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I. Introduction
Platelet-rich fibrin (PRF) is an autologous fibrin matrix rich in leukocyte cytokines and platelets (thrombocytes) and represents the second generation of platelet concentrates1. The creation of the PRF simplified the preparation of platelet concentrates since using bovine thrombin or anticoagulant is unnecessary. Since no anticoagulant is present, most of the blood sample’s platelets that come into contact with the tube walls activate within a few minutes, causing the coagulation cascades to be released2. PRF contributes to tissue regeneration through a combination of biological mechanisms. It functions as a bioactive scaffold capable of releasing essential growth factors, such as platelet-derived growth factor (PDGF-a/b and c), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), epidermal growth factor (EGF), connective tissue growth factor (CTGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF), and transforming growth factor β13, while also exerting immunomodulatory effects by favoring the polarization of macrophages toward the anti-inflammatory M2 phenotype and attenuating pro-inflammatory cytokines, including TNF-α and IL-64,5. In parallel, PRF activates key regenerative signaling pathways that collectively promote cell recruitment, proliferation, and differentiation, as well as angiogenesis and extracellular matrix deposition6.
Different plasma element concentrations and physicochemical properties can be obtained depending on the preparation technique utilized to create PRF, including leukocyte platelet-rich fibrin (L-PRF)7, advanced platelet-rich fibrin (A-PRF)8, injectable platelet-rich fibrin (i-PRF)9, and concentrated platelet-rich fibrin (C-PRF)10, each with unique properties and applications. In the preparation of L-PRF, the primary focus of this work, fibrinogen is initially concentrated in the upper section of the tube before being transformed into fibrin through the action of circulating thrombin. Subsequently, a fibrin clot, enriched with serum and platelets, and positioned between the acellular plasma at the top and the red blood cells at the bottom, is extracted from the center of the tube1.
In the context of oral and maxillofacial surgeries, L-PRF is particularly promising as a regenerative tool for bone and soft tissue procedures11, such as implant therapy (18.68%), periodontal regeneration (22.42%), and oral surgery (31.14%)4. L-PRF promotes accelerated healing by creating a fibrin network that mimics the natural fibrin matrix. Clinical outcomes commonly associated with L-PRF include rapid tissue remodeling and a low incidence of infections12. These results can be attributed to the slow fibrin polymerization that occurs during the PRF processing, which facilitates the incorporation of platelet cytokines and glycan chains into the fibrin mesh. Additionally, during the centrifugation of L-PRF, extensive platelet degranulation indicates a gradual release of cytokines throughout the remodeling of the fibrin matrix13.
The applicability of L-PRF in oral and maxillofacial surgery is gaining recognition for its unique characteristics that distinguish it from other biomaterials and regenerative techniques. The absence of external additives and the gradual release of growth factors are significant advantages, making it a valuable tool in clinical practice14. Furthermore, the autologous nature of L-PRF addresses the growing demand for safe, biocompatible treatments that minimize immunological risks while promoting tissue regeneration in a more physiological manner12. Therefore, this paper aims to add to the literature by describing a series of cases that illustrate the versatility and efficacy of L-PRF in various maxillofacial surgical interventions, providing a more detailed overview of its practical indications and limitations.
II. Patients and Methods
Six patients underwent a complete clinical and imaging evaluation and were recommended for surgical treatment with L-PRF under local anesthesia. The steps of L-PRF preparation, followed by case presentations, will be described below, divided among different applications of L-PRF in the fields of oral and maxillofacial surgery.
