European Journal of Orthodontics, 2024, 46, 1–9

https://doi.org/10.1093/ejo/cjad056
Randomized Controlled Trial (RCT)

Evaluation of the effectiveness of the platelet-rich plasma

compared to the injectable platelet-rich fibrin on the rate
of maxillary canine retraction: a three-arm randomized

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controlled trial
Ali Mohsen Ammar1, Rabab Al-Sabbagh2 and Mohammad Younis Hajeer3,*
1
Department of Orthodontics, Arab Private University for Science and Technology, Hama, Syria
2
Department of Orthodontics, University of Hama Dental School, Hama, Syria
3
Department of Orthodontics, University of Damascus Dental School, Damascus, Syria
*
Corresponding author. Department of Orthodontics, Faculty of Dentistry, Damascus University, P.O. Box 9309, Mazzeh, Damascus, DM72 HAJ, Syria. E-mail:
[email protected]

Summary
Background: Blood-derived materials have been used recently to accelerate orthodontic tooth movement, but there are conflicting reports on
their effectiveness.
Objective: To evaluate the potential effect of local injection of platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) on the rate of
orthodontic tooth movement.
Trial design: A single-center, three-arm, parallel-group randomized controlled trial.
Materials and Methods: The sample consisted of 60 patients aged between 18 and 25 years (mean age: 21.1 ± 2.2 years) with Class II div-
ision 1 malocclusion requiring anterior retraction. Using a computer-generated list of random numbers, patients were assigned to three groups
of canine retraction: (i) assisted with PRP injection (PRP group), (ii) assisted with i-PRF group, and (iii) conventional treatment with no injections
(Cont. group). In the interventional groups, injections were done immediately and at 8 weeks after the onset of canine. Transpalatal arches (TPAs)
were used to reinforce anchorage. The upper canines were distalized on 0.019 × 0.025-inch stainless archwires using coil springs with a force of
150 g. The primary outcome was the amount of canine retraction, whereas the secondary outcomes were canine rotation and anchoring loss.
Assessment was done at five-time points: the beginning of tooth movement (T0) and at 4, 8, 12, and 16 weeks following T0 on three-dimensional
superimposed digital models
Results: Sixty patients were randomized and included in this study (20 patients in each group), there were no dropouts. The rate of canine re-
traction was faster in the experimental groups. The PRP group showed a significantly slower movement in the second and fourth months than
the i-PRF group while in the first and third months, there were nonsignificant differences between the two experimental groups.
Limitations: Blinding was not possible during the clinical stage of this trial.
Conclusions: PRP and i-PRF were found to be effective in accelerating orthodontic tooth movement during canine retraction. However, the
effect of i-PRF was longer than that of PRP.
Trial registration: ClinicalTrials.gov (ID: NCT05335824).
Keywords: platelet-rich plasma; platelet-rich fibrin; acceleration; tooth movement; canine retraction

Introduction were described in the literature [5]. Surgically assisted ap-

Shorter orthodontic treatment time is considered to be the proaches that depend on the so-called regional acceleration
main demand of adult patients who seek the treatment with phenomenon such as corticotomy, corticision, and micro-
less or no side effects [1, 2]. osteoperforations have in general high success rates, but they
Compared to adolescents, adults have more bone density rely on incurring an injury to bone tissues [6]. Most patients
and less bone turnover, besides their periodontal ligament do not accept the intervention due to its aggressive nature,
contains fewer cells, so adult patients suffer wider glass and side effects that could happen to the targeted teeth. Also,
hyalinization areas inside the periodontal ligament which the intervention requires help from another specialist and has
need more time to transcend orthodontic movement phases a higher cost, so these techniques have not gained popularity
[3], as well as, they have higher root resorption during ortho- in every orthodontist’s clinic [7–9].
dontic treatment [4]. Recently, it has been demonstrated that orthodontic tooth
To accelerate orthodontic tooth movement (OTM) and movement can be accelerated by using platelet-based pre-
surpass these limits, surgical and nonsurgical techniques parations from the patient’s own blood, such as platelet-rich
plasma (PRP) and platelet-rich fibrin (PRF) [10, 11]. PRP is

