Platelet-Rich Fibrin provides numerous growth factors, biochemical activators, biologic glue, and scaffolding matrix for accelerated tissue repair

Platelet-Rich Fibrin (PRF) provides a fibrin scaffolding matrix with numerous growth factors, biochemical activators, and cellular glue that have been shown to enhance healing and regeneration of tendon, ligament, muscle, and joints. PRF is a biomaterial and orthobiologic agent that promotes optimal healing with an activated fibrin matrix that helps "glue" damaged connective tissues like tendon, ligament, labrum, cartilage, meniscus, and muscle, thereby giving the injured tissue a scaffolding on which to build new tissue as well as many cellular growth factors that drive tissue repair. White blood cells (leukocytes) also influence the early differentiation of bone, cartilage, and tendon progenitor cells (and in fact are an essential factor in animals that can regenerate body parts), and specific PRF protocols can activate white blood cells (particularly monocytes and platelets in the matrix) to secrete cell signaling growth factors like BMP-2, BMP-7, FGF, VEGF, PDGF, IGF-1, TGF-Beta, Thrombospondin, and α2-macroglobulin, which act at the targeted injection site over many days to weeks to accelerate and strengthen tissue repair with improved collagen synthesis [1-12, 88-89]. These same growth factors from platelets are what initiate healing of cuts, wounds, scrapes, and bruises in superficial wounds, but we further concentrate and maximize these natural healing factors directly at your injury site under image-guidance for maximal benefit in tendon, ligament, labrum, meniscus, and cartilage injuries as well as bone fractures. With each type of injury, it is also essential to understand when to use leukocyte-rich versus leukocyte-poor preparations, when to use platelet-rich fibrin versus plasma, and how to inject at the optimal site of an injury using image-guidance.

With its many healing factors, PRF has been shown to enhance repair of discs, joints, tendon, ligament, cartilage, meniscus, nerve, muscle, and bone, producing specific effects on proliferation of myocytes, fibroblasts, osteocytes, chondrocytes, tenocytes, and myelinating cells [1-15, 18-47, 50-80]. For example, meta-analysis review of multiple high-quality randomized clinical studies of PRP therapy for tendinopathy found significant benefits of PRP over any other interventional therapy, with a beneficial effect size approximately 2-3X greater than controls or corticosteroid injections [30,102-103], and these benefits were further enhanced when ultrasound-guidance was used for the injection as we always do at our clinic. These studies did not even account for the many different types and grading stages of tendinopathy which influence treatment plans, nor did they combine other regenerative agents, nor did they utilize newer techniques and more effective variations of plasma-derived agents like PRF [28-30]. PRF and its signaling factors have been shown to activate recruitment and differentiation of Mesenchymal Stem Cells (MSCs) as well as enhance expression of several essential tissue remodeling genes [66-69]. PRF can also be used as a medium for numerous types of stem cells which enhances stem cell survival, proliferation, and differentiation in mesenchymal tissue injuries of tendon, ligament, cartilage, muscle, and bone [63-75]. There are many types of meniscus tears, and PRF or PRP can be injected around the meniscal tear or directly into the injury site under ultrasound guidance (depending on the type of tear) to maximize healing of this poorly-vascularized tissue [91-97]. PRF can also be used to stimulate and accelerate repair of muscle injuries and may also provide ergogenic effects that enhance muscle performance (particularly via the growth factors of IGF-1, VEGF and bFGF), and neither PRF nor PRP are banned by anti-doping agencies [1,89].

Alpine Athletic Medicine was one of the first clinics to perform PRF repair and to use direct ultrasound-guided visualization to maximize repair at the exact injury site while minimizing any needle damage. For tissue and joint regeneration, PRF has the advantage of causing platelet binding to fibrin, which initiates biochemical activation of certain cells, platelets, and growth factors and also provides an organized scaffolding matrix and fibrin glue. Furthermore, PRF has been shown to help regenerate new hyaline cartilaginous matrix even in full-thickness articular cartilage defects, making it a powerful tool in the investigation and treatment of severe osteoarthritis as well as other arthropathies. It can also be effectively applied to ligament strains and joints to help heal, seal, anneal, strengthen, tighten, and stabilize these kinds of tissue and joint injuries, and ongoing studies have also shown significant effectiveness in low back pain and spinal disorders like facet joint arthritis, discogenic pain, and other spine pathologies [1-6, 8-9].

