Received: 12 July 2021

DOI: 10.1002/term.3290

RESEARCH ARTICLE
- -Revised: 1 February 2022 Accepted: 2 February 2022

A comparative evaluation of the effect of platelet rich fibrin

matrix with and without peripheral blood mesenchymal stem
cells on dental implant stability: A randomized controlled
clinical trial

Laveena Singhal1,2 | Sphoorthi Anup Belludi1 | Neha Pradhan1 | Supriya Manvi3

1
Department of Periodontics, KLE Society's
Institute of Dental Sciences, Bangalore, India
2
Anandam ENT Head and Neck Super
Speciality Centre, Siliguri, West Bengal, India
3
Department of Implantology, KLE Society's
Institute of Dental Sciences, Bangalore, India
Correspondence
Sphoorthi Anup Belludi, KLE Society's
Institute of Dental Sciences, No. 20
Yeshwanthpur Suburb, II Stage, Tumkur Road,
Bangalore—560022, India.
Email: doc_sphoo@yahoo.com
Funding information
Medical Education Research Trust, Bangalore
Abstract
Technological advances in the field of implantology have led to the concept of
surface modifications to enhance implant stability by utilization of current concepts
of tissue engineering and materials such as platelet concentrates and stem cells. The
purpose of the present randomized controlled clinical trial was to evaluate and
compare the effect of platelet rich fibrin matrix (PRFM) with and without peripheral
blood mesenchymal stem cells (PBMSCs) on implant stability; by assessing the bone
to implant contact (BIC) using resonance frequency analysis (RFA), insertion torque
and also to establish and correlate the same with implant stability quotient (ISQ). A
total of 15 patients with 30 sites ensuring a minimum of two dental implants
adjacently placed in an edentulous area; with the age group of 25–50 years of both
the sexes were categorized into Group 1 (dental implant with PRFM) and Group 2
(dental implant with PBMSCs embedded in PRFM). Insertion torque values at the
time of dental implant placement and ISQ using RFA was recorded at 1 week,
1 month, and 3 months post operatively. There was no significant difference
(p = 0.81) in Insertion torque values between both the groups (G1 and G2). Platelet
rich fibrin matrix along with PBMSCs enhanced implant stability as higher and
statistically significant ISQ values were noted at 1 week (p = 0.18), 1 month
(p ≤ 0.001), and 3 months (p ≤ 0.001) intervals in the G2 group. Platelet rich fibrin
matrix and PBMSCs showed promising results as a potential regenerative material
for increasing and enhancing BIC and hence implant stability.

KEYWORDS
dental implant, insertion torque, peripheral blood mesenchymal stem cells, platelet rich fibrin
matrix, resonance frequency analysis

1 | INTRODUCTION mechanically to the surrounding bone) and secondary implant sta-

bility (a biological process involving the remodeling and regeneration
Osseointegration is crucial for the success of dental implants as of bone) are imperative to implant integration (Javed et al., 2013).
implant integration is critical for any type of implant procedure to Discomfort, inconvenience and anxiety are the challenges faced

-
succeed as it denotes a standard measurement of implant stability by both clinicians as well as the patients in the waiting period in
(Goutam et al., 2013). The two terms primary (implant engaging 2‐stage surgical protocol which is generally a minimum of

422 J Tissue Eng Regen Med. 2022;16:422–430. wileyonlinelibrary.com/journal/term © 2022 John Wiley & Sons Ltd.
SINGHAL ET AL.
- 423

