What is Platelet-Rich Fibrin (PRF)?

What is Platelet-Rich Fibrin (PRF)?

PRF is a second-generation autologous platelet concentrate derived from the patient's own blood that forms a three-dimensional fibrin matrix containing concentrated platelets, leukocytes, and growth factors, prepared through simple centrifugation without chemical additives or anticoagulants. 1

Classification and Variants

PRF exists within a broader classification system of autologous platelet concentrates that distinguishes products based on cellular composition 1:

• PRF (Platelet-Rich Fibrin): Contains <1% leukocytes and <10% red blood cells 1
• L-PRF (Leukocyte-Rich PRF): Contains ≥1% leukocytes, the most commonly used variant in clinical practice 1
• Red-PRF: Contains ≥10% red blood cells 1
• Red-L-PRF: Contains both ≥1% leukocytes and ≥10% red blood cells 1

The classification system also accounts for activation method (none, with activator, or with specific protocols), platelet concentration levels (A, B, or C), and preparation technique (gravitational centrifugation, cell separators, or plateletpheresis) 1.

Preparation Method

Standard L-PRF Protocol

The preparation is straightforward and performed chairside 1:

1. Blood Collection: Draw 4-8 tubes (9-10 mL each) of blood using 21G butterfly needle into special glass tubes or silica-coated plastic tubes that promote coagulation 1
2. Immediate Processing: Rotate tubes immediately after blood draw to increase contact between inner tube surface and blood, accelerating coagulation 1
3. Centrifugation: Centrifuge at 408g (relative centrifugal force) for minimum 12 minutes after the last tube is loaded 1
4. Extended Time for Anticoagulated Patients: If patient takes anticoagulant medication, extend centrifugation to 18-20 minutes 1
5. Clot Extraction: Remove L-PRF clots from tubes and carefully separate from red blood cells, preserving the face portion which contains the highest biological activity 1

Creating L-PRF Membranes

After clot formation 1:

• Place L-PRF clots in compression box for gentle compression by gravity using light metal plate
• After 5 minutes, membranes are ready for use
• Membranes remain viable for at least 3 hours when kept covered in compression box to prevent drying 1

Biological Properties and Mechanisms

PRF functions through multiple regenerative pathways 1, 2:

• Controlled Growth Factor Release: Sustained release of growth factors from platelet α-granules that stimulate angiogenesis, cell migration, proliferation, and differentiation 3, 4
• Structural Scaffold: Three-dimensional fibrin architecture with high density, elasticity, flexibility, and strength provides temporary matrix for cellular regeneration and tissue remodeling 3, 2, 4
• Enhanced Angiogenesis: Promotes new blood vessel formation critical for tissue healing 1, 2
• Antibacterial and Analgesic Activity: Reduces infection risk and provides significant post-operative pain reduction 1, 2
• Stem Cell Differentiation: Promotes stem cell differentiation toward osteoblasts for bone regeneration 1, 2
• Anti-inflammatory Effects: Shifts macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype 1, 2
• Cell Attachment: Fibrous structure conducive to cell attachment and migration 1, 2

Clinical Applications

Established Dental and Oral Surgery Uses

The most robust evidence supports PRF in oral and maxillofacial applications 1:

• Alveolar Ridge Preservation: Maintains bone volume after tooth extraction 1
• Guided Tissue Regeneration (GTR): Promotes periodontal tissue regeneration 1, 5
• Guided Bone Regeneration (GBR): Enhances bone formation when combined with bone grafts 1, 5
• Sinus Floor Elevation: Both lateral window approach and transcrestal technique 1, 5
• Endodontic Surgery: Promotes healing of periapical tissues 1
• Medication-Related Osteonecrosis Treatment: Aids in managing jaw bone necrosis 1
• Periodontal Plastic Surgery: Including gingival recession treatment where 3-4 L-PRF membranes provide results comparable to connective tissue grafts with significantly less post-operative pain 1, 2

Facial Esthetics and Dermatology

PRF shows promise in cosmetic applications 1:

• Acne scarring treatment 1
• Skin rejuvenation and anti-aging 1, 6
• Melasma management 1
• Vitiligo treatment 1
• Stretch mark reduction 1
• Peri-orbital and peri-oral rejuvenation 1
• Hair regeneration for androgenetic alopecia 1, 7
• Volumizing effects when used as injectable PRF or albumin gel formulations lasting 4-6 months 1

Recent studies demonstrate superior outcomes using PRF compared to traditional PRP in facial esthetics, though the evidence base remains limited by small sample sizes and lack of standardized protocols 1.

Applications with Uncertain Evidence

The International Society on Thrombosis and Haemostasis rates several applications as uncertain (median scores 4-6.5 out of 9) 1, 3:

• Burn injuries
• Tendon injuries
• Acute muscle injuries
• Bone healing in orthopedics
• Sports injuries
• Osteoarthritis treatment

Advantages Over First-Generation PRP

PRF offers distinct advantages over traditional platelet-rich plasma 8, 6, 9:

• No Chemical Additives: Completely autologous without anticoagulants or bovine thrombin 8, 9
• Simplified Preparation: Single-spin centrifugation protocol versus two-spin PRP preparation 9
• Prolonged Growth Factor Release: Fibrin matrix provides sustained release over 7-14 days versus rapid release with PRP 6, 9
• Superior Handling: Solid membrane form allows suturing and precise placement versus liquid PRP 2, 8
• Enhanced Cellular Content: Contains higher concentrations of leukocytes and their associated growth factors 9
• Cost-Effective: Minimal instrumentation required, no expensive activation agents needed 8, 7

Critical Limitations and Standardization Issues

The field suffers from severe lack of standardization that directly impacts clinical outcomes 1, 3, 2:

• Different preparation techniques result in significant variations in platelet yields, concentration, purity, viability, and activation status 3, 2
• Many clinical trials fail to adequately define or quantify PRF biological properties, leading to varying efficacies and unreliable conclusions 2
• The International Society on Thrombosis and Haemostasis notes insufficient data exist to develop evidence-based guidelines for most regenerative medicine applications, requiring consensus-based recommendations instead 2, 4
• Small deviations from optimal protocol can result in unfavorable clinical outcomes 1
• Violations from optimal surgical technique or treatment by less experienced clinicians often explain failures 2

Safety Profile

PRF demonstrates excellent safety characteristics 1, 3, 4:

• Completely autologous nature minimizes immunogenicity risk and foreign body reactions 1, 4
• Cost-effective and minimally invasive 1, 3, 4
• No reported serious adverse events in clinical literature 8
• Proper sterile technique during preparation and application remains essential 4

Future Directions

The field requires 1, 3:

• Well-designed randomized controlled trials with appropriate controls (split-face comparisons for esthetics)
• Standardized protocols for optimal number of sessions and intervals between treatments
• Objective improvement scoring systems
• Quality control measures ensuring clear correlations between product characteristics and clinical outcomes
• Further mechanistic studies on platelet tissue regeneration to identify optimal combinations of bioactive factors