Clinical application of platelet-rich fibrin to enhance dental implant stability: A systematic review and meta-analysis

doi:10.21203/rs.3.rs-1210665/v1

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Research Article

Clinical application of platelet-rich fibrin to enhance dental implant stability: A systematic review and meta-analysis

https://doi.org/10.21203/rs.3.rs-1210665/v1

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Background: Platelet-rich fibrin (PRF) is widely used in bone graft surgery; however, the effects of PRF on the increase in the implant site or postoperative bone mass and on the improvement in implant stability remain unclear and controversial. The present systematic review and meta-analysis were performed to assess whether PRF has a significant effect on the stability of dental implants after implant surgery.

Methods: Three databases, namely, PubMed, Embase, and China National Knowledge Infrastructure, were searched until December 31, 2020. The search terms “platelet-rich fibrin,” “dental implants,” “single-tooth,” “stability,” “implant stability quotient,” “alveolar bone regeneration,” “alveolar ridge augmentation,” “alveolar bone loss,” and “bone resorption” were used in combination to identify publications reporting data for dental implant stability related to the use of PRF. Fixed- or random-effects meta-analyses were used to pool the estimates of the mean differences with 95% confidence intervals.

Results: After screening based on the inclusion criteria, nine randomized controlled trials were included. Low heterogeneity was observed in study characteristics, outcome variables, and estimation scales (I² = 34%, P=0.15). The qualitative and meta-analysis results showed that PRF increased the effect of implant stabilizers after implant surgery regardless of implant site (upper or lower jaw). Application of a combination of PRF and biomaterials did not significantly increase the implant stability quotient compared with application of PRF alone.

Conclusions: The results of the present systematic review and meta-analysis suggest that PRF can increase implant stability after implant surgery regardless of whether the implant site is in the maxilla or mandible. PRF may also have a role in accelerating bone healing and tends to promote the formation of new bone at the implant site.

Registration: The review methodology was registered with PROSPERO (CRD42021230308).

dental implants

platelet-rich fibrin

implant stability

meta-analysis

Implant surgery is one of the most common surgeries performed by oral and maxillofacial surgeons. Dental implants are used to support fixed prostheses or removable overdentures for missing teeth. A successful implant is characterized by osseointegration, which is observed as close contact between the bone and the implant.¹ However, there is usually a loss of alveolar ridge height or width at the missing tooth sites, which influences implant osseointegration. Moreover, the quality of bone formation plays a key role in implant stability.² Studies have been conducted to enhance implant osseointegration by exploring implant designs, preservation of the host site, modification of surgical techniques or implant surface, loading time, and addition of bioactive materials into the prepared osteotomy site immediately before dental implant fixture insertion.^3-6 In various studies, the use of materials for guiding and promoting bone formation has been suggested as an effective means to enhance the bone quality and volume of implant sites.

A lack of bone in the edentulous alveolar ridge mainly results in increased challenges during dental implant treatments.^7-8 Various bone graft materials are used for ridge preservation and bone graft augmentation to maintain the bone volume of the edentulous alveolar ridge at the dental implant insertion site.⁹ The most popular materials are xenografts and autografts. Xenografts are subject to cellular rejection, which is similar to that observed with allografts that also possess the risk of disease transmission. Synthetic graft substitutes (e.g., β-calcium phosphate tribasic, deproteinized bovine bone mineral [DBBM], and bone morphogenetic proteins) differ in their osteoinductive or osteogenic properties and are associated with a range of bone formation rates. Moreover, some disadvantages, mainly related to a prolonged healing time and impact on immune responses, can occur when using these materials.¹⁰ The gold standard approach for bone grafting is harvesting autologous cortical and cancellous bones from the iliac crest.¹¹ However, autografts also present some disadvantages, such as limited sources, additional surgical trauma, postoperative pain, and complications, which limit the clinical applications of autologous bone.^12-13

