Implants with or without Leukocyte- and Platelet-Rich Fibrin (L-PRF): A Systematic Review on Dental Implant Stability

Abstract

Background

To examine the impact of applying leukocyte- and platelet-rich fibrin (L-PRF) on the stability of dental implants using implant stability quotient (ISQ) measurements.

Methods

A systematic search of the main databases was conducted to source the literature. Studies that met the established inclusion and exclusion criteria were selected for this review. The focus was solely on randomized controlled trials (RCTs) and controlled clinical trials (CCTs).

Results

After conducting a comprehensive search, a total of 1984 studies were identified. Following evaluation based on our inclusion and exclusion criteria, a refined selection of 7 studies was chosen for detailed review in this analysis.

Conclusions

Our findings indicate that the use of leukocyte- and platelet-rich fibrin (L-PRF) may enhance the stability of implants following surgical procedures. This suggests that L-PRF may accelerate the healing process, reduce the loading time, and improve outcomes for patients undergoing implant surgery, potentially reducing the risk of implant failures and complications.

Background

Within the field of platelet concentrates, a variety of methodologies are implemented, yielding distinct products characterized by unique attributes. These products can be categorized into four primary classes of platelet derivatives, delineated by their leukocyte content and fibrin architecture: pure platelet-rich plasma (P-PRP), leukocyte and platelet-rich plasma (L-PRP), pure platelet-rich fibrin (P-PRF), and leukocyte and platelet-rich fibrin (L-PRF) [1]. Pure platelet-rich plasma (P-PRP), also referred to as leukocyte-poor platelet-rich plasma, is a sophisticated biological formulation devoid of leukocytes and distinguished by its sparse fibrin network upon activation. These products, by their very nature, can be employed either in a liquid state or as a gel once activated. This versatility allows for their injection in clinical scenarios such as sports medicine, or for their topical application during the gelling process on cutaneous wounds or sutures, much like the application of fibrin adhesives [2]. Leukocyte- and platelet-rich plasma (L-PRP) products are characterized by their incorporation of leukocytes alongside a low-density fibrin network that materializes post-activation. Analogous to their P-PRP counterparts, these formulations can be employed in a liquid state or transformed into an activated gel. This adaptability permits their application via injection, particularly within the domain of sports medicine, or their use in a gelled state on skin lesions or sutures. Pure platelet-rich fibrin (P-PRF), also known as leukocyte-poor platelet-rich fibrin, represents a class of preparations that are devoid of leukocytes and are characterized by a dense fibrin network. Unlike other similar products, P-PRF exclusively exists in a highly activated gel form, rendering it unsuitable for injection or use as conventional fibrin glues. However, the robust fibrin matrix of P-PRF grants it a solid consistency, allowing it to be manipulated as a tangible material for various other medical applications [2]. L-PRF, a second-generation platelet concentrate developed by Choukroun et al., includes leukocytes and cytokines within a strong fibrin matrix and is produced without anticoagulants. This protocol is notable for its speed, cost-effectiveness, ease of use, and high product yield (see Fig. 1). The robust fibrin matrix resists rapid dissolution, enabling the gradual release of growth factors that support angiogenesis and osteoblast proliferation and differentiation [3, 4].

Fig. 1.

Clinical and histological depiction of L-PRF. A The clinical preparation of platelet concentrates, their various types and classes, along with visual representations of several platelet-rich fibrin (PRF) and leukocyte- and platelet-rich fibrin (L-PRF) preparations in the form of membranes. B An illustrative breakdown of PRF's composition. This includes a schematic portrayal of PRF's bio-components and SEM (scanning electron microscope) images showcasing the polymerized, interconnected fibrin network and the abundant living cell population within the PRF membranes [5]

In recent times, there has been a notable upswing in suggested uses for L-PRF in surgical interventions within the oral field. A specific application entails the integration of L-PRF onto the surface of an implant, with the aim of enhancing bone-to-implant contact (BIC) and facilitating bone regeneration. This, in turn, leads to an acceleration in bone healing and the process of osseointegration, concurrently fortifying the stability of endosseous implants [4]. Another proposition advocates for the utilization of L-PRF in the vicinity of an implant to induce thickening of the soft tissues. This action serves to augment the stability of peri-implant tissues and mitigate any potential loss of marginal bone [6].

