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Safety and Feasibility of Extended Platelet‐Rich Fibrin as a Solo Barrier Membrane for Ridge Preservation: A Case Series
2026
Introduction Platelet‐rich fibrin (PRF) has been commonly utilized for ridge preservation techniques either to introduce supraphysiological concentrations of autologous growth factors to the defect area (typically when mixed within a bone graft) or utilized alone as a solo “barrier” membrane. Noteworthy, however, one of the commonly reported drawbacks of PRF is its relatively short resorption period characterized by lasting roughly 2 weeks. This may therefore be insufficient for complete soft tissue closure and/or preventing soft tissue cells from infiltrating into the bony compartment. Recently, it was discovered that by heating plasma and denaturing albumin using the Bio‐Heat technology, the resorption properties of PRF could be extended from a standard 2–3 week period toward 4–6 months. The aim of the present human case series was to investigate for the first time the safety and applicability of utilizing this novel 100% autologous extended‐PRF (e‐PRF) membrane for ridge preservation. Materials and Methods Twenty‐two patients requiring 22 single tooth posterior extractions were included in this case series. In all cases, atraumatic extractions were performed, and the sites were grafted using a combination of bone allograft and standard PRF to create “sticky bone.” Noteworthy, the barrier membrane utilized over top of the bone graft was the novel e‐PRF, which was utilized as a solo membrane in place of standard collagen or polytetrafluoroethylene (PTFE) membranes. Cone‐beam computed tomography scans were taken immediately after extractions and at 3 months postoperatively. Ridge width at 1, 3, and 5 mm apical to the crest, and buccal and lingual height dimensions were recorded at both time intervals. Additionally, buccal bone thickness at 1, 3, and 5 mm apical to the crest was recorded at baseline. Results All extraction sites healed uneventfully without any postoperative complications. No clinical signs of infection or other complications were detected. The mean change in ridge width at 1, 3, and 5 mm apical to the crest was −1.27 ± 0.70, −0.94 ± 0.80, and −0.69 ± 0.79 mm, respectively. The mean change in buccal height and lingual height was −1.25 ± 1.16 and −0.94 ± 1.07 mm, respectively. Conclusions The use of e‐PRF membranes in place of collagen membranes for ridge preservation was shown to be an effective, safe, and predictable treatment modality. The e‐PRF membranes can be fabricated at low cost with a barrier function that resorbs much more slowly over time when compared to standard PRF membranes. While this preliminary report demonstrated successful outcomes, additional randomized controlled clinical trials investigating soft tissue outcomes of the e‐PRF membranes when compared to more conventionally utilized membranes are further necessary to support these novel findings. Clinical Relevance The use of e‐PRF membranes in ridge preservation is a safe, predictable, and all‐natural alternative to traditional membranes.
Journal Article
Evaluation of 24 protocols for the production of platelet-rich fibrin
by
Zhang, Yufeng
,
Sculean, Anton
,
Miron, Richard J.
in
A-PRF
,
Advanced platelet-rich fibrin
,
Anticoagulants
2020
Background
The aim of this study was to evaluate 24 protocols for the production of platelet rich fibrin (PRF) produced via horizontal centrifugation to better understand cell separation following protocols at various times and speeds.
Methods
All protocols were compared utilizing a recent method to quantify cells in PRF in 1 mL sequential layers pipetted from the upper layer downwards until all 10 mL were harvested. In total, 960 complete blood counts (CBCs) were investigated. Both solid and liquid-based PRF protocols were investigated following 24 protocols involving 6 relative centrifugal force (RCF) values (100, 200, 400, 700, 1000 and 1200
g
) at 4 centrifugation times (3, 5, 8 and 12 min).