© The Author(s) 2023. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please
email: [email protected]
2 European Journal of Orthodontics, 2024

obtained via centrifuge of patients’ blood and is defined as Reviewing the available literature indicates that only one
an autologous concentration of platelets in a small volume of randomized controlled clinical trial has compared the PRP
plasma [12]. The number of platelets is about 150 000-450 with the i-PRF in terms of the rate of orthodontic tooth move-
000/μl of blood, whereas the number of platelets in PRP is ment [26]. The design of this experiment was a split-mouth
about 1 000 000/μl [13]. one which is not suitable in this context because autologous
When the platelets in the PRP are activated, the α-granules platelet concentrates may trigger a systemic effect as men-
are degranulated and release the growth factors (GFs) and tioned before [24]. Besides, the anchorage loss evaluation
cytokines, several important GFs released by platelets in PRP was inaccurate since the arch halves were not symmetrical
like vascular endothelial GF, fibroblast GF, platelet-derived regarding intervention. While the first molars on the left and
GF, epidermal GF, hepatocyte GF, and insulin-like GF 1, 2 right sides were joined by TPA, so the movement of one of
(IGF-1 and IGF-2), in addition to interleukin 8 [14]. them would affect the other. In addition, they started the re-

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The variety of GFs in PRP may have the ability to stimulate traction after 14 days of extraction which could interfere with
the activation of osteoblasts and osteoclasts together, which the effect of PRP and i-PRF [26].
supports the idea that PRP can affect orthodontic tooth move- Furthermore, a recent systematic review [27] about the ef-
ment, especially with its rich content of cytokines which play fect of autologous platelet concentrates on orthodontic tooth
a vital role in mediation, variation, activation, and keeping movement emphasized the need for further randomized clin-
the osteoblasts alive [15, 16]. ical trials. Therefore, the current trial was conducted to in-
PRF is defined as the second generation of blood-derived vestigate whether the PRP and the i-PRF affect OTM, and
biological materials. Contrary to PRP, PRF is prepared to compare these two platelet concentrates in terms of upper
without the use of anticoagulants. And it is obtained by a canine retraction rate. The secondary objectives were to as-
single centrifugation of blood, as opposed to PRP, which sess canine rotation and anchorage loss during retraction. The
needs two stages of centrifugation [17]. There are many types null hypothesis stated that there were no differences between
of PRF that differ from each other via their containing of the two techniques in terms of canine retraction rate, canine
cytokines and GFs. They are obtained by modifying the speed rotation, and anchorage loss when performing this ortho-
and time of the centrifuge. And include leukocyte-platelet- dontic tooth movement.
rich fibrin (L-PRF), Titanium platelet-rich fibrin (T-PRF),
advanced platelet-rich fibrin (A-PRF), advanced platelet-rich
fibrin + (A-PRF +), and injectable platelet-rich fibrin (i-PRF) Materials and methods
which can be injected like PRP [18]. Study design and settings
PRF (in its different types) contains ingredients such as This study was a three-arm, parallel-group RCT accom-
protease and antiprotease which motivate the formation of plished at the Department of Orthodontics at the University
new blood vessels and remodeling of the current blood ves- of Hama Dental School from February 2019 to December
sels, besides cytokines, and chemokines which are essential 2020. The Local Research Ethics Committee Approval was
in bone and blood vessels formation [19]. Wang et al. [20] obtained (UHDS-2804-2019PG). This trial was funded
have reported that i-PRF affects the osteoclasts behavior ob- by the University of Hama Postgraduate Research Budget
viously via affecting its migration, differentiation, and repro- (UHDS- 00477212-PG) and was retrospectively registered at
duction which motivates cells activation and accelerates bone ClinicalTrials.gov (ID: NCT05335824).
remodeling and healing.
Conflicting results have emerged about the effectiveness Estimation of the sample size
of blood-derived materials in accelerating OTM. Liou [21]
Estimation of sample size was done by using G*Power 3.1.3
in his case series report concluded that one injection of PRP
(Heinrich-Heine-Universität, Düssel- dorf, Germany) with the
had a positive effect that lasted for 5 to 6 months with the
assumption of a power of 90% with a permissible (α) error
largest effect in the second to fourth month after the injec-
of 5%. The smallest difference requiring detection in canine
tion. Whereas, El-Timamy et al. [22] in a split-mouth trial,
retraction was assumed to be 0.5 mm/month with a standard
reported that the third month after injection showed a statis-
deviation of 1.03 mm (from a previous study [28])a sample
tically significantly slower rate on the intervention side. Angel
of 57 subjects was needed, three additional patients were in-
et al. [23] in their split-mouth randomized controlled trial
cluded to consider sample attrition, and total sample size be-
(RCT) showed a significant increase of 35% in maxillary ca-
came 60 patients.
nine retraction during the first month, which declined to 14%
at the end of the second month. Besides the design of these
trials was a split-mouth one which is not suitable because au-
Patients’ recruitment and entry into this trial
tologous platelet concentrates may trigger a systemic effect One hundred and twenty-two patients from the Department
once injected in the oral mucosa, and the effect cannot be of Orthodontics at the University of Hama Dental School
confirmed to be locally restricted [24]. were examined and the treatment procedures were clari-
When it comes to the evaluation of the effectiveness of fied to 82 patients who had met the inclusion criteria. Then,
using PRF, Tehranchi et al. [11] assessed the rate of canine 60 out of the 74 individuals who accepted to participate
movement in a randomized split-mouth trial using L-PRF in this trial were randomly chosen. Information sheets were
to preserve the socket immediately after the extraction, they given, and written informed consent was obtained from all
concluded that the use of L-PRF might accelerate tooth move- the patients or their legal representatives. The inclusion cri-
ment. However, a contradictory result was found by Pacheco teria were: (i) both male and female patients, (ii) ages 18
et al. [25] who reported that the rate of canine retraction in to 25 years, (iii) Class II division 1 malocclusion, maxil-
the L-PRF side was significantly smaller than that of the con- lary first premolars were removed as part of the treatment,
trol side. (iv) complete permanent dentition, and (v) good oral and
A. M. Ammar et al. 3

