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.44 In 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, 31 Four 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.27 In 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.51 Implant 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.24 The 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.