Results
In general, platelets could more easily accumulate in the upper 4 layers when compared to leukocytes owing to their lower cellular density. Protocol time seemed to have a greater impact on the final cell layer separation when compared to the effect of speed. Protocols of greater than 8 min at 400
g
led to no leukocyte accumulation in the upper PRF layers (found specifically within the buffy coat). Protocols at or below 200
g
were unable to effectively accumulate platelets/leukocytes. The optimal centrifugation speed and time for solid-PRF ranged between 400 and 700
g
for 8 min. It was noted that variability in patient baseline platelet/leukocyte/erythrocyte counts (hematocrit) significantly affected cell layer separation. This finding was more pronounced at lower centrifugation speeds.
Conclusions
Within the investigated ranges, a protocol of 700
g
for 8 min presented the highest yield of platelets/leukocytes evenly distributed throughout the upper PRF layers.
Journal Article
A technical note on contamination from PRF tubes containing silica and silicone
2021
Background
Platelet-rich fibrin (PRF) has been widely utilized in modern medicine and dentistry owing to its ability to rapidly stimulate neoangiogenesis, leading to faster tissue regeneration. While improvements over traditional platelet rich plasma therapies (which use chemical additives such as bovine thrombin and calcium chloride) have been observed, most clinicians are unaware that many tubes utilized for the production of ‘natural’ and ‘100% autologous’ PRF may in fact contain chemical additives without appropriate or transparent knowledge provided to the treating clinician. The aim of this overview article is therefore to provide a technical note on recent discoveries related to PRF tubes and describe recent trends related to research on the topic from the authors laboratories.
Methods
Recommendations are provided to clinicians with the aim of further optimizing PRF clots/membranes by appropriate understanding of PRF tubes. The most common additives to PRF tubes reported in the literature are silica and/or silicone. A variety of studies have been performed on their topic described in this narrative review article.
Results
Typically, PRF production is best achieved with plain, chemical-free glass tubes. Unfortunately, a variety of other centrifugation tubes commonly used for lab testing/diagnostics and not necessarily manufactured for human use have been utilized in clinical practice for the production of PRF with unpredictable clinical outcomes. Many clinicians have noted an increased variability in PRF clot sizes, a decreased rate of clot formation (PRF remains liquid even after an adequate protocol is followed), or even an increased rate in the clinical signs of inflammation following the use of PRF.
Conclusion
This technical note addresses these issues in detail and provides scientific background of recent research articles on the topic. Furthermore, the need to adequately select appropriate centrifugation tubes for the production of PRF is highlighted with quantitative data provided from in vitro and animal investigations emphasizing the negative impact of the addition of silica/silicone on clot formation, cell behavior and in vivo inflammation.
Journal Article
Autologous platelet concentrates in maxillofacial regenerative therapy
by
Wang, Jen‐Chyan
,
Chou, Tsau‐Mau
,
Chang, Hong‐Po
in
Anticoagulants
,
Automation
,
Biological products
2020
Platelet concentrates have emerged as innovative autologous blood products that enhance tissue healing and regeneration in regenerative therapy. A common feature of these products is their higher than baseline platelet concentration, which improves wound healing and tissue repair. Four main categories of products can be easily defined, based on their leukocyte content and fibrin architecture: pure platelet‐rich plasma, such as Cell Separator PRP or Anitua' PRGF; leukocyte‐ and platelet‐rich plasma (L‐PRP), such as PCCS or Ace PRP; pure platelet‐rich fibrin (P‐PRF), such as Fibrinet PRFM; and leukocyte‐ and platelet‐rich fibrin (L‐PRF), such as Choukroun's PRF. Two families contain significant concentrations of leukocytes: L‐PRP and L‐PRF. These four families of products have different biological signatures and mechanisms and obviously different clinical applications. An L‐PRF membrane releases growth factors and matrix proteins over a period longer than 7 days, whereas a PRP gel matrix releases and disperses its growth factors in a relatively quick download. In the near future, simple and inexpensive products such as L‐PRF are expected to have applications in oral‐maxillofacial surgery, periodontal surgery, plastic surgery, orthopedic surgery, and sports medicine. Leukocytes substantially affect the intrinsic biology and properties of platelet concentrates, not only because they enhance immune function and antibacterial potential, but also because they have essential roles in the wound healing process. Unfortunately, their impact has been almost completely neglected in the literature. Improved understanding of the effects of leukocytes in wound healing is essential for development of new clinical applications of platelet concentrates.