3–6 months so as to not to disturb the implant site for achieving
adequate stability (Kim & Park, 2009). Though osseointegration and
specifically the primary stability are affected because of various
factors such as bone quality, density, surgical technique, implant
characteristics etc; studies have long been focused on improving and
shortening the time (6–8 weeks) taken for osseointegration by
modifying the surface properties (macro, micro, and nano level) of
dental implants. Alterations in the designs and surface topography of
implants by mechanical, chemical and physical alterations such as
machining, plasma spray coating, grit blasting, acid etching, sand
blasted and acid etching, and biomimetic coating have led to changes
in surface chemistry, and thereby contributed to increased bone‐to‐
implant contact (BIC), primary stability, osteogenesis and faster
healing (Hong & Oh, 2017). However this has led to increased surface
roughness leading to excessive biofilm accumulation and peri‐
implantitis (Kligman et al., 2021). Hence there has been an aligned
focus on the application of bioactive materials like growth factors,
regenerative materials or molecules to the implant surface as a
parallel approach to enhance BIC (Lynch, 1994; Oncu & Alaaddino-
glu, 2015). Experimental studies have shown that titanium implant
surfaces coated with cell adhesion molecules or bone morphogenetic
proteins and newer applications of materials like growth factors,
mesenchymal stem cells and platelet concentrates (PCs) could
increase osteoblastic differentiation and integration (Oncu &
Alaaddinoglu, 2015; Qu et al., 2021; Smeets et al., 2016).
Advancement and ease of procurement of PCs has led to the
evolution of various techniques and products with diverse biology,
potential applications and its effectiveness in significantly improving
the implant stability in the short term (Dohan Ehrenfest et al., 2009;
Malathi et al., 2013; Qu et al., 2021).
Platelet rich fibrin matrix (PRFM) is one such variant of PC
procured, without using any exogenous thrombin by a two‐step
centrifugation technique. This technique ensures the isolation and
preservation of platelets. This allows for a sustained and effective
release of growth factors in a temporal and spatial manner into the
wound site (Carroll et al., 2006). On the other hand, peripheral blood
mesenchymal stem cells (PBMSCs) has gathered increasing research
interest because they show identical biological characteristics as that
of bone marrow derived mesenchymal stem cells with an added
convenience of procuring without the need of aspiration from bone
marrow of the patient, which could cause morbidity and pain of the
donor sites (Zheng et al., 2015). Peripheral blood mesenchymal stem
cells could be procured and expanded to adequate numbers, main-
conducted to evaluate the potential of this novel material that is,
PRFM and PBMSCs in combination, or PRFM alone. Hence, the aim
of this study is to evaluate PRFM and PBMSCs as potential novel
autologous materials in enhancing BIC and thereby increasing
implant stability in the early healing phase.
2 | MATERIALS AND METHOD
2.1 | Source of data
The participants for this study were enrolled from the department of
periodontics, KLE Society's Institute of Dental Sciences and Hospital,
Bangalore, Karnataka. Fifteen patients with 30 sites, aged between
25 and 50 years (39.4 � 6.6; five females and 10 males; Table 1)
ensuring a minimum of two dental implants adjacently placed in an
edentulous area were inducted into the study by random method of
sampling (Figure 1). A written consent was taken from the subjects
after informing them that their participation was purely voluntary.
Clearance for the study was obtained from the institutional ethics
committee ((K.L.E Dental College [KLEDC]/institutional ethics com-
mittee [IEC]/16‐2017/) and conducted in accordance with the
Helsinki Declaration of 1975 as revised in 2013. This clinical trial was
conducted from November 2017 to October 2018 and registered
with U.S. National Institutes of Health Clinical Trials Registry (Reg-
ister No—NCT03044119).
2.2 | Selection criteria
2.2.1 | Inclusion criteria
Patients should have had extractions at least 6 months prior to the
study. Radiographic assessment (Intraoral direct digital periapical
radiovisiograph [RVG‐Suni Medical Imaging, Apteryx Inc.] and cone
beam computed tomography) indicating sufficient residual bone
volume of the site where two or more implants of diameter ≥3.5 mm
and length of 11.0 mm can be placed adjacent to each other.
TABLE 1 Age and gender distribution among study subjects
Variables Category n %
Age <30 years 5 33.3%

taining their osteogenic capacity in a clinically acceptable set up and 31–40 years 6 40.0%
period. 41–50 years 4 26.7%
The above background and studies suggesting promising results
Mean SD
with bioactive modification of implant surfaces by addition of
autologous regenerative materials led to the idea of increasing the Mean & SD 39.4 6.6