Implant surgeries within the oral and maxillofacial fields are routinely conducted by practitioners. Dental implants are utilized to provide support for both fixed prostheses and removable overdentures, particularly in cases of tooth loss. The pivotal criterion for gauging the success of an implant hinges on the achievement of osseointegration, denoted by the close proximity of bone-implant contact. However, the deficiency in alveolar ridge dimensions at sites where teeth are missing can exert an influence on the process of implant osseointegration. Additionally, the quality of bone formation assumes paramount importance in determining the stability of the implant. Diverse studies have explored possibilities aimed at enhancing implant osseointegration. These investigations encompass a spectrum of factors, including variations in implant design, the preservation of host site conditions, alterations in surgical methodologies or implant surface characteristics, loading durations, and the incorporation of bioactive substances into the osteotomy site prior to the insertion of the dental implant fixture. The adoption of guiding materials and substances conducive to bone growth has been advocated in numerous research endeavors to effectively amplify both the quality and quantity of bone at implantation sites. It is worth noting that the insufficiency of bone in the edentulous alveolar ridge poses heightened challenges during dental implant procedures [7, 8]. To counter this, a diverse array of bone graft materials, including xenografts and autografts, find application in ridge preservation and bone augmentation. This ensures the preservation of bone volume at the site of dental implant insertion [9, 10].

While xenografts and autografts are frequently selected options, it is imperative to acknowledge their inherent constraints. Xenografts, akin to allografts, carry the risk of eliciting cellular rejection and potential transmission of diseases. Synthetic graft substitutes, distinguished by their varying osteoinductive and osteogenic properties, manifest disparate rates of bone formation [11]. Nonetheless, their utilization may introduce certain drawbacks, such as extended healing durations and potential impacts on immune responses. The optimal approach, widely regarded as the gold standard, continues to be the procurement of autologous cortical and cancellous bones from the iliac crest [12]. However, autografts are not devoid of their own set of limitations, which encompass restricted availability, added surgical trauma, postoperative discomfort, and potential complications, thereby constraining their clinical applicability [13, 14].

In response to these intricate challenges, materials exhibiting osteoinductive properties, such as bone morphogenetic proteins, concentrated growth factors (CGFs), and platelet-rich fibrin (PRF), have garnered substantial interest in tissue engineering [15–17]. PRF, notably, has emerged as a highly promising substance for managing bone formation, presenting a novel method of platelet concentration that circumvents the requirement for thrombin, as delineated by Choukroun et al. [18]. Experimental studies conducted in controlled laboratory settings have showcased PRF's proficiency in augmenting cellular processes including proliferation, migration, adhesion, and osteogenic differentiation across an array of cell types. Additionally, it has demonstrated the capacity to activate critical cell signaling pathways [19]. Moreover, PRF exhibits anti-inflammatory attributes, impedes the formation of osteoclasts, and heightens the expression of diverse growth factors within mesenchymal cells.

In order to gauge the efficacy of L-PRF in augmenting bone volume and its application in dental implant procedures, we undertook a review encompassing clinical standard randomized controlled trials (RCTs). This comprehensive assessment was designed to provide clarity regarding the influence of L-PRF on implant stability. The present systematic review adhered to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) [20]. To construct the search strategy, the Population, Intervention, Comparison, Outcome, and Study design (PICOS) framework was employed, as recommended in the literature [21].

Methods

As outlined in Table 1, the inclusion and exclusion criteria are as follows:

Table 1.

Inclusion and exclusion criteria

Inclusion criteria	Exclusion criteria
Randomized controlled clinical trials (RCTs) or controlled clinical trials (CCTs)	Case reports, case series, retrospective studies, case–control studies…
Studies regarding implant surgery (peri-implant bone stability)	Studies regarding periodontal surgery: intrabony defects, furcation defects, and periodontal plastic surgery
Articles written in English language	Other applications of L-PRF in dentistry and medicine
Studies conducted in humans	Other growth factors such as platelet-rich plasma (PRP), plasma rich in growth factors (PRGFs), advanced platelet-rich fibrin (A-PRF), and injectable platelet-rich fibrin (I-PRF)…
Using L-PRF in implant fixture insertion	Animal studies, in vivo, in vitro
	Using L-PRF in combination with other materials

Inclusion Criteria

1. Randomized controlled clinical trials (RCTs) or controlled clinical trials (CCTs)

2. Studies pertaining to implant surgery, specifically focusing on peri-implant bone stability.

3. Studies published in the English language

4. Studies exclusively conducted on human subjects

5. Using L-PRF in implant fixture insertion

Exclusion Criteria

1. Case reports, case series, retrospective studies, and case–control studies.

2. Studies measuring outcomes other than implant stability following implant surgery, such as those focusing on: periodontal surgery outcomes (e.g., intrabony defects, furcation defects, and periodontal plastic surgery) and other postsurgical factors not related to implant stability.

