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 Abstract
2
Anandam ENT Head and Neck Super Technological advances in the field of implantology have led to the concept of
Speciality Centre, Siliguri, West Bengal, India
surface modifications to enhance implant stability by utilization of current concepts
3
Department of Implantology, KLE Society's
Institute of Dental Sciences, Bangalore, India
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
Correspondence
compare the effect of platelet rich fibrin matrix (PRFM) with and without peripheral
Sphoorthi Anup Belludi, KLE Society's
Institute of Dental Sciences, No. 20 blood mesenchymal stem cells (PBMSCs) on implant stability; by assessing the bone
Yeshwanthpur Suburb, II Stage, Tumkur Road, to implant contact (BIC) using resonance frequency analysis (RFA), insertion torque
Bangalore—560022, India.
Email: [email protected] 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
Funding information
adjacently placed in an edentulous area; with the age group of 25–50 years of both
Medical Education Research Trust, Bangalore
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 conducted to evaluate the potential of this novel material that is,
adequate stability (Kim & Park, 2009). Though osseointegration and PRFM and PBMSCs in combination, or PRFM alone. Hence, the aim
specifically the primary stability are affected because of various of this study is to evaluate PRFM and PBMSCs as potential novel
factors such as bone quality, density, surgical technique, implant autologous materials in enhancing BIC and thereby increasing
characteristics etc; studies have long been focused on improving and implant stability in the early healing phase.
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 2 | MATERIALS AND METHOD
implants by mechanical, chemical and physical alterations such as
machining, plasma spray coating, grit blasting, acid etching, sand 2.1 | Source of data
blasted and acid etching, and biomimetic coating have led to changes
in surface chemistry, and thereby contributed to increased bone‐to‐ The participants for this study were enrolled from the department of
implant contact (BIC), primary stability, osteogenesis and faster periodontics, KLE Society's Institute of Dental Sciences and Hospital,
healing (Hong & Oh, 2017). However this has led to increased surface Bangalore, Karnataka. Fifteen patients with 30 sites, aged between
roughness leading to excessive biofilm accumulation and peri‐ 25 and 50 years (39.4 � 6.6; five females and 10 males; Table 1)
implantitis (Kligman et al., 2021). Hence there has been an aligned ensuring a minimum of two dental implants adjacently placed in an
focus on the application of bioactive materials like growth factors, edentulous area were inducted into the study by random method of
regenerative materials or molecules to the implant surface as a sampling (Figure 1). A written consent was taken from the subjects
parallel approach to enhance BIC (Lynch, 1994; Oncu & Alaaddino- after informing them that their participation was purely voluntary.
glu, 2015). Experimental studies have shown that titanium implant Clearance for the study was obtained from the institutional ethics
surfaces coated with cell adhesion molecules or bone morphogenetic committee ((K.L.E Dental College [KLEDC]/institutional ethics com-
proteins and newer applications of materials like growth factors, mittee [IEC]/16‐2017/) and conducted in accordance with the
mesenchymal stem cells and platelet concentrates (PCs) could Helsinki Declaration of 1975 as revised in 2013. This clinical trial was
increase osteoblastic differentiation and integration (Oncu & conducted from November 2017 to October 2018 and registered
Alaaddinoglu, 2015; Qu et al., 2021; Smeets et al., 2016). with U.S. National Institutes of Health Clinical Trials Registry (Reg-
Advancement and ease of procurement of PCs has led to the ister No—NCT03044119).
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; 2.2 | Selection criteria
Malathi et al., 2013; Qu et al., 2021).
Platelet rich fibrin matrix (PRFM) is one such variant of PC 2.2.1 | Inclusion criteria
procured, without using any exogenous thrombin by a two‐step
centrifugation technique. This technique ensures the isolation and Patients should have had extractions at least 6 months prior to the
preservation of platelets. This allows for a sustained and effective study. Radiographic assessment (Intraoral direct digital periapical
release of growth factors in a temporal and spatial manner into the radiovisiograph [RVG‐Suni Medical Imaging, Apteryx Inc.] and cone
wound site (Carroll et al., 2006). On the other hand, peripheral blood beam computed tomography) indicating sufficient residual bone
mesenchymal stem cells (PBMSCs) has gathered increasing research volume of the site where two or more implants of diameter ≥3.5 mm
interest because they show identical biological characteristics as that and length of 11.0 mm can be placed adjacent to each other.
of bone marrow derived mesenchymal stem cells with an added
convenience of procuring without the need of aspiration from bone TABLE 1 Age and gender distribution among study subjects
marrow of the patient, which could cause morbidity and pain of the
Variables Category n %
donor sites (Zheng et al., 2015). Peripheral blood mesenchymal stem
cells could be procured and expanded to adequate numbers, main- 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 ET AL.