Journal Article
Use of platelet-rich fibrin for the treatment of periodontal intrabony defects: a systematic review and meta-analysis
by
Zhang, Yufeng
,
Ferenc, Döri
,
Kawase, Tomoyuki
in
Alveolar Bone Loss - diagnostic imaging
,
Alveolar Bone Loss - drug therapy
,
Alveolar Bone Loss - surgery
2021
Objectives
This study aims to compare the treatment outcomes of periodontal intrabony defects by using platelet-rich fibrin (PRF) with other commonly utilized modalities.
Materials and methods
The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with that of other modalities. Studies were classified into 10 categories as follows: (1) open flap debridement (OFD) alone versus OFD/PRF; (2) OFD/bone graft (OFD/BG) versus OFD/PRF; (3) OFD/BG versus OFD/BG/PRF; (4–6) OFD/barrier membrane (BM), OFD/PRP, or OFD/enamel matrix derivative (EMD) versus OFD/PRF; (7) OFD/EMD versus OFD/EMD/PRF; (8–10) OFD/PRF versus OFD/PRF/metformin, OFD/PRF/bisphosphonates, or OFD/PRF/statins. Weighted means and forest plots were calculated for probing depth (PD), clinical attachment level (CAL), and radiographic bone fill (RBF).
Results
From 551 articles identified, 27 RCTs were included. The use of OFD/PRF statistically significantly reduced PD and improved CAL and RBF when compared to OFD. No clinically significant differences were reported when OFD/BG was compared to OFD/PRF. The addition of PRF to OFD/BG led to significant improvements in CAL and RBF. No differences were reported between any of the following groups (OFD/BM, OFD/PRP, and OFD/EMD) when compared to OFD/PRF. No improvements were also reported when PRF was added to OFD/EMD. The addition of all three of the following biomolecules (metformin, bisphosphonates, and statins) to OFD/PRF led to statistically significant improvements of PD, CAL, and RBF.
Conclusions
The use of PRF significantly improved clinical outcomes in intrabony defects when compared to OFD alone with similar levels being observed between OFD/BG and OFD/PRF. Future research geared toward better understanding potential ways to enhance the regenerative properties of PRF with various small biomolecules may prove valuable for future clinical applications. Future research investigating PRF at histological level is also needed.
Clinical relevance
The use of PRF in conjunction with OFD statistically significantly improved PD, CAL, and RBF values, yielding to comparable outcomes to OFD/BG. The combination of PRF with bone grafts or small biomolecules may offer certain clinical advantages, thus warranting further investigations.
Journal Article
Next-generation platelet concentrate: Alb-PRF outperformed PRP and H-PRF in promoting endothelial function and wound healing
2026
Angiogenesis underpins regenerative success and refined autologous platelet concentrates (APCs) are therefore under continual optimization. This study compared optimized thermally-induced albumin hydrogel cross-linked with horizontally centrifuged platelet-rich fibrin (Alb-PRF) against traditional platelet-rich plasma (PRP) and standardized horizontal PRF (H-PRF). Alb-PRF was generated using specific centrifugation protocols. Each APC was co-cultured with human umbilical vein endothelial cells (HUVECs) respectively. Live/dead assay confirmed universal biocompatibility and safety, showing no significant differences in apoptosis among all groups. Additoinally, viability assay revealed possibly superior proliferation by Alb-PRF compared to PRP and H-PRF. Immunofluorescent cytoskeleton and morphology staining showed enhanced proliferative effects with Alb-PRF. Moreover, Alb-PRF significantly increased cell migration. Notably, LPS-induced inflammatory damage led to more apoptotic HUVECs in PRP and H-PRF groups, whereas Alb-PRF rescued this damage. Alb-PRF conferred cytoprotection and upregulated expression of CD31, suggesting an augmented vascular regeneration capacity. Altogether, Alb-PRF outperformed PRP and H-PRF in driving angiogenic potential under both normal and inflammatory conditions. Our findings underscore the translational promise of Alb-PRF, particularly as an innovative solution for wound healing in regenerative medicine.