3. Studies investigating other applications of L-PRF within the fields of dentistry and medicine.

4. Consideration of alternate types of platelet concentrates, including platelet-rich plasma (PRP), plasma rich in growth factors (PRGFs), advanced platelet-rich fibrin (A-PRF), injectable platelet-rich fibrin (I-PRF), etc.

5. Animal studies in vivo, in vitro

6. Using L-PRF in combination with other materials

Table 2 contains excluded articles and reason for their exclusion.

Table 2.

Excluded articles and reason for exclusion

References	Reason for exclusion
Gayathri Devi [22]	Using L-PRF in combination with other materials
Karagah et al. [23]	Comparing L-PRF with FDBA
Pirpir et al. [24]	Using concentrated growth factor (CGF)
Angelo et al. [25]	Using A-PRF
Marenzi et al. [26]	Using (L-PRF) in the healing of simple postextraction sockets
Toffler et al. [27]	Did not contain ISQ measurement
Simonpieri et al. [28]	Not an RCT nor a CCT
Marrelli and Tatullo [29]	Retrospective study
Boora et al. [6]	PRF in peri-implant tissues
Hehn et al. [30]	PRF in peri-implant tissues
Temmerman et al. [31]	PRF in peri-implant tissues
Khan et al. [32]	PRF in peri-implant tissues
Öncü et al. [33]	Animal study
Tajima et al. [34]	PRF in sinus augmentation preceding the implant placement

Sources of Information

A comprehensive search strategy was devised and executed, encompassing both electronic and manual methods, to ascertain pertinent studies with the potential for incorporation.

Electronic Databases

The databases were systematically queried from their inception up until January 14th, 2024.

1. The Cochrane Central Register of Controlled Trials (CENTRAL)

2. Google Scholar

3. EMBASE

4. Web of Science

5. PubMed/MEDLINE

A supplementary search was conducted to identify ongoing trials, utilizing the databases of the US National Library of Medicine (NLM) and the National Institutes of Health (NIH) registry, accessible at www.ClinicalTrials.gov.

A manual search was undertaken, spanning from the current date back to the year 2003, focusing on journals deemed most pertinent to the subject matter of the present review.

1. International Journal of Oral & Maxillofacial Surgery

2. Clinical Implant Dentistry and Related Research

3. International Journal of Oral Implantology

4. Clinical Oral Implant Research

5. British Journal of Oral & Maxillofacial Surgery

6. Journal of Dental Research

7. International Journal of Oral & Maxillofacial Implants

8. International Journal of Implant Dentistry

Search Strategy

Incorporation of the study population into the search strategy was achieved through the utilization of terms and keywords derived from both a scoping search and expert knowledge in the respective subject field.

Intervention and population terms are as follows. It is important to emphasize that the current sequence is randomized and does not signify any particular hierarchy or preference among the intervention terms.

Intervention Terms: Platelet Concentrate Therapy, Autologous Platelet Therapies, L-PRF, PRF, Leukocyte Platelet-Rich Fibrin, Platelet Rich Plasma, Platelet-Rich Fibrin, Platelet Rich Fibrin, Platelet-Rich Plasma, Leukocyte- and platelet-rich fibrin.

Population Terms: Intraosseous Implants, Osseointegrated Implants, Bone Augmenting Procedures, Alveolar Ridge Preservation, Maxillary Sinus Floor Elevation, Sinus Augmentation Techniques, Guided Bone Regeneration Procedures, Osseointegration, Dental Implants, Tooth Implant, Dental Implantation, Endo-osseous Implants, Endosseous Implants, Bone Augmentation, Ridge Preservation, Sinus Lift, Sinus Augmentation, Guided-Bone Regeneration, GBR, Block Grafts.

Study Selection

The information sources underwent independent screening by two reviewers, namely DM and FS. Utilization of EndNote™ facilitated the record management process subsequent to duplicate removal. Following this, the titles and abstracts were scrutinized and categorized into "definitely eligible," "definitely not eligible," or "questionable" to streamline the assessment process [35]. Full-text articles were acquired for the studies categorized as definitely eligible or questionable, based on the researchers' discretion. In cases of disagreement between the two reviewers, a discussion was held involving two additional reviewers, AS and FP, and a consensus was reached regarding the inclusion or exclusion of the respective studies.