Fibrin sealant can be used to help patch and seal annular and radial tears of spinal discs, and more importantly can also serve as an essential anchoring matrix to help stem cells stick, integrate, and rebuild injured tissues. PRF thus provides not only a tissue sealant and scaffolding matrix for strengthening and repairing connective tissues, but also provides many healing growth factors to optimize repair integrity. Fibrin has also been used by many neurosurgeons to repair peripheral nerves, and with proper use PRF has been shown to promote schwann cell proliferation and remyelination of peripheral nerves [31-47, 98, 106-108], which is immensely useful in cases of nervous system injuries, neural trauma, peripheral neuropathy, and nerve repair, especially when used in combination with stem cells. Dr. McMurtrey originally developed image-guided regenerative PRF repair techniques for his own tendon, ligament, spine, and nerve injuries. PRF has shown such good regenerative potential in a variety of connective tissues and can be highly effective in numerous other tendon, joint, meniscus, cartilage, and ligament injuries like shoulder labrum tears, rotator cuff tears, tendinopathies, joint separations, non-healing bone fractures, SI joints, hip joints, knee joints, patellar tendonosis, epicondylar tendonitis, achilles tendonitis, plantar fasciitis, ligament laxity, and many other tendon and ligament injuries, helping to enhance healing and avoid surgery [1-6, 10-15, 18-31, 50-80, 104-105].

PRF vs PRP: Both of these orthobiologic agents are drawn from your own blood and purified into specific layers in a centrifuge. Specific proteins, platelets, cells, cell lysates, and growth factors are super concentrated to address your specific pathology and match the specific needs of the tissue injury. For example, PRP can be a powerful supply of regenerative growth factors as well as a lubricant in joints. However, research has shown that maximizing the concentration of platelets, fibrin, and circulating stem cells (which are a small percentage cells in the white blood cell layer) is significantly more effective than traditional platelet-rich plasma in many applications, and this is achieved with new PRF purification techniques. PRF can be customized to contain different amounts of specific factors (such as fibrin, leukocytes, monocytes, glucose, and circulating stem cells) depending on your particular injury or condition, and PRF does not contain artificial anticoagulants or additives like PRP often does. Instead, PRF contains significantly higher concentration of platelets (3-5X higher than PRP) which are vesicles that provide growth factors to stimulate tissue repair. More importantly, PRF also contains highly concentrated fibrin matrix, which serves multiple roles as a reparative scaffolding graft to accelerate healing in injured tissues, as an essential binder and activator of platelets to stimulate release of their growth factors at the injury site, and as a guiding matrix for stem cell migration into the target area [57, 81-88]. However, in certain cases there may be indications for PRP only, and we are able to do leukocyte-rich or leukocyte-poor PRP preparations depending on your needs.

Advanced PRF protocols can maximize α2-macroglobulin ("alpha-2M" or "A2M") in the PRF as a potent regenerative and protective therapy for osteoarthritis conditions [51-56]. Alpha-2-Macroglobulin can be purified from your own blood proteins, and it acts as a master inhibitor of many types of cartilage-destroying enzymes and inflammatory signals, which makes it a novel therapeutic agent for treating cartilage diseases such as osteoarthritis, post-traumatic arthritis, degenerative disc disease, and many other arthropathies and inflammatory conditions (without all the downsides of steroid injections). Also, certain fibrin and plasma preparations have been shown to lubricate arthritic joints, fill cartilage defects, and suppress inflammation and pain in osteoarthritis [76-80]. Similarly, "Autologous Conditioned Serum" (ACS) can also be purified and used for many conditions of arthritis, nerve compression, tendinopathies, and musculoskeletal pathologies. Additional novel osteoarthritis treatments can also be combined with PRF (including certain glycosaminoglycans and peptides) for numerous degenerative joint and spinal conditions, and these are some of the only therapies that have evidence of regenerating cartilage degradation and protecting against osteoarthritic changes [51-61, 65-68, 74-90].