periodontal health (Plaque index ≤ 1, Gingival index ≤ 1) unsealed only after making all patients’ assessments and pre-
[29]. The exclusion criteria were: (i) severe skeletal Class II molar extractions. The random allocation sequence and par-
malocclusion, overjet > 10 mm ANB > 7◦, (ii) illnesses and ticipants’ allocation to one of the three groups were done by
drugs that might have an impact on bone biology, (iii) in- one of the academic staff (not involved in the current study)
adequate oral hygiene, (iv) previous orthodontic treatment, at the Department of Orthodontics. The 60 patients were dis-
(v) having a cigarette, (vi) having coagulation problems or tributed randomly into three groups with similar severities of
taking anticoagulants. During the time of enrollment, pa- malocclusion (P > 0.001; Table 1).
tients were chosen based on the inclusion and exclusion cri-
teria, and complete preoperative records were gathered. The
flow diagram of patient recruitment and inclusion in this Treatment sequence
trial is given in Fig. 1. Transpalatal arches (TPAs) were used as anchorage devices

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then the patients were sent to extract the first upper pre-
molars by the same surgeon to eliminate the differences.
Randomization and allocation concealment MBT 0.022-inch slots brackets (Votion®, Ortho Technology,
Minitab® (Version 17; Minitab, LLC, State College, Pa) West Columbia, SC, USA) were bonded. Leveling and align-
was used to regulate allocation of patients among the three ment were accomplished until 0.019 × 0.025-inch stainless
groups, using a set of random numbers with an alloca- steel archwire was reached. At this point, injections were first
tion ratio of 1:1:1. The allocation sequence was concealed done in PRP and i-PRF groups and this was followed by a
using numbered, opaque, and closed envelopes, which were canine retraction procedure as explained in the control group
section.

The platelet-rich plasma group

PRP tubes with anticoagulant Acid citrate dextrose‑A
(ACD‑A) were used after extracting 20 ml of venous blood
from each patient. PRP was prepared using a double-spin
process as mentioned by Marx [12]. The injection sites were
anesthetized with lidocaine 2% with epinephrine 1/80 000
and left for 10 min. On the distal surface of the upper canines,
15 units (0.15 ml) of PRP were injected intraligamentally in
the middle, distobuccal, and disto-palatal regions (five units
in each area) in addition to buccal and palatal submucosal
injections (100 units and 50 units, respectively). The patients
were injected immediately before canine retraction and after
8 weeks of the onset of retraction.