Data Collection

The data collection process involved the creation of a standardized extraction form utilizing Microsoft Office Excel, which was subsequently employed independently by two reviewers (RF and SA) for extracting and compiling relevant data. In cases of potential disagreements, resolution was attained through the collaborative efforts of two additional reviewers, DM and KSO.

Data Item

The data items extracted from the included studies encompassed the following:

1. Population: number of participants and number of implants placed.

2. Country of Origin, Author, Funding sources, Year of publication.

3. Study Design: Categorized into Controlled Clinical Trials (CCTs), Randomized Controlled Trials (RCTs), and Split-Mouth RCTs.

4. Demographics: age and gender.

5. ISQ value

6. Insertion torque (Ncm).

Assessment of Bias in Individual Studies

An examination of potential bias was conducted on the included studies, employing the Cochrane tool expounded upon in the eighth chapter of the Cochrane Handbook for Systematic Reviews of Interventions [36]. The subsequent domains were evaluated for potential bias:

1. Performance bias by the lack of blinding among both patients and personnel.

2. Attrition bias due to incomplete recording of outcome data.

3. Selection bias by means of inadequate concealment of allocation prior to assignment.

4. Reporting bias, when outcomes were selectively reported.

5. Selection bias due to a non-randomized sequence generation.

6. Detection bias when there was no blinding in the assessment of outcomes.

7. There may be other sources of bias not addressed in the aforementioned categories.

In the analysis, every integrated study was subject to an autonomous evaluation regarding potential bias risk, overseen by MA and SS. If there were discrepancies, DM and AS contributed their perspectives. A qualitative analysis of the included studies is outlined in Table 3. The result of this assessment culminated in the classification of each study's bias risk as: [37]

Table 3.

Qualitative analysis of the included studies

Randomization	Allocation concealment	Blinding of participant's personnel	Blinding of outcome assessors	Completeness of follow-up	Selective reporting (statistical reporting)	Other bias	References
NA	NA	–	+	+	NA	+	Alhussaini [38]
NA	NA	–	NA	+	+	+	Torkzaban et al. [39]
NA	NA	–	NA	+	+	+	Öncü and Alaaddinoglu [40]
+	NA	–	NA	NA	+	+	Diana et al. [41]
+	NA	NA	NA	+	+	+	Öncü and Alaaddinoglu [42]
+	+	NA	NA	+	+	+	Tabrizi et al. [3]
+	+	–	+	+	+	+	Darestani et al. [43]

Categorized as (1) "Low" risk of bias were those studies where all relevant domains were deemed to manifest a diminished risk of bias. (2) If there was at least one domain prompting uncertainty about bias risk, the classification was marked as "Unclear." (3) "High" risk of bias was attributed if there was at least one domain indicating a heightened potential for bias.

In summary, the principal metric assessed in this review pertained to variations in implant stability values between the control and experimental groups, as determined by ISQ measurements.

Quality Assessment and Risk of Bias

The assessment of article quality involved four authors, in addition to the corresponding author. This evaluation was based on the Cochrane Collaboration's risk of bias tool [35], and the results are summarized in Table 4. Articles were categorized as follows: adequate (+), inadequate (−), unclear (*), or not applicable (NA) based on the following criteria: (a) randomization, (b) allocation concealment, (c) blinding of participants, personnel, and outcome assessors, (d) completeness of follow-up, (e) selective reporting (statistical reporting), and (f) other bias. A low risk of bias was attributed when all of these criteria were met. A moderate risk of bias was assigned if one or more key domains were unclear, while a high risk of bias was indicated if one or more key domains were not met. It is important to note that the risk of bias assessment was not conducted for articles categorized as case reports and case series.

Table 4.

