What are the differences and applications of Platelet-Rich Plasma (PRP), Platelet-Rich Fibrin (PRF), and Growth Factor Concentrate (GFC) in medical treatments?

Comparison of PRP, PRF, and GFC in Regenerative Medicine

PRF offers theoretical advantages over PRP due to its sustained growth factor release and simpler preparation without chemical activation, though both remain poorly standardized with uncertain clinical efficacy across most applications. 1

Fundamental Differences in Preparation and Composition

Platelet-Rich Plasma (PRP)

• Requires double-spin centrifugation at higher speeds to concentrate platelets, achieving 1 to 1.5 million platelets per microliter 1, 2
• Demands chemical activation using calcium chloride, autologous thrombin, or collagen type I to release growth factors 2
• Must use citrate, ACD, or CPD anticoagulants—never EDTA, which causes premature platelet activation 1, 2
• Preparation is time-sensitive: process within 1 hour of collection and use within 4-6 hours 2
• Results in liquid platelet suspension that requires activation before clinical use 1

Platelet-Rich Fibrin (PRF)

• Uses single, low-speed centrifugation without anticoagulants or chemical additives 3, 4
• Forms natural three-dimensional fibrin scaffold that entraps platelets, leukocytes, and growth factors 1, 4
• Provides slow, sustained growth factor release over days to weeks, unlike PRP's immediate burst release 3, 4
• No activation required—the fibrin matrix forms naturally during preparation 1, 4
• More cost-effective and simpler to prepare with minimal instrumentation 1, 5
• Contains higher concentrations of collagen type-1 and lymphocytes compared to PRP 5

Growth Factor Concentrate (GFC)

• No specific evidence provided in the available guidelines or research distinguishing GFC as a separate entity from PRP or PRF 1
• The term appears to be marketing terminology rather than a scientifically distinct preparation method

Critical Standardization Problems Affecting All Preparations

The International Society on Thrombosis and Haemostasis emphasizes that clinical preparations are severely poorly standardized, with content, purity, and biological properties varying widely and directly impacting clinical efficacy. 1

• Centrifugation protocols dramatically alter outcomes: platelet concentration, yield, and recovery depend entirely on g-force, duration, and collection methods 1
• Most clinical trials fail to define the content, purity, and biological properties of their platelet preparations 1
• The term "PRP" is confusing, too general, and incomplete according to expert consensus 1
• Temperature control during preparation shows strong positive correlation (r = 0.79) with efficacy 6

Clinical Applications and Evidence Quality

Androgenetic Alopecia (Hair Loss)

• PRF demonstrates clinical efficacy with safe, cost-effective results and theoretical advantages over PRP 1
• PRP evidence remains controversial despite increased clinical trials, due to variable preparations, protocols, and inadequate follow-up periods 1
• Indian Association of Dermatologists recommends for PRP: 3-5 sessions at 1-month intervals, 5-7 mL per session, using double-spin method, with 1 to 1.5 million platelets/μL 1
• PRF protocol: 1 session every 4-6 weeks for 3 sessions annually, then maintenance every 6 months 1

Wound Healing and Tissue Regeneration

• General wound healing is the only established application with ISTH expert score of 7/9 for PRP 7
• PRF promotes soft tissue healing and wound closure through its fibrin scaffold and sustained growth factor release 1, 4
• Both are considered clinically safe due to autologous nature with minimal immunogenicity risk 1, 7

Musculoskeletal Applications

• Evidence is uncertain for tendon injuries, acute muscle injuries, bone healing, sports injuries, and osteoarthritis (ISTH median scores 4-6.5/9) 7
• American Academy of Orthopaedic Surgeons lacks definitive endorsement despite acknowledging potential benefits 7
• VA/DoD guidelines found mixed results for knee and hip osteoarthritis, unable to recommend for or against use 8

Dermatologic Applications

• Fluid PRF shows significantly higher therapeutic response than PRP for atrophic acne scars, both alone and combined with microneedling 3
• PRF produces higher cumulative growth factor release making it ideal for tissue regeneration and growth stimulation 3

Practical Clinical Algorithm

When considering autologous platelet concentrates:

1. First, recognize the evidence limitations: Both PRP and PRF have uncertain efficacy for most applications except general wound healing 1, 7

2. Choose PRF over PRP when:

   • Seeking sustained growth factor release over days to weeks 3, 4
   • Wanting simpler, more cost-effective preparation 1, 5
   • Treating androgenetic alopecia or acne scars 1, 3
   • Avoiding chemical activation is preferred 1, 4

3. Choose PRP when:

   • Following established protocols with specific platelet concentration requirements 1, 2
   • Immediate growth factor release is desired 3
   • Using in combination with specific surgical procedures requiring liquid form 2

4. Avoid GFC terminology as it lacks scientific distinction and represents marketing rather than evidence-based classification 1

Critical Pitfalls to Avoid

• Never use EDTA anticoagulant for PRP preparation—it causes premature platelet activation 1, 2
• Do not store PRP at 4°C—cold activation occurs prematurely 2
• Avoid claiming equivalence between different preparation methods—they produce fundamentally different products with varying efficacy 1, 6
• Do not promise definitive outcomes—evidence remains uncertain for most applications beyond general wound healing 1, 7
• Never skip documentation of specific preparation methods, as this critically impacts reproducibility and outcomes 2, 6
• Avoid activation of PRP for androgenetic alopecia—it is not required and may be counterproductive 1

Mechanism of Action Differences

PRP delivers immediate burst release of growth factors from α-granules upon activation, promoting rapid angiogenesis, cell migration, and proliferation 7, 4

PRF provides sustained release through its fibrin matrix that acts as a temporary three-dimensional scaffold, supporting cellular regeneration and tissue remodeling over extended periods 1, 7, 4

Both contain multiple growth factors including PDGF, VEGF, and others that promote local angiogenesis, stem cell homing, and tissue differentiation 7, 8