Platelet-Rich Plasma (PRP): What Is PRP and What Is Not PRP?

Abstract

Platelet-rich plasma (PRP) has been a breakthrough in the stimulation and acceleration of bone and soft tissue healing. It represents a relatively new biotechnology that is part of the growing interest in tissue engineering and cellular therapy today. Because of its newness, there is a potential for misunderstanding, misuse, and application of what the practitioner may incorrectly think is PRP. The purpose of this paper is to discuss the definition of PRP, its safety, its proper development, and its most efficacious means of application. What is PRP? Platelet-rich plasma is just that; it is a volume of autologous plasma that has a platelet concentration above baseline. Normal platelet counts in blood range between 150,000/μl and 350,000/μl and average about 200,000/μl. Because the scientific proof of bone and soft tissue healing enhancement has been shown using PRP with 1,000,000 platelets/μl, it is this concentration of platelets in a 5-ml volume of plasma which is the working definition of PRP today. Lesser concentrations cannot be relied upon to enhance wound healing, and greater concentrations have not yet been shown to further enhance wound healing (Fig. 1).Fig. 1: Human platelet-derived growth factor AB (PDG-AB). Graph of PDGF-ab versus platelet count indicates growth factors available to tissues as directly proportional to the concentration of platelets.What is PRP in Relation to Recombinant Growth Factors? Because PRP is developed from autologous blood, it is inherently safe and is free from transmissible diseases such as HIV and hepatitis. Within PRP, the increased number of platelets delivers an increased number of growth factors to the surgical area. The seven known growth factors in PRP are: platelet derived growth factor aa (PDGFaa), PDGFbb, PDGFab, transforming growth factor beta-1 (TGF-b1), TGF-b2, vascular endothelial growth factor (VEGF), and epithelial growth factor (EGF). These are native growth factors in their biologically determined ratios. This is what distinguishes PRP from recombinant growth factors. Recombinant growth factors are pure human growth factors, but they are not native growth factors. Human cells such as platelets do not synthesize them. Instead they are synthesized usually by a culture of Chinese hamster ovarian cells that have a human gene inserted into their nucleus through a bacterial plasmid vector. Recombinant growth factors are single growth factors and are delivered in high doses within either a synthetic carrier or a carrier derived from processed animal proteins. PRP is the combination of seven native growth factors within a normal clot as the carrier. The clot is composed of fibrin, fibronectin, and vitronectin, which are cell adhesion molecules required for cell migration such as is seen in osteoconduction, wound epithelialization, and osseointegration. PRP, however, contains only the same concentrations of these cell adhesion molecules as does a normal blood clot (200 μg-400 μg/ml). Therefore, PRP is not a fibrin glue. Platelet Rich Plasma is also not osteoinductive. It cannot induce new bone formation de novo. Only the bone morphogenetic proteins (BMPs) are known to induce bone de novo. However, the prolonged length of time required by recombinant BMP to produce de novo new bone formation and its immature osteoid nature suggest an opportunity for PRP to accelerate BMP activity in the future. PRP acts on healing capable cells to increase their numbers (mitogenesis) and stimulate vascular ingrowth (angiogenesis). Therefore, it is unlikely to significantly promote bone substitutes and other non-cellular graft materials. However, because it has been shown to stimulate autogenous marrow grafts, it is likely to enhance the bone formation when applied to combinations of cellular autogenous bone and non-cellular bone substitutes. Terminology There has already been some mistaken terminology related to PRP. Some have advanced the term “platelet concentrate.” This is not correct because a platelet concentrate is a solid composition of platelets without plasma, which would therefore not clot. The clinically useful product is a concentration of platelets in a small volume of plasma and is therefore a “platelet-rich plasma.” Some have advanced the term “platelet gel.” This is also incorrect because PRP is nothing more than a human blood clot with increased platelet numbers. The clot by virtue of its cell adhesion molecules has additional biologic activity, whereas a gel does not. Still others have reversed the term platelet-rich plasma into plasma rich in platelets, plasma very rich in platelets, and even plasma very very rich in platelets. The ludicrousness of this terminology is obvious and is more reminiscent of a coffee house than a clinical science. Processing PRP and PRP Devices The professions have already seen numerous individuals and corporations promoting devices to processes PRP for either cost savings or economic rewards. The practitioner should keep in mind