Journal Article
Reduction of relative centrifugation force within injectable platelet-rich-fibrin (PRF) concentrates advances patients’ own inflammatory cells, platelets and growth factors: the first introduction to the low speed centrifugation concept
2018
PurposeThe aim of this study was to analyze systematically the influence of the relative centrifugation force (RCF) on leukocytes, platelets and growth factor release within fluid platelet-rich fibrin matrices (PRF).Materials and methodsSystematically using peripheral blood from six healthy volunteers, the RCF was reduced four times for each of the three experimental protocols (I–III) within the spectrum (710–44 g), while maintaining a constant centrifugation time. Flow cytometry was applied to determine the platelets and leukocyte number. The growth factor concentration was quantified 1 and 24 h after clotting using ELISA.ResultsReducing RCF in accordance with protocol-II (177 g) led to a significantly higher platelets and leukocytes numbers compared to protocol-I (710 g). Protocol-III (44 g) showed a highly significant increase of leukocytes and platelets number in comparison to -I and -II. The growth factors’ concentration of VEGF and TGF-β1 was significantly higher in protocol-II compared to -I, whereas protocol-III exhibited significantly higher growth factor concentration compared to protocols-I and -II. These findings were observed among 1 and 24 h after clotting, as well as the accumulated growth factor concentration over 24 h.DiscussionBased on the results, it has been demonstrated that it is possible to enrich PRF-based fluid matrices with leukocytes, platelets and growth factors by means of a single alteration of the centrifugation settings within the clinical routine.ConclusionsWe postulate that the so-called low speed centrifugation concept (LSCC) selectively enriches leukocytes, platelets and growth factors within fluid PRF-based matrices. Further studies are needed to evaluate the effect of cell and growth factor enrichment on wound healing and tissue regeneration while comparing blood concentrates gained by high and low RCF.
Journal Article
Evaluation of local hemostatic efficacy after dental extractions in patients taking antiplatelet drugs: a randomized clinical trial
by
Brancaccio, Ylenia
,
Giudice, Amerigo
,
Antonelli, Alessandro
in
Aged
,
Aged, 80 and over
,
Antiplatelet therapy
2021
Objectives
The purpose of this study was to evaluate clinical efficacy of four different local hemostatics in patients taking oral antiplatelet therapy, after multiple dental extractions without discontinuing drugs.
Materials and methods
Study sample included 102 patients (mean age 64.1 ± 17.4 years) in treatment with oral antiplatelet agents needing multiple dental extractions. After surgery, the sockets were randomly sealing with suture alone (control group), hemostatic plug (HEM), advanced platelet-rich fibrin (A-PRF+), and leukocyte-platelet-rich fibrin (L-PRF). Primary outcomes were post-operative bleeding, wound healing index, and possible complications. Secondary outcomes were correlation between primary outcomes and patient’s comorbidities and voluptuous habits. Descriptive statistics, bivariate comparisons, and logistic regression analysis were performed (
p
< 0.05).
Results
Both A-PRF+ and L-PRF showed a reduced bleeding risk when compared with suture alone (OR = 0.09,
p
= 0.001 for A-PRF+; OR = 0.09,
p
= 0.005 for L-PRF). Only L-PRF showed a reduced risk for incomplete wound healing when compared with the control site (OR = 0.43,
p
= 0.019). Patients affected by hypertension (OR 3.91,
p
= 0.015) and diabetes (OR 3.24,
p
= 0.026) had the highest bleeding risk. Smoking (OR 4.30,
p
= 0.016) and diabetes (OR 3.79,
p
= 0.007) interfered with healing process.
Conclusion
L-PRF and A-PRF represent a valid alternative to the traditional hemostatics, reducing post-surgical bleeding and promoting wound healing.
