The Effect of Platelet-Rich Plasma on Normal Soft Tissues in the Rabbit
Harris NL, Huffer WE, von Stade E, Larson AI, Phinney S, Purnell ML. J Bone Joint Surg Am. 2012 May 2;94(9):786-93.
The fascination of using biologics in the field of sports medicine has been a growing area of interest over the past few years. Unfortunately, much of the clinical data for its use has been anecdotal and well-designed clinical studies have been lacking in the past. However, more clinically relevant trials have and are being carried out to determine the true efficacy of autologous platelet-rich plasma (PRP) for musculoskeletal injuries. The authors in this study hoped to add a new piece to this puzzle by examining the effects of PRP injection into various normal soft tissues. Eighteen adult New Zealand White rabbits were injected with 0.5 mL of PRP into the quadriceps muscles, Achilles tendon, medial lateral ligament (MCL), subcutaneous tissue, tibial periosteum, and ankle joint. The PRP was prepared by drawing 50 mL of blood from each rabbit, centrifuging the sample, and activating the plasma with a combination of topical thrombin and calcium chloride to form the final gel. A saline solution was injected into each contralateral site that served as controls. Soft tissues were examined histologically at 2 and 6 weeks (6 rabbits each), with the 6 remaining rabbits undergoing reinjection at 6 weeks and then examined histologically at 12 weeks. The authors observed calcification in these first 3 groups within muscular and subcutaneous tissues after injections, so added a 4th group of rabbits that used a calcium-free solution with the PRP to examine the development of soft-tissue deposition. With gross examination, the authors found a superficial skin reaction of a raised red lesion in 17 of 18 rabbits that resolved after 6 days. Muscle tissue showed an inflammatory cell (monocytic and lymphocytic) infiltrate with edema, necrosis, and calcium deposition in the muscle fibers at 2 weeks. Subcutaneous sites demonstrated collagen nodules and new fibrous tissue at 2 weeks. The tendon site and MCL showed monocytic and lymphocytic inflammatory cells with thickening of the soft tissues at 2 weeks, along with collagen deposition. Ankle joint tissue showed villous synovial hyperplasia (increase in epithelial cells and finger like projections of the tissue that lines the joint) and chronic synovitis at 2 weeks. These sites at 6 and 12 weeks showed persistent but diminished inflammatory infiltrates. The periosteum did not show any evidence of new bone formation at any of the time frames.
PRP has long been used for various clinical applications. However, new data is needed to determine what musculoskeletal conditions would benefit most, if at all, from this therapy and at what stage of treatment should it be utilized. The authors found that PRP injected into healthy tissue caused a similar acute inflammatory reaction as seen with an acute injury or healing response. The potential benefits seen after 6 weeks may be viewed as beneficial to healing in tissues with chronic degenerative changes, but detrimental to normal tissue. The third rabbit group, which was reinjected with PRP at 6 weeks, mimicked a clinical situation where sometimes a patient is reinjected at a later time point to boost the effect of the initial injection. This study did not show a return of the acute inflammatory response or increase in vascularity or scar formation. This is another clinically relevant point that needs to be further studied as some provider’s protocols include a series of PRP injections, but this study does not support that practice if pathologic tissue would have a similar response. Negative effects found from this study include the local skin reaction and the reaction from the intramuscular injection of PRP that included thrombosis and necrosis (cell death). Also, with the results from the 4th group of rabbits having less calcium deposition, further studies need to look at calcium being used as a thrombin activator. One limitation of this study is that authors only examined normal tissue and these results might not be similar with pathologic tissue. This study can add to the list of potential risks and benefits that need to be discussed with each patient prior to injection. How do you view the results from this study? Does this study make you more or less likely to recommend PRP to patients?
Written by: Kris Fayock, MD and Peter Vitanzo, MD
Revised by: Jeffrey Driban
Harris NL, Huffer WE, von Stade E, Larson AI, Phinney S, & Purnell ML (2012). The effect of platelet-rich plasma on normal soft tissues in the rabbit. The Journal of Bone and Joint Surgery. American volume, 94 (9), 786-93 PMID: 22552667