FIGURE 1 Consort flowchart

2.2.2 | Exclusion criteria control measures and received preliminary periodontal therapy
comprising of scaling as well as root planing (SRP). Occlusal adjust-
Patients under bisphosphonates, corticosteroid therapy, chemo- ment was done in areas indicated. Oral hygiene and tissue response
therapy, localized radiotherapy of the oral cavity were not included. were re‐evaluated at 4–6 weeks following SRP.
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 2.4 | Allocation and randomization
diseases who have been contraindicated for any surgical procedures
were not included. Patients consuming excessive alcohol and/or who Patients who fulfilled all the criteria were included into the surgical
smoke >10 cigarettes per day were excluded from the study. 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
2.3 | Study design area ensuring a minimum of two dental implants placed adjacent in
situ) into (G1)—Dental implant with PRFM and (G2)—Dental implant
This study was a single centered randomized controlled clinical trial with PBMSCs embedded in PRFM (Supercell). The data generated
incorporating an edentulous area ensuring a minimum of two dental was securely enclosed in envelopes and was disclosed to the operator
implants placed adjacent in situ with a follow up period of 3 months. A (Laveena Singhal) just before the surgery. The operator knew the
thorough dental and medical history was recorded. Patients were treatment procedure whereas the patients and the investigator
advised to get a routine hemogram and radiographic imaging (intra oral (Sphoorthi Anup Belludi) were blinded for the same.
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 2.5 | Surgical procedure
was assessed and classified according to Lekholm and Zarb (1985).
Two grams of amoxicillin was given 1 h prior to the procedure
(Esposito et al., 2013). Two percantage of Xylocaine HCl with
2.3.1 | Initial therapy (pre‐surgical procedure) adrenaline (1: 80,000; Indoco remedies LTD) was administered to
anesthetize the operative site. A crestal incision was made, and a
All selected patients, following an initial examination and discussion mucoperiosteal flap elevated after adequate anesthesia was ach-
of treatment plan were given detailed instructions regarding plaque ieved. Implant osteotomies were prepared according to the
SINGHAL ET AL.
- 425

recommendations of the Ankylos implant system (Ankylos implant Liability Partnership [LLP]) tube and spun in the centrifuge (REMI‐8C,
system, Nobel Biocare Select Replace). Implant osteotomy in- REMI) for 6 min at 3400 rpm to separate the blood into PBMSC
corporates series of drilling into the underlying bone. A small round suspension and supernatant plasma. Post centrifugation, 0.5–1 ml of
bur is used to mark the implant site to a depth of 1–2 mm. A small stem cells present above the gel was separated and transferred to
twist drill usually 2 mm diameter at a speed of 800–1200 rpm with another vial for further use. At this point, either 8 ml of patients'
copious irrigation is used to establish the depth and align the long blood was aspirated and combined with the previously prepared 1 ml
axis of the recipient site. Followed by series of drills to systematically of stem cells or 9 ml of patients' blood without combining with the
widen the size and a final drill to accommodate the selected size of PBMSC was transferred into the Merisis PRFM tube (DiponEd Bio-
implants (Venkatakrishnan et al., 2017). The implant platform was intelligence LLP) and spun for 5 min at 3400 rpm to procure supercell
positioned 1.5 mm apical to the crest of the alveolar bone. The sur- and PRFM, respectively. Supercell was formed due to the subsequent
gical site was thoroughly irrigated with normal saline. 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
2.6 | Fabrication of PBMSCs embedded in PRFM implant osteotomy site (G2), following which the implants were
(supercell) and PRFM inserted (Figure 3).