Included studies

Article (year)	Study design, duration	Number of participants (implants)	Mean age ± SD	Type of surgery Implant type (dimensions)	Groups: control: C Intervention: I	Insertion Torque (Ncm) ± SD, Statistical Significance	L-PRF formulation	Results Mean ISQ ± SD
Darestani et al. [43]	RCT, 12weeks	14 (28)	48.93 ± 13.36	6 months healed bone	C: 14 implants I: 14 implants	25 Ncm	2700 rpm, 12′	SN in both groups over time
Alhussaini [38]	RCT, 12 weeks	32(102)	NR ≥ 18	6 months healed bone	C: 102 implants BMP—PRF - I: 102 BMP + PRF +	NR	3000 rpm, 12′	SN in PRF group compared to control group
Torkzaban et al. [39]	RCT, 4 weeks	10 (50)	45.3 (NR)	6 months healed bone Dio(4,11.5 mm)	C: 25 implants L-PRF - I: 25 implants L-PRF +	C: In type 2 bone, 24.50 ± 2.84 In type 3 bone 24.33 ± 3.72 Ncm I: 24.62 ± 2.47 Ncm In type 2 bone. 26.25 ± 3.77 Ncm In type 3 bone (according to the Lekholm and Zarb classification)	400 g RCF or 2,000 rpm, 10′ Froilabo Velocity14R, Paris, France	SN after implant placement, SS ↑ after—1 week: C: 55.99 ± 3.39 I: 59.85 ± 5.32 (P = 0.004) SS ↑ in ISQ after one months: C: 63.23 ± 4.74 I: 66.62 ± 4.77 (P = 0.015)
Öncü and Alaaddinoglu [40]	RCT, 4 weeks	20 (64)	44.2 ± 12.5	≥ 6 months healed bone Dentsply Ankylos®C/X(NR)	C: 33 implants L-PRF (−) I: 31 implants L-PRF (+)	C: 25.61 ± 11.97 I: 27.10 ± 12.83 SN P = 0.632	2,700 rpm 12’ PC-02, Process Ltd	SS ↑ in ISQ values after - 1 week (C: 60.0 ± 12.2, I: 69.2 ± 10.5, P = 0.002) - 4 weeks (C: 70.4 ± 7.7, I: 77.1 ± 6.0. P = 0.001)
Diana et al. [41]	RCT, 1 year	29 (41)	39.6 ± 6.7	NR BEGO implant systems (4.5 mm, 10 mm)	C: No PRF, 20 implants I: PRF 21 implants	NR	28000 rpm 12´	I: t0 = 56.58 ± 18.81 t1: 60.61 ± 11.49 C: t0 = 71.32 ± 7.82 t1:70.06 ± 8.69
Öncü and Alaaddinoglu [42]	RCT 12 weeks	26 (60)	40.2 ± 11.5	Immediate implant Implant socket gap < 1 mm Straumann®SLActive (4.1 mm, 12 mm)	C: 30 implants L-PRF (−) I: 30 implants L-PRF (+)	NR	2,700 rpm 12’ PC-02, Process Ltd	SS ↑ in ISQ values after: - 1 weeks (C: 48.67 ± 13.61, I: 54.36 ± 15.88, P = 0.002) - 4 weeks (C: 61.03 ± 12.02, I: 69.99 ± 11.87, P = 0.002) SN ↑ in ISQ values after: - 12 weeks 35 (C: 70.08 ± 11.2, I: 71.19 ± 10.31, P = 0.682
Tabrizi et al. [3]	RCT 6 weeks	20 (40)	39.6 ± 6.74	≥ 6 months healed bone BEGO (4,5 mm, 10 mm)	C: 20 implants L-PRF (−) I: 20 implants L-PRF (+) (10)	NR	2,700 rpm 12’ IntraSpin™ Intra-Lock, Boca-Raton, FL, USA	SS ↑ in ISQ value after: - 2 Weeks (C: 58.2 ± 3.6, I: 60.6 ± 3.4, P = 0.04) - 4 weeks (C: 67.1 ± 4.3, I: 70.3 ± 3.3, P = 0.014) - 6 weeks (C: 76.1 ± 2.9, I: 78.5 ± 3.3, P = 0.027

NR not reported, RCT randomized controlled trial, rpm rounds per minute, SS statistically significant, SN statistically nonsignificant

Results

Study Selection

During the systematic examination of the existing literature, it was found that there were 134 potential references in EMBASE, 74 in PubMed/Medline, 1130 in Web of Science, and 324 in CENTRAL. The inter-reviewer agreement coefficient, denoted as κ, was established at 1. Furthermore, an additional 322 records were identified through manual scrutiny and exploration using Google Scholar. After the elimination of duplicate entries, a total of 1504 unique references remained. Subsequent to an initial screening based on titles and abstracts, 55 scholarly works were singled out for a thorough evaluation of their complete texts. It was subsequently determined that 48 articles did not meet the criteria for further consideration, resulting in a final selection 7 studies deemed appropriate for data extraction. (See Fig. 2).

Fig. 2.

Flowchart of database search and study selection process

Results of Individual Studies

Implant stability was reported in all the included studies by means of ISQ values by measurements of resonance frequency analysis (RFA). The detailed findings of each study are presented in Table 4.