III. Results
1. Venipuncture and blood collection
The L-PRF preparation technique begins with blood collection from the patient.(Fig. 1) Initially, the clinician must prepare all the necessary materials, wear appropriate personal protective equipment (PPE), and ensure proper hand hygiene.(Fig. 1. A) The patient’s selected arm should be positioned slightly downward and supported on a stable surface. A tourniquet is then applied approximately 5-10 cm above the intended puncture site.(Fig. 1. B) To enhance visualization of the venous network, the patient may be instructed to open and close their hand repeatedly. Commonly chosen veins for blood collection include the median cubital and cephalic veins, located near the antecubital fossa. The puncture site should be disinfected using gauze or cotton soaked in the antiseptic of choice (e.g., 70% isopropyl alcohol), applied in a single circular motion or a unidirectional stroke from the wrist towards the elbow.(Fig. 1. C) Once the skin is dry, the needle is inserted into the vein with the bevel facing upward.(Fig. 1. D)
The blood collection tube should be inserted into the needle holder until the cap of the tube is punctured.(Fig. 1. E) Since each tube corresponds to one L-PRF membrane, it is essential to estimate the number of membranes needed in advance to determine the total number of tubes to be collected. After the first tube is filled, it should be removed while keeping the needle in place, allowing for the insertion of the next tube.(Fig. 1. F, 1. G) Each filled tube must be placed upright in a tube rack to maintain a vertical position. This process should continue until the required number of tubes has been collected. Finally, after the needle is removed, the puncture site should be compressed with sterile gauze.(Fig. 1. H) In cases where it is difficult to visualize the vein, a portable ultrasound device may help identify the optimal puncture site.(Fig. 1. I-1. L)
2. PRF preparation
To prepare L-PRF, blood is first drawn into 10 mL tubes without an anticoagulant. The tubes are then centrifuged at an angle of 45° for 12 minutes at 3,000 rpm1.(Fig. 2. A) In contrast, A-PRF is produced by centrifuging the tubes for 14 minutes at 1,500 rpm8.(Table 1) Both L-PRF and A-PRF are solid forms of PRF, but A-PRF represents a more recent palette concentrate with specific enhancements, such as increased porosity, which aids in releasing growth factors and facilitates angiogenesis. After centrifugation, the solid fibrin clot is extracted from the tube and separated from the red cell layer.(Fig. 2. B-2. D) Depending on the intended application, these solid forms of PRF can be shaped into either a membrane (Fig. 2. F, 2. H) or a plug.(Fig. 2. G, 2. I) Additionally, both L-PRF and A-PRF can be divided into smaller fragments and mixed with bone grafts to enhance regenerative procedures.
To create the liquid version of PRF, known as i-PRF (Fig. 2. K), blood is drawn into a tube without any additives and centrifuged at 3,300 rpm for 2 minutes.(Table 1)15 After centrifugation, two distinct phases are visible in the tube: a yellowish upper phase, i-PRF, and a lower phase containing red blood cells. The i-PRF (Fig. 2. E) can be drawn up with a syringe and used as an injectable in deep spaces, for treating open wounds, or mixed with bone graft particles.(Fig. 2. L)
3. Closure of oroantral communication
Patient 1 went through a resection procedure to treat an ameloblastoma. After that, a communication between the mouth and the maxillary sinus in the right maxilla was developed. Initial treatment involved a vestibular flap to close the oroantral communication. However, smaller fistulas remained, causing symptoms of fluid return to the nasal cavity.(Fig. 3) From that, it was suggested that an L-PRF membrane be used to aid in closing the fistula. The initial steps of the surgery went similar to the traditional technique of closure of oroantral communication. First, the surgeon cut around the fistula and removed the internal epithelial tissue. Then, the surgeon created a vestibular flap with two divergent incisions. After the divulsion of the region, two L-PRF membranes were placed over the communication, covering them with the flap and securing them with stitches. The patient remains asymptomatic, is under surveillance for potencial ameloblastoma recurrence, and is awaiting prosthetic rehabilitation.
4. Sinus lift
An edentulous patient (Patient 2) with pneumatization of the left maxillary sinus was indicated for a sinus lift procedure using L-PRF membranes for subsequent implant placement.(Fig. 4) Initially, an incision was made in the molar region, followed by flap elevation. A lateral window was then created using a round bur. With the aid of curettes, the maxillary sinus membrane was carefully detached and elevated superiorly. The space created was sequentially filled with PRF membranes with biomaterial particles, sticky bone, and L-PRF membranes. The vestibular flap was repositioned and secured with sutures to protect the grafted area. Satisfactory bone regeneration was achieved for future implant rehabilitation.
5. Bone socket preservation after tooth extraction
Patients requiring tooth extraction for future dental implant placement, with bone socket preservation using L-PRF, were indicated for this procedure. In Case 3 (Fig. 5. A-5. F), an elderly male patient presented with extensive coronal destruction of tooth 16, requiring extraction to proceed with implant treatment. In Case 4 (Fig. 5. G-5. I), an elderly female patient required the extraction of a residual root in the region of tooth 15, adjacent to previously placed implants, to continue with implant rehabilitation. In Case 5 (Fig. 5. J-5. L), an elderly male patient with a history of cancer treatment required the extraction of teeth 11 and 21. In all cases, following incision and flap reflection, extractions were performed using elevators. After cleaning the sockets, an L-PRF plug was inserted into each socket and covered with an L-PRF membrane. The surgeries were completed with sutures to secure the L-PRF in position. The patients presented absence of postoperative complications and satisfactory alveolar preservation for future rehabilitation.
6. Mandibular third molar surgery
Patient 6, a young female, presented with a mesioangular lower third molar that required extraction.(Fig. 6. A-6. D) The procedure was performed under local anesthesia with an envelope flap incision. Osteotomy and odontosection techniques were used to remove the tooth. After the extraction, an L-PRF plug was placed at the extraction site and covered by two L-PRF membranes, which were positioned beneath the flap. The site was then sutured to ensure proper healing. Patient 7, a young woman, presented with a complaint related to frequent pericoronitis of a lower third molar (tooth 38), which required extraction. The tooth was extracted under local anesthesia using an envelope flap, osteotomy, and odontosection techniques. After the extraction, the alveolar region and the area beneath the flap were irrigated with i-PRF.(Fig. 6. E-6. H) Finally, the site was closed with sutures. The patients evolved without complications.