To overcome these shortcomings, new materials with osteoinductive properties, such as bone morphogenetic proteins, concentrated growth factors (CGFs), and platelet-rich fibrin (PRF), have garnered great interest in the field of tissue engineering. PRF has been introduced as an additional or replacement material in bone augmentation procedures for guiding bone formation. PRF represents a novel strategy for concentrating platelets (preparation without thrombin), as described by Choukroun.¹⁴ In vitro studies have shown that PRF enhances cell proliferation, migration, adhesion, and osteogenic differentiation in a variety of cell types, along with cell signaling activation.¹⁵ Furthermore, PRF reduces inflammation, suppresses osteoclastogenesis, and increases the expression of various growth factors in mesenchymal cells.^16-17 In the field of otolaryngology, a study conducted by Huseyin et al. showed that better results were obtained with the effects of PRF on wound healing in terms of adhesion, infection, bleeding, granulation, and frontal ostium stenosis after endoscopic sinus surgery.¹⁸ In addition, Cieslik-Bielecka et al. introduced the potential application of PRF in esthetic plastic surgery and regenerative medicine for the skin.¹⁹ Although PRF is widely used in bone graft surgery, the effectiveness of PRF in increasing the implant site or postoperative bone mass and improving implant stability remains controversial.

In this study, we performed a meta-analysis of clinical standard randomized controlled trials (RCTs) using PRF in bone volume augmentation and dental implant surgeries to evaluate the application value of PRF with respect to bone mass increase, implant stability, and alveolar bone growth.

This study was performed in strict accordance with the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.²⁰In addition, the review methodology was registered with PROSPERO (CRD42021230308).

2.1 Search strategy and information sources

An electronic search of three databases (PubMed, Embase, and China National Knowledge Infrastructure [CNKI]) was performed. Articles published up to December 31, 2020, were considered. No time restrictions were applied during the search. However, only studies written in English or Chinese were included in the selection.

2.2 Search terms

The electronic search strategy included terms related to the intervention, and we used the following combination of keywords: “Platelet-rich fibrin (PRF)” AND “dental implants, single-tooth” OR “dental implants” OR “tooth implant” OR “stability” OR “implant stability quotient” OR “alveolar bone regeneration” OR “alveolar ridge augmentation” OR “alveolar bone loss” OR “bone resorption.” Cochrane search filters for RCTs were implemented; cohort trials were also included. Only human studies were included.

2.3 Eligibility criteria

RCTs, including parallel RCTs and split-mouth RCTs, with at least 10 patients/sites were considered for inclusion. Only approved RCTs that followed a reliable ethics committee guideline were included.

2.4 Exclusion criteria

In vitro and preclinical studies, cohort studies, case series, case studies, retrospective studies, RCTs involving less than 10 patients/sites, and studies that did not meet all inclusion criteria were excluded.

2.5 Study selection

The publication records and titles retrieved following electronic or manual searches were independently screened by two reviewers (GS and ZXK) based on the inclusion criteria. Discrepancies were resolved by consulting with a third reviewer (NCL). Cohen’s kappa coefficient was used as a measure of agreement between readers. Thereafter, full texts of the selected abstracts were obtained. If the full text was not available, then the author and journal editor were contacted to obtain the full text. Two reviewers independently performed the entire screening process. Articles that met the inclusion criteria were processed for data extraction.

2.6 Data extraction and quality assessment

Studies were classified according to study design and type of intervention. The outcomes were then compiled in tables. All extracted data were double-checked, and any questions that arose during the screening and data extraction were discussed between this study’s authors to reach a consensus. Two reviewers (GS and ZXK) independently evaluated the methodological quality of all the included studies using the Cochrane Collaboration tool for assessing the risk of bias in randomized trials. All included studies were checked for the following criteria: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcomes, incomplete outcome data, selective reporting, and other biases. Each study was classified into the following groups: low risk of bias, if all quality criteria were judged to be met; moderate risk of bias, if aspects of one or more of the key criteria mentioned above were unclear; and high risk of bias, if one or more key criteria aspects were not met.²¹

