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Scientific Articles   |    
The Effect of Platelet-Rich Plasma on Normal Soft Tissues in the Rabbit
N. Lindsay Harris, MD; William E. Huffer, MD; Eleanor von Stade, MD; Andrew I. Larson, BSME; Shawn Phinney, MA; Mark L. Purnell, MD
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Investigation performed at Aspen Orthopaedic Associates, Aspen, and University of Colorado Health Sciences Center, Denver, Colorado



Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. In addition, one or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, one or more of the authors has had another relationship, or has engaged in another activity, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2012 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2012 May 02;94(9):786-793. doi: 10.2106/JBJS.J.00984
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Abstract

Background: 

Platelet-rich plasma is reported to contain multiple growth factors, and has been utilized in orthopaedic surgery to aid healing in multiple tissues. To date, the use of autologous platelet-rich plasma has not been studied for its effects on normal soft tissue.

Methods: 

Eighteen adult New Zealand White rabbits were injected with 0.5 mL of autologous platelet-rich plasma in the right or left quadriceps muscle, Achilles tendon, medial collateral ligament, subcutaneous tissue, tibial periosteum, and ankle joint. Saline solution was injected on the contralateral side as a control. The soft tissues were examined histologically at two weeks (six rabbits) and six weeks (six rabbits), and soft tissues from six rabbits that had been reinjected at six weeks were examined at twelve weeks.

Results: 

Inflammatory skin lesions were visible at forty-eight hours at superficial platelet-rich plasma sites. All lesions resolved by six days. Compared with findings in control specimens, histological analysis of platelet-rich plasma injection sites at two weeks showed a marked inflammatory infiltrate with lymphocytic and monocytic predominance. Intra-articular injection showed villous synovial hyperplasia and chronic synovitis. Tendon and ligament sites showed new collagen deposition. Intramuscular injection sites showed thrombosis, necrosis, and calcium deposition. Subcutaneous sites also showed calcium deposition without necrosis as well as collagen nodules representing early scar tissue. Histological examination of platelet-rich plasma injection sites at six and twelve weeks demonstrated a persistent but diminished inflammatory infiltrate. Focal areas of scar tissue were seen with fibroblasts, collagen formation, and neovascularity. All saline solution sites at all times were nonreactive.

Conclusions: 

Platelet-rich plasma can initiate an inflammatory response in the absence of an inciting injury in normal soft tissue in rabbits.

Clinical Relevance: 

Platelet-rich plasma has gained widespread use clinically in the treatment of a variety of orthopaedic injuries and as a surgical adjunct; however, its in vivo effect on normal tissues has not been examined in a controlled laboratory study.

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    References

    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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    Lindsay Harris, Mark Purnell, Andrew Larson
    Posted on June 05, 2012
    Study Objective
    Aspen Orthopaedic Associates

    Thank you Dr. Label for your interest in our study. The primary objective of this study was to examine platelet-rich plasma (PRP) injected into various soft tissues for any histologic response (inflammatory or other). We hypothesized that PRP would initiate a histologic response in soft tissue that would be significantly different when compared with the saline solution injections (control). We purposely chose saline as a control because of its assumed neutrality to soft tissues. The purpose of the “control” injection was to evaluate for soft tissue response to the needle’s trauma and/or volumetric effect of the injection. The finding of an inflammatory response was not necessarily expected, therefore we did not incorporate other inflammatory agents in the experimental design. Comparing the inflammatory response of PRP to other known inflammatory agents (such as talc) may provide useful information regarding the type/degree of histologic response, and may serve as a useful follow-up study. This would however, increase the complexity of the study, taking into account grading scales for the inflammatory response and a more complex dose-response relationship for PRP.

    David Eduard Lebel M.D, PhD
    Posted on May 07, 2012
    A standard inflammatory response to an injected material or a marketing spin?
    Hospital For Sick Children, Toronto, Ontario, Canada

    It is always a pleasure to read basic science papers in a leading musculoskeletal journal.  Basic understanding of this potentially potent agent, which is being used for variety of indications, is of great importance. Although the topic is fascinating and important due to ongoing clinical research that was mentioned at the discussion section, I found the study interestingly designed. While controlling with saline injected animals we were supposed to be convinced that the inflammatory response to the injected platelet rich plasma (PRP) is unique and of a clinico-pathologic importance, I found it bothering. Wouldn’t it be better while designing the study to control with a different agent such as injected BMP or even talc powder dissolved in saline?  Since the study is completely based on histology analysis, I can't read the results other than normal inflammatory response to an injected material. A proper control would be injection of other inflammation-causing reagents and looking for the different histology of the inflammatory response. Another option is downstream biochemical study to find out the biochemical distinct response to injected platelet rich plasma. Otherwise, I refer to previous cited articles in this journal evaluating clinical studies dealing with efficacy of PRP(1,2). Lack of supporting clinical evidence regarding PRP might be not only from poor study design as stated previously(1), but from lack of proper biological activity as might be interpreted from reading this article.

    REFERENCES: (1) Sheth U, Simunovic N, Klein G, Fu F, Einhorn TA, Schemitsch E, Ayeni OR, Bhandari M. Efficacy of autologous platelet-rich plasma use for orthopaedic indications: a meta-analysis. J Bone Joint Surg Am. 2012 Feb 15;94(4):298-307.  (2). Matava MJ. Platelet-rich plasma: the next big thing? Commentary on an article by Ujash Sheth, BHSc, et al.: 'Efficacy of autologous platelet-rich plasma usefor orthopaedic indications: a meta-analysis'. J Bone Joint Surg Am. 2012 Feb15;94(4):e25

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