Of note, many practitioners continue to use high-dose steroid injections ("cortisone shots") as a shotgun approach for many orthopedic ailments even though these medications cause atrophy of tendon, ligament, cartilage, bone, and skin due to downregulation and suppression of collagen synthesis, thus causing worsening degradation or recurrence of the problem and deleterious feedback cycles [17-24, 62]. There are actually only a few instances where corticosteroids should be used (primarily for actual inflammatory processes, for certain types of joint diseases, for some types of ligament thickening, for nerve entrapments, and rarely for some types of chronic or repetitive degradative injuries, etc). Many other options-- including PRF, peptides, biologics, and other medications-- promote connective tissue rebuilding rather than inhibit it as corticosteroids do, and have proven significant improvements in many conditions like tendinopathy [1-6, 18-31].

Interestingly, because of the many biochemical healing factors in these plasma therapies, PRF and PRP are being studied for many other applications and therapies like neuroprotection and nerve repair as described above. Recent new studies have also shown the ability of PRP to restore olfactory neuron function in patients with anosmia (smell loss) due to COVID viral infection [99-101]. In addition, due to the presence of specific growth factors in PRF, injections of PRF along with certain peptides have been shown to restore hair follicle stem cell growth and enhance hair regrowth in the scalp [48-49], and PRF can also easily be used in the clinic as a natural filler for skin wrinkles and cosmetic procedures like natural butt lift or breast augmentations.