BIC and thereby reducing the time frame for achieving primary Range 25–50 years
implant stability by modifying the surface with the innovative com- Sex Males 10 66.7%
bination of materials in the present study. Search in literature does
Females 5 33.3%
not provide any evidence of a human clinical trial that has been
424
- SINGHAL
FIGURE 1 Consort flowchart
2.2.2 | Exclusion criteria
Patients under bisphosphonates, corticosteroid therapy, chemo-
therapy, localized radiotherapy of the oral cavity were not included.
Patients with poor oral hygiene and para‐functional habits were
excluded. Patients with mucocutaneous lesions or diseases, immu-
nosuppression, liver, blood, and/or kidney diseases, or any systemic
diseases who have been contraindicated for any surgical procedures
were not included. Patients consuming excessive alcohol and/or who
smoke >10 cigarettes per day were excluded from the study.
2.3 | Study design
This study was a single centered randomized controlled clinical trial
incorporating an edentulous area ensuring a minimum of two dental
implants placed adjacent in situ with a follow up period of 3 months. A
thorough dental and medical history was recorded. Patients were
advised to get a routine hemogram and radiographic imaging (intra oral
peri‐apical [IOPA]/Orthopantomagram [OPG]/cone beam computed
tomography [CBCT]/RVG) of the area of interest to receive two or
more adjacent implants. After analyzing the CBCT, the bone quality
was assessed and classified according to Lekholm and Zarb (1985).
2.3.1 | Initial therapy (pre‐surgical procedure)
All selected patients, following an initial examination and discussion
of treatment plan were given detailed instructions regarding plaque
ET AL.
control measures and received preliminary periodontal therapy
comprising of scaling as well as root planing (SRP). Occlusal adjust-
ment was done in areas indicated. Oral hygiene and tissue response
were re‐evaluated at 4–6 weeks following SRP.
2.4 | Allocation and randomization
Patients who fulfilled all the criteria were included into the surgical
phase of therapy. The recruiter (Neha Pradhan) not involved in the
treatment aspect of the study, through computer tabulation method
generated and randomly assigned the selected sites (an edentulous
area ensuring a minimum of two dental implants placed adjacent in
situ) into (G1)—Dental implant with PRFM and (G2)—Dental implant
with PBMSCs embedded in PRFM (Supercell). The data generated
was securely enclosed in envelopes and was disclosed to the operator
(Laveena Singhal) just before the surgery. The operator knew the
treatment procedure whereas the patients and the investigator
(Sphoorthi Anup Belludi) were blinded for the same.
2.5 | Surgical procedure
Two grams of amoxicillin was given 1 h prior to the procedure
(Esposito et al., 2013). Two percantage of Xylocaine HCl with
adrenaline (1: 80,000; Indoco remedies LTD) was administered to
anesthetize the operative site. A crestal incision was made, and a
mucoperiosteal flap elevated after adequate anesthesia was ach-
ieved. Implant osteotomies were prepared according to the
SINGHAL ET AL.
- 425

recommendations of the Ankylos implant system (Ankylos implant
system, Nobel Biocare Select Replace). Implant osteotomy in-
corporates series of drilling into the underlying bone. A small round
bur is used to mark the implant site to a depth of 1–2 mm. A small
twist drill usually 2 mm diameter at a speed of 800–1200 rpm with
copious irrigation is used to establish the depth and align the long
axis of the recipient site. Followed by series of drills to systematically
widen the size and a final drill to accommodate the selected size of
implants (Venkatakrishnan et al., 2017). The implant platform was
positioned 1.5 mm apical to the crest of the alveolar bone. The sur-
gical site was thoroughly irrigated with normal saline.
2.6 | Fabrication of PBMSCs embedded in PRFM
(supercell) and PRFM
Patient's blood of 9 ml by the standard phlebotomy procedure was
drawn into the Merisis supercell (DiponEd Biointelligence Limited
Liability Partnership [LLP]) tube and spun in the centrifuge (REMI‐8C,
REMI) for 6 min at 3400 rpm to separate the blood into PBMSC
suspension and supernatant plasma. Post centrifugation, 0.5–1 ml of
stem cells present above the gel was separated and transferred to
another vial for further use. At this point, either 8 ml of patients'
blood was aspirated and combined with the previously prepared 1 ml
of stem cells or 9 ml of patients' blood without combining with the
PBMSC was transferred into the Merisis PRFM tube (DiponEd Bio-
intelligence LLP) and spun for 5 min at 3400 rpm to procure supercell
and PRFM, respectively. Supercell was formed due to the subsequent
fibrin polymerization (Figure 2).
Platelet rich fibrin matrix was placed in one implant osteotomy
site (G1) and PBMSCs embedded in PRFM was placed in the other
implant osteotomy site (G2), following which the implants were
inserted (Figure 3).
Insertion torque values (ITV) were recorded during placement of
the implants. The implant was torqued into the prepared osteotomy
site by increasing the torque by 5 Ncm incrementally till the implant