IV. Discussion
The application of L-PRF in various oral and maxillofacial surgical procedures has demonstrated promising outcomes, enhancing wound healing, reducing inflammation, and promoting tissue regeneration12. L-PRF was used in different clinical contexts in this case series, from sinus lifting with bone grafting to socket preservation and third molar extractions. The outcomes observed align with the literature, highlighting L-PRF’s potential to improve soft and hard tissue regeneration due to its autologous nature and ability to gradually release growth factors11. This series underscores L-PRF’s versatility and effectiveness as an adjunct in surgical procedures aimed at bone preservation, infection control, and postoperative healing.
The development of different types of PRF reflects an evolution in protocols to meet diverse clinical needs. Initially, L-PRF and i-PRF were introduced. L-PRF is a solid PRF membrane that aggregates leukocytes and platelets and can be used to fill and cover various surgical wounds7. In contrast, i-PRF is a liquid version with a high cell concentration that can be used to irrigate surgical sites, be mixed with bone biomaterials, or even be injected in orofacial procedures15. In vitro studies suggest that L-PRF and i-PRF differ in their fibrin ultrastructure: L-PRF presents dense, rough-surfaced fibrin, whereas i-PRF consists of thinner, smoother fibrin, potentially affecting their scaffold functions. However, i-PRF has a lower platelet concentration than solid PRF, which may influence its applications16.
Following these initial developments, A-PRF was introduced as a modification of L-PRF. A-PRF, also a solid version, is produced with a slightly longer centrifugation time and a significantly lower centrifugation speed8. A-PRF membranes are smaller than L-PRF membranes and tend to disintegrate more quickly, lasting less than three days in vitro compared to at least seven days for L-PRF17. However, A-PRF contains higher levels of growth factors and leukocytes, especially neutrophils, which enhance its regenerative properties18,19. More recently, A-PRF+ and C-PRF have been developed. A-PRF+ is a refined version that enhances growth factor release for up to ten days, providing a sustained regenerative effect. C-PRF, also a PRF liquid form, is obtained through progressive pipetting and has the highest cellular concentration among platelet aggregates18. Each PRF type offers unique advantages; for example, while i-PRF is suited for early cell differentiation, A-PRF+ shows more significant potential for mineralization in osteogenic applications20. Consequently, the choice of PRF protocol and preparation should be tailored to the specific clinical objectives of each procedure.
In the present study, i-PRF was prepared following the original protocol, using centrifugation at 3,300 rpm for 2 minutes15. More recent investigations have introduced the “low-speed centrifugation concept”, which applies reduced centrifugal forces (approximately 700 rpm for 3 minutes) and has been associated with higher concentrations of platelets, leukocytes, and circulating progenitor cells, thereby promoting a more sustained release of growth factors and cytokines10,21. Nevertheless, the classical protocol was adopted in the present work to ensure methodological consistency, facilitate comparison with previous studies, and align with the standardized procedures routinely employed in our laboratory.
Due to its 10- to 14-day resorption period, complete biocompatibility, and size adequate to cover most small perforations, L-PRF is recommended as a treatment for Schneiderian membrane perforations. However, for ethical reasons, randomized controlled trials assessing L-PRF specifically for this application are not feasible, as they would require either intentionally created membrane tears or a large sample size to capture the relatively rare cases of accidental perforations22. Nonetheless, observational studies have shown promising results. Increased angiogenesis was observed in the sinus area in patients treated with L-PRF after maxillary sinus membrane perforations. Additionally, implant survival rates were reported as 100%, with no signs of peri-implant bone loss23. In line with these findings, our study successfully used L-PRF as a secondary measure to address persistent oroantral communication after initial surgical attempts.
In sinus lift procedures, a systematic review found no significant difference in the percentage of new bone formation when L-PRF was added to a bone substitute compared to when it was not22. However, Tatullo et al.24 demonstrated that combining L-PRF with biomaterial reduced healing time to approximately 106 days, promoting optimal bone regeneration and achieving favorable primary stability for endosseous implants. Clinically, the association of PRF with biomaterial is also considered more manageable to handle compared to biomaterial moistened only with saline solution. In addition, one of the benefits of using L-PRF during maxillary sinus lift procedures is its ability to replace collagen membranes. Studies have shown that L-PRF membranes offer similar outcomes to commercially available collagen membranes25, with additional benefits: they are more cost-effective and derived from the patient’s blood, enhancing biocompatibility22. Although the case presented here uses L-PRF combined with biomaterial as a membrane to protect the lateral window, reports support L-PRF isolated use in sinus-lifting procedures26.
