Poor Standardization in Platelet‐Rich Therapies Hampers Advancement

We have read the article by Valentí Nin et al.1Valentí Nin J.R. Mora Gasque G.Valentí Azcarate A. Aquerreta Beola J.D. Hernandez Gonzalez M. Has platelet-rich plasma any role in anterior cruciate ligament allograft healing?.Arthroscopy. 2009; 25: 1206-1213Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar entitled “Has Platelet-Rich Plasma Any Role in Anterior Cruciate Ligament Allograft Healing?” with great interest. The authors evaluated the effect of a particular platelet-rich (PR) therapy (referred to as platelet-derived growth factor [PDGF]) in anterior cruciate ligament (ACL) surgery in a randomized trial and concluded that their intervention (PDGF) does not work under these circumstances. To establish the degree of generalization for their results in the field of PR therapies, however, it is logical to analyze 2 essential issues—the manufacturing procedure and the protocol for PDGF application during surgery. The manufacturing procedure may result in varying qualities of plasma products and efficacies from patient to patient. It should be noted that PDGF has not followed US Food and Drug Administration (FDA) 510(k) or European regulatory agency (CE marking) submission. These submissions allow the FDA or European authorities to determine whether a device is “substantially equivalent” to a similar one (predicate) already on the market. Compliance ensures important parameters, such as reproducibility, platelet functionality, and clot properties. Furthermore, CE and FDA registration also implies the use of material compliant to ISO 10993, which involves studies for cytotoxicity, mutagenicity, hemolysis, and other appropriate parameters that ensure biocompatibility and biosafety and that may influence the efficacy of the PR plasma. For this reason, the results of this clinical trial with PDGF cannot be generalized. The so-called PDGF does not have a substantial equivalent; it is obtained by means of an in-house procedure involving a 2-step centrifugation and several manual manipulations that are difficult to understand. The authors misapply several terms, challenging comprehension (e.g., they indiscriminately use “serum” for “plasma,” although serum is the liquid fraction released after blood coagulation and plasma is the fluid part of the blood with all of its clotting mechanism intact). With regard to terminology, their use of the term “PDGF” is blurred and confusing. In scientific writing, PDGF stands for 1 particular platelet-released protein among the 300 proteins identified in the platelet secretome (products secreted by a platelet).2Nurden A.T. Nurden P. Sánchez M. Andia I. Anitua E. Platelets and wound healing.Front Biosci. 2008; 13: 3532-3548PubMed Google Scholar In addition, the composition of the clot is only described in terms of platelet enrichment; other relevant parameters (e.g., platelet functionality, clot strength, leukocyte content, or growth factor concentrations) are omitted.3Hall M.P. Band P.A. Meislin R.J. Jazrawi L.M. Cardone D.A. Platelet-rich plasma: Current concepts and applications in sports medicine.J Am Acad Orthop Surg. 2009; 17: 602-608Crossref PubMed Scopus (289) Google Scholar Many ways in which PR therapies may be applied in ACL surgery have been described to date, making it difficult to assess the value of the principles underlying this technique and compromising the applicability of the results. Valentí Nin et al.1Valentí Nin J.R. Mora Gasque G.Valentí Azcarate A. Aquerreta Beola J.D. Hernandez Gonzalez M. Has platelet-rich plasma any role in anterior cruciate ligament allograft healing?.Arthroscopy. 2009; 25: 1206-1213Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar showed no efficacy of the PR intervention when they sutured their clot along the allograft. Conversely, our protocol for PR plasma preparation and application in ACL reconstruction4Sánchez M. Anitua E. Azofra J. Prado R. Muruzabal F. Andia I. Ligamentization of tendon grafts treated with an endogenous preparation rich in growth factors: Gross morphology and histology.Arthroscopy. 2010; 26: 470-480Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar stands in contrast to the present protocol and so does the clinical efficacy of our procedure. Indeed, we condition the graft by injecting liquid-activated plasma throughout the length of the tendon, following the direction of the collagen fibers. In addition, after ACL reconstruction, we fill the joint with liquid-activated plasma. These actions intend to deliver appropriate cues in proximity to target cells and to promote cell migration from the biological environment. In conclusion, the results of this clinical trial may not be meaningful to other PR therapies. Well-characterized plasma products used along with rigorously defined protocols for application in the patient are critical conditions for research. Only when these conditions are met may randomized clinical trials be the foundation of clinical knowledge and practice. Has Platelet-Rich Plasma Any Role in Anterior Cruciate Ligament Allograft Healing?ArthroscopyVol. 25Issue 11PreviewThe aim of this study was to evaluate and compare the clinical and inflammatory parameters with the addition of platelet-derived growth factor (PDGF) in primary anterior cruciate ligament (ACL) reconstruction with bone–patellar tendon–bone allograft. Full-Text PDF Author's ReplyArthroscopyVol. 26Issue 6PreviewFirst, we thank the authors for the feedback in their letter because this team has among the most extensive experience in the world related to growth factors applied to the musculoskeletal system.