F I G U R E 2 (a) Meresis stem cell tube. (b) Withdrawal of 9 ml of venous blood. (c) 9ml of blood transferred to stem cell tube. (d) Stem cell
tube spun for 6 min at 3400 rpm. (e) 0.5–1 ml of stem cells obtained above separator gel. (f) 1ml of stem cells is transferred into platelet rich
fibrin matrix (PRFM) kit. (g) 8ml of blood is drawn again and mixed with 1 ml of stem cells prepared previously. (h) Supercell (peripheral blood
mesenchymal stem cell [PBMSC] and PRFM) obtained [Colour figure can be viewed at wileyonlinelibrary.com]
426
- SINGHAL ET AL.

F I G U R E 3 (a) Flap reflection. (b) Placement of platelet rich fibrin matrix (PRFM) followed by dental implant insertion (G1). (c) Placement of
Supercell followed by dental implant insertion (G2). (d) Recording of implant stability quotient (ISQ) values at 1 week, 1 month and 3 months
using resonance frequency analysis (RFA). (e) Postoperative view after 1 month of implant placement [Colour figure can be viewed at
wileyonlinelibrary.com]

was completely inserted into the bone. The torque that was obtained
when the implant was completely inserted into the prepared site was
the maximum insertion torque which was noted as ITV. Mucoper-
iosteal flaps were brought into their original positions. Healing caps
were left uncovered and flaps were sutured with 4‐0 vicryl sutures.
Following the surgery, patients were advised to apply cold
compresses to decrease edema. Medications prescribed for post-
surgical use by the patients included antibiotics (Amoxicillin 500 mg
three times per day for 5 days) and analgesic (Ibuprofen 400 mg
three times per day; Karaky et al., 2011) Antiseptic oral rinse (0.2%
chlorhexidine gluconate mouthwash two times per day) was advised
for a week (Abraham et al., 2015).
Every patient was provided with written post‐operative in-
structions along with verbal instructions.
2.7 | Post‐surgical procedure
the ISQ instrument and a SmartPeg, which is a metallic rod with a
small magnet on top of it, which can be screwed to the implant or
abutment. The transducer probe was held so that the probe tip was
aimed at the small magnet on the top of the SmartPeg at a distance of
2–3 mm. The probe was held still during the pulsing time until the
instrument beeped and displayed ISQ value.
2.8 | Calibration of the study examiner
A single therapist (Laveena Singhal) performed all the procedures
was not blinded. The other examiners (blinded) recorded all the
clinical measurements (Sphoorthi Anup Belludi and Supriya Manvi).
Intra‐examiner consistency was assessed using the intra‐class cor-
relation coefficient (ICC). It was found that the level of agreement
was high (ICC = 0.9).

One week following surgery, the periodontal dressing and sutures
were removed and the area was irrigated thoroughly with saline. The
patient was inquired about symptoms of pain and discomfort. Implant
stability quotient (ISQ) using resonance frequency analysis (RFA)
with the help of osstell device (Osstell AB) were analyzed at 1 week,
1 month and 3 months post operatively. The magnetic resonance
analyzer used in this study consists of a probe that is connected to
2.9 | Statistical analysis
The sample size has been estimated using statistical software (GPo-
wer software v. 3.1.9.2. Heinrich‐Heine University) considering the
effect size to be measured (f) at 25% (dz) at 80% for two‐tailed hy-
pothesis (Based on the results from previous literature by Oncu &
Alaaddinoglu, 2015), power of the study at 80% and the margin of the
SINGHAL ET AL.
- 427