2.7 Statistical analysis

Statistical analysis was performed using Stata, version 16.0 (StataCorp LLC, College Station, TX, US). Split-mouth and parallel group studies were combined using the generic inverse variance option in the statistical software program. Heterogeneity was assessed using the I² statistic (a test for heterogeneity) at the level of p ≥ 0.10. If there was considerable or substantial heterogeneity (I²> 50%), then a random-effects model was adopted; otherwise, a fixed-effects model was used.²² Treatment effect results are presented as mean differences (MDs) with 95% confidence intervals (CIs). Statistical significance was calculated at p = 0.05 (two-tailed z tests). The relative influence of each study on the pooled estimate was assessed by sequentially excluding each study for sensitivity analysis. Publication bias was evaluated based on the visual inspection of the symmetry of the funnel plot and the results of Begg’s and Egger’s tests (P < 0.05 was considered to indicate statistical significance).²³

3.1 Literature search

The literature search identified 390 potential references in PubMed, 376 in Embase, and 71 in CNKI, of which 21 were eligible after screening of the title and abstract. Of the 21 full-text articles, 12 studies did not meet the inclusion criteria and were excluded (Table 1). Following selection according to our pre-established protocol, nine RCTs were included in the quantitative meta-analysis.^24-32 The details of the search procedure are presented in Figure 1.

3.2 Analysis of implant stability quotient heterogeneity and model analysis

The implant stability quotient (ISQ) was selected as an important parameter to evaluate the stability of implants in the nine studies (Table 2). We selected the ISQ data of the final experimental and control groups. The results of the heterogeneity test were I²= 34% (<50%) and p = 0.15 (>0.1), which suggested low heterogeneity among the selected studies. Therefore, a fixed-effects model was used for the meta-analysis. The variables of the studies were continuity variables; therefore, MDs were analyzed using the common-effect inverse-variance model. The MD of the nine studies was 1.857, and the 95% CI was 0.888–2.827 (z = 3.755, p < 0.05) (Figure 2). The results suggested that PRF had increased implant stability after implant surgery. To measure if the heterogeneity of the biomaterials used or location of implant sites would affect the overall effect, we performed subgroup analyses according to different biomaterials and implant sites.

3.3 Study of ISQ: analysis of biomaterial subgroup fixed-effects models

To measure whether the heterogeneity of the biomaterials placed in the control group would affect the results, we performed a subgroup analysis to determine whether the control group received a biomaterial, including Biomaterials (e.g., Bio-oss combined with PRF, DBBM combined with PRF, Bio-oss, and DBBM, named group 1) or not (blank; named group 0). In all included studies, PRF alone group was set to the experimental group.

We independently compared the implant sites in group 1 to those of group 0 (no PRF) to determine the effects of PRF application. There was low heterogeneity between the two groups. We found statistically significant differences in the implant stability in group 0 (I²= 34%, MD = 3.112, 95% CI 1.68–4.542, z = 4.268, p < 0.05) (Figure 3). The results suggested that compared with the blank group (no PRF), the “PRF alone” group had a significantly increased implant stability quotient after implant surgery.

In group 1, we found no significant difference in implant stability between the experimental group (PRF alone) and biomaterial control group (I²= 0%, MD = 0.788, 95% CI 0.532–2.107; z = 1.170, p > 0.05). The results suggested that the application of PRF combined with biomaterials or biomaterials alone did not significantly promote the ISQ when compared with PRF alone (Figure 3). However, we found that the variables of the experimental and control groups were not uniform, and in other previous studies, the measurement times differed between the two groups; therefore, their results were not reliable.

3.4 Study of ISQ: analysis of implant site subgroup using the fixed-effects model

Considering that differences in the implant sites may affect the postoperative ISQ, we then separately performed an analysis between the maxilla-mandibular group (named group 2) and the maxilla group (named group 3) according to the implant site in the trials. There was low heterogeneity between groups 2 and 3. We found significant differences in the implant stability in group 2 (I²= 35.6%, MD = 4.042, 95% CI 1.949–6.135; z = 3.785, p < 0.05). These results suggest that the placement of PRF can significantly improve the stability of implants, regardless of the implant site location in the upper and lower jaws. The results for the maxilla group indicate that PRF placement in the maxilla had an increased effect on the postoperative stability of the implant (I²= 0%, MD = 1.261, CI 0.167–2.355; z = 2.258, p < 0.05) (Figure 4).