(1) Platelet-Rich Fibrin and Its Emerging Therapeutic Benefits for Musculoskeletal Injury Treatment
(2) Platelet-Rich Fibrin Scaffolds for Cartilage and Tendon Regenerative Medicine: From Bench to Bedside
(3) Advanced Platelet-Rich Fibrin: Biological Achievements and Clinical Advances in Modern Surgery
(4) Leucocyte and Platelet‐rich Fibrin: a carrier of autologous multipotent cells for regenerative medicine
(5) Cytokine and Growth Factor Delivery from Implanted Platelet-Rich Fibrin Enhances Rabbit Achilles Tendon Healing
(6) Do the fibrin architecture and leukocyte content influence the growth factor release of platelet concentrates?
(7) The impact of the centrifuge characteristics and centrifugation protocols on the cells, growth factors, and fibrin architecture of a leukocyte- and platelet-rich fibrin (L-PRF) clot and membrane
(8) Blood products in the management of chronic low back pain: a critical review
(9) Use of Blood Products in Treating Low Back Pain: A Review of the Current Literature
(10) Biologically based strategies to augment rotator cuff tears
(11) Platelet-Rich Fibrin Clot–Augmented Repair of Horizontal Cleavage Meniscal Tear
(12) Effect of Autologous Platelet Rich Fibrin on the Healing of Experimental Articular Cartilage Defects of the Knee in an Animal Model
(13) Advancing regenerative surgery in orthopaedic sports medicine: the critical role of the surgeon
(14) The Clinical Use of Human Culture-Expanded Autologous Bone Marrow Mesenchymal Stem Cells Transplanted on Platelet-Rich Fibrin Glue in the Treatment of Articular Cartilage Defects
(15) Platelet-Rich Fibrin and Soft Tissue Wound Healing: A Systematic Review
(16) Reduction of Relative Centrifugal Forces Increases Growth Factor Release within Solid Platelet-Rich-Fibrin (PRF) Matrices
(17) Glucocorticoids and collagen synthesis
(18) A Double Blind Randomised Control Trial of High Volume Image Guided Injections in Achilles and Patellar Tendinopathy
(19) The Effect of Glucocorticoids on Bone and Muscle
(20) Molecular Actions of Glucocorticoids in Cartilage and Bone
(21) Downregulation of Type I Collagen Expression in the Achilles Tendon by Dexamethasone
(22) The Effect of Intra-articular Corticosteroids on Articular Cartilage
(23) Systemic Corticosteroids in the Early Inflammatory Phase
(24) Arthritis and the Role of Endogenous Glucocorticoids
(25) Fibroblast Growth Factors: Biology, Function, and Application for Tissue Regeneration
(26) Chronic lateral epicondylitis: challenges and solutions
(27) Evaluation and Management of Elbow Tendinopathy
(28) Injection Therapies for Lateral Epicondylalgia: a Systematic Review and Bayesian Network Meta-Analysis
(29) Comparative Effectiveness of Injection Therapies in Lateral Epicondylitis: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
(30) The Effectiveness of Platelet-Rich P in the Treatment of Tendinopathy: A Meta-Analysis of Randomized Controlled Clinical Trials
(31) Effects of Leukocyte-Platelet Rich Fibrin (L-PRF) on Suppression of the Expressions of the Pro-Inflammatory Cytokines, and Proliferation of Schwann Cell, and Neurotrophic Factors
(32) Comparison of the Regenerative Effects of Platelet-Rich Fibrin and Plasma Rich in Growth Factors on Injured Peripheral Nerve: An Experimental Study
(33) Effect of Platelet Rich Fibrin on Sciatic Nerve Regeneration in a Rat Model
(34) Platelet-Rich P Combined with Low-Dose Ultrashort Wave Therapy Accelerates Peripheral Nerve Regeneration
(35) Platelet-Rich P: a Promising Product for Treatment of Peripheral Nerve Regeneration after Nerve Injury
(36) Effect of Platelet-Rich P on Peripheral Nerve Regeneration
(37) Experimental Study on Autologous Injectable Platelet Rich Fibrin Combined with Bone Mesenchymal Stem Cells in Treating Sciatic Nerve Injury in Rats
(38) Effects of Platelet-Rich Fibrin/Collagen Membrane on Sciatic Nerve Regeneration
(39) Efficacy of Platelet-Rich Fibrin and Tacrolimus on Facial Nerve Regeneration: an Animal Study
(40) Effect of Platelet-Rich and Platelet-Poor Plasma on Peri-Implant Innervation in Dog Mandibles
(41) Platelet-Rich P gel in Combination with Schwann Cells for Repair of Sciatic Nerve Injury
(42) Inside-Out and Standard Vein Grafts Associated with Platelet-Rich P in Sciatic Nerve Repair. A Histomorphometric Study
(43) The use of fibrin glue in repair of peripheral nerves
(44) Heterologous fibrin sealant potentiates axonal regeneration after peripheral nerve injury
(45) Fibrin Glue and Its Alternatives in Peripheral Nerve Repair
(46) Overall assessment of regeneration in peripheral nerve lesion repair using fibrin glue, suture, or a combination
(47) Multiple uses of fibrin sealant for nervous system treatment following injury and disease
(48) The Efficacy of Platelet-Rich P in the Field of Hair Restoration and Facial Aesthetics-- A Systematic Review and Meta-analysis
(49) Platelet-Rich P, the Ultimate Secret for Youthful Skin Elixir and Hair Growth Triggering
(50) Extracorporeal Shockwave Therapy Versus Plasma for Achilles Tendinopathy
(51) Identification of Alpha 2 Macroglobulin (A2M) as a master inhibitor of cartilage degrading factors that attenuates post-traumatic osteoarthritis progression
(52) α2-Macroglobulin: Autologous Protease Inhibition Technology
(53) Targeted designed variants of alpha-2-macroglobulin (A2M) attenuate cartilage degeneration in a rat model of osteoarthritis induced by anterior cruciate ligament transection
(54) Application of co-expressed genes to articular cartilage: new hope for the treatment of osteoarthritis
(55) The Effectiveness of Alpha-2-Macroglobulin Injections for Osteoarthritis of the Knee
(56) Injection of an Autologous A2M Concentrate Alleviates Back Pain in FAC-positive Patients