alpha error at 5%, the total sample size needed was 30. Each study
group will comprise of 15 samples (15 samples � 2 groups = 30
samples).
For intergroup comparison (comparison between G1 and G2
groups) student paired ‘t’ test was used to determine whether there
was a statistical difference between two groups in the parameters
measured. Based on the difference in means from baseline values,
analysis of the treatment effects was carried out. Significance of
differences was evaluated by this statistical method and p
values < 0.05 were considered significant.
For intra‐group comparison (comparison of 1 week to 1 month
and 3 months values) repeated measures of ANOVA with a Bonfer-
roni correction: to determine if the parameters in the group differed
at different time points and post hoc tests for pairwise comparison
were used.
3 | RESULTS
Forty‐three subjects were assessed for eligibility. Of which 15 patients
diagnosed with an edentulous area allowing for the placement of a
minimum of two adjacent dental implants, contributing to 30 sites and
meeting the inclusion criteria were enrolled (Figure 1) for the study by
random sampling method. Table 2 depicts the distribution of implant
placement in accordance to classification of bone quality.
3.2 | Resonance frequency analysis (RFA)
Implant stability quotient values were recorded at 1 week, 1 month
and 3 months after the implant placement in both G1 and G2. At the
end of first week after implant placement, the mean ISQ of G1 was
77.60 � 2.35 and the mean ISQ was 78 � 2.10 in the G2 group. These
results showed a statistically non‐significant difference (p = 0.18) in
the ISQ values between the two groups (G1 and G2) at 1 week. The
mean ISQ values at the end of 1 month were 75.80 � 3.12 and
78.47 � 2.00 for G1 and G2 groups respectively, showing a statistical
significance (p ≤ 0.001) with significantly higher values in the G2
group. At the end of 3 months, the mean ISQ values were
74.60 � 2.95 in G1 group and 79 � 2.07 in G2 group, showing a
statistically significant difference (p ≤ 0.001) between the groups
(Table 4).
The mean ISQs in G1 group decreased by 1.8 units at the end of
1 month and further decreased by 1.2 units at the end of 3 months.
There was a reduction of 3 units between the end of 1 week and the
end of 3 months in G1 group. The difference in the values was sta-
tistically significant (Table 4).
The mean ISQs increased steadily in the G2 group (Table 4).
There was an increase by 0.47 units at the end of 1 month and
further increase of 0.53 units at the end of 3 months. There was
statistically significant difference in the mean values at the end of
3 months and 1 week in G2 group (p ≤ 0.001; Table 4).

3.1 | Analysis of parameters: Insertion torque value 3.3 | Correlation between ITV and ISQ values
(ITV)
The relation of ITV and ISQ values were calculated by the Pearson
The ITV was recorded at the time of dental implant placement for correlation. It was found to be negative and statistically insignificant
both the groups. The mean ITV of the implants were 42 � 8.19 Ncm in both the groups (Table 5).
for G1 group and 41.67 � 7.48 Ncm for G2 group. There was no
significant difference (p = 0.81) between groups in ITV (Table 3).
4 | DISCUSSION
T A B L E 2 Distribution of implants according to bone quality
(Lekholm & Zarb, 1985) The level of primary stability achieved during implant loading de-
pends on various factors such as bone quality, density, surgical
Bone quality No. %
technique and macro and micro characteristics of implant (Javed &
Type 1 4 13.4
Romanos, 2010). It has always been a challenge for the implantolo-
Type 2 18 60.0 gists to achieve an early osseointegration, adequate primary stability
Type 3 8 26.6 with shorter healing periods and early loading of implants. Recent

Type 4 0 0 trends focus toward the principles of tissue engineering and hence
osseoinductive materials are the need of the hour to achieve this
Total 30 100.0
goal. On these grounds, PRFM is a biologic autologous material

TABLE 3 Comparison of mean insertion torque values (ITV) between Group 1 and Group 2 using student paired t‐test

95% CI

Groups N Mean SD Mean diff t Lower Upper p‐value

Group 1 15 42.00 8.19 0.33 0.25 −2.53 3.19 0.81

Group 2 15 41.67 7.48

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- SINGHAL ET AL.

T A B L E 4 Comparison of mean
95% CI
implant stability quotient (ISQ; by
Time Groups N Mean SD Mean diff Lower Upper t p‐value resonance frequency analysis [RFA])
values between Group 1 and Group 2 at
1 week Group 1 15 77.60 2.35 −0.40 −1.02 0.22 −1.382 0.18
different time intervals using student
Group 2 15 78.00 2.10 paired t‐test
1 month Group 1 15 75.80 3.12 −2.67 −3.93 −1.40 −4.513 <0.001*

Group 2 15 78.47 2.00

3 months Group 1 15 74.60 2.95 −4.40 −5.60 −3.20 −7.872 <0.001*

Group 2 15 79.00 2.07

*—Statistically significant.

