With the rise in popularity of platelet-rich plasma (PRP) in regenerative medicine, many systems and methods of preparation have been proposed. However, it is important to understand that not all PRP preparations are created equal and therefore may not provide the optimal conditions for healing.
In this blog post, we will discuss the “points to consider” when selecting a commercial system for generating PRP. This may also serve as a helpful reminder of what your current system can (or can't!) do.
Platelet-Rich Plasma (PRP)
For the uninitiated, PRP is an autologous biologic derived from whole blood that is preferentially enriched for platelets. While platelets are the primary component of PRP, preparations may also contain other cellular components such as white blood cells (WBCs) and circulating progenitor cells. These components all play a critical role in the healing process and are provided at concentrated levels in PRP.
Key Components Of PRP
Let’s do a deeper dive into the key components of PRP and understand what they do.
Platelets
Platelets play a critical role in several aspects of the healing process. Activated platelets express adhesion molecules that support clot formation for hemostasis. They also release several antimicrobial peptides that deliver properties for infection control. Most importantly as it relates to healing, platelets also release numerous growth factors, including PDGF, TGF-β, VEGF and SDF-1α, that have been shown to orchestrate key biological processes, including angiogenesis, inflammation resolution and tissue regeneration (1,2,3,4).
Progenitor cells
Progenitor cells convert to terminal tissue and support angiogenesis. Endothelial progenitor cells also retain the ability to differentiate into other cell types, but to a lesser extent than stem cells (5,6).
White blood cells
White blood cells (WBCs; leukocytes) play a key role in protecting the body from infection and coordinating the inflammatory response. The three primary classes of cells found in the WBC population each provide unique biological functionalities:
Granulocytes (neutrophils) are the “immediate response” cells for prevention of infection, granulocytes are key mediators of inflammatory response through phagocytosis and release of reactive oxygen species (ROS).
Lymphocytes like T-lymphocytes help regulate the function of other immune cells and directly attack various infected cells and tumors. B-lymphocytes make antibodies, which are proteins that target unwanted bacteria, viruses and other foreign material.
Monocytes assist in pathogen recognition and eventually become macrophages, which engulf and destroy pathogens.
Not All PRP Preparations Are Equal! Points to Consider
When selecting a PRP system, it is important to consider how each system modulates these key components to optimize the conditions for healing. These are the main points to consider:
Platelet Concentration
The concentration of platelets in a PRP sample is dependent on the performance of the system as well as the volume of PRP. Samples that have a smaller quantity of PPP will yield higher concentrations of platelets per microliter.
When more platelets are concentrated in a PRP preparation, more growth factors are delivered to the application site. These growth factors support several key processes, including stem cell recruitment, angiogenesis, cell proliferation and differentiation (7). A platelet concentration of 4x above baseline is the consensus threshold for a solution to be considered Platelet-Rich Plasma. Pioneering work by Giusti has determined the most effective concentration of platelets for the stimulation of angiogenesis was 1.5 million platelets/μL, which is roughly ~6x above baseline (8).
PRP should not be defined as a plasma fraction of a whole blood sample that has a platelet concentration above baseline. Platelet concentration of <500 x 103/μL supports proliferation (or angiogenesis determinant) no better than platelet poor plasma (9,10).
White Blood Cells (WBCs) PRP preparations should include the correct composition of WBCs to effectively modulate the healing response. There are two types of PRP that cover the absence and presence of WBCs –
Leukocyte Poor (LP) - PRP - also known as "Clear" or "Pure" PRP. Removing all WBCs may be desirable for certain indications when clinicians wish to control localized inflammation, such as Intra-articular joint injections.
Leukocyte Rich (LR) - PRP - In soft tissue applications, reducing Granulocytes (Neutrophils) and increasing Mononuclear cells (Lympocytes & Monocytes) contributes to the efficacy of a PRP solution (10).
System Technology & Dynamics
How a system generates PRP and its unique dynamics are critical in allowing you to modify the output of your PRP.
Technology - PRP preparation systems with an automated double-spin process and platelet separation technology enable both the isolation and concentration of platelets. This increases both platelet capture efficacy and total platelet concentration over single-spin systems (9).
This is an example of a system that has platelet isolation technology. The platelet concentrate process disposable includes a proprietary, self-calibrating floating shelf for concentrating platelets and reducing blood cells.
Flexibility - as the science of PRP evolves, clinicians should look towards a PRP system that allows them to effectively modulate the individual components of PRP to provide the optimal solution for their patient.
Sterility - Systems containing injection ports allow clinicians to maintain sterile technique as they can be disinfected between use, unlike luer locks.
We hope you now know more about how PRP systems and their biological outputs differ from one another. If you are interested in discussing how MDBiologix can help you find the right system for your practice, please reach out!
References
Tang Y, Yeaman M, Selsted M. Antimicrobial peptides from human platelets. Infect Immun. 2002;70(12):6524-6533.
Drago L, Bortolin M, Vassena C, et al. Antimicrobial activity of pure platelet-rich plasma against microorganisms isolated from oral cavity. BMC Microbiol. 2013:13(47):1-5.
Amable P, Carias R, Teixeira M, et al. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors. Stem Cell Res Ther. 2013;4(3):67.
Ríos D, López C, Carmona J. Platelet-rich gel supernatants stimulate the release of anti-inflammatory proteins on culture media of normal equine synovial membrane explants. Vet Med Int. 2015;2015:547052.
Jung Y, Song J, Shiozawa Y, et al. Hematopoietic stem cells regulate mesenchymal stromal cell induction into osteoblasts thereby participating in the formation of the stem cell niche. Stem Cells. 2008;26(8):2042-2051.
Kuroda R, Matsumoto T, Kawakami Y, Fukui T, Mifune Y, Kurosaka M. Clinical impact of circulating CD34-positive cells on bone regeneration and healing. Tissue Engineering Part B: Reviews. 2014;20(3):190-199.
Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet-rich plasma: implications for wound healing. Plast Reconstr Surg. 2004;114(6):1502-1508.
Giusti I, Rughetti A, D’Ascenzo S, et al. Identification of an optimal concentration of platelet gel for promoting angiogenesis in human endothelial cells. Transfusion. 2009;49(4):771-778.
Kevy, S, Jacobson, M. and Mandle, B., Defining the Concentration and Composition of Platelet-Rich Plasma (PRP). Presented at the North America Platelet-Rich Plasma Symposium, September 9, 2011, Toronto, ON, Canada.
Kevy, S, Defining the Concentration and Composition of Platelet-Rich Plasma (PRP) and Bone Marrow Concentrate (BMAC) for use in Regenerative Medicine. Presented at the Bone Marrow Stem Cell Platelet-Rich Plasma Symposium – The Natural Choice for Optimizing Healing, March 27, 2011, Seoul, Republic of Korea.