The injectable platelet-rich fibrin group

i-PRF was prepared with the use of 20 ml of blood drawn
from the patient into dry sterile tubes without anticoagulant
(quickly before coagulation starts) by following the centri-
Figure 1. CONSORT flow diagram of patients’ recruitment and follow-up. fugation protocol requiring one cycle only (700 rpm for 3

Table 1. Comparison of the baseline mean values of the patients in the three groups.

Control PRP i-PRF P-value*

Mean ± SD Mean ± SD Mean ± SD

SNA (º) 82.13 ± 2.70 81.63 ± 2.71 81.99 ± 2.52 0.828

SNB (º) 76.12 ± 2.81 75.55 ± 2.65 75.79 ± 2.48 0.797
ANB (º) 6.01 ± 0.73 6.07 ± 0.81 6.20 ± 0.77 0.746
GoGn-SN (º) 29.05 ± 3.77 28.11 ± 3.53 28.55 ± 3.53 0.884
PP-MP (º) 27.23 ± 3.77 25.86 ± 3.50 26.97 ± 3.42 0.995
U1-SN (º) 108.79 ± 5.04 106.14 ± 4.76 108.19 ± 4.74 0.788
IMPA (º) 97.55 ± 4.84 98.20 ± 5.51 96.91 ± 4.74 0.898
Overjet (mm) 6.83 ± 0.20 6.13 ± 0.21 6.70 ± 0.20 0.537
Overbite (mm) 3.13 ± 0.87 2.88 ± 0.76 2.44 ± 0.93 0.760
TSALD (mm) 4.22 ± 1.38 4.37 ± 1.56 3.92 ± 1.13 0.575

SD: standard deviation, PRP: platelet-rich plasma, i-PRF: injectable platelet-rich fibrin, TSALD: tooth-size-arch-length-discrepancy.
*
One-way ANOVA test.
4 European Journal of Orthodontics, 2024

min) as reported by Miron et al. [30], the prepared i-PRF

remained injectable for 10–15 after centrifugation. Injection
procedures, sites, units, and time was similar to the PRP
group.

The control group

After inserting the 0.019 × 0.025-inch SS archwire, 150 g of
force was applied using NiTi closed-coil springs (American
Orthodontics, Sheboygan, WI) extended from the band hook
of the first molar to the canine bracket on both sides. A force

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gauge was used to check the generated force (040-711-00
Dentaurum, Ispringen, Germany) to guarantee a constant and
equal force in all subjects. Patients had follow-up visits every
2 weeks. Each time, the coil spring’s force was assessed and,
if necessary, readjusted to maintain it at 150 g level. Also,
the appliances were checked for any chewing-related deform- Figure 3. Calculating the angle of canine rotation.
ation or displacement. Canine distalization continued until
reaching Class I canine relationship.

Outcome measures
Rate of canine retraction, canine rotation, and anchorage
loss
Alginate impressions for the upper arches were taken before
canine retraction (T0) and every 4 weeks till the 16 weeks
(T0–T4), i.e. five assessment times. Study models were
made and scanned using R500TM (3shape, Copenhagen,
Denmark). 3D models were saved in the STL format. The
five 3D digital models were superimposed using Ortho
analyzerTM software (3shape, Copenhagen, Denmark). The
inferior tip of the incisive papilla and the medial end of
the third palatal rugae were used as reference points for
the superimposition, these points were used in similar re-
searches [23, 31].
The amount of canine distalization per month was esti-
mated by calculating the distance between the canine cusp tip
in the baseline model to the canine cusp tip in the subsequent
Figure 4. Measuring the distance between mesial central fossa of a
superimposed model (Fig. 2). Canine rotation and molar maxillary first molar in the superimposed models.
anchorage loss were also assessed on the 3D models. The
canine’s mesial and distal contact points were used to create
a horizontal line that would form an angle with the similar line in the next superimposed model, this angle represented
the degree of canine rotation between the two superimposed
models (Fig. 3). Mesial central fossas of maxillary first molars
from the baseline model and the next superimposed model
were used to calculate anchorage loss in the digital models
that were superimposed (Fig. 4).

Blinding
Blinding of patients and clinicians was not feasible for this
trial due to its nature. However, all digital models were coded.
This ensured that the investigator (AMA) was blinded to
which group the models belonged. Blinding was also applied
during data analysis.

