Platelet Rich Plasma & Platelet Rich Fibrin Matrix
Platelet-Rich Plasma therapy or PRP® refers to a sample of autologous plasma with platelet concentrations greater than baseline values (13). This blood concentrate contains numerous cytokines and growth factors which can help to initiate and promote healing by stimulating stem cell migration, cell proliferation, angiogenesis, and extracellular matrix synthesis. While clinical studies show mixed results in terms of efficacy, PRP® treatments are being widely utilized today in the treatment of more than 30 diseases and degenerative conditions (2). There are numerous cell-based studies that have demonstrated the positive effects of PRP® preparations on many types of human connective tissue without an apparent increase in adverse events (13).
CytoVive® is proud to offer RegenLab's industry leading family of FDA Approved Class 2 medical devices, Approved for the safe and rapid preparation of autologous platelet rich plasma (PRP) from a small sample of blood at the patient’s point of care. The PRP is mixed with autograft and/or allograft bone prior to application to a bony defect for improving handling characteristics. The RegenKit®-BCT Family Kits are for single use only.
RegenKit® Advantages:
Leukocyte Rich PRP
Leukocyte Poor PRP
Naïve PRP
Naturally Activated PRP
Exogenously Activated PRP
High Concentration PRP
Physiological Concentration PRP
Platelet Poor Plasma
FDA Approved Device
Closed System Design
Simple 3 Step Protocol
5 Minute Single Spin Centrifugation
Proprietary Gel Separator Technology
Regen Lab® USA's industry leading PRP® products feature a proprietary thixotropic gel separator technology. This gel separator not only streamlines the entire protocol, it allows for the recovery of viable and intact platelets while eliminating a multitude of proinflammatory cytokines from the PRP® sample. The Regen® gel is 100% inert (does not interact with blood) and mobilizes to migrate up the wall of the BCT tube during centrifugation, then resolidifies as the centrifuge concludes its 5 minute spin cycle. Upon re-solidification, this gel separator forms a physical barrier that:
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Eliminates 99.7% of Red Blood Cells
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Eliminates 85% of All Leukocytes
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Eliminates 96% of Neutrophils (Granulocytes)
RegenLab® proprietary gel separator technology ensures a 100% reproducible final PRP® product that is vastly superior in terms of quality of the PRP® cocktail and overall protocol efficiency (12.).
The RegenKit®-BCT and RegenKit®-BCT Plus product families (BK110061) are indicated by the U.S. FDA for the safe and rapid preparation of autologous platelet rich plasma from a small sample of blood at the patient’s point of care. The platelet rich plasma is mixed with autograft and/or allograft bone prior to application to a bony defect for improved handling characteristics (12).
The RegenKit® BCT Protocol
Proprietary and Revolutionary
Various Growth Factors Identified Within PRP® and
Their Respective Physiologic Effects
Biological Regeneration of Tissues - Latest Therapeutic Approach Using Platelet Rich Plasma [Internet]: Blood Research and Transfusion Journal; c2017 [cited 2017 10/9]. Available from: https://juniperpublishers.com/oabtj/pdf/OABTJ.MS.ID.555553.pdf.
White Blood Cells and Tissue Regeneration
Leukocyte Poor PRP® vs. Leukocyte Rich PRP®
Leukocytes (white blood cells) are known to play key roles in the inflammatory process and as such, their presence within PRP® preparations has been the subject of much research and debate. Granulocytes are a specific type of leukocyte that serve as a primary defense against foreign pathogens. These pathogen-attacking cells are capable of releasing a multitude of highly active antimicrobial substances and proteases. Uncontrolled release of these factors can result in tissue damage, delayed healing, and increased scar tissue formation (4). The Regen® system was specifically designed to eliminate over 96% of granulocytes from Regen® PRP® samples. The small number of white blood cells that do remain are largely lymphocytes and monocytes, which have both been shown to contribute to the healing process (1,3).
