Evaluation of L‐PRF combined with
of investigative and clinical dentistry. 2017 deproteinized bovine bone mineral for early
Aug; 8(3):e12231. implant placement after maxillary sinus
14. Fouad W, Osman A, Atef M, Hakam M. Guided augmentation: a randomized clinical trial.
maxillary sinus floor elevation using Clinical implant dentistry and related research.
deproteinized bovine bone versus graftless 2019 Apr;21(2):253-62.
Schneiderian membrane elevation with 26. Ali S, Bakry SA, Abd-Elhakam H. Platelet-rich
simultaneous implant placement: Randomized fibrin in maxillary sinus augmentation: a
clinical trial. Clin Implant Dent Relat Res systematic review. Journal of Oral
2018;20:424-33. Implantology. 2015 Dec 1; 41(6):746-53.
15. Feldman AT, Wolfe D. Tissue processing and 27. INCHINGOLO F, Tatullo M, Marrelli M, Inchingolo
hematoxylin and eosin staining. Histopathology: AM, SCACCO S, Inchingolo AD, et al. Trial with
methods and protocols. 2014:31-43. Platelet-Rich Fibrin and Bio-Oss used as grafting
16. McCaffery M, Beebe A. Pain: Clinical manual materials in the treatment of the severe maxillar bone
atrophy: clinical and radiological evaluations.
for nursing practice. (No Title). 1989 Feb.
European Review for Medical & Pharmacological
Sciences. 2010 Dec 1; 14(12).

11
Alexandria Dental Journal. Volume x Issue x
Ibrahim.et.al Titanium Prepared Platelet Rich Fibrin For Sinus Lift

28. Zhang Y, Tangl S, Huber CD, Lin Y, Qiu L, 35. Chen H, Zhou L, Wu D, Zhang J, Zheng Y,
Rausch-Fan X. Effects of Choukroun’s platelet- Chen Y. Osteotome sinus floor elevation with
rich fibrin on bone regeneration in combination concentrated growth factor and simultaneous
with deproteinized bovine bone mineral in implant placement with or without bone
maxillary sinus augmentation: a histological and grafting: a retrospective study. International
histomorphometric study. Journal of Cranio- Journal of Oral and Maxillofacial Surgery. 2022
Maxillofacial Surgery. 2012 Jun 1; 40(4):321-8. Aug 1; 51(8):1078-84.
29. Bolukbasi N, Ersanlı S, Keklikoglu N, 36. Dai Y, Han XH, Hu LH, Wu HW, Huang SY,
Basegmez C, Ozdemir T. Sinus augmentation Lü YP. Efficacy of concentrated growth factors
with platelet-rich fibrin in combination with combined with mineralized collagen on quality
bovine bone graft versus bovine bone graft in of life and bone reconstruction of guided bone
combination with collagen membrane. Journal regeneration. Regenerative biomaterials. 2020
of oral implantology. 2015 Oct 1; 41(5):586-95. Jun; 7(3):313-20.
30. Malcangi G, Patano A, Palmieri G, Di Pede C, 37. Ghasemirad M, Chitsazi MT, Faramarzi M,
Latini G, Inchingolo AD, et al. Maxillary Sinus Roshangar L, Babaloo A, Chitsazha R.
Augmentation Using Autologous Platelet Histological examination of the effect of
Concentrates (Platelet-Rich Plasma, Platelet- concentrated growth factor (CGF) on healing
Rich Fibrin, and Concentrated Growth Factor) outcomes after maxillary sinus floor
Combined with Bone Graft: A Systematic augmentation surgery. Journal of Medicine and
Review. Cells. 2023 Jul 6; 12(13):1797. Life. 2023 Feb; 16(2):267.
31. Kempraj J, Sundaram SS, Doss GP, Nakeeran 38. Merli M, Moscatelli M, Merli M, Mariotti G,
KP, Raja VK. Maxillary sinus augmentation Pagliaro U, Nieri M. Lateral Sinus Floor
using xenograft and choukroun’s platelet-rich Elevation in the Severely Atrophied Maxilla:
fibrin as grafting material: A radiological study. Concentrated Growth Factors Versus Bone
Journal of Maxillofacial and Oral Surgery. 2020 Substitutes. A Controlled Clinical Trial.
Jun;19:263-8. International Journal of Periodontics &
32. van HINSBERGH VW, Collen A, Koolwijk P. Restorative Dentistry. 2022 Jan 1; 42(1).
Role of fibrin matrix in angiogenesis. Annals of 39. Kim TH, Kim SH, Sándor GK, Kim YD.
the New York Academy of Sciences. 2001 Jun; Comparison of platelet-rich plasma (PRP),
936(1):426-37. platelet-rich fibrin (PRF), and concentrated
33. Galindo‐Moreno P, de Buitrago JG, Padial‐ growth factor (CGF) in rabbit-skull defect
Molina M, Fernández‐Barbero JE, Ata‐Ali J, O′ healing. Archives of oral biology. 2014 May 1;
Valle F. Histopathological comparison of 59(5):550-8.
healing after maxillary sinus augmentation 40. Simonpieri A, Del Corso M, Vervelle A, Jimbo
using xenograft mixed with autogenous bone R, Inchingolo F, Sammartino G, et al. Current
versus allograft mixed with autogenous bone. knowledge and perspectives for the use of
Clinical oral implants research. 2018 Feb; platelet-rich plasma (PRP) and platelet-rich
29(2):192-201. fibrin (PRF) in oral and maxillofacial surgery
34. Anitua E, Prado R, Orive G. Bilateral sinus part 2: Bone graft, implant and reconstructive
elevation evaluating plasma rich in growth surgery. Current pharmaceutical biotechnology.
factors technology: a report of five cases. 2012 Jun 1; 13(7):1231-56.
Clinical implant dentistry and related research.
2012 Mar; 14(1):51-60.

12
Alexandria Dental Journal. Volume x Issue x