Error of the method

Twenty 3D digital models were randomly chosen to evaluate
the error of the method. Within a 3-week interval, super-
impositions on the rugae area, canine retraction, canine ro-
tation, and molar movement were measured twice. The
intraclass correlation coefficients (ICCs) were used to deter-
Figure 2. Measuring the distance between canine cusp tip in the
mine the intra-observer reliability (or random error). Two-
superimposed models. sample t-tests were employed to detect systematic errors.
A. M. Ammar et al. 5

Statistical analysis
Statistical analysis was accomplished using the SPSS/
SPSS® v 20.0 (IBM corporation, Armonk, NY). Since all
of the variables have normal distributions according to
the Kolmogorov–Smirnov test, parametric statistics were
applied. Paired t-test was used to calculate the amount of
canine retraction between the right and left sides of the
patient. One-way analysis of variance (ANOVA) test was
calculated to compare the results among the three groups.
Least significant difference (LSD) test was used to deter-
mine the statistical significance of differences between two

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of the three groups when needed. The level of significance
was set at 5%.

Figure 5. Line chart displaying the rate of canine movement in the three
RESULTS groups.
Error of the method
No significant differences were observed between the first
and second measurements indicating no systematic error differences were found (P > 0.05). So, the average values of
(P > 0.05). Using Dahlberg’s formula, the mean errors ranged the left and right sides were used in the following statistical
from 0.02 to 0.05 mm and from 0.02° to 0.04° for the linear analysis. Over the 4-month observation period, the mean
and angular measurements, respectively. The ICCs ranged overall canine retraction was 4.26 ± 0.64, 4.98 ± 1.01, and
from 0.970 to 0.999 demonstrating the measures’ high 3.34 ± 0.51 mm in the PRP group, i-PRF group, and control
reliability. group, respectively. The differences among the three groups
were statistically significant (P < 0.001; Table 2). The canine
Participant flow and follow-up movement was faster in the two experimental groups than
Sixty patients were enrolled (36 females, 24 males; mean age in the control group (Fig. 5). Inter-group differences at each
21.1 ± 2.2 years) with 20 patients in each group. No patients assessment time were also statistically significant (P < 0.001,
were lost to follow-up (Fig. 1). Therefore, intention-to-treat Table 2).
analysis was performed. Changes in canine movement rates over the four assess-
ment times in the i-PRF group (P = 0.060) and the control
Rate of canine retraction group (P = 0.335) were statistically insignificant. However, in
A canine relationship of Class I was not achieved in any pa- the PRP group, there was a statistically significant difference
tient at the end of the third month of observation. However, over the observation period between the assessment times
by the end of the fourth month of observation, the number (P < 0.001, Table 2).
of patients who ended with a Class I canine relationship was Inter-group comparisons revealed that there was no signifi-
zero, three, and six in the control group, PRP group, and cant difference between the PRP and i-PRF groups regarding
i-PRF group, respectively. Among these patients, two in the canine movement during the first and third months following
PRP group and four in the i-PRF group achieved bilateral the intervention, whereas significant differences existed be-
Class I canine relationship. tween the two groups in the second and fourth months (Table
The monthly rate of canine retraction between the right 3).
and left sides of patients’ dental arches was evaluated to de-
tect any significant differences and no statistically significant Canine rotation and anchorage loss
The degree of canine rotation and the amount of molar me-
sial movement between the two sides of the patient were
Table 2. Mean values for the rate of canine retraction in each month in examined using paired t-tests and no statistically significant
three groups (mm/month). differences were found (P > 0.05). So, the average values
of the left and right sides were used in the statistical ana-
Month Control PRP i-PRF P-value† lysis. The mean total canine rotation during the observation
period was 10.47 ± 1.23°, 9.87 ± 2.38°, and 10.94 ± 1.99°
Mean ± SD Mean ± SD Mean ± SD
in the PRP group, i-PRF group, and control group, respect-
1st month 0.87 ± 0.12 1.2 ± 0.16 1.36 ± 0.32 <0.001* ively (Table 4). Differences in canine rotation were statistic-
2nd month 0.84 ± 0.12 0.89 ± 0.14 1.18 ± 0.19 <0.001* ally insignificant among the three groups at all the assessment
3rd month 0.81 ± 0.12 1.28 ± 0.33 1.29 ± 0.3 <0.001* times (P > 0.05). The mean total first molar mesial movement
4th month 0.8 ± 0.14 0.88 ± 0.13 1.15 ± 0.23 <0.001*
during the same period was 1.66 ± 0.19 mm, 2.09 ± 0.20 mm,
and 1.06 ± 0.09 mm in the PRP group, i-PRF group, and con-
P-value‡ 0.335 <0.001* 0.060
trol group, respectively (Table 5). Differences in molar mesial
Total 3.34 ± 0.51 4.26 ± 0.64 4.98 ± 1.01 <0.001* movement among the three groups were statistically signifi-
cant (P < 0.001; Table 5). The molar movement was larger
SD: Standard Deviation, PRP: platelet-rich plasma, i-PRF: injectable in the two experimental groups than in the control group.
platelet-rich fibrin, *Statistically significant, P-value†: One-way ANOVA Inter-group differences at each assessment time were also stat-
test, P-value‡: One-way ANOVA test for the rate of canine retraction in
each group in the 4 months. istically significant (P < 0.001, Table 5).
6 European Journal of Orthodontics, 2024