Insertion torque values (ITV) were recorded during placement of
Patient's blood of 9 ml by the standard phlebotomy procedure was the implants. The implant was torqued into the prepared osteotomy
drawn into the Merisis supercell (DiponEd Biointelligence Limited 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 the ISQ instrument and a SmartPeg, which is a metallic rod with a
when the implant was completely inserted into the prepared site was small magnet on top of it, which can be screwed to the implant or
the maximum insertion torque which was noted as ITV. Mucoper- abutment. The transducer probe was held so that the probe tip was
iosteal flaps were brought into their original positions. Healing caps aimed at the small magnet on the top of the SmartPeg at a distance of
were left uncovered and flaps were sutured with 4‐0 vicryl sutures. 2–3 mm. The probe was held still during the pulsing time until the
Following the surgery, patients were advised to apply cold instrument beeped and displayed ISQ value.
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 2.8 | Calibration of the study examiner
three times per day; Karaky et al., 2011) Antiseptic oral rinse (0.2%
chlorhexidine gluconate mouthwash two times per day) was advised A single therapist (Laveena Singhal) performed all the procedures
for a week (Abraham et al., 2015). was not blinded. The other examiners (blinded) recorded all the
Every patient was provided with written post‐operative in- clinical measurements (Sphoorthi Anup Belludi and Supriya Manvi).
structions along with verbal instructions. 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).
2.7 | Post‐surgical procedure

One week following surgery, the periodontal dressing and sutures 2.9 | Statistical analysis
were removed and the area was irrigated thoroughly with saline. The
patient was inquired about symptoms of pain and discomfort. Implant The sample size has been estimated using statistical software (GPo-
stability quotient (ISQ) using resonance frequency analysis (RFA) wer software v. 3.1.9.2. Heinrich‐Heine University) considering the
with the help of osstell device (Osstell AB) were analyzed at 1 week, effect size to be measured (f) at 25% (dz) at 80% for two‐tailed hy-
1 month and 3 months post operatively. The magnetic resonance pothesis (Based on the results from previous literature by Oncu &
analyzer used in this study consists of a probe that is connected to 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 3.2 | Resonance frequency analysis (RFA)
group will comprise of 15 samples (15 samples � 2 groups = 30
samples). Implant stability quotient values were recorded at 1 week, 1 month
For intergroup comparison (comparison between G1 and G2 and 3 months after the implant placement in both G1 and G2. At the
groups) student paired ‘t’ test was used to determine whether there end of first week after implant placement, the mean ISQ of G1 was
was a statistical difference between two groups in the parameters 77.60 � 2.35 and the mean ISQ was 78 � 2.10 in the G2 group. These
measured. Based on the difference in means from baseline values, results showed a statistically non‐significant difference (p = 0.18) in
analysis of the treatment effects was carried out. Significance of the ISQ values between the two groups (G1 and G2) at 1 week. The
differences was evaluated by this statistical method and p mean ISQ values at the end of 1 month were 75.80 � 3.12 and
values < 0.05 were considered significant. 78.47 � 2.00 for G1 and G2 groups respectively, showing a statistical
For intra‐group comparison (comparison of 1 week to 1 month significance (p ≤ 0.001) with significantly higher values in the G2
and 3 months values) repeated measures of ANOVA with a Bonfer- group. At the end of 3 months, the mean ISQ values were
roni correction: to determine if the parameters in the group differed 74.60 � 2.95 in G1 group and 79 � 2.07 in G2 group, showing a
at different time points and post hoc tests for pairwise comparison statistically significant difference (p ≤ 0.001) between the groups
were used. (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.
3 | RESULTS 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-
Forty‐three subjects were assessed for eligibility. Of which 15 patients tistically significant (Table 4).
diagnosed with an edentulous area allowing for the placement of a The mean ISQs increased steadily in the G2 group (Table 4).
minimum of two adjacent dental implants, contributing to 30 sites and There was an increase by 0.47 units at the end of 1 month and
meeting the inclusion criteria were enrolled (Figure 1) for the study by further increase of 0.53 units at the end of 3 months. There was
random sampling method. Table 2 depicts the distribution of implant statistically significant difference in the mean values at the end of
placement in accordance to classification of bone quality. 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

428
- 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 ranging from 25 to 50 years (39.4 � 6.6; five females and 10 males;
thrombin by a two‐step centrifugation technique. In the preparation Table 1) who were identified with an edentulous area ensuring a
of PRFM, the blood cell layer (white and red cells) is separated using minimum of two dental implants placed adjacent in situ and thereby
a patent thixotropic separator gel (Selphyl, Esthetic factors) from the 30 sites were enrolled into the study by random sampling method.