Initial Post-insertion Measurement

The majority of the included studies reported the baseline ISQs for intervention and control groups. Only the study of Tabrizi et al. [3] lacks this report.

Öncü and Alaaddinoglu [40] in their study in 2015 indicated that immediate postsurgical ISQs were 59.39 ± 15.88 for intervention group and 62.67 ± 13.61 for control group. Therefore, primary stability in both groups was similar. Öncü and Alaaddinoglu [42] reported a mean ISQ of 26.10 ± 12.83 for Intervention group and 24.61 ± 11.97 for control group. The difference between groups was not significant again (P-value = 0.632).

Diana et al. [41] indicated that there was no statistically significant difference between control and study groups in terms of initial ISQ values (P > 0.05). These results were similar in studies of Torkzaban et al. [39], Alhussaini et al., and Darestani et al. [38, 43].

One-Week Post-insertion

Beside the studies of Diana et al. [41] and Alhussaini et al. [38], all other included studies reported one-week postsurgical ISQ measurements.

At the end of the first week, Öncü and Alaaddinoglu [40] reported that the mean ISQ was 69.29 ± 10.51 in intervention group and 60.03 ± 12.2 in the control group. These results were statistically significantly different (P = 0.002). It should be noted that the mean ISQs in the control group decreased by 2.63 units at the end of the first week.

In another study, Öncü and Alaaddinoglu [42] demonstrated a mean ISQ of 48.67 ± 13.61 for the control group and 54.39 ± 15.88 for the study group, with a P-value of 0.002. This difference was also significant.

(P < 0.05) Torkzaban et al. [39] stated a mean ISQ score of 59.85 ± 5.32 in the PRF group and 55.99 ± 3.39 in the control group. This difference was statistically significant (P = 0.004). Darestani et al. [43] reported no significant difference 1 week post-insertion.

While not reporting the first week measurments, Tabrizi et al. [3] indicated that at 2 weeks after insertion, the mean ISQ was 60.60 ± 3.42 in study group and 58.25 ± 3.64 in control group (P = 0.04).

Four-Week Post-insertion

While studies by Diana et al. [41] and Alhussaini et al. [38] lack reporting the findings in four-week follow-ups, Oncu et al. [40] stated that the mean ISQs at the end of the fourth week were 77.19 ± 6.06 for the study group and 70.49 ± 7.74 for the control group (P-value = 0.001) which showed an increased difference in ISQ values in both groups by the fourth week. Mean ISQs increased continuously for the study group, while for the control group, an increase was seen only between the first and fourth weeks. In their 2019 study, Öncü and Alaaddinoglu [42] reported a mean ISQ of 61.03 ± 12.02 for the control group and 69.99 ± 11.87 for the study group after one month of follow-ups. This difference was also reported to be significant (P-value = 0.002).

Tabrizi et al. [3] reported a mean ISQ of 70.30 ± 3.36 in the study group and 67.15 ± 4.33 in the control group after 4 weeks. Analysis of the data demonstrated a significant difference between the two groups at this time point (P = 0.014). Similar results were reported in studies by Torkzaban et al. [39], indicating that the differences between the groups were statistically significant (P-value < 0.05). While these studies reported a statistically significant difference, Darestani et al. [43] believed there was no significant difference in their study 4 weeks post operation.

Six- and Twelve-Week Post-insertion

In the 2019 study, Öncü and Alaaddinoglu [42] reported a mean ISQ of 70.08 ± 11.2 for the control group and 71.19 ± 10.31 for the study group after 3 months post-insertion (P-value = 0.682).

Tabrizi et al.'s [3] 6-week follow-ups demonstrated a mean ISQ of 78.45 ± 3.36 in the study group and 76.15 ± 2.94 in the control group. Assessment of the data showed a significant difference between groups at this time point (P-value = 0.027).

Diana et al. [41] reported measurement of ISQs after 3 months of fixture insertion as 71.32 ± 7.82 for the study group and 70.06 ± 8.69 for the control group. The difference between the two groups was not significant (P-value > 0.05); however, Darestani et al. [43] noted that there was no notable difference between the two groups after 6 weeks.

With an extended follow-up, Alhussaini et al. [38] reported an ISQ of 67.2 ± 8.2 for the control group and 71.0 ± 7.3 for the PRF study group at 6 weeks; moreover, the 12-week follow-up revealed an ISQ of 70.8 ± 8.3 and 74.5 ± 8.1 for both groups, respectively, showing no significant difference between the two groups during either time frame.