Table 3. Comparison of the rate of canine retraction among each month Table 5. Rate of molar movement (mm/month) among the three groups.
among the three groups (mm/month).
Month Control PRP i-PRF P-value†
Canine Group Group Mean P- value†
retraction rate (I) (J) difference (I-J) Mean ± SD Mean ± SD Mean ± SD

1st month Con- PRP –0.329 <0.001* 1st month 0.35 ± 0.07 0.55 ± 0.08 0.56 ± 0.02 <0.001*
trol 2nd month 0.29 ± 0.03 0.32 ± 0.07 0.49 ± 0.05 <0.001*
i-PRF –0.487 <0.001* 3rd month 0.21 ± 0.02 0.56 ± 0.04 0.56 ± 0.03 <0.001*
PRP i-PRF –0.128 0.058 4th month 0.21 ± 0.02 0.23 ± 0.06 0.48 ± 0.05 <0.001*
2nd month Con- PRP –0.047 0.35 P-value‡ 0.070 <0.001* 0.136

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trol Total 1.06 ± 0.09 1.66 ± 0.19 2.09 ± 0.20 <0.001*
i-PRF –0.335 <0.001*
PRP i-PRF –0.288 <0.001*
SD: standard deviation, PRP: platelet-rich plasma, i-PRF: injectable
3rd month Con- PRP –0.467 <0.001* platelet-rich fibrin, *Statistically significant, P-value†: One-way ANOVA
trol test, P-value‡: One-way ANOVA test for the rate of molar movement in
each group in the 4 months.
i-PRF –0.473 <0.001*
PRP i-PRF –0.006 0.945
4th month Con- PRP –0.082 0.15 studies have reported a positive effect of PRP and i-PRF on
trol orthodontic treatment [10, 11], whereas other studies have
i-PRF –0.349 <0.001* reported no significant benefit [25, 33]. To the best of our
knowledge, the current study is the first three-arm random-
PRP i-PRF –0.267 <0.001*
ized controlled clinical trial evaluating the effectiveness of
injecting the PRP versus the i-PRF on the orthodontic tooth
†
: LSD was used to detect significant, *Statistically significant, PRP: movement when retracting upper canines in extraction-
platelet-rich plasma, i-PRF: injectable platelet-rich fibrin.
based treatments.
Age is a significant factor affecting the biological response
Table 4. Rate of canine rotation rate (°/month) among the three groups. to orthodontic tooth movement and it is well documented
that adult patients have a significantly slower rate of tooth
Canine rotation Group Mean ± SD Lower Upper P-value† movement [34, 35]. This might be attributed to the tissue re-
sponse to orthodontic forces involving both cell mobilization
1st month Control 2.46 ± 0.7 1.19 3.35 0.675
and conversion of collagen fibers that are slower in adults
PRP 2.77 ± 0.63 1.45 3.2 than in children and teenagers [36]. In a study employing
i-PRF 2.36 ± 0.61 1.48 3.15 L-PRF in periodontally accelerated osteogenic orthodontics,
2nd month control 2.83 ± 1.19 1.16 4.95 0.342 Muñoz et al. [37] had a wide age range of 15–51 years which
PRP 2.64 ± 0.48 1.95 3.25 could affect the accuracy of the results. While in this study
i-PRF 2.44 ± 0.6 1.65 3.24 adult patients 18–25 years were chosen to reduce the effect of
3rd month control 2.77 ± 0.99 1.15 4.3 0.594 age on the rate of tooth movement.
PRP 2.61 ± 0.51 1.84 3.45
Tooth extraction can rise inflammatory markers activity
which can interfere with the effect of PRP and PRF [38], to
i-PRF 2.54 ± 0.56 1.75 3.25
decrease this probability, the extraction was made at the start
4th month control 2.88 ± 1.01 1.25 4.2 0.167