T A B L E 5 Comparison of mean implant stability quotient (ISQ; by resonance frequency analysis [RFA]) values between different time
intervals within Group 1 using repeated measures of ANOVA followed by Bonferroni's post hoc analysis

95% CI

Time N Mean SD Lower Upper F p‐valuea Sig. diff p‐valueb

1 week 15 77.60 2.35 76.30 78.90 29.077 <0.001* 1W versus 1M 0.003*

1 month 15 75.80 3.12 74.07 77.53 1W versus 3M <0.001*

3 months 15 74.60 2.95 72.97 76.23 1M versus 3M 0.005*

a
p‐value obtained by Greenhouse Geisser method of repeated measures of ANOVA.
b
p‐value obtained by Bonferroni's post hoc analysis.
*—Statistically significant.

procured from the whole blood without using any exogenous
thrombin by a two‐step centrifugation technique. In the preparation
of PRFM, the blood cell layer (white and red cells) is separated using
a patent thixotropic separator gel (Selphyl, Esthetic factors) from the
platelets and plasma. It is then the platelet rich plasma and platelet
poor plasma layers that are centrifuged, after re‐calcification in the
second faster and longer spin. The fibrin gets cross linked amid the
second spin, leading to the formation of a dense fibrin matrix, with a
presence of concentrated viable platelets (Simon et al., 2011). The
cross‐linking stabilizes the clot, prevents retraction, creating a con-
sistency that resists displacement, maintains space and thereby
inhibiting the soft tissue invasion. In our study, we have procured
PRFM as well as PBMSCs using the Meresis kit (DiponEd Bio-
intelligence LLP). The Meresis kit provided an advantage of procuring
PRFM with a single spin rather than centrifuging the blood twice.
This gave an edge over the conventional PRFM preparation as the
latter requires considerable time and effort. Likewise, PBMSCs were
also amassed and expanded to adequate numbers, maintaining their
osteogenic potential within a clinically favorable period (Belludi
et al., 2021).
The various properties and advantages of both these novel ma-
terials that is PBMSCs and PRFM and their promising results in the
field of regeneration, led to the present in vivo randomized controlled
clinical study which was conducted in an attempt to evaluate and
compare the effect of PRFM with and without PBMSCs on implant
stability. To the best of our knowledge this study is the first of its kind
to be conducted in the field of implantology. Fifteen patients, age
ranging from 25 to 50 years (39.4 � 6.6; five females and 10 males;
Table 1) who were identified with an edentulous area ensuring a
minimum of two dental implants placed adjacent in situ and thereby
30 sites were enrolled into the study by random sampling method.
This excludes the influence of different bone types (Chrcanovic
et al., 2017) and facilitates the interpretation of the trial by mini-
mizing the effect of inter‐bone variability within the groups (G1 and
G2). The bone quality around the adjacent implant site was estimated
and standardized using CBCT (Table 2). Patients with good systemic
health and no contraindication for periodontal surgery were selected,
to ensure a non‐compromised wound healing response (Whitman &
Berry, 1998).
Implant insertion torque is the maximum insertion torque
necessary to sink the implant into the prepared bone cavity which
should ideally range from 35 to 50 Ncm (Goswami et al., 2013). In the
present study, ITV was recorded at the time of dental implant
placement for both the groups (G1 and G2). The mean ITV of the
implants were 42 � 8.19 Ncm for G1 group and 41.67 � 7.48 Ncm
for G2 group. The result showed no significant difference (p = 0.81)
between groups in ITV which might be because of standardization of
the bone quality in the recipient adjacent sites (G1 and G2). The
result obtained in this study was in accordance with the results of the
study (Oncu & Alaaddinoglu, 2015).
In the current study, ISQ values were recorded at 1 week,
1 month and 3 months after the implant placement in both G1 and
G2 groups. Mean ISQ values steadily increased in G2 group
(Table 4), where both PRFM and PBMSCs were placed, while in
SINGHAL ET AL.
the G1 group, a decrease in ISQ values were seen between the
first week and the third month (Table 4). Usually, a decrease in
stability is observed during the first to sixth week period (Anitua
et al., 2008; Aparicio et al., 2006; Boronat et al., 2008; Simunek
et al., 2012) and similar results were seen in G1 group. The results
obtained in this study demonstrated that in G2 group where
PBMSCs were used; there was a steady rise in the ISQ values
(Table 4) during the recall periods. This may be associated to the
fact that PBMSCs embedded in PRFM enhanced BIC and thereby
increased and maintained the stability of the implants throughout