platelets and plasma. It is then the platelet rich plasma and platelet This excludes the influence of different bone types (Chrcanovic
poor plasma layers that are centrifuged, after re‐calcification in the et al., 2017) and facilitates the interpretation of the trial by mini-
second faster and longer spin. The fibrin gets cross linked amid the mizing the effect of inter‐bone variability within the groups (G1 and
second spin, leading to the formation of a dense fibrin matrix, with a G2). The bone quality around the adjacent implant site was estimated
presence of concentrated viable platelets (Simon et al., 2011). The and standardized using CBCT (Table 2). Patients with good systemic
cross‐linking stabilizes the clot, prevents retraction, creating a con- health and no contraindication for periodontal surgery were selected,
sistency that resists displacement, maintains space and thereby to ensure a non‐compromised wound healing response (Whitman &
inhibiting the soft tissue invasion. In our study, we have procured Berry, 1998).
PRFM as well as PBMSCs using the Meresis kit (DiponEd Bio- Implant insertion torque is the maximum insertion torque
intelligence LLP). The Meresis kit provided an advantage of procuring necessary to sink the implant into the prepared bone cavity which
PRFM with a single spin rather than centrifuging the blood twice. should ideally range from 35 to 50 Ncm (Goswami et al., 2013). In the
This gave an edge over the conventional PRFM preparation as the present study, ITV was recorded at the time of dental implant
latter requires considerable time and effort. Likewise, PBMSCs were placement for both the groups (G1 and G2). The mean ITV of the
also amassed and expanded to adequate numbers, maintaining their implants were 42 � 8.19 Ncm for G1 group and 41.67 � 7.48 Ncm
osteogenic potential within a clinically favorable period (Belludi for G2 group. The result showed no significant difference (p = 0.81)
et al., 2021). between groups in ITV which might be because of standardization of
The various properties and advantages of both these novel ma- the bone quality in the recipient adjacent sites (G1 and G2). The
terials that is PBMSCs and PRFM and their promising results in the result obtained in this study was in accordance with the results of the
field of regeneration, led to the present in vivo randomized controlled study (Oncu & Alaaddinoglu, 2015).
clinical study which was conducted in an attempt to evaluate and In the current study, ISQ values were recorded at 1 week,
compare the effect of PRFM with and without PBMSCs on implant 1 month and 3 months after the implant placement in both G1 and
stability. To the best of our knowledge this study is the first of its kind G2 groups. Mean ISQ values steadily increased in G2 group
to be conducted in the field of implantology. Fifteen patients, age (Table 4), where both PRFM and PBMSCs were placed, while in
SINGHAL ET AL.
- 429

the G1 group, a decrease in ISQ values were seen between the 5 | CONCLUSION
first week and the third month (Table 4). Usually, a decrease in
stability is observed during the first to sixth week period (Anitua Within the scope and limitations of the study it can be concluded that
et al., 2008; Aparicio et al., 2006; Boronat et al., 2008; Simunek although the present study showed that both the treatment modal-
et al., 2012) and similar results were seen in G1 group. The results ities (PRFM + PBMSC and PRFM alone with dental implants)
obtained in this study demonstrated that in G2 group where increased the implant stability, incorporation of PBMSCs into PRFM
PBMSCs were used; there was a steady rise in the ISQ values demonstrated better results than PRFM alone (ISQ values were
(Table 4) during the recall periods. This may be associated to the significantly higher in G2 group with steady increase during the study
fact that PBMSCs embedded in PRFM enhanced BIC and thereby time period). Hence the added advantages of incorporating PBMSCs
increased and maintained the stability of the implants throughout into PRFM may prove this combination to be a better osseoinductive
this crucial period. These results were in accordance with previous material and can help in minimizing the loading time of an implant by
studies demonstrating that osseoinductive materials increase the enhancing implant stability.
implant stability over time (Barewal et al., 2003; Friberg
et al., 1999; O'Sullivan et al., 2000). However, the higher values of A C K NO W L E D G M EN T
ISQ showed better results in our study attributing to the This clinical study was partially funded by the Medical Education
osseoinductive qualities and the addition of PBMSCs into PRFM. Research trust (MERT). With regard to the novelty of the study the
There is a void in the literature about the relationship between funding was purely for academic purpose and the trust neither has
IT and RFA methods as IT is a measurement that can be performed at any conflict of interest nor do any of the authors have any com-
only one time which (time of implant placement), while RFA can be mercial relationship with the funding body.