3.5 Analysis of the proportion of newly formed bone

The studies presented high heterogeneity (I²= 95%). Therefore, this meta-analysis was not feasible to analyze the proportion of newly formed bone (Table 3) (Figure 5).

3.6 Migration analysis

We constructed funnel graphs to investigate whether there was publication offset in this study. The funnel plot of this study was performed as follows. The symmetry test of the abovementioned image was carried out (Figure 6). We measured p > 0.05 indicating that the funnel diagram was symmetrical, suggesting that there was no publication offset in this study (Figure 6a). Similarly, we used each subgroup for migration analysis and found p values of 0.806, 0.734, 0.308, and 1.000, respectively, which were all greater than 0.05, indicating that each funnel plot was symmetric and unbiased (Figure 6b-6e).

3.7 Sensitivity analysis

None of the nine articles significantly interfered the structure of the sensitivity meta-analysis. This indicates that our study has good stability (Figure 7).

3.8 Bias assessment

The nine studies were also assessed qualitatively using the tools recommended by the Cochrane Collaboration for the risk of bias. A graph and summary of the selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases identified in each study are presented in Figure 8a and b. With fewer than 10 studies, publication bias was not formally assessed because the power to detect publication bias was limited.

The present systematic review analyzed RCTs using PRF in implant dentistry, focusing on aspects including ISQ, implant sites, sinus floor augmentation, and biomaterial implants. The aim of the present study was to evaluate the current literature with regard to the clinical indications for PRF in increasing the stability of dental implants.³³

PRF has gained tremendous attention in recent years because of its capacity to successfully regenerate both soft and hard tissues, enhancing new blood vessels (angiogenesis) and tissue formation during healing.³⁴ In clinical applications, PRF has been used in the treatment of periodontal defects, sinus floor elevation, and preservation of the alveolar ridge after tooth extraction.^25-27,^{35, 36} Clinical studies have shown that PRF enhances osseointegration in the early phase³⁷ and increases the width of the keratinized mucosa around implants.³⁸ However, the clinical value of PRF placement in implant sites to improve the survival rate of dental implants remains unclear, especially when compared to the other types of implanted biomaterials. The objective of this systematic review and meta-analysis was to evaluate which indications of PRF have been shown to be effective in dental implant procedures. Mechanistically, previous studies have revealed the roles of PRF in providing biocompatible scaffolds, continuously releasing cytokines and growth factors, and containing beneficial cell populations for tissue formation and osteogenesis.^{39, 40} PRF is a fibrin network containing nanoscale fibers that can act as a scaffold for cell proliferation, migration, and differentiation.⁴¹ PRF also acts as a drug delivery system for growth factors, leading to the promotion of neoangiogenesis.⁴² This may facilitate early bone-healing processes.

4.1 Implant Stability Quotient

Our results show that PRF is effective in improving the stability of dental implants.^24-32 Resonance frequency analysis (RFA) was used as the standard to measure implant stability in seven of the nine articles.^26-32 Meredith et al. first proposed RFA as for measuring implant stability.⁴³ RFA assesses implant stability as a function of the stiffness of the implant–bone interface and is affected by several factors.⁴⁴In their study, Elif et al. used RFA to evaluate implant stability. The average ISQ was calculated by measuring the resonance frequency measurements twice at the mesiodistal position and buccolingual position.³¹ Pichotano et al.’s results showed that the application of PRF at 3–4 months after implant placement significantly improved ISQ values compared to the control group.^24,^{26, 30} Elif and Tabrizi et al. found a significant increase in ISQ values in the PRF group 1 month after implantation.^27,³¹Four of the articles used different postoperative observation time points, but they finally reached a similar conclusion.^24,^{26, 27, 30} After meta-analysis, we found that PRF could promote stability and accelerate bone healing after implant surgery. The finding that compared with no intervention, the application of PRF alone led to an increased stability of implants was proved by the meta-analysis of five articles included.^{25, 27, 29-31} A previous study suggests that the stability of implants increases with healing time.²⁷In addition, PRF can be used for alveolar bone healing and the creation of an optimal epithelial wound healing microenvironment. and has a role similar to that of other biological materials in the promotion of bone healing. Several studies have shown that PRF can promote bone regeneration without complications.⁴⁰ The results of the present study, which relied on the evaluation of ISQ, showed higher implant stability in the PRF group, which demonstrated that PRF is beneficial for enhancing implant osseointegration.

