Unlocking the Regenerative Power of Platelet-Rich Fibrin

In recent years, regenerative medicine has made a remarkable impact, showing its potential across different fields, including dentistry. Platelet-rich fibrin (PRF), a platelet concentrate derived from the patient’s own blood, has gained significant attention for its wound healing and tissue regeneration properties. This article explores the benefits, applications, and evolving role of PRF in modern dentistry.

PRF is an autologous concentration of platelets in a fibrin matrix.¹ The process entails a simplified method in which a patient’s blood is centrifuged at specific speeds, leading to the formation of PRF clot which is rich in natural platelets, growth factors, and leukocytes. Unlike platelet-rich plasma (PRP), PRF does not require biochemical handling and is therefore simple to prepare and apply.

The initial concept behind creating platelet concentrates was to collect concentrated platelets and natural growth factors in plasma solutions, which could then be applied to surgical sites to enhance local healing.² This technique, introduced in the late 1990s, became known as PRP.³ PRP consists mostly of platelets that release growth factors to actively start the wound healing process and enhance cell adhesion, proliferation, and migration.⁴ Around the same time, another platelet concentrate was introduced that used anticoagulants called platelet-rich growth factor (PRGF).⁵

However, there are several limitations to using PRP and PRGF. Their preparation requires additional coagulation factors such as bovine thrombin or CaCl2. The process also involves two separate centrifugation stages to concentrate platelets without including leukocytes, which sometimes can take up to an hour. The resulting liquid nature of PRP complicates handling, limiting its applications, as it needs to be used with other biomaterials to improve handling. Additionally, PRP has a very short growth factor release profile, hindering its potential for bone regeneration.⁶ These challenges have led to the creation of a second-generation platelet concentrate, PRF, which is made entirely from autologous sources.⁷

Biological Rationale

PRF’s underlying strength lies in its naturally formed concentration mixture of growth factors including platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-b), vascular endothelial growth factor (VEGF), and various cytokines.⁸ These growth factors play a pivotal role in tissue healing and regeneration by stimulation normal cell proliferation, migration, and differentiation.

Physiologically, after an injury is made, wound healing occurs in four overlapping phases: initial hemostasis, the inflammatory phase, the proliferative phase, and the remodeling phase. Platelets manage hemostasis by blocking blood vessels and promoting fibrin clot formation. During the inflammatory phase, white blood cells and platelets release cellular products that start the healing process. Applying PRF to a wound site enhances healing due to the concentrated growth factors in PRF, which facilitate cell migration, proliferation, and differentiation.⁹ Table 1 shows the applications in dentistry.^10-13

Sinus Lift Procedures

The versatility of PRF to promote bone healing with regards to sinus augmentation has been documented in recent years both as a sole material but also in combination with other biomaterials. Traditionally, sinus lift procedures, as described by Boyne and James in 1980, involved access to the sinus via a lateral window.¹⁴ The use of graft materials, including autogenous bone, allografts, xenografts, and combinations of the various materials, have been well studied as part of the traditional sinus lift.¹⁵

The use of PRF in a sinus lift procedure represents a different modality to maxillary sinus grafting. When used in combination with grafting material or independently, PRF can provide a reservoir for growth factors to act directly on osteoblasts, fibroblasts, and endothelial cells.¹⁶ This interaction can lead to tissue regeneration, potential to recruit circulating stems cells, and the ability to promote wound closure using epithelial tissues.

A recent systematic review found that nine out of 13 controlled studies reported positive results for PRF in soft tissue regeneration and wound healing. Histomorphometry assessments have shown that new bone formation with the combination of PRF and biomaterials ranges from 17% to 45%, compared to 13% to 33% with biomaterials alone.¹⁷ Meta-analysis indicated a 1.98% increase in new bone formation with the addition of PRF to biomaterials, though these findings were not statistically significant and exhibited moderate heterogeneity across studies. Regarding residual biomaterial, pooled analysis demonstrated a statistically significant reduction of 4.60% when PRF was used.

Dental Extraction Procedures

PRF significantly accelerates both soft and hard tissue healing. The high concentration of platelets and growth factors stimulates cell proliferation, differentiation, and extracellular matrix formation essential for wound healing. Studies indicate that PRF enhances tissue regeneration and accelerates the healing process, leading to quicker recovery times and improved patient comfort.¹⁸ One of the primary benefits of PRF in dental extractions is its ability to reduce post-operative pain, swelling, and the risk of complications such as dry sockets. By forming a protective barrier over the wound, PRF maintains the integrity of the blood clot, which is critical for proper healing, and protects the extraction site from bacterial invasion and external irritants.¹⁹ PRF is particularly beneficial in cases requiring bone regeneration, such as in patients undergoing bone grafting procedures.