assessed in all the phases of implant (Kastala, 2008; Lages
et al., 2018). Although insertion torque and RFA, measured as ISQ, C O NF L I CT O F I NT ER E S T
are indicators of the stability of the implant, they do not measure or The authors have no conflict of interest to disclose.
reflect exactly the same mechanical conditions. Insertion torque
measures the mechanical frictional resistance of the bone bed to A U T HO R C O NT R I B U TI O NS
apical implant advance, rotating about its longitudinal axis. Whereas Laveena Singhal performed the experiments and wrote the manu-
ISQ is based on the rigidity of an implant contact with its bed, script. Sphoorthi Anup Belludi collected the data and designed and
therefore its resistance to lateral displacement. Similarly in the pre- wrote the manuscript. Neha Pradhan recruited the subjects for the
sent study, the correlation in the ITV and ISQ values were negative study and edited the manuscript. Supriya Manvi collected the data,
and statistically insignificant in both the groups (Table 5). Similar supervised and reviewed the manuscript.
results were found in the study (Brizuela‐Velasco et al., 2015;
Levin, 2016). D AT A A V A I L A B I L I T Y S T A T EM E N T
Some of the limitations of the study were that though the sample Research data are not shared.
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 ORCID
reproduce the protocol of the present study with a larger sample size Sphoorthi Anup Belludi https://orcid.org/0000-0003-1148-7873
to revalidate the present study findings. Owing to the limited sample
size, we accept the study lacks external validity or generalizability.
R EF E R E N CE S
But, the future recommendations will always seek to revalidate the
Abraham, H. M., Philip, J. M., Kruppa, J., Jain, A. R., & Krishnan, C. V.
present study findings with larger sample size to generalize the re- (2015). Use of chlorhexidine in implant dentistry. Biomedical and
sults to wider population. Pharmacology Journal, 8, 341–345.
Due to ethical restraints, surgical re‐entry and histologic inves- Anitua, E., Orive, G., Aguirre, J. J., Ardanza, B., & Andia, I. (2008). 5‐year
clinical experience with BTI dental implants: Risk factors for
tigation were not performed to assess the nature of the regenerated
implant failure. Journal of Clinical Periodontology, 35, 724–732.
bone. Gender of the patient was not taken into consideration, though https://doi.org/10.1111/j.1600‐051X.2008.01248.x
studies have shown that higher ISQ values were observed in females. Aparicio, C., Lang, N. P., & Rangert, B. (2006). Validity and clinical signif-
Within the scope and limitations of this study, improvement in icance of biomechanical testing of implant/bone interface. Clinical
Oral Implants Research, 17, 2–7. https://doi.org/10.1111/j.1600‐
parameters was observed in both the groups. However, the G2 group
0501.2006.01365.x
showed better results as compared to G1 group, which were statis-
Barewal, R. M., Oates, T. W., Meredith, N., & Cochran, D. L. (2003).
tically significant. Resonance frequency measurement of implant stability in vivo on
In the light of the findings of this study, the null hypothesis implants with a sandblasted and acid‐etched surface. The Interna-
stating that, ‘there will not be any significant difference in implant tional Journal of Oral & Maxillofacial Implants, 18, 641–651.
Belludi, S. A., Singhal, L., & Gubbala, M. (2021). Peripheral blood mesen-
stability in the osteotomy site, G1 (Dental Implant + PRFM) in
chymal stem cells and platelet rich fibrin matrix in the management
comparison to the adjacent osteotomy site, G2 (Dental of class II gingival recession: A case report. Journal of Dentistry, 22,
Implant + PRFM + PBMSCs) has been rejected. 67–70. https://doi.org/10.30476/DENTJODS.2020.81784.0
430
- SINGHAL ET AL.

Boronat, L. A., Balaguer, M. J., Lamas, P. J., Carrillo, G. C., & Penarrocha, torque and resonance frequency analysis: A systematic review.