Clinical relevance
In patients taking antiplatelet drugs, different local hemostatics are useful to control potential post-operative bleeding and to favor wound healing. However, comorbidities and voluptuous habits may increase bleeding risk, interfering with healing process.
Journal Article
Impact of Thermal Treatment on Growth Factor Levels in Injectable Horizontal Platelet‐Rich Fibrin: An In Vitro Study
2026
Background Platelet‐rich fibrin (PRF) is widely recognized for its regenerative properties in periodontal therapy, particularly through the release of endogenous growth factors. Injectable horizontal PRF (H‐PRF), a recent advancement, has gained interest due to its improved cell distribution and structural integrity. The aim of this study was to analyze and compare the levels of growth factors released from injectable H‐PRF subjected to different thermal treatments. Methods Venous blood samples from 16 healthy participants (aged 18–25 years) were collected and divided into four groups: Group I (unheated control), Group II (37°C), Group III (45°C), and Group IV (60°C). Liquid H‐PRF was prepared using horizontal centrifugation (700 RCF, 8 min), followed by controlled heating. Growth factor quantification was performed using the LEGENDplex Human Growth Factor Panel. Solidification and degradation profiles were also recorded. Statistical analyses included ANOVA and Bonferroni post hoc tests (significance at p < 0.05). Results The solidification time decreased significantly with increasing temperature, ranging from 24 min in Group I to 5 min in Group IV. After 24 days, heated H‐PRF gels (especially 45°C and 60°C) retained greater mass, indicating slower degradation. Significant intergroup differences were observed for angiopoietin‐2 (p < 0.001), PDGF‐AA (p = 0.002), TGF‐α (p = 0.036), and VEGF (p = 0.011), with Group II showing the highest levels of angiogenic factors. No significant differences were noted for EGF, FGF‐basic, HGF, and PDGF‐BB. Conclusion Thermal treatment of H‐PRF at moderate temperatures (particularly 37°C and 45°C) enhances the release of angiogenic growth factors while improving the mechanical stability of the gel. However, the heating protocol will need to be customized based on the intended clinical applications.
Journal Article
Comparative release of growth factors from PRP, PRF, and advanced-PRF
by
Kobayashi, Eizaburo
,
Miron, Richard J.
,
Sawada, Kosaku
in
Adult
,
Blood Platelets - metabolism
,
Dentistry
2016
Objectives
The use of platelet concentrates has gained increasing awareness in recent years for regenerative procedures in modern dentistry. The aim of the present study was to compare growth factor release over time from platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and a modernized protocol for PRF, advanced-PRF (A-PRF).
Materials and methods
Eighteen blood samples were collected from six donors (3 samples each for PRP, PRF, and A-PRF). Following preparation, samples were incubated in a plate shaker and assessed for growth factor release at 15 min, 60 min, 8 h, 1 day, 3 days, and 10 days. Thereafter, growth factor release of PDGF-AA, PDGF-AB, PDGF-BB, TGFB1, VEGF, EGF, and IGF was quantified using ELISA.
Results
The highest reported growth factor released from platelet concentrates was PDGF-AA followed by PDGF-BB, TGFB1, VEGF, and PDGF-AB. In general, following 15–60 min incubation, PRP released significantly higher growth factors when compared to PRF and A-PRF. At later time points up to 10 days, it was routinely found that A-PRF released the highest total growth factors. Furthermore, A-PRF released significantly higher total protein accumulated over a 10-day period when compared to PRP or PRF.
Conclusion
The results from the present study indicate that the various platelet concentrates have quite different release kinetics. The advantage of PRP is the release of significantly higher proteins at earlier time points whereas PRF displayed a continual and steady release of growth factors over a 10-day period. Furthermore, in general, it was observed that the new formulation of PRF (A-PRF) released significantly higher total quantities of growth factors when compared to traditional PRF.
Clinical relevance
Based on these findings, PRP can be recommended for fast delivery of growth factors whereas A-PRF is better-suited for long-term release.
Journal Article