Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing.
ABSTRACT Circulation-derived cells play a crucial role in the healing processes of tissue. In early phases of tendon healing processes, circulation-derived cells temporarily exist in the wounded area to initiate the healing process and decrease in number with time. We assumed that a delay of time-dependent decrease in circulation-derived cells could improve the healing of tendons. In this study, we injected platelet-rich plasma (PRP) containing various kinds of growth factors into the wounded area of the patellar tendon, and compared the effects on activation of circulation-derived cells and enhancement of tendon healing with a control group (no PRP injection). To follow the circulation-derived cells, we used a green fluorescent protein (GFP) chimeric rat expressing GFP in the circulating cells and bone marrow cells. In the PRP group, the numbers of GFP-positive cells and heat-shock protein (HSP47; collagen-specific molecular chaperone)-positive cells were significantly higher than in the control group at 3 and 7 days after injury. At the same time, the immunoreactivity for types I and III collagen was higher in the PRP group than in the control group at early phase of tendon healing. These findings suggest that locally injected PRP is useful as an activator of circulation-derived cells for enhancement of the initial tendon healing process.
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ABSTRACT: The purpose of this study was to evaluate the efficacy of multiple platelet-rich plasma (PRP) injections on the healing of chronic refractory patellar tendinopathy, and report the quality and duration of the clinical improvement up to a medium-term follow-up. Forty-three patients (mean age, 30.6 years; mean BMI, 24.7; 42 men, one woman) affected by chronic patellar proximal tendinopathy were enrolled in this trial. Eleven patients were affected by bilateral tendinopathy. They underwent three ultrasound guided intra-tendinous injections of five millilitres PRP, two weeks apart from each other. Patients were prospectively evaluated initially, then after two, six, and up to mean 48.6 ± 8.1 months of follow-up (minimum evaluation at 36 months). The following evaluation tools were used: Blanzina, VISA-P, EQ-VAS for general health, and Tegner scores. Patients' overall satisfaction and time to return to sport were also reported. Good and stable results were documented over time, with the VISA-P score increasing from 44.1 ± 15.6 at baseline to 61.4 ± 22.2 at two months, 76.6 ± 25.4 at six months, and 84.3 ± 21.6 at four years' follow-up. The same trend was confirmed by the other scores used, and 80 % of the patients were satisfied and returned to previous sports activities. Significantly poorer results were obtained in patients with a longer history of symptoms, and poor results were also observed in bilateral lesions. No correlation between ultrasonographic and clinical findings could be found. Multiple injections of PRP provided a good clinical outcome for the treatment of chronic recalcitrant patellar tendinopathy with stable results up to medium-term follow-up. Patients affected by bilateral pathology and presenting a long history of pain obtained significantly poorer results.International Orthopaedics 06/2013; · 2.32 Impact Factor
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ABSTRACT: BACKGROUND: Platelet-rich plasma (PRP) is an autologous platelet concentrate. It is prepared by separating the platelet fraction of whole blood from patients and mixing it with an agent to activate the platelets. In a clinical setting, PRP may be reapplied to the patient to improve and hasten the healing of tissue. The therapeutic effect is based on the presence of growth factors stored in the platelets. Current evidence in orthopedics shows that PRP applications can be used to accelerate bone and soft tissue regeneration following tendon injuries and arthroplasty. Outcomes include decreased inflammation, reduced blood loss and post-treatment pain relief. Recent shoulder research indicates there is poor vascularization present in the area around tendinopathies and this possibly prevents full healing capacity post surgery (Am J Sports Med 36(6):1171--1178, 2008). Although it is becoming popular in other areas of orthopedics there is little evidence regarding the use of PRP for shoulder pathologies. The application of PRP may help to revascularize the area and consequently promote tendon healing. Such evidence highlights an opportunity to explore the efficacy of PRP use during arthroscopic shoulder surgery for