D. M. (2008). Resonance frequency analysis of dental implant sta- Clinical Implant Dentistry and Related Research, 0, 26–33. https://doi.
bility during the healing period. Medicina Oral, Patologia Oral Cirugia org/10.1111/cid.12565
Bucal, 13(4), E244–E247. Lekholm, U., & Zarb, G. A. (1985). In P. I. Branemark, G. A. Zarb, &
Brizuela‐Velasco, A., Alvarez‐Arenal, A., Gil‐Mur, F. J., Herrero‐Climent, M., T. Albrektsson (Eds.), Patient selection and preparation. Tissue inte-
Chavarri‐Prado, D., Chento‐Valiente, Y., & Dieguez‐Pereira, M. grated prostheses: Osseointegration in clinical dentistry. Quintessence
(2015). Relationship between insertion torque and resonance fre- Publishing Company.
quency measurements, performed by resonance frequency analysis, in Levin, BP. (2016). The correlation between immediate implant insertion
micromobility of dental implants: An in vitro study. Implant Dentistry, torque and implant stability quotient. The International Journal of
24, 607–611. https://doi.org/10.1097/ID.0000000000000318 Periodontics and Restorative Dentistry, 36, 833–840. https://doi.org/
Carroll, R. J., Arnoczky, S. P., Graham, S., & O'Connell, S. M. (2006). 10.11607/prd.2865
Characterization of autologous growth factors in cascade platelet‐rich Lynch, SE. (1994). The role of growth factors in periodontal repair and
fibrin matrix (PRFM). Musculoskeletal Transplant Foundation. regeneration. In A. M. Polson (Ed.), Periodontal regeneration—current
Chrcanovic, B. R., Albrektsson, T., & Wennerberg, A. (2017). Bone quality status and directions (Vol. 24, pp. 179–198).
and quantity and dental implant failure: A systematic review and Malathi, K., Muthukumaraswamy, A., & Beri, S. (2013). Periodontal
meta‐analysis. The International Journal of Prosthodontics, 30, regeneration of an intrabony osseous defect with combination of
219–237. https://doi.org/10.11607/ijp.5142 platelet rich fibrin and bovine derived demineralized bone matrix: A
Dohan Ehrenfest, D. M., Rasmusson, L., & Albrektsson, T. (2009). Classi- case report. IOSR Journal of Dental and Medical Sciences, 4, 20–26.
fication of platelet concentrates: From pure platelet‐rich plasma (P‐ Oncu, E., & Alaaddinoglu, E. E. (2015). The effect of platelet‐rich fibrin on
PRP) to leucocyte‐ and platelet‐rich fibrin (L‐PRF). Trends in implant stability. The International Journal of Oral & Maxillofacial Im-
Biotechnology, 27, 158–167. https://doi.org/10.1016/j.tibtech.2008. plants, 30, 578–582. https://doi.org/10.11607/jomi.3897
11.009 O'Sullivan, D., Sennerby, L., & Meredith, N. (2000). Measurements
Esposito, M., Grusovin, M. G., & Worthington, H. V. (2013). Interventions comparing the initial stability of five designs of dental implants: A
for replacing missing teeth: Antibiotics at dental implant placement human cadaver study. Clinical Implant Dentistry, 2, 85–92. https://doi.
to prevent complications. Cochrane Database of Systematic Reviews, 7, org/10.1111/j.1708‐8208.2000.tb00110.x
CD004152. Qu, C., Luo, F., Hong, G., & Wan, Q. (2021). Effects of platelet concentrates
Friberg, B., Sennerby, L., Meredith, N., & Lekholm, U. (1999). A comparison on implant stability and marginal bone loss: A systematic review and
between cutting torque and resonance frequency measurements of meta‐analysis. BMC Oral Health, 21, 579. https://doi.org/10.1186/
maxillary implants: A 20‐month clinical study. International Journal of s12903‐021‐01929‐x
Oral and Maxillofacial Surgery, 28, 297–303. Simon, B. I., Gupta, P., & Tajbaksh, S. (2011). Quantitative evaluation of
Goswami, M. M., Kumar, M., Vats, A., & Bansal, A. S. (2013). Evaluation of extraction socket healing following the use of autologous platelet
dental implant insertion torque using a manual ratchet. Medical rich fibrin matrix in humans. The International Journal of Periodontics
Journal Armed Forces India, 71, 327–332. https://doi.org/10.1016/j. and Restorative Dentistry, 31, 285–295.
mjafi.2013.07.010 Simunek, A., Kopecka, D., Brazda, T., Strnad, I., Capek, L., & Slezak, R.