Discussion

The purpose of this study was to meticulously scrutinize and evaluate the effect of L-PRF on dental implant stability. It should be highlighted that the quantity of implants in the research by Darestani et al. [43] might be insufficient, potentially affecting the reliability of their findings. Also, Alhussaini et al. compared the effect of length and diameter of dental implants on their stability and concluded that there was a notable correlation between the diameter of the dental implants and their stability [38]. Leukocyte- and platelet-rich fibrin (L-PRF) is rich in growth factors, including interleukin-1 (IL-1), platelet-activating factor 4 (PAF-4), PDGF1, TGFβ2, IL-2, TGFβ1, VEGF, basic fibroblast growth factor (FGF-β), and platelet-derived endothelial growth factors (PD-ECGF) [18, 44, 45]. Research in the past has examined how components found in platelets can significantly enhance the repair process of bones and soft tissues. Furthermore, there has been a growing interest in the application of PRF across various dental and medical disciplines. This substance has proven effective in tissue regeneration, managing cyst-related issues such as treating radicular cysts, performing sinus lifting procedures, ensuring the proper maintenance and recovery of the alveolar bone, and other periodontal challenges (see Fig. 3) [5, 18, 31, 46–54]. Given that specific growth elements like BMPs and TGF-β have been verified to foster bone regeneration surrounding implants, coupled with the fact that PRF is a bountiful reservoir of these elements, our anticipation is heightened. Utilizing this compound in the osteotomy socket could likely lead to increased stability, hasten the recuperative process of the tissues, and enhance the secondary stability around the implant [55, 56]. Given that a precise assessment of these specifics can only be genuinely achieved through histological examination of tissue specimens, it becomes challenging to ascertain with certainty the healing modality, duration, and osseointegration mechanism surrounding the osteotomy socket. However, when observing the healing and bone formation proximate to the osteotomy socket, a notable indication typically emerges: the firm structure of the bone-to-implant contact. This specific feature can be evaluated using RFA as a tool [57]. Furthermore, it's been proposed that ISQ values share a relationship with histological findings [58]. Following implant insertion, it's the implant itself that grants the foundational steadiness solely via its physical engagement with the bone structure. As time progresses, this mechanical reliability of the implant gives way to a more organic or secondary form of stability during the healing phase. The gradual enhancement in ISQ measurements can be elucidated by the phenomenon of osteogenesis upon contact, coupled with the transformation from peri-implant woven bone to a more organized lamellar bone structure. This transformation, rooted in early mechanical interaction, paves the way for a natural healing progression that ensures long-term stability [59, 60].

Fig. 3.

An illustration of L-PRF application can be seen in surgical interventions, notably in maxillary sinus augmentation. Clinical case demonstration of A the utilization/application of prepared L-PRF in B a procedure for maxillary sinus floor elevation and augmentation, conducted before (C) the immediate placement of a dental implant (D) [5]

The studies incorporated in the analysis were chosen exclusively due to their use of L-PRF/Choukroun's platelet-rich fibrin, excluding any alternative varieties of platelet concentrates, including but not limited to P-PRF (pure platelet-rich fibrin), P-PRP (pure platelet-rich plasma), PRF (platelet-rich fibrin), or PRP (platelet-rich plasma). It is imperative to underscore that many studies mixed up different platelet classifications, amalgamating them as identical entities.

Research findings suggest that combining platelet-rich fibrin (PRF) with other grafting biomaterials may seem to yield additional beneficial effects [61]. The scientific literature has extensively discussed the variability observed in platelet concentrates. L-PRF, a type of platelet concentrate, finds broad application in various fields [62–65]. Both in vitro and in vivo studies have provided evidence of the positive impact of L-PRF on osteoblastic activity. Temmerman et al. reported improved quantity and quality of newly formed bone when L-PRF was utilized, as demonstrated by their split-mouth randomized controlled trial (RCT) employing micro CT/CBCT quantitative analysis [66]. Similarly, in an in vitro study conducted by He et al. [67], they found that L-PRF exhibited a more pronounced and sustained enhancement of osteoblastic proliferation and differentiation compared to PRP.

Attaining clinical success with osseointegrated implants heavily relies on implant stability, which is regarded as a crucial factor. Implant stability plays a vital role in ensuring the long-term success of implant placement. It can be categorized into two types: mechanical (primary) stability and biological (secondary) stability [68]. In a study conducted by Simunek et al., involving 90 interforaminally placed implants with alkali-treated surfaces, the stability of these implants was assessed at various time intervals ranging from one to ten weeks. The results revealed a notable decrease in ISQ values during the first week following insertion. Interestingly, the study also found that implants with initially low mechanical stability demonstrated a significant increase in stability during the healing period, whereas implants with high mechanical stability showed a decline in stability over time [69].

