IOC consensus paper on the use of platelet-rich plasma in sports medicine

There is a limited amount of basic science research on the influence of PRP on the inflammation and repair of connective tissue and skeletal muscle. There is an even greater paucity of well-conducted clinical studies on the use of PRP to manage sport injuries. For clinicians, the generalisability of basic science must be tempered by clinical studies that inherently contain factors controlled for in basic science experiments. For these reasons, the design of robust clinical studies is essential for conclusions to be assigned sufficient validity to be used in clinical practice. Although PRP has been in clinical use for decades, some basic science issues still require further investigation. Several techniques are available to prepare PRP; however, there is no evidence of standardisation of preparation (in terms, for example, of length and speed of centrifugation) and use of PRP. In addition, different methods of preparation may produce different platelet concentrations such as storing the PRP for differing lengths of time before use, using different anticoagulants and variable degrees of other cells such as red and white cells in the PRP preparation. It is therefore possible that each preparation method may lead to a different product with different biology and potential uses. As stated, all these variables may produce PRPs in which the amount and type of growth factors are different. Therefore, a classification system for different PRPs should be developed and should be used to define the PRPs used by different research and treatment groups. For clinical applications, based on different clinical conditions, the best time to inject PRP must be determined according to the different tissues and body districts. The kinetics of cytokine release from various PRPs with/without other biomaterials needs further investigation, as this may ultimately determine the best time for injection for a given PRP formulation. Furthermore, the tissue-specific effects of PRP should be compared, as the underlying cellular and molecular processes for a particular tissue healing may be markedly quite different. For instance, muscle and bone healing need vascularisation. However, a high degree of vascularisation may not be required for tendon and articular cartilage injuries. In fact, it is plausible that the effect of PRP on a given tissue is influenced by the microenvironment within that tissue, and therefore PRP activation may not be required prior its use. Lastly, the optimal use of PRP for regenerative medicine is still under investigation. Although application of the PRP may enhance mesenchymal stem cell proliferation and migration, exposure of cells to PRP may also limit differentiation of those cells into the appropriate cell lineages.17 The question arises in this consensus statement as to whether we as clinicians should use a treatment with very little scientific evidence supporting its clinical efficacy and with limited evidence supporting its safety. Medical ethics is anchored by the concepts of benefi - cence (doing good) and non-maleficence (do no harm). Medical ethics includes the concept of patient autonomy (selfdetermination). Western medicine tends to hold to the principle that patients can determine their treatment themselves, even if beneficence or non-malfi cence is not proved. For the doctor, nonmalficence is the principal determinant of medical practice. While limited, current evidence suggests the use of PRP to be safe, and therefore the non-maleficence principal is probably upheld; however, there are few if any studies that document adverse or serious adverse events, and there are no studies at all looking at long-term effects. As there is little scientific evidence that PRP injections are of clinical benefit, beneficence is at this time not proven. Current medical ethics generally allows clinicians to make an individual choice to prescribe treatments that have not shown beneficence as long as the treatment is non-maleficent. With respect to PRP, its increasing popularity appears to have outreached in some respects the principle of medical ethics and the usual conservatism that new treatments are taken up by the clinicians. Part of the answer to this would be that PRP is presently marketed and widely perceived as a natural healing method with the implications of minimal maleficence. The role of PRP in tissue healing and regeneration may open a new area in regenerative medicine, but there remains a large amount of work required toward understanding the mechanism of action of PRP in the regeneration and repair process of a given tissue. Firm recommendations on the effectiveness of PRP in the clinical setting to support the healing processes of muscle, tendon, ligament and cartilage injuries cannot be given. Results of studies on PRP are difficult to interpret, as the methodological quality of published investigations varies substantially. More attention should be paid to methodological quality when designing, performing and reporting clinical trials. The final recommendation of this consensus group would be to proceed with caution in the use of PRP in athletic sporting injuries. We believe more work on the basic science needs to be undertaken, and greater rigour should be implemented in developing robust clinical trials to demonstrate the efficacy or otherwise of PRP.