According to current research, L-PRF enhances alveolar preservation around dental implants and in extraction sockets22. When comparing L-PRF-treated sites to control sites with only blood clots, studies have shown significant improvements in alveolar ridge contour, socket bone fill, vertical gain of the buccal cortical plate, and bone density11. Additionally, L-PRF has been associated with reduced patient discomfort, as indicated by visual analog scale scores27. In third molar extractions, L-PRF has been shown to decrease the incidence of alveolar osteitis in the first week after mandibular third molar surgery, reducing the risk by 62% compared to untreated sites22. L-PRF also correlates with less postoperative pain, reduced swelling28,29, and improved hard tissue healing30. For post-extraction socket management, we recommend placing an L-PRF plug in the socket to accelerate angiogenesis, facilitate tissue remodeling, promote cell migration, prevent necrosis, and reduce infection risk. Additionally, covering this plug with an additional L-PRF membrane can help protect and close the wound, stimulate the wound margins, act as a barrier against contaminants, and prevent competing tissue ingrowth.
In addition to the uses of L-PRF discussed in the clinical cases presented in this article, such as closing oroantral communications, post-extraction treatment of third molars, sinus lifting, and alveolar preservation, other studies highlight additional applications of L-PRF. For instance, L-PRF combined with iliac crest grafts has significantly improved outcomes in promoting bone regeneration for alveolar cleft reconstruction22. In partially edentulous patients, L-PRF reduced peri-implant bone resorption following tooth extraction with immediate implant placement31, enhancing implant stability during the early healing phase and promoting faster osseointegration32. L-PRF has also effectively filled bone defects in cystic lesions post-enucleation33. In cases of osteonecrosis of the jaw, L-PRF promoted rapid epithelialization within 4 weeks to 3 months, resulting in complete bone closure in most cases11.
However, it is essential to highlight that the technique can be sensitive to the operator and their ability to collect the blood and quickly centrifuge the sample. This is because, in the absence of an anticoagulant, blood samples coagulate nearly instantly as they come into contact with the tube walls, and centrifugation only takes a few minutes to concentrate fibrinogen in the tube34. Quick handling is the only way to obtain a clinically usable L-PRF clot. Consequently, failure will result from an excessively lengthy time needed to gather blood and begin centrifugation; the fibrin will polymerize in the tube, dispersed, producing only a tiny, inconsistent blood clot1. In that way, the quickness of blood collection and prompt transfer to the centrifuge, typically within a minute, are critical to the L-PRF technique’s success7. The fibrin architecture of L-PRF is significantly affected by the centrifugation procedures and the properties of the centrifuge itself. A concern arises from vibrations exceeding the recommended levels in some machines on the market. Elevated vibration levels during the centrifugation process can harm the cellular content and disrupt the organization of fibrin17.
Regarding venipuncture, a peripheral venous catheter can be used for administering fluids, nutrients, medications, and blood products, as well as for collecting blood for laboratory testing, as in the present study. However, its use is not without risk of complications, which may include local or systemic events that compromise patient safety35. Phlebitis and catheter-associated infections are among the most common complications associated with this procedure. To minimize such risks, it is recommended to select appropriate devices based on the insertion site, to use disposable tourniquets at a safe distance from the puncture site, and to adopt tools that assist in the visualization of blood vessels through imaging devices36. To reduce the occurrence of these complications and improve the technique, simulation-based education has been increasingly incorporated into the training of healthcare professionals. As applied in this study, simulated skills training using mannequins or anatomical models that mimic the human body allows for repeated practice of the procedure prior to performing it on actual patients, thereby reducing potential risks37.
The cases presented confirm that PRF can enhance healing, reduce post-operative discomfort, and support bone regeneration in oral and maxillofacial surgery11,24,27. However, its inclusion should be evaluated case by case, considering patient-specific needs and treatment goals. While PRF is not necessary in all procedures, it is highly recommended in cases requiring accelerated healing, reduced infection risk, or enhanced bone formation, such as complex extractions or bone defect treatments12,22,30,38. Future studies, particularly large randomized trials, are suggested to standardize PRF protocols and assess long-term outcomes across different patient profiles, especially those with systemic health conditions. The use of PRF is a promising, cost-effective, and biocompatible option to improve outcomes in suitable cases.
V. Conclusion
The clinical cases presented in this study underscore the effective application of PRF in various oral and maxillofacial procedures. From post-extraction socket preservation to the closure of oroantral communications and sinus lift, PRF proved to be a cost-effective, biocompatible solution with significant potential to improve patient outcomes.
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