of the therapy before leveling and alignment.
PRP 2.94 ± 0.51 2.18 3.79 Acid citrate dextrose‑A (ACD‑A), trisodium citrate (TSC),
i-PRF 2.52 ± 0.61 1.65 3.45 citrate phosphate dextrose adenine (CPDA), heparin, and
Total Control 10.94 ± 1.99 8.05 15.09 0.221 EDTA are some of the common anticoagulants used for many
PRP 10.47 ± 1.23 8.69 12.52 different purposes of preparation of blood components.
i-PRF 9.87 ± 2.38 6.53 13.07 When compared to ACD-A, the anticoagulant CPDA has been
found to be 10% less effective in maintaining platelet viability
[12]. EDTA has also been found to harm the platelet mem-
SD: standard deviation, PRP: platelet-rich plasma, i-PRF: injectable brane, so it is not advisable for use in the preparation of PRP
platelet-rich fibrin, P-value†: One-way ANOVA test.
[39]. Lei et al. [40] discovered that ACD-A outperformed TSC
and heparin in preserving the integrity of the platelet mem-
Harms brane and avoiding unintentional platelet activation during
No harms were detected during the course of this trial. No centrifugation. Therefore, ACD-A was used in this work as
complications were encountered during the injection of the selecting the appropriate anticoagulant is an essential step in
tested materials. the preparation of PRP.
Sham injections could have been used in the control group
to simulate what would happen in the other two groups re-
DISCUSSION garding periodontal ligament (PDL) tissue damage caused by
The use of platelet concentrations has increased in re- the injection and its effect on OTM, but for ethical reasons,
cent years to accelerate tissue healing and regeneration placebo injections were not used. Since the main purpose of
in various fields of medicine and dentistry [32]. But their this trial was to compare the effects of PRP and i-PRF on
use to accelerate OTM remains a continuous issue as some OTM.
A. M. Ammar et al. 7

In the current study, a significant increase in the canine shift during canine distalization, and considered an unsteady
movement was observed in the PRP group in the first and point. As well they used a flexible ruler to measure the canine
third months as compared to the control group. Patients retraction while the superimposition of digital casts was used
were subjected to a PRP injection in the first month and in this study.
another one in the third month. This could explain the ac- In the current study, a significant increase in the molar
celeration observed in the immediate postinjection period in mesial movement was observed in the experimental groups
these 2 months. It seems that the injection effect lasted only compared to the control group, which could be explained
for 1 month, as the canine movement returned to a lower by the extension of the positive effect of PRP and i-PRF
level of speed in the second and fourth months. This might on the acceleration of OTM to posterior teeth. The larger
be related to the short effect of PRP [41]. This finding was amounts of PRP and i-PRF that were injected into patients
in agreement with the results of El-Timamy et al. [22] who were buccal and palatal submucosal injections (i.e. 100