rotator cuff pathologies.Methods/design: PARot is a single center, blinded superiority-type randomized controlled trial assessing the clinical outcomes of PRP applications in patients who undergo shoulder surgery for rotator cuff disease. Patients will be randomized to one of the following treatment groups: arthroscopic subacromial decompression surgery or arthroscopic subacromial decompression surgery with application of PRP.The study will run for 3 years and aims to randomize 40 patients. Recruitment will be for 24 months with final follow-up at 1 year post surgery. The third year will involve collation and analysis of the data. This study will be funded through the NIHR Biomedical Research Unit at the Oxford University Hospitals NHS Trust.Trial registration: Current Controlled Trials: ISRCTN10464365.Trials 06/2013; 14(1):167. · 2.21 Impact Factor
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ABSTRACT: Objective-To determine efficacy of a single intra-articular injection of an autologous platelet concentrate for treatment of osteoarthritis in dogs. Design-Randomized, controlled, 2-center clinical trial. Animals-20 client-owned dogs with osteoarthritis involving a single joint. Procedures-Dogs were randomly assigned to a treatment or control group. In all dogs, severity of lameness and pain was scored by owners with the Hudson visual analog scale and the University of Pennsylvania Canine Brief Pain Inventory, respectively, and peak vertical force (PVF) was determined with a force platform. Dogs in the treatment group were then sedated, and a blood sample (55 mL) was obtained. Platelets were recovered by means of a point-of-use filter and injected intra-articularly within 30 minutes. Control dogs were sedated and given an intra-articular injection of saline (0.9% NaCl) solution. Assessments were repeated 12 weeks after injection of platelets or saline solution. Results-Dogs weighed between 18.3 and 63.9 kg (40.3 and 140.6 lb) and ranged from 1.5 to 8 years old. For control dogs, lameness scores, pain scores, and PVF at week 12 were not significantly different from pretreatment values. In contrast, for dogs that received platelet injections, lameness scores (55% decrease in median score), pain scores (53% decrease in median score), and PVF (12% increase in mean PVF) were significantly improved after 12 weeks, compared with pretreatment values. Conclusions and Clinical Relevance-Results suggested that a single intra-articular injection of autologous platelets resulted in significant improvements at 12 weeks in dogs with osteoarthritis involving a single joint.Journal of the American Veterinary Medical Association 11/2013; 243(9):1291-7. · 1.72 Impact Factor
Platelet-rich plasma enhances the initial mobilization of
circulation-derived cells for tendon healing.
Kajikawa Y, Morihara T, Sakamoto H, Matsuda KI, Oshima Y, Yoshida A, Nagae M,
Arai Y, Kawata M, Kubo T.
J. Cell Physiology Jan. 2008
Circulation-derived cells play a crucial role in the healing processes of tissue. In early phases of tendon
healing processes, circulation-derived cells temporarily exist in the wounded area to initiate the healing
process and decrease in number with time. We assumed that a delay of time-dependent decrease in
circulation-derived cells could improve the healing of tendons. In this study, we injected platelet-rich plasma
(PRP) containing various kinds of growth factors into the wounded area of the patellar tendon, and
compared the effects on activation of circulation-derived cells and enhancement of tendon healing with a
control group (no PRP injection). To follow the circulation-derived cells, we used a green fluorescent protein
(GFP) chimeric rat expressing GFP in the circulating cells and bone marrow cells. In the PRP group, the
numbers of GFP-positive cells and heat-shock protein (HSP47; collagen-specific molecular chaperone)-
positive cells were significantly higher than in the control group at 3 and 7 days after injury. At the same
time, the immunoreactivity for types I and III collagen was higher in the PRP group than in the control group
at early phase of tendon healing. These findings suggest that locally injected PRP is useful as an activator of
circulation-derived cells for enhancement of the initial tendon healing process. J. Cell. Physiol. (c) 2008
Research, use of platelet-rich plasma continues to expand
Platelet-rich plasma (PRP)—a component of whole blood containing powerful, transforming growth factors—has
garnered worldwide attention as a possible biologic method to treat tendinosis and tendon tears, as well as many
other challenging conditions.