Goutam, M., Chandu, G. S., Mishra, S. K., Singh, M., & Tomar, B. S. (2013). (2012). Development of implant stability during early healing of
Factors affecting osseointegration: A literature review. Journal of immediately loaded implants. The International Journal of Oral &
Orofacial Research, 3, 197–201. https://doi.org/10.5005/jp‐journals‐ Maxillofacial Implants, 27, 619–627.
10026‐1095 Smeets, R., Stadlinger, B., Schwarz, F., Beck‐Broichsitter, B., Jung, O.,
Hong, D. G. K., & Oh, J. H. (2017). Recent advances in dental implants. Precht, C., Kloss, F., Gröbe, A., Heiland, M., & Ebker, T. (2016).
Maxillofacial Plastic and Reconstructive Surgery, 39, 33–40. https://doi. Impact of dental implant surface modifications on osseointegration.
org/10.1186/s40902‐017‐0132‐2 BioMed Research International, 2016, 6285620. https://doi.org/10.
Javed, F., Ahmed, H. B., Crespi, R., & Romanos, G. E. (2013). Role of primary 1155/2016/6285620
stability for successful osseointegration of dental implants: Factors of Venkatakrishnan, C. J., Bhuminathan, S., & Chandran, C. R. (2017). Implant
influence and evaluation. Interventional Medicine and Applied Science, 5, insertion torque load analysis for mandible using CBCT images.
162–167. https://doi.org/10.1556/IMAS.5.2013.4.3 World Journal of Dentistry, 8, 183–189.
Javed, F., & Romanos, G. E. (2010). The role of primary stability for suc- Whitman, D. H., & Berry, R. L. (1998). A technique for improving the
cessful immediate loading of dental implants: A literature review. handling of particulate cancellous bone and marrow grafts using
Journal of Dentistry, 38, 612–620. https://doi.org/10.1016/j.jdent. platelet gel. Journal of Oral and Maxillofacial Surgery, 56, 1217–1218.
2010.05.013 https://doi.org/10.1016/s0278‐2391(98)90776‐5
Karaky, A. E., Sawair, F. A., Al‐Karadsheh, O. A., Eimar, H. A., Algarugly, Zheng, R. C., Park, Y. K., Kim, S. K., Cho, J., Heo, S. J., Koak, J. Y., Lee, S. J., Park,
S. A., & Baqain, Z. H. (2011). Antibiotic prophylaxis and early dental J. M., Lee, J. H., & Kim, J. H. (2015). Bone regeneration of blood‐derived
implant failure: A quasi‐random controlled clinical trial. European stem cells within dental implants. Journal of Dental Research, 94,
Journal of Oral Implantology, 4, 31–38. 1318–1325. https://doi.org/10.1177/0022034515590368
Kastala, V. H. (2008). Methods to measure implant stability. Journal of
Dental Implants, 8, 3–8.
Kim, D. S., Kim, D. G., Park, C.‐J., & Cho, L.‐R. (2009). Histomorphometry How to cite this article: Singhal, L., Belludi, S. A., Pradhan, N.,
and stability analysis of early loaded implants with two different
& Manvi, S. (2022). A comparative evaluation of the effect
surface conditions in beagle dogs. Journal of Advanced Prosthodontics,
1, 10–18. https://doi.org/10.4047/jap.2009.1.1.10 of platelet rich fibrin matrix with and without peripheral blood
Kligman, S., Ren, Z., Chung, C. H., Perillo, M. A., Chang, Y.‐C., Koo, H., mesenchymal stem cells on dental implant stability: A
Zheng, Z., & Li, C. (2021). Modifications on osseointegration and randomized controlled clinical trial. Journal of Tissue
biofilm formation. Journal of Clinical Medicine, 10, 1641. https://doi.
Engineering and Regenerative Medicine, 16(4), 422–430. https://
org/10.3390/jcm10081641
Lages, F. S., Douglas‐de Oliveira, D. W., & Costa, F. O. (2018). Relationship doi.org/10.1002/term.3290
between implant stability measurements obtained by insertion
Copyright of Journal of Tissue Engineering & Regenerative Medicine is the property of John
Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to
a listserv without the copyright holder's express written permission. However, users may
print, download, or email articles for individual use.