The current systematic review findings suggest that L-PRF generally may have a positive impact on secondary stability. None of the included studies that reported baseline values immediately after implant insertion found any statistically significant differences in ISQ values between the L-PRF test group and the control group. However, a statistically significant increase in secondary stability was observed during the 1-week interval in studies conducted by Öncü and Alaaddinoglu [40], Torkzaban et al. [39], and Öncü and Erbeyoğlu [70]. These four studies, along with Tabrizi et al. [3, 39, 40, 70], also reported a significant increase in secondary stability at the 4-week interval post-insertion. Alhussaini [71] provided measurements at 6 and 12 weeks, noting that the PRF group showed better results than the control group at the 12-week mark, although the difference was not statistically significant. Similarly, Diana et al. [41] and Öncü and Erbeyoğlu [70] compared stability between the two groups at the 12-week time point and found no statistically significant differences. It should be highlighted that Darestani et al. [43] did not report any significant difference between the two groups during postoperative assessments. The findings of this study were not surprising since it is logical to assume that L-PRF may have the potential to expedite the osseointegration process in terms of secondary stability, but it may not necessarily enhance the ultimate outcome.

L-PRF is extensively utilized across various fields, including orthodontics, endodontics, periodontics, skull surgeries, aesthetic plastic surgeries, and the treatment of androgenetic alopecia [64, 72–75]. The process of obtaining L-PRF involves employing different techniques and protocols, which depend on factors such as the rate and duration of centrifugation and specific settings. These variables directly impact chairside procedures, histomorphometrical analysis, and clinical outcomes [76, 77]. Modifying the time of centrifugation, speed, or even using different types of centrifuges can significantly influence the final L-PRF product [76, 78]. Consequently, numerous researchers concur that establishing a clear, standardized protocol is highly necessary. Furthermore, other platelet concentrates like A-PRF and PRP have shown comparable efficacy in certain contexts, necessitating further investigation [79]. As a result, it remains to be determined which combination of the aforementioned parameters would yield the highest quality product with the greatest potential benefits, requiring rigorous evaluation through high-quality studies.

Conclusion

In this systematic review, we comprehensively analyzed multiple studies and gathered data from various sources. Our findings indicate that the use of leukocyte- and platelet-rich fibrin (L-PRF) may enhance the stability of implants following surgical procedures. This suggests that L-PRF may accelerate the healing process, reduce the loading time, and improve outcomes for patients undergoing implant surgery, potentially reducing the risk of implant failures and complications.

Abbreviations

L-PRF

Leukocyte- and platelet-rich fibrin

ISQ

Implant stability quotient

RCT

Randomized controlled trials

CCT

Controlled clinical trials

PRP

Platelet-rich plasma

PRF

Platelet-rich fibrin

P-PRP

Pure platelet-rich plasma

L-PRP

Leukocyte- and platelet-rich plasma

P-PRF

Pure platelet-rich fibrin

SEM

Scanning electron microscope

BIC

Bone-to-implant contact

CGF

Concentrated growth factors

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analysis

PICOS

Population, intervention, comparison, outcome, and study design

CENTRAL

Cochrane Central Register of Controlled Trials

EMBASE

Excerpta Medica database

NLM

National Library of Medicine

NIH

National Institutes of Health

NR

Not reported

SD

Standard deviation

RCF

Relative centrifugal force

Author contributions

KSO and DM performed database search, tabulation, and manuscript write-up. FP and RF participated in database search, discussions, tabulation, check, and artwork. JS conducted database search, tabulation, and manuscript write-up. AS carried out database search, tabulation, check, quality assessment, and RoB. FP and AM involved in database search, tabulation, and selected study analysis. KSO did review idea, database check, discussions, manuscript, writing, editing, closing remarks, and overall supervision of work. All authors contributed to the article and approved the submitted version. Mohammadamin Damsaz: DM, Fatemeh Rahmani: RF, Sarah Arzani: AS, Sepideh Jafari: JS Pegah Farzanegan: FP, Mohammad Hosein Amirzade-Iranaq: AM, and Seied Omid Keyhan: KSO.

Funding

Not applicable.

Availability of Data and Materials

Not applicable.

Declarations

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.