PRF has been shown to promote osteogenic differentiation in bone marrow mesenchymal stem cells, human adipose-derived stem cells, and periodontal ligament stem cells.^45-47 Some cell signal channels are involved in the mechanisms of osteogenic differentiation.^48-50 Kargarpour et al. have found that PRF membranes can inhibit the formation of osteoclasts from hematopoietic progenitors in bone marrow cultures, suggesting that PRF suppresses osteoclastogenesis in vitro.¹⁷ Dental implant osseointegration results from functional coupling and equilibrium between osteoblasts and osteoclasts, as well as between bone tissue and the immune system.⁵¹Implant osseointegration is a dynamic process closely related to peri-implant osteoclasts and peri-implant osteoblasts.⁵² Therefore, local application of PRF in implant sites probably enhances implant osseointegration by playing a role in the functions of osteoblasts and osteoclasts through the cell signal channels involved in the osteogenic mechanism. By contrast, Pichotano et al. suggest that PRF has no effect on implant stability after implant surgery.^25,26 Both studies compared biomaterials, such as DBBM or allografts, to a combination of PRF and DBBM or PRF alone. All studies could be divided into two groups, namely, biomaterials and biomaterials combined with PRF, biomaterials and PRF, or PRF and blank, which could be the reason for the lack of significant differences.

4.2 Biomaterial subgroup

After platelet-rich plasma (PRP), PRF became a popular material for clinical applications in bone-preserving and augmentation surgeries. Various bone graft materials such as β-calcium phosphate tribasic and DBBM have also been commonly used to promote bone mass. As mentioned above, placing PRF in implant sites can significantly increase the ISQ after implant surgery compared with that in routine implant procedures. With the development and application of PRP, PRF, and CGFs, some researchers have explored the methods and mechanisms of bone healing acceleration and new bone formation by adding a combination of PRF and biomaterials. In the present study, four of the nine articles focused on whether PRF could promote bone formation or improve the efficiency of bone healing compared to biomaterials alone.^{24-26, 28} To analyze the potential effect of PRF on implant sites and the potential effect of other biomaterials, we extended our research further.

Four articles included biomaterial-subgroup analysis evaluating the stability of implants when a combination of PRF/PRF and biomaterials (e.g., Bio-oss and DBBM) was applied to implant sites, and the group that received biomaterials alone was used as a control group.^24-26,28 We failed to observe that the application of a combination of PRF and biomaterials can promote the ISQ when compared with the application of biomaterials alone. Considering the inconsistency in the variables of the experimental group and the control group, and the differences in the measurement times of some articles, the results were considered unreliable.

Previous studies drew different conclusions regarding the use of biomaterials for implant site preservation, sinus augmentation, and accelerated bone healing. Kasabah et al. showed that Bio-Oss increased the survival rate of maxillary implants and was a suitable material for sinus augmentation.⁵³ Zhao et al. showed that on-site preservation using DBBM provided no additional benefit in terms of post-extraction new bone formation in comparison with natural healing.⁵⁴ Although our study did not demonstrate any significant result, a combination of PRF and biomaterials seemed to accelerate bone formation compared to biomaterials alone. Pichotano et al. showed that the addition of leukocyte and platelet-rich fibrin (L-PRF) to DBBM into the maxillary sinus allowed earlier implant placement (4 months) with increased new bone formation compared to DBBM alone after 8 months of healing.²⁶ Xie et al. showed that injectable-platelet-rich fibrin is a safe and reliable material for sinus lifts and can effectively shorten the healing time and enhance osteogenesis.²⁴The effect of PRF on bone healing and bone formation requires further study.