this crucial period. These results were in accordance with previous
studies demonstrating that osseoinductive materials increase the
implant stability over time (Barewal et al., 2003; Friberg
et al., 1999; O'Sullivan et al., 2000). However, the higher values of
ISQ showed better results in our study attributing to the
osseoinductive qualities and the addition of PBMSCs into PRFM.
There is a void in the literature about the relationship between
IT and RFA methods as IT is a measurement that can be performed at
only one time which (time of implant placement), while RFA can be
assessed in all the phases of implant (Kastala, 2008; Lages
et al., 2018). Although insertion torque and RFA, measured as ISQ,
are indicators of the stability of the implant, they do not measure or
reflect exactly the same mechanical conditions. Insertion torque
measures the mechanical frictional resistance of the bone bed to
apical implant advance, rotating about its longitudinal axis. Whereas
ISQ is based on the rigidity of an implant contact with its bed,
therefore its resistance to lateral displacement. Similarly in the pre-
sent study, the correlation in the ITV and ISQ values were negative
and statistically insignificant in both the groups (Table 5). Similar
results were found in the study (Brizuela‐Velasco et al., 2015;
Levin, 2016).
Some of the limitations of the study were that though the sample
size used in this study was within the range adopted by the vast
majority of clinical regenerative studies in humans, there is a scope to
reproduce the protocol of the present study with a larger sample size
to revalidate the present study findings. Owing to the limited sample
size, we accept the study lacks external validity or generalizability.
But, the future recommendations will always seek to revalidate the
present study findings with larger sample size to generalize the re-
sults to wider population.
Due to ethical restraints, surgical re‐entry and histologic inves-
tigation were not performed to assess the nature of the regenerated
bone. Gender of the patient was not taken into consideration, though
studies have shown that higher ISQ values were observed in females.
Within the scope and limitations of this study, improvement in
parameters was observed in both the groups. However, the G2 group
showed better results as compared to G1 group, which were statis-
tically significant.
In the light of the findings of this study, the null hypothesis
stating that, ‘there will not be any significant difference in implant
stability in the osteotomy site, G1 (Dental Implant + PRFM) in
comparison to the adjacent osteotomy site, G2 (Dental
Implant + PRFM + PBMSCs) has been rejected.
- 429
5 | CONCLUSION
Within the scope and limitations of the study it can be concluded that
although the present study showed that both the treatment modal-
ities (PRFM + PBMSC and PRFM alone with dental implants)
increased the implant stability, incorporation of PBMSCs into PRFM
demonstrated better results than PRFM alone (ISQ values were
significantly higher in G2 group with steady increase during the study
time period). Hence the added advantages of incorporating PBMSCs
into PRFM may prove this combination to be a better osseoinductive
material and can help in minimizing the loading time of an implant by
enhancing implant stability.
A C K NO W L E D G M EN T
This clinical study was partially funded by the Medical Education
Research trust (MERT). With regard to the novelty of the study the
funding was purely for academic purpose and the trust neither has
any conflict of interest nor do any of the authors have any com-
mercial relationship with the funding body.
C O NF L I CT O F I NT ER E S T
The authors have no conflict of interest to disclose.
A U T HO R C O NT R I B U TI O NS
Laveena Singhal performed the experiments and wrote the manu-
script. Sphoorthi Anup Belludi collected the data and designed and
wrote the manuscript. Neha Pradhan recruited the subjects for the
study and edited the manuscript. Supriya Manvi collected the data,
supervised and reviewed the manuscript.
D AT A A V A I L A B I L I T Y S T A T EM E N T
Research data are not shared.
ORCID
Sphoorthi Anup Belludi https://orcid.org/0000-0003-1148-7873
R EF E R E N CE S
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How to cite this article: Singhal, L., Belludi, S. A., Pradhan, N.,
& Manvi, S. (2022). A comparative evaluation of the effect
of platelet rich fibrin matrix with and without peripheral blood
mesenchymal stem cells on dental implant stability: A
randomized controlled clinical trial. Journal of Tissue
Engineering and Regenerative Medicine, 16(4), 422–430. https://
doi.org/10.1002/term.3290
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