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reported a statistically significant increase in the rate of ca- units and 50 units, respectively). These injections may be
nine retraction after PRP injections. They also found that responsible for the extended effect of PRP and i-PRF, since
PRP did not exhibit long-term acceleration effects as the rate 15 units only of PRP and i-PRF were injected into the PDL.
of canine distalization was nonsignificant on the interven- These findings agree with Tehranchi et al. [11] and Nemtoi
tion side in the second month following cessation of PRP et al. [46].
injections. The results of our study indicated that there were insignifi-
In a recent spilt-mouth trial aimed to evaluate the rate of cant differences regarding canine rotation among the three
PRP-enhanced canine distalization in 10 patients, Angel et groups, which were in line with the results of Naji et al. [26].
al. [23] found a significant increase of 35% in maxillary ca- But their mean values were double those of the current study.
nine retraction movement during the first month after PRP The high rotation observed in Naji et al. study could be at-
injection. But it decreased to 14% after 60 days of injection, tributed to the use of Ricketts’ retraction spring, whereas a
which reflected the short acceleration effects of PRP. This re- sliding technique was used in the current work.
sult comes in concurrence with the results of our study.
In the i-PRF group, the increased rate of canine retraction Limitations
was significant at all-time points during the 4-month period Patient-reported outcomes such as pain and discomfort were
when compared with the control group, and that could be not evaluated in this trial. The evaluation of the type of ca-
explained by the long-lasting effect of i-PRF as a new study nine movement was not assessed in terms of angulation in the
has shown that new forms of PRF (A-PRF and i-PRF) have current study. Blinding of the researcher was not possible in
gradual secretion of GFs [42]. the current study during the clinical stage period, as the inves-
Unlike PRP, PRF comes from a natural and gradual poly- tigator was able to know the type of the injected substance
merization that takes place during centrifugation. The (PRP or i-PRF). Which may have increased the possibility of
resulting fibrin network has an especially homogenous three- bias. Patients in the control group did not receive placebo
dimensional organization. And this fibrin matrix has the cap- injections which could affect orthodontic movement, due to
acity to store the proteins within it allowing the slower release the tissue damage caused by the injection, especially regarding
of GFs over time [43]. Furthermore, a polymerization mode PDL injections. This study was a 4-month observation period,
suggests a greater incorporation of circulating cytokines into only two injections were delivered throughout that period.
the fibrin meshes. Such a configuration proposes that these Therefore, multi-arm studies with longer observation time to
cytokines will live longer since they will only be emitted and compare different injection protocols (one, two, three, or even
utilized during the first stage of cicatricial matrix remodeling four injections) are needed in future research work to study
(long-term effect) [44]. the effect of repeated injections during orthodontic treatment.
The results of our study are in line with the results of
Erdur et al. [45] who found in a randomized spilt-mouth
clinical study on 20 patients with an average age of Conclusion
21.4 ± 2.9 years that i-PRF injections accelerate OTM sig-
nificantly as the rate of canine distalization was higher in During canine retraction, the use of PRP and i-PRF was a suc-
the study group than the control group at all assessment cessful way to accelerate orthodontic tooth movement. The
times. They added that the beneficial impact of i-PRF on PRP effect lasted for 1 month only, while the i-PRF had a
the rate of tooth movement began in the first week and was prolonged acceleration effect.
seen during the follow-up time (12 weeks) although i-PRF
injections were stopped in the second week of canine re-
traction, which supports the idea of the long-lasting effect Author contributions
of i-PRF. Tehranchi et al. [11] and Nemtoi et al. [46] also Ali Ammar (Formal analysis [lead], Funding acquisition [sup-
found similar results using PRF clots (PRF) placed in ex- porting], Investigation [lead], Methodology [lead], Visualization
traction sockets. [lead], Writing—original draft [equal], Writing—review
Pacheco et al. [25] in a split-mouth study reported that & editing [equal]), Rabab Al-Sabbagh (Conceptualization
the rate of canine retraction in the L-PRF side was signifi- [lead], Formal analysis [supporting], Funding acquisition
cantly lower than the control side. However, that study has [lead], Investigation [supporting], Methodology [supporting],
a clear risk of bias because there was no blinding of oper- Supervision [lead], Visualization [supporting], Writing—ori-
ators. So the surgeon and the orthodontist knew the experi- ginal draft [supporting], Writing—review & editing [lead]), and
mental side, furthermore, the use of the central incisor in their Mohammad Y Hajeer (Conceptualization [supporting], Formal
study as a reference point to calculate the amount of canine analysis [supporting], Supervision [supporting], Writing—ori-
retraction was questionable because the central incisor could ginal draft [lead], Writing—review & editing [lead]).
8 European Journal of Orthodontics, 2024

Conflict of interest a histometric study in dogs. J Periodontol 2008;79:888–95. https://

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