Altogether, these results show that PRF alone may have a similar effect with that of other biomaterials. Although the statistical methods applied were insufficient and the sample size was small, the results suggest that the use of PRF alone could be a suitable clinical option in a range of implant surgeries in the future.

4.3 Implant site subgroup

The results of most studies showed a poorer clinical outcome of dental implants in the maxilla than in the mandible.⁵⁵ Schwartz-Arad et al. showed that the total 10-year cumulative oral implant survival rate was 95.4% (maxilla, 83.5%; mandible, 99.5%).^{56, 57}To study whether PRF plays a role in improving the clinical outcomes of dental implants in the maxilla, subgroup analysis was carried out to compare the ISQ between the maxilla and the mandible according to the implant site. Five of the nine studies reported the maxilla alone as the implant site.^24-28 The remaining four articles studied the maxilla and the mandible as the implant sites.^29-32 Our meta-analysis results showed that PRF placement can significantly improve implant stability regardless of the implant site, with no significant differences between the two subgroups. Öncü et al. and Tabrizi et al. measured the mean ISQ of the “PRF alone” group at the end of 4 weeks and found that PRF application increased implant stability during the early healing period.^25,29,30 This leads us to conclude that the application of PRF is beneficial for early bone integration, especially for maxillary implants. One limitation of the present study was the lack of long-term postoperative evaluation (evaluation after 1 year postoperatively). Further research on long-term implant retention is required.

4.4 Evaluation of newly-formed bone

Since clinical studies on the use of PRF in implant surgery are difficult to perform at the histological level, we found only two articles in the literature that evaluated the ratio of postoperative newly formed bone by measuring the new and old cross-sectional area of trabeculae with Masson trichrome staining.^25,26 Bone biopsies were collected during two-stage maxillary sinus augmentation and second surgeries for implant placement for histomorphometric evaluation in both studies. The presence of newly formed bone, residual graft particles, and connective tissue was then evaluated between the test groups (PRF or DBBM + PRF) and the control group. In Pichotano et al.’s clinical study, the percentage of newly formed bone was determined by histological evaluation in the test group (DBBM + PRF) and the control group (DBBM). The results showed that the amount of newly formed bone in the DBBM + L-PRF group was significantly higher than that in the control group.²⁶ By contrast, Olgun et al. showed that the rate of newly formed cancellous bone in the titanium-prepared platelet-rich fibrin group was higher than that in the allograft group, but this difference was not statistically significant.²⁵ The results of the two studies indicate that the application of PRF alone or in combination with DBBM was associated with positive clinical and histomorphometric results. PRF has been proven to be effective in accelerating the formation ratio of new bone in maxillary sinus augmentation.

Conversely, Knapen et al.’s study drew a contrasting conclusion. Their results showed that L-PRF does not improve the dynamics, mass, or quantity of bone in guided bone regeneration. They reported that further research considering critical-size defect models is necessary to confirm their findings.⁵⁸

Based on the histological evaluation, the application of PRF showed a tendency to promote the formation of new bone at the implant site, which warrants confirmation in further studies correcting the design of the clinical experiments and increasing the sample sizes.

Altogether, the results of this systematic review and meta-analysis suggest that PRF can increase implant stability after implant surgery regardless of whether the implant site is in the maxilla or the mandible. The application of PRF may accelerate the bone healing process compared with that of other biomaterials. Furthermore, PRF tends to promote the formation of new bone at the implant site. Additional research is warranted to further determine the role of PRF in increasing the rate of new bone formation.

CGF: concentrated growth factor

CI: confidence interval

CNKI: China National Knowledge Infrastructure

DBBM: deproteinized bovine bone mineral

ISQ: implant stability quotient

L-PRF: leukocyte and platelet-rich fibrin

MD: mean difference

PRF: platelet-rich fibrin

PRP: platelet-rich plasma

RCT: randomized controlled trial

RFA: resonance frequency analysis

Ethics approval and consent to participate: Not applicable

Consent for publication: Not applicable

Availability of data and materials: Not applicable

Competing interests: The authors declare no conflict of interest.

