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

Related Posts:

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