The growth factors in PRF enhance the production of new bone cells, accelerating bone regeneration and ensuring proper healing of the extraction site. This is crucial for maintaining the structural integrity and functionality of the jawbone, especially in preparation for dental implants. PRF also aids in graft stabilization, providing a scaffold for new bone growth and improving the outcomes of grafting procedures.¹⁸

Periodontal Defects

PRF has been particularly effective in the treatment of periodontal intrabony defects. When applied to these defects, PRF enhances bone regeneration and supports the healing of the periodontal ligament and cementum. Meta-analyses demonstrate that using PRF alone or in combination with other regenerative materials significantly improves clinical outcomes compared to traditional treatments.²⁰

PRF significantly enhances periodontal tissue regeneration by releasing key growth factors such as PDGF and TGF-β. These growth factors stimulate the proliferation and differentiation of cells essential for tissue repair, including fibroblasts and osteoblasts. A 2023 systematic review and network meta-analysis found that the use of PRF in periodontal intrabony defects significantly improves clinical parameters such as probing depth, clinical attachment level, and bone fill compared to other treatments.²¹

Additionally, a recently randomized controlled trial highlighted that the adjunctive use of collagen membrane with PRF in the treatment of periodontal intrabony defects resulted in significantly better clinical outcomes than PRF alone.²² These studies have supported the evidence that PRF enhances bone regeneration and supports the healing of the periodontal ligament and cementum. This is crucial in ensuring the long-term stability and functionality of the periodontium. Therefore, when possible, the use of PRF in periodontal intrabony defects may result in significant improvements in clinical outcomes compared to traditional methods.

Endodontic Therapy

PRF has been effectively used in conjunction with other materials for root canal treatments, leading to improved clinical outcomes. For example, PRF combined with calcium hydroxide has shown enhanced results in promoting periapical healing. Additionally, PRF can be used as a scaffold for regenerative endodontic procedures, supporting the regeneration of pulp-dentin complex in immature teeth with necrotic pulps.²³

Traditional methods, like apexification, have aimed to stimulate the formation of a calcific barrier at the root apex. However, newer techniques involving biological materials such as PRF and demineralized bone matrix (DMBM) are emerging as promising alternatives. In a case report on an 18-year-old man who presented with a fractured upper central incisor with an open apex from previous trauma, apexification was performed using DMBM and PRF along with mineral trioxide aggregate (MTA) as an apical barrier. After removal of necrotic pulp tissue, irrigating with sodium hypochlorite, and placing a calcium hydroxide medicament, a mixture of DMBM and PRF was placed into the canal to form an apical barrier, followed by MTA placement and final restoration. During the subsequent follow up visits, radiographic evidence indicated bone healing and complete apical closure after 3 months.²⁴

In surgical endodontic procedures, such as apicoectomy, the application of PRF has enhanced healing of the surgical site. PRF serves as a matrix that supports new tissue growth and helps seal the surgical site, which reduces the risk of post-surgical complications and improves overall healing outcomes. In a recent case report, PRF was used in conjunction with an apicoectomy for treatment of a radicular cyst, resulting in an accelerated healing rate.²⁵

Implant Dentistry

One of the primary benefits of PRF in implant dentistry is its ability to enhance osseointegration.²⁶ PRF provides a scaffold for new bone growth and delivers essential growth factors that stimulate osteoblast activity. Studies have demonstrated that the application of PRF around dental implants can significantly increase bone-to-implant contact, thereby improving the stability and integration of the implant into the surrounding bone.

PRF has also been shown to accelerate soft tissue healing around dental implants. The fibrin matrix in PRF acts as a scaffold for cell migration and proliferation, promoting the formation of new blood vessels and connective tissue. This results in faster wound healing and improved gingival health, which is crucial for the long-term success of dental implants.²⁷

Advantages of Platelet-Rich Fibrin

PRF offers a wide array of benefits in the practice of dentistry, including but not limited to:

1. PRF’s natural biological structure includes PDGF, TGF-b, and VEGF which accelerate wound healing, support the formation of new blood vessels (angiogenesis), and stimulate the proliferation of osteoblasts and fibroblasts.²⁸
2. The fibrin matrix of PRF enhances tissue regeneration by providing a natural scaffold that supports cell migration and proliferation.²⁸
3. Recent studies have shown that PRF has inherent antimicrobial properties that reduce post-operative infections.²⁹
4. The use of PRF is a minimally invasive procedure utilizing the patient’s blood, thus eliminating the risk of allergic reactions and disease transmission.¹⁹
5. The preparation of PRF is straight forward with appropriate training, minimal cost to both the practitioner and patient, and versatile in its dental applications.
6. As an alternative to using costly biomaterial for regeneration, PRF utilizes a patient’s own autologous nature.

Conclusion

In summary, this review highlights the extensive application of PRF in various dental clinical settings. Despite being relatively unfamiliar to many clinicians, the accumulated evidence over the years supports PRF’s effectiveness in enhancing tissue regeneration. PRF is a valuable addition to the dental regenerative toolbox. PRF combined with regenerative therapy has shown significant promise for periodontal repair of intrabony and furcation defects, as well as soft tissue root coverage for gingival recessions.

Additionally, literature suggests that PRF can reduce infection post-tooth extraction and potentially minimize dimensional changes following tooth loss. The versatility of PRF in clinical applications is evident in its use for various bone grafting procedures, including socket preservation, ridge augmentation, and sinus lifts. Studies have shown that PRF not only enhances the integration of graft materials but also stabilizes them, ensuring better retention and effectiveness. However, more research is needed to determine its efficacy in bone defect regeneration, including guided bone regenerative procedures and sinus elevation. Despite this, its ease of use, low cost, and autologous nature make it a valuable biomaterial for further exploration in dental surgery.

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From Decisions in Dentistry. March/April 2025;11(2):40-45.