PRP® Concentration - Tissue Specific Versatility
Platelet concentration is one of many factors that contribute to the regenerative potential of a PRP® sample. Tissue specific PRP protocols continue to expand with increasing research. The Regen® system is specifically designed with this in mind to produce an autologous PRP® sample with a baseline platelet concentration of 1.6X. This proprietary protocol gives clinicians the freedom to manipulate PRP® concentration to their preference depending on the tissue specific application being performed (12). After centrifugation is performed, a predetermined amount of Platelet Poor Plasma (PPP) can be aspirated from the PRP tube prior to homogenizing the platelet aggregate in order to achieve any PRP concentration that a clinician may choose to use.
Activated PRP (aka PRF or PRFM) vs. Naïve PRP
A physician may choose to treat specific indications with activated PRP® as opposed to PRP® in its resting state. When PRP® is "activated" there are two things that occur, the first is an immediate degranulation of the platelets which release growth factors from their α-granules. The other process that takes place following PRP® activation is fibrinogen cleavage which initiates a matrix-like clot to form within the activated PRP® sample (14). This clot can manifest itself as a gel-like a solidification within minutes of activation which may impact several clinical applications (5). For example, if an activated PRP® preparation is to be delivered through a syringe, then the injection must take place immediately following activation in order for the concentrate to pass through the injection needle before it solidifies.
Platelet activation achieves the goal of facilitating rapid growth factor release, but it is also important to consider that growth factors maintain short half-lives. If these growth factors do not bind to cellular receptors immediately following alpha-granule release then they may be degraded before they can be metabolized in ways that contribute to the regenerative process. A rapid activation of platelets may actually be associated with a decrease in the overall amount of growth factors available at the treatment site over time, however some indications have been shown to benefit from a less-sustained growth factor release (11).
Activated PRP® in its gel form allows for the blood concentrate to remain at the treatment site for an extended period of time (6). This PRP® gel can also be used as a suturable membrane in some surgical settings. Naive liquid PRP® on the other hand has the benefit of providing increased plasma dispersion, which can increase the target tissue area and may enhance clinical outcomes in other applications (7). Naive PRP® and activated PRP® have both been shown to promote significant healing across a wide spectrum of clinical settings. There is currently a lack of standardization in PRP® treatment application techniques and protocols so it is very important that clinicians continue to stay informed on the latest application techniques for the specific indications that they are treating in order to facilitate an optimal healing environment for each treatment site.
Regen Lab® Activated Platelet Rich Plasma - 100% Natural
The RegenKit®-BCT Plus product family is used for the preparation of autologous PRP® activated by an autologous thrombin serum. This is a 100% natural activation process that does not require the addition of any exogenous chemicals. Upon addition to the PRP® concentrate, the Regen® ATS (Autologous Thrombin Serum) provides thrombin enzymes that immediately begin to cleave fibrinogen (present in the PRP® sample) into fibrin monomers. These fibrin monomers then undergo polymerization as they form a clot that serves as a three dimensional matrix that acts like a framework for new tissue reconstruction. This matrix also keeps platelets entrapped at the treatment site and allows for long lasting growth factor release at that precise location. The addition of Regen® ATS serum to Regen® PRP® allows for the formation of fibrin polymers to take on several different forms such as:
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Platelet Rich Fibrin Gel
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Platelet Rich Fibrin Glue
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Platelet Rich Fibrin Topical Spray
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Suturable Platelet Rich Fibrin Membrane (12).
The FDA's Stance on Platelet Rich Plasma
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Per the FDA, PRP®'s intended use is in an operative setting to be mixed with bone graft materials in order to enhance bone graft handling and healing properties for orthopaedic and dental applications. PRP® use outside of this setting is considered to be "off label".
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It is important to note that the FDA does not regulate the practice of medicine. Clinicians are free to use a product off label as long as certain responsibilities are met:
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Clinicians using PRP® off label (office injections) as part of good medical practice and in the best interest of the patient have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to keep records of its use; however, they do not require submission of an IND or IDE to the FDA or oversight from an institutional review board (IRB).