In Europe, PRP is being used to treat conditions ranging from tendinosis to osteitis pubis. This past November, I had
the opportunity to take a European “PRP Tour”—to share my clinical work on PRP and to learn about and witness
how European orthopaedists are using PRP to enhance healing. I was also invited to speak at several meetings
focused on research and clinical experiences with PRP.
Achilles tendon repair in Sweden
Upon my arrival in Linköping, about two hours west of Stockholm by train, I met with Per Aspenberg, MD, PhD, the
author of several articles on the successful use of PRP to enhance tendon healing. We discussed the number of
researchers around the world who are investigating and assessing the value of PRP in orthopaedic surgery.
The next morning, I was asked if I would like to observe Dr. Aspenberg and his colleague, Torsten Schepull, MD,
perform an Achilles tendon repair. I welcomed the opportunity. The nurses and operating room staff were very cordial
and, fortunately for me, spoke excellent English.
As the patient was prepped for surgery, I was asked whether I would like to scrub in on the case. The patient was
lightly sedated and in a prone position; a local anesthetic was injected around the incision site. After the surgery had
started, I was informed that this patient was the first case in a prospective, randomized trial to measure the impact of
receiving autologous PRP in an Achilles tendon repair.
The lead surgeon made the incision, expertly mobilizing the tendon edges. After checking the treatment allocation
data on the computer, the surgeons found that this patient would receive PRP. Although the patient was awake,
headphones prevented him from hearing any of the discussion, so he remained unaware of the randomization
decision. To ensure the accuracy of the research, no further discussion on the use of PRP was permitted around this
Just before the surgeon closed the tendon sheath, he embedded 0.8 mm tantalum balls into the tendon above and
below the tear site. This allows for noninvasive analysis of tendon elongation at 6- to 10-week intervals postsurgery.
Researchers will be able to calculate and compare tendon length among patients in the PRP group and those in the
control group. I found this to be a particularly unique and novel method, which will provide information for the clinical
trial and additional noninvasive biomechanical data on the differences between the two groups. The PRP was
injected into and around the repaired tendon after the surgeon closed the tendon sheath.
Other uses for PRP
In the afternoon, orthopaedic surgeons from throughout northern and Eastern Europe attended a meeting to discuss
their research and clinical experiences with PRP.
From his studies with rat models, Dr. Aspenberg demonstrated how PRP enhances Achilles tendon stiffness and
force to failure. Taco Grosen, MD, from the Netherlands, presented preliminary data from his prospective,
randomized trial of PRP versus cortisone for treating chronic tennis elbow.
Dr. Grosen demonstrated how PRP produces significantly better statistical outcomes than cortisone for pain relief and
functional scoring at 6 months after a single injection. This is consistent with my findings in “Treatment of Chronic
Elbow Tendinosis with Buffered Platelet-Rich Plasma,” published in the American Journal of Sports Medicine.
Orthopaedic surgeons from Sweden, Finland, and Poland also made presentations on PRP. Ongoing investigations
include the use of PRP in the treatment of partial tears of the anterior cruciate ligament (ACL), meniscal tears, and
Krzysztof Ficek, MD, from Poland, reported that he has some success using PRP with osteitis pubis—a notoriously
difficult condition. Eight of nine patients treated with PRP are doing very well.
Italian Ministry of Health funds PRP study
At the Galeazzi Orthopedic Institute, in Milan, I met with Professor Giuesppe Banfi and Laura de Girolamo, MD, about
their prospective study of tendinosis funded by the Italian Ministry of Health.
We discussed the confusion they routinely encounter in Italy about the growth factors in PRP. Some patients and
Italian ministry administrators think growth factors are growth hormones. Part of their job is convincing patients and
administrators that PRP is not a growth hormone!