(57) Injectable-platelet rich fibrin using the low speed centrifugation concept improves cartilage regeneration when compared to platelet-rich plasma
(58) Sodium pentosan polysulfate resulted in cartilage improvement in knee osteoarthritis-- an open clinical trial
(59) Growth Factor Delivery to a Cartilage-Cartilage Interface Using Platelet-Rich Concentrates on a Hyaluronic Acid Scaffold
(60) Pentosan Polysulfate: a Novel Glycosaminoglycan-Like Molecule for Effective Treatment of Alphavirus-Induced Cartilage Destruction and Inflammatory Disease
(61) Treatment Effects of Subcutaneous Injections of Pentosan Polysulfate Sodium Versus Placebo in Participants With Knee Osteoarthritis Pain
(62) Corticosteroids and local anesthetics decrease positive effects of plasma: an in vitro study on human tendon cells
(63) The effect of L-PRF membranes on bone healing in rabbit tibiae bone defects: micro-CT and biomarker results
(64) Positive effects of different plasma methods on human muscle, bone, and tendon cells
(65) Influence of plasma on chondrogenic differentiation and proliferation of chondrocytes and mesenchymal stem cells
(66) Proliferation-promoting effect of plasma on human adipose-derived stem cells and human dermal fibroblasts
(67) Plasma enhances mesenchymal stem cell proliferation and chondrogenic differentiation
(68) Human plasma stimulates migration and chondrogenic differentiation of human subchondral progenitor cells
(69) Adult and umbilical cord blood-derived plasma for mesenchymal stem cell proliferation, chemotaxis, and cryo-preservation
(70) Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices
(71) Treatment of tendon and muscle using plasma
(72) Plasma compared with corticosteroid injection for chronic lateral elbow tendinosis
(73) Effects of repetitive plasma application on human tenocyte proliferation
(74) Regenerative potentials of plasma enhanced by collagen in retrieving pro-inflammatory cytokine-inhibited chondrogenesis
(75) Human platelet lysate successfully promotes proliferation and subsequent chondrogenic differentiation of adipose-derived stem cells: a comparison with articular chondrocytes
(76) Molecular basis of anti-inflammatory action of plasma on human chondrocytes: mechanisms of NF-κB inhibition via HGF
(77) Plasma Increases Anti-inflammatory Markers in a Human Coculture Model for Osteoarthritis
(78) Anti-inflammatory and matrix restorative mechanisms of plasma in osteoarthritis
(79) Plasma releasate inhibits inflammatory processes in osteoarthritic chondrocytes
(80) Plasma stimulates cell proliferation and enhances matrix gene expression and synthesis in tenocytes from human rotator cuff tendons with degenerative tears
(81) Evaluation of 24 protocols for the production of platelet-rich fibrin
(82) Role of Platelet-Rich Fibrin (PRF) and Platelet-Rich Plasma (PRP) in Oro-Facial Tissue Regeneration: A Narrative Review
(83) Fibrin and Activated Platelets Cooperatively Guide Stem Cells to a Vascular Injury and Promote Differentiation
(84) Effect of scaffold dilution on migration of mesenchymal stem cells from fibrin hydrogels
(85) Shedding light in the controversial terminology for platelet-rich products: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), platelet-leukocyte gel (PLG), preparation rich in growth factors (PRGF) classification
(86) Platelet-rich fibrin (PRF): A second-generation platelet concentrate. Part IV: Clinical effects on tissue healing
(87) Platelet-rich fibrin: evolution of a second-generation platelet concentrate
(88) Human fibrin is a physiologic delivery system for bone morphogenetic protein
(89) The systemic effects of platelet-rich plasma injection
(90) Autologous Conditioned Serum
(91) The Role of Intraarticular Platelet Rich Plasma (PRP) Injection in Patients with Internal Knee Derangements
(92) Percutaneous injections of Platelet rich plasma for treatment of intrasubstance meniscal lesions
(93) Intra-articular Platelet-Rich Plasma Injections for Treating Knee Pain Associated with Articular Cartilage and Degenerative Meniscal Lesions
(94) Treatment of degenerative meniscal tear with intrameniscal injection of platelet rich plasma
(95) Ultrasound-Guided Meniscal Injection of Autologous Growth Factors: A Brief Report
(96) Effects of Platelet-Rich Plasma and Bone Marrow Mesenchymal Stem Cells on Meniscal Repair in the White-White Zone of the Meniscus
(97) Efficacy of Autologous Platelet-Rich Plasma Injections for Grade 3 Symptomatic Degenerative Meniscal Lesions: A 1-Year Follow-up Prospective Study
(98) Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair
(99) COVID and Smell Loss: Answers Begin to Emerge
(100) Effectiveness and Safety of PRP on Persistent Olfactory Dysfunction related to COVID-19: Towards a New Therapeutic Hope
(101) The Use of Platelet-Rich Plasma in Treatment of Olfactory Dysfunction
(102) Platelet rich plasma versus steroid on lateral epicondylitis: meta-analysis of randomized clinical trials
(103) Platelet-rich plasma versus corticosteroid injection for recalcitrant lateral epicondylitis: clinical and ultrasonographic evaluation
(104) Effects of leukocyte- and platelet-rich plasma on tendon disorders based on in vitro and in vivo studies
(105) Platelet rich plasma injections for lateral epicondylitis of the elbow reduce the need for surgical intervention.
(106) Potential of Fibrin Glue and Mesenchymal Stem Cells (MSCs) to Regenerate Nerve Injuries: A Systematic Review
(107) Exploitation of fibrin-based signaling niche for deriving progenitors from human adipose-derived mesenchymal stem cells towards potential neural engineering applications
(108) Fibrin functionalization with synthetic adhesive ligands interacting with α6β1 integrin receptor enhance neurite outgrowth of embryonic stem cell-derived neural stem/progenitors