Funding: This study was supported by a grant-in-aid from The Natural Science Foundation of Hebei Province (No. H2020206387) and a grant-in-aid for Outstanding Clinical Medical Research from the Government of Hebei Province (No. 361029).

Authors’ contributions: Shuai Guan was responsible for drafting the article and performing statistical analyses. Xiangjun Li conceived the study concept and design of the article. Lei Yang provided guidance on statistical analyses and performed data interpretation. Jiuping Bai and Chunliu Ning analyzed the subgroup data. Tiepeng Xiao critically revised and approved the article. Xingkui Zhang assisted with data collection.

Acknowledgements: Not applicable

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Strauss F J , A Stähli, Gruber R . The use of platelet-rich fibrin to enhance the outcomes of implant therapy: A systematic review[J]. Clinical Oral Implants Research, 2018, 29:6-19. https://doi.org/10.1111/clr.13275
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Table 1. List of excluded full-text papers and reasons for exclusion following full‐text screening

Author and year	Reasons for exclusion
Warisara Ouyyamwongs(2019)	No control group
Temmerman, A(2018)	Not appropriate PRF protocol
Zia Arshad Khan(2017)	Not appropriate PRF protocol
Nejat Nizam(2017)	No control group
Julia Hehn(2016)	No control group
Andy Temmerman(2016)	Not appropriate ISQ
Mahmoud Moussa(2016)	Not appropriate ISQ
Boora, Priyanka(2015)	Not appropriate ISQ
Elton Carlos Pichotano(2018)	CASE Report
Nilüfer Bölükbaşı(2015)	Not appropriate ISQ
Volker Gassling(2013)	Not appropriate ISQ
Kanokporn Areewong DDS(2019)	Not appropriate ISQ

Table 2. Included studies: implant stability quotient (ISQ)

Study(year),

funding

Studydesign,

duration

No.of

patients(implants)

PRF

preparation

Group T:test

C:control

Outcome

R.Tabrizi(2018)

International Journal of Oral and Maxillofacial Surgery

RCT,

split‐mouth

6 weeks

20 (40implant)

2800 rpm for

12 min

Hardware

T:PRF

n=20

No PRF

n=20

At 2 weeks after insertion, the mean ISQ was 60.60 ± 3.42 in group 1 and 58.25± 3.64 in group 2. There was a statistically signifificant difference between the two groups (P = 0.04). At 4 weeks after insertion, the mean ISQ was 70.30± 3.36 in group 1 and 67.15 ±4.33 in group 2. Analysis of the data demonstrated a signifificant difference between the two groups at this time point (P = 0.014). The mean ISQ was 78.45 ±3.36 in group 1 and 76.15± 2.94 in group 2 at 6 weeks afterinsertion. Assessment of the data showed a signifificant difference between group 1 and group 2 at this time point (P = 0.027)

Elif Öncü(2017)

Periodontics

Restorative Dentistry

RCT,

split‐mouth

1 year

26 (60implant)

2700rpm for

12 min

Hardware

PRF membranes

T:PRFn=30

C:No

PRF n=30

T: t0:26.10±12.83 t1:54.39±15.88 t2:69.99±11.87 t3:71.19±10.31;

C: t0:24.61±11.97 t1:48.67±13.61 t2:61.03±12.02 t3:70.08±11.2

Elton Carlo Pichotano(2018)

Journal of Oral Implantology

RCT,

split‐mouth

8 months

12 (38implants)

10 min at 300g (3000 rpm)

T:PRF

n=19

C:No

PRF

N=19

Control group showed statistically higher ISQ values compared to the test group (75.13 ± 5.69; and 60.90 ± 9.35 for the control and test group, respectively). This outcome might be attributed to the difference in the healing time between both groups. According to a previous study,31 ISQ values after sinus augmentation utilizing L-PRF progressively increase over time, meaning that the time for implant healing play a crucial role for increased secondary implant stability. This was confirmed in our studies because the ISQ values at loading demonstrated a significant increase in the test group compared to the initial value immediately at implant placement (60.90 ± 9.35 and 76.08 ± 5.86).T:P=0.0014 C:P=0.9927

Elif Öncü(2015)