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Drs. Banfi and Girolamo provided the following statement about their study. “All the patients suffer from chronic
osteoarticular pathology and are exposed to a nonsteroidal anti-inflammatory drug (NSAID) therapy. They will
undergo either anterior cruciate ligament reconstruction surgery with PRP or Achilles/patellar tendon surgery with
PRP and will be clinically evaluated for 12 months according to a predetermined protocol.
“A biopsy of the patient’s cartilage tissue will be evaluated by other centers during an in-vitro study culturing the
patient’s chondrocytes with their PRP. The aim of the in-vitro study is to evaluate a number of inflammatory markers
and molecular ‘targets’ implicated in the inflammatory and healing response of the cartilage taken from patients
exposed to NSAID and to the PRP treatment, which in the future might be used for diagnostic and therapeutic
The investigators have asked me to evaluate their protocol and to contribute to their study.
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Genoa: PRP and the treatment of tendinopathy
In Italy, I also attended the 15th annual meeting of the Ligurian Arthroscopy Association organized by Ferdinando
Priano, MD. I had been asked to give two lectures—one on the basic science of PRP and the other on my own
clinical experiences with it.
With more than 300 orthopaedic surgeons, basic scientists, and hematologists in attendance, the meeting focused on
the potential use of PRP in the treatment of tendinopathy.
Dr. Priano shared his experience using hyaluronic acid for tendon-related disorders. Piero Volpi, MD, presented the
results of a study using ultrasonic guided injections of PRP for patellar tendinosis. Pietro Randelli, MD, showed an
excellent video of his technique using PRP to augment arthroscopic rotator cuff repairs.
My week in Europe showed me that interest in PRP as a treatment to enhance healing has grown quite dramatically,
with speculation about using this technology for cartilage, ligament, and even disk pathology. Significantly more basic
science and clinical investigations, however, will be required to fully validate the use of PRP.
I plan to continue these interactions with my esteemed European colleagues via the Internet and in person at future
meetings. I have been honored to be part of the PRP discussions in both the United States and Europe. I recently
learned that orthopaedic surgeons in Brazil, Australia, and Hong Kong have also used PRP in orthopaedic surgery. I
look forward to hearing the results from my orthopaedic colleagues throughout the world.
Disclosure information for Allan K. Mishra, MD, can be found online at www.aaos.org
Dr. Mishra can be reached at email@example.com
How does PRP work?
Platelet-rich plasma (PRP) contains powerful growth factors. including transforming growth factor-beta (TGF-β) and
vascular endothelial growth factor (VEGF). PRP has been shown to enhance the proliferation and migration of a
variety of cell types including tenocytes and mesenchymal stem cells. This in-vitro data helps explain why PRP may
be helpful for patients with chronic tendinosis. Published studies also note that PRP has a strong stimulant effect on
capillary regeneration. This improved vascularity may be another way PRP improves overall tendon health.
Not all PRP is the same. PRP that has not been activated by thrombin or calcium may be the preferred form. The
collagen within tendons can be expected to activate the platelets slowly, resulting in a sustained release of growth
factors. PRP activated by thrombin and or calcium, however, results in rapid discharge of growth factors, which may
not be ideal.
Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med.
Mishra et al. Buffered Platelet Rich Plasma Enhances Mesenchymal Stem Cell Proliferation and Chondrogenic
Differentiation. AAOS Annual Meeting; Poster Presentation, 2007
Eppley BL, Woodell JE, Higgins J. Platelet quantification and growth factor analysis from platelet rich plasma:
implications for wound healing. Plast Reconstr Surg. 2004 Nov:114(6):1502-8
Schnabel LV, Mohammed HO, Miller BJ, et al. Platelet rich plasma (PRP) enhances anabolic gene expression
patterns in flexor digitorum superficialis tendons. J Ortho Res. 2007 Feb;25(2):230-240
Woodall JR, Tucci M, Mishra A, Benghuzzi H. Cellular Effects of Platelet Rich Plasma: A Study on HL-60
Macrophage-like Cells. Biomed Sci Instrum. 2007, 43:266-71