PRP – The Next Big Biologic?
An off-label procedure becoming increasingly performed before resorting to orthopedic surgery is injecting a patient’s own platelet-rich plasma (PRP) into an injured tendon, cartilage, muscle, etc. PRP is thought to facilitate healing due to a mixture of growth factors such as TGF-ß1 and TGF-ß2, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF). These growth factors appear to play an important role in wound healing and are assumed promoters of hard and soft tissue regeneration.
AAOS presentations and abstracts described PRP’s use in acute treatment of Achilles tendon rupture and rotator cuff repair. PRP can also be used in the treatment of cartilage defects, both for defects resulting from traumatic injury or osteoarthritis. PRP may also be used to treat chronic conditions, such as plantar fasciitis or medial/lateral epicondylitis.
At the 2011 PRP Forum, an international group of orthopedic surgeons and researchers agreed that PRP injections have become an option for many orthopedic conditions. The effects of PRP, however, are not adequately proven. The Forum endorsed the development of standards in the manufacture of PRP and established a study group to follow up on contraindications and other recommendations.
The American Journal of Sports Medicine in November 2010 cited more than 16 available platelet separation systems that each produce a PRP with differing platelet concentrations. The journal and the PRP Forum experts agreed that all PRPs are not the same. Each patient has a different white count and each separation system is slightly different. Preparations can vary as much as 10-fold in the number of platelets. In addition, the role of specific growth factors within the PRP is unclear. Since there is great variation in PRP composition, comparing results is difficult.
There is a significant need for better characterization of the content of PRP produced by the various commercial systems. A few systems have generated data, as reported by The American Journal of Sports Medicine in November 2010: 1) MTF Sports Medicine’s CASCADE system, 2) Biomet’s GPS III system, and 3) Ateriocyte’s Magellan system. Surprisingly, these three systems, though starting with different volumes of blood, all ended up with comparable volumes of PRP. However, the platelet capture efficiency was better in the CASCADE and Magellan systems, which can get the same amount of PRP from a smaller amount of blood. The CASCADE system also produces leukocyte-poor PRP, whereas GPS III and Magellan produce leukocyte rich PRP. The clinical value of these different PRP formulations remains unknown.
The MTF System allows the surgeon to produce an injectable liquid or a suturable matrix, unlike the other two systems, which produce only an injectable liquid-like substance. The leukocyte-rich PRP (from GPS III and Magellan) had higher increases in concentrations of PDGF and VEGF compared with CASCADE’s leukocyte-poor PRP. There may be a link to increased inflammation with leukocyte-rich PRP compared to leukocyte-poor PRP, but further study is needed. In addition, it is necessary to characterize the platelet and growth factor content produced by the commercial separation systems so that physicians can make informed decisions as to what system to use for which indication and which patient.
Companies are likely to capitalize on the excitement around PRP, creating a propritery product to be mixed with a patient’s own PRP. BioMimetic (BMTI) has created a bone graft solution using PDGF, and is looking for FDA approval. Mixing PRP with chondrocytes or other growth factors may repair tendons or regenerate cartilage better than traditional procedures, such as autologous chondrocyte implantation (ACI) for cartilage repair. Seeding a proprietary PRP product on a porous scaffold would be an improvement to the ACI options currently available on the US market. Overall, the orthopedic market is looking for inejctables to prevent or at least postpone surgery. Adoption of these products would likely increase with successful large-scale studies, which are almost exclusively done on propritary products.
Sources: The Daily Edition - AAOS Now “PRP an Unproven Option, Says Experts,” Wednesday, February 16, 2011, p. 1 & 14. The American Journal of Sports Medicine pp 1-6, November 2010, Castillo et al “Comparison of Growth Factor and Platelet Concentration Form Commercial Platelet-Rich Plasma Separation Systems.”
Expert Insight in PRP
In an Expert Roundtable titled, “Sports Medicine Magic: Is PRP the be-all end-all?” Dr. Scott Rodeo spoke on PRP and its potential in the orthopedic area. Dr. Rodeo is a clinician-scientist at the Hospital for Special Surgery (HSS), with appointments in the Department of Orthopedic Surgery and the Research Department. He is Professor of Orthopedic Surgery at the Weill Cornell Medical College and Co-Chief of the Sports Medicine and Shoulder Service at the Hospital for Special Surgery. He is the associate team physician of the New York Giants football team, and he served as Team Physician for the 2004 and 2008 U.S.A. Olympic Team.
Dr. Rodeo has confidence in PRP increasing healing, but he sees a great need for further study. PRP turns on cell proliferation and protein synthesis, improving healing. It is important to identify which growth factors in PRP facilitate the healing and whether or not certain factors are better in one anatomic and/or tissue area versus another. Also, consistency in PRP make up is difficult, as each patient’s blood consists of different levels of platelet counts. For example, white cell count will differ in each patient, causing more or less VEGF growth factor in the PRP. White cells may promote pro- or anti-inflammatory mediators, depending on their molecular surroundings. Inflammation-causing factors may be useful in some healing, such as muscular repair, but not useful in other areas, like tendon repair.
PRP has been used in orthopedic practices for the last 6–8 years. In-patient procedures are sometimes reimbursed in the US. Surgeons bill for the injection. Outpatient reimbursement is less likely. There are typically $700-$800 of disposable costs associated with the procedure. At HSS, it is self-pay for outpatients. Dr. Rodeo finds PRP particularly useful in tendon repair; results with muscle injuries have been mixed.
Dr. Rodeo performed several rotator cuff studies with PRP. Of those, two had no statistically significant improvement in healing compared to placebo, and two did show statistically significant improved healing. He wants to see more study.