The International journal of oral & maxillofacial implants

RCT,

1 months

20 (64implants)

2700 rpm for

12 min

T:PRF

N=31

C:No

PRF N=33

T: t0:59.39±15.88 t1:69.29±10.51 t2:77.19±6.06

C: t0:62.67±13.61 t1:60.03±12.2 t2:70.49±7.74

P1=0.002

P2=0.001

XIE Hui(2018)

Shanghai Journal of Stomatology

RCT,

1 year

700 rpm for 3min

T: t0=50.68±5.17 t1=72.31±5.06

C: t0=72.31±5.06 t1=73.98±5.38

t0=4 months t1=6 months

P1=(P＜0.05)，P2=(P＞0.05)(4 months/6months)

C. Diana, S.Mohanty(2018)

International Journal of Oral and Maxillofacial Surgery

RCT,

1 year

29 (41 implant)

2700 rpm

for 12min

T:PRF

N=21

C:No

PRF

N=20

T: t0=56.58±18.81 t1:60.61±11.49

C: t0=71.32±7.82 t1:70.06±8.69

Ebru Olgun(2018)

Journal of Investigative and Clinical Dentistry

RCT,

6 months

18 (37implants)

2800rpm

for 12min

T:PRF

N=10

C:No PRF

N=8

T:68.50 ±8.87

C:66.37 ±8.31 P=0.611

Ali H. Abbas Alhussaini (2019)

The Journal of Craniofacial Surgery

RCT,

12 weeks

32(102implants)

3000 rpm

for 12 min

T:PRF

N=27

C:No PRF

N=51

No significant statistical difference existed in primary implant stability between the groups (P =0.054). An

improvement in implant stability was observed in the PRF group(ISQ=71.0±7.3) compared with control group(ISQ=67.2±8.2) 6 weeks after implant insertion. After 12 weeks, implant stability was further enhanced in the PRF group (ISQ=74.5±8.1) compared with control group(ISQ=70.8±8.3).

Romesh Soni(2020)

National Journal of Maxillofacial Surgery

RCT,

4 months

16(16implants)

1300 rpm for 8 min

T:PRF

N=8

C: No PRF

N=8

PRF membrane group’s average ISQ ranged from 38.5

to 61 (mean=43.06,SD=7.41) at baseline and ranged 66.5-71.5(mean=69.12,SD=1.78) at second-stage surgery.

Collagen membrane group’s average ISQ ranged from 34.5 to 40.5 (mean=41.68, SD=7.2) at baseline and ranged 65.5–71.5(mean=68.56,SD=1.52) at second‑stage surgery.

Note. RCT, randomized controlled clinical trial; SD, standard deviation; NR, not reported; w/wo, with or without; wo, without; SS, statistical significant difference; NS, no statistical difference; ISQ, Implant stability quotient

Table 3. Included studies: Proportion of newly formed bone

Study(year),

funding

Study design,

duration

No. of patients

(implants)

Mean age ± SD and/or range

PRF preparation

GroupsT:test C:control

Outome

Ebru Olgun

(2018)

Journal of Investigative and Clinical Dentistry

RCT,

6months

18(37implants)

T:51±7.94Years

C:53 ± 8.96

Years

2800rpm

for

12min

T:PRF

N=10

C:No PRF

N=8

Difference of proportion of newly formed bone: less difference in width from baseline in the PRF group (T: 17.28 (2.53)% C:16.58 (1.05)%; p=0.005)

Elton Carlos Pichotano(2018)

Journal of Oral Implantology

RCT，split‐mouth

8months

12(38implants)

mean age of 54.17 ± 6.95 years

10 min at 300g

(3000) rpm

T:PRF

n=19

C:No

PRF

N=19

T: 16.58 (1.05)%(2.35 ± 0.73) C:17.28 (2.53)% P=0.851

Note. RCT, randomized controlled clinical trial; SD, standard deviation; NR, not reported; w/wo, with or without; wo, without; SS, statistical significant difference; NS, no statistical difference

No competing interests reported.

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Clinical application of platelet-rich fibrin to enhance dental implant stability: A systematic review and meta-analysis

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