AAMI © 2021 All Rights Reserved

*Disclaimer: The information presented here is for informational use and cites the ongoing cutting-edge research and medical advancements on these relevant topics. There are many treatments, interventions, and protocols routinely practiced in medicine and surgery which the FDA has not studied nor formally approved yet which have demonstrated overwhelming evidence of efficacy and clinical benefit. The FDA does not regulate the practice of medicine but rather regulates medical marketing of devices and drugs. The FDA does not conduct clinical trials or attempt to discover new treatments, but rather requires companies or other entities to fund marketing approvals. Breakthrough technologies typically require years to decades of research work to optimize the technology and collect enough data to prove efficacy and superiority, which in some cases can optionally be submitted to the FDA if there is sufficient financial backing to market a specific product or drug. Thus the FDA has not yet studied, evaluated, or formally approved many regenerative therapies currently practiced by many of the top physicians and surgeons in the United States and around the world. Some therapies, products, or interventions may still be considered investigational or "off-label" even with substantial evidence of efficacy, and many different applications of regenerative therapies continue to be researched by our institute and other top institutions around the world. We seek to always provide the highest-quality evidence-based care to our patients, which may include FDA-approved therapies as well as additional investigational or alternative therapies. We always discuss potential risks and benefits of all these options. The rapid evolution and advancement of medicine demands that physicians continually update their knowledge and practice techniques to adapt to future improvements and advancing technologies. These statements have not been evaluated by the FDA, and the treatments and products presented here are for informational purposes and not intended or guaranteed to diagnose, treat, cure, or prevent any specific disease or condition. All injuries and conditions should be formally evaluated by a knowledgeable medical professional whereby standard treatments and/or additional therapeutic interventions may be considered with the diagnosis and treatment plan.