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The language in 21 CFR 1271 regarding the manipulation of cells has impacted the use of cultured stem cells, causing concern for some over activated PRP®. Clinicians using activated PRP® should be mindful of these concerns and continue to stay informed (13).
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References
1.) Barbul A, Shawe T, Rotter S, Efron J, Wasserkrug H, Badawy S. Wound healing in nude mice: A study on the regulatory role of lymphocytes in fibroplasia. 1989 06/1989;105(6):764--769
2.) Biological Regeneration of Tissues - Latest Therapeutic Approach Using Platelet Rich Plasma [Internet]: Blood Research and Transfusion Journal; c2017 [cited 2017 10/9]. Available from: https://juniperpublishers.com/oabtj/pdf/OABTJ.MS.ID.555553.pdf.
3.) Brancato S. and Albina J. Wound macrophages as key regulators of repair: Origin, phenotype, and function. The American Journal of Pathology 2011 08/2010;178(1):19--25.
4.) Brubaker A, Schneider D, Kovacs E. Neutrophils and natural killer T cells as negative regulators of wound healing. Expert Rev Dermatol 2011 2/1/2011;6(1):5--8.
5.) Cavallo C, Roffi A, Grigolo B, Mariani E, Pratelli L, Merli. G., Kon E, Marcacci M, Filardo G. Platelet-rich plasma: The choice of activation method affects the release of bioactive molecules. Hindawi Publishing Company, BioMed Research International 2016;2016.
6.) DeLong M, Russell P, Mazzocca D. Platelet-rich plasma: The PAW classification system. Arthroscopy 2012;28(7):998--1009.
7.) Filardo G, Kon E, Roffi A, Di Matteo B, Merli L, Marcacci M. Platelet rich plasma: Why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration. Knee Surgery, Sports Traumatology, Arthroscopy 2015;23(9):2459--2474.
8.) Graziani F, Ivanovski S, Cei S, Ducci F, Tonetti M, Gabriele M. The in vitro effect of different PRP concentrations on osteoblasts and fibroblasts. Clinical Oral Implants Research 2006 08/2006;17(2):212--219.
9.) Intellectual Property Rights (IPRs) as Core Assets [Internet]En Budron, Switzerland: Regen Lab®; c2018 [cited 2018 4/22]. Available from: https://www.regenlab.com/corporate/patents/.
10.) Leon J, Driver V, Fylling C, Carter M, Anderson C, Wilson J, Dougherty R, Fuston D, Trigilia D, Valenski V, et al. The clinical relevance of treating chronic wounds with an enhanced near-physiological concentration of platelet-rich plasma gel. Advances in Skin & Wound Care 2011 08/2011;24(8):357--369
11.) Martineau I, Lacoste E, Gagnon G. Effects of calcium and thrombin on growth factor release from platelet concentrates: Kinetics and regulation of endothelial cell proliferation. Biomaterials 2004;25(18):4489--4502.
12.) Regen Lab® USA LLC. Regen Lab® PRP® & cell therapy specialists product manual. RegenLab® A-PRP® Technology 2018:3--4.
13.) US Definitions, Current Use, and FDA Stance on Use of Platelet-Rich Plasma in Sports Medicine [Internet]: The Journal of Knee Surgery; c2014 [cited 2017 10/9]. Available from: https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0034-1390030.
14.) Wasterlain S, Braun J, Dragoo L. Contents and formulations of platelet-rich plasma. Operative Techniques in Orthopaedics 2012;22(1):33--42.
15.) Weibrich G, Hansen T, Kleis R, Buch C, Hitzlerd E. Effect of platelet concentration in platelet-rich plasma on peri-implant bone regeneration. Bone 2004;34:665--671.
16.) What is A-PRP / PRP? [Internet]En Budron, Switzerland: RegenLab®; c2017 [cited 2017 10/9]. Available from: https://www.regenlabusa.com/#video.
