By Barbara D. Boyan, PhD
Platelet rich plasma (PRP) has been used clinically since the 1970s. Recent advances in methods for PRP preparation and use have made it possible for surgeons to take advantage of this concentrated form of growth factors and cytokines that are naturally present in blood clots.
The concept is attractive because the patient’s own blood is used, limiting the potential for disease transmission. This is also a major limitation to the predictability of PRP as a therapeutic modality. The composition of PRP varies from patient to patient and may also vary with the device used to prepare it, the time and method of storage until it is used, and whether it is used or interacts with other biologics or materials.
Effective use of PRP requires an understanding of exactly what it is. When an injury occurs, platelets release factors within the clot that stimulate the recruitment of mesenchymal cells to the site and promote their proliferation. These factors also reduce inflammation and stimulate angiogenesis.
Major components of PRP include transforming growth factor-beta (TGF-ßs), platelet-derived growth factors (PDGF), insulin-like growth factor (IGF), vascular endothelial growth factors (VEGF), and fibroblast growth factor-2 (FGF-2). TGF-ß1, IGF-1, and PDGF stimulate proliferation of mesenchymal cells; TGF-ß1 in particular stimulates extracellular matrix production, including collagen.
These factors are important for stabilizing tissue during the initial phases of tissue repair, but they can also lead to fibrous connective tissue and scar formation. VEGF and FGF-2 are important for stimulating new blood vessel formation to bring nutrients and progenitor cells to the site. Additional factors are needed for stabilization of the neovasculature. Thus, PRP must be considered as an adjunctive therapy for specific applications.
Early on, PRP was used as an additive for bone graft and bone graft substitutes. It was hoped that the factors present in PRP would augment the properties of bone graft, making it as effective as bone morphogenetic protein (BMP) and more cost-effective. BMPs are found in the clot but in insufficient levels for the clot to be osteoinductive. Neither is PRP by itself osteoinductive. Moreover, it inhibits both the osteoinductive properties of demineralized bone matrix and the osteogenic effects of BMPs on osteoblast-like cells in vitro. This may explain why PRP has not been effective as a treatment for spine fusion.
Recent studies suggest that PRP may have potential in orthotopic applications where enhanced angiogenesis and vasculogenesis are critical, such as in the treatment of traumatic injuries or large bone defects. This is particularly the case for tendon repair, where PRP has shown the greatest promise. Several recent studies in animal models and in patients indicate that the use of PRP improves tendon healing. The mechanisms involved are not known, but one study suggested that the improvement was due to an increase in angiogenesis because of the VEGF in the PRP.
A variety of methods are now commercially available for preparing PRP and a similar material termed “autologous growth factors,” which is PRP plus the white blood cell buffy coat obtained during PRP preparation. In addition, methods for combining PRP with other biologics or substitutes have also been commercialized. The use of these devices has helped to reduce variability resulting from processing but not variability due to donor differences.
The length of time involved in collecting the patient’s blood, concentrating the platelet releasate, and preparing the material for implantation also affect the final composition of growth factors and cytokines. Although all PRP preparations contain the basic set of growth factors, the proteases present in the platelet releasate may degrade some of the growth factors, reducing the availability of bioactive factors, changing the composition of the PRP, and altering its clinical effectiveness for specific applications. Inconsistencies in clinical findings reported in the literature, even when using the same animal model, may be the result of donor differences in PRP composition.
In summary, available data suggest that PRP may be valuable in enhancing soft-tissue repair, particularly for tendons, and in wound healing. The clinical role of PRP in bone repair remains controversial. PRP is not uniformly successful as an adjuvant to bone grafting procedures, and may promote or inhibit bone formation, depending on it quality and the setting in which it is used. Continued research is needed to optimize the preparation and use of PRP during surgery and to determine the best ways to use it to improve healing.
Disclosure information: Dr. Boyan—TitanSpine, Inc.; Exactech, Inc; Musculoskeletal Transplant Foundation; National Institutes of Health; Institut Straumann AG; MedShape Solutions; Arthrocare; Carticept Medical, Inc.; Journal of Biomedical Materials Research; International Conferences on the Chemistry and Biology of Mineralized Tissue; Dr. Schwartz—no conflicts.
Barbara D. Boyan, PhD, and Zvi Schwartz, DMD, PhD, are part of the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. Dr. Boyan can be reached at firstname.lastname@example.org
September 2010 Issue
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