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Curr Phys Med Rehabil Rep (2014) 2:1–15
DOI 10.1007/s40141-013-0039-5

MUSCULOSKELETAL REHABILITATION (NA SEGAL, SECTION EDITOR)

PRP: review of the current evidence for musculoskeletal
conditions
Gerard A. Malanga • Michael Goldin

Published online: 25 January 2014
Springer Science + Business Media New York 2014

Abstract Injection of platelet-rich plasma (PRP) is an
evolving treatment option for various musculoskeletal
injuries. There is basic scientific evidence that suggests that
the various growth factors present in PRP can help to
augment the body’s natural healing. There are also clinical
studies suggesting efficacy for several conditions, particularly tendinopathy and osteoarthritis. This article reviews
the definition and first uses of PRP, the basic scientific
rationale for its use, and the basic science and evidence for
its use in the treatment of tendon, joint, ligament, and
muscle injuries. There are varying levels of evidence for
and against the use of PRP for these types of injuries, and
this article reviews studies that support as well as studies
that refute the use of this new treatment. There are several
studies that have assessed the basic science supportive of
PRP treatments, as well as the clinical efficacy of this
treatment in vivo. While the current evidence is mixed,
several recent studies have demonstrated therapeutic benefit in the treatment of various tendinopathies and degenerative joint diseases of the knee. There are several factors
that need to be addressed to elucidate whether PRP is truly
effective. These include fully defining the PRP mixture
(e.g. concentration, growth factor levels, presence of white
cells and red cells, etc.), determining the optimal preparation and delivery of the PRP graft, calculating the

G. A. Malanga M. Goldin
New Jersey Sports Medicine, LLC, New Jersey Regenerative
Institute, New Brunswick, NJ, USA
G. A. Malanga (&) M. Goldin
Department of Physical Medicine and Rehabilitation, Rutgers
University-New Jersey Medical School, New Brunswick, NJ,
USA
e-mail: gerardmalanga@gmail.com

appropriate number of injections for each specific pathologic process, and defining optimal post-procedure
rehabilitation.
Keywords PRP Tendinopathy Treatment Arthritis
Growth factors

Introduction
Platelet-rich plasma (PRP) has evolved as a treatment
option for a variety of orthopedic conditions over the past
decade. PRP treatments have historically been used in
cardiac and dental procedures in humans. Since these initial uses, it has been used in a variety of musculoskeletal
conditions in humans over the past 10 years. Initial studies
were directed at treatment of chronic, refractory tendinopathy, in particular chronic tennis elbow pain. Over the
past decade, its use has been expanded to treating a variety
of other musculoskeletal conditions including ligament
injuries, muscle tears, and osteoarthritis.
In this article, we will review the current evidence
regarding PRP for musculoskeletal injuries. We will first
review the basic science of PRP and the rationale for its use
in tendinopathy and other musculoskeletal conditions. This
review will primarily focus on the evidence specifically for
non-invasive management of pathologic processes involving tendons, joints, ligaments, and fibro-cartilaginous
structures.

Definition
PRP has been defined as a volume of autologous plasma
that has a platelet concentration above baseline [1]. The

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process of concentrating the platelets necessitates two sets
of centrifugation, one after the other. The first spin (a hard
spin) separates the red blood cells from the plasma, the
latter of which contains platelets, white blood cells, and
clotting factors [1]. The second spin (a soft spin) finely
separates the platelets and white blood cells, together with
a few red blood cells [1]. In 2003, Weibrich et al. [2] felt
that the optimum platelet concentration in PRP to have a
positive effect on bone regeneration was around 1 million
platelets/microliter (ll), and above that, there was an
inhibitory effect on healing. However, several recent articles have produced different conclusions about ideal
platelet count and challenged these initial theories. Giusti
et al. found the optimal platelet concentration for angiogenesis was 1.5 million/ll (5–79 baseline). Lower levels
produced less angiogenesis, and inhibition was not noted
until levels reached 2–3 million/ll (109 baseline) [3].
Finally, Kevy documented that the ideal platelet concentration is 1.5 million/ll (5–79 baseline) and could be as
high as 3 million/ll (109 base-line). Kevy and Jacobson
[4] also noted that current commercially available PRP
devices could not attain levels higher than 109 baseline
levels.

First uses
In 1987, Ferrari et al. [5] used autologous PRP and red
blood cell concentrates as an autologous transfusion for
support of cardiac surgery patients in 15 operations. No
homologous blood products were required. In 1990, DelRossi et al. [6] showed that in patients undergoing heart
operations on cardiopulmonary bypass, PRP-infused
patients required 65 % less banked blood products compared to patients not receiving this infusion. In 1998, Marx
et al. [7] assessed PRP and its effect on increasing the rate
of bone graft maturity of dental implants compared to a
control group. This study demonstrated that an average
concentration of 338 % of baseline platelet count resulted
in greater trabecular bone density relative to bone grafts
that were not augmented with PRP [7].

Rationale for use of PRP
Platelets have several components that may help to augment healing. Dense granules within the platelets have
compounds that influence cell migration, cell proliferation,
and vascular tone [8]. They contain several types of
granules, each with different components and various roles
in platelet activities. These granules include dense granules, alpha granules, lysosomal granules, etc. Alpha granules have several proteins with various functions including

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Curr Phys Med Rehabil Rep (2014) 2:1–15

platelet-derived growth factors (PDGF) such as PDGFaa,
PDGFbb, and PDGFab; TGFb1 and TGFb2; vascular
endothelial growth factor (VEGF), transforming growth
factor beta (TGFB), insulin-like growth factor (IGF), vascular endothelial growth factor (VEGF), basic fibroblast
growth factor (BFGF), and epithelial growth factor (EGF).
The functional groupings of these proteins include adhesive proteins, clotting factors, fibrinolytic factors, proteases, growth factors, cytokines, basic proteins, antimicrobial proteins, and membrane glycoproteins [8].
PDGF and epidermal growth factors are present in tendons during the tendon healing process [9]. TGFb has been
shown to increase type I and type III collagen production in
tendon sheath cells, epitenon cells, and endotenon cells [10].
Marui et al. [11] showed that TGFb-1 increased collagen and
non-collagen protein synthesis in the medial collateral ligament and anterior cruciate ligament fibroblasts in a dosedependent manner. Koch et al. [12] studied TGFb-1 in mice,
finding that the release of this growth factor from platelets
and macrophages may actually increase inflammation and
slow wound closure. In the early stages of inflammation,
matrix metalloproteinases activate TGFb-1 from macrophages, which acts as a chemoattractant for neutrophils [11]
and, later on in the process, promotes tissue repair [13].
In contrast, in a study using a mouse model, TGFb-3
was found to progressively decrease during the onset of
osteoarthritis [14]. However, TGFb-3 was found to be
strongly expressed in chondrocyte clusters just prior to
osteophyte formation [12]. In a human model, Verdier
et al. [15] demonstrated that TGFb-1 had decreased
expression in degraded cartilage. However, in osteophytes,
there was a marked increase in expression of TGFb-1 and
TGFb-3. This research suggests that these growth factors
have different functions depending on the stage of degeneration of the joint. Marui et al. [11] also showed that
BFGF administration was not associated with an increase
in collagen or non-collagen protein synthesis.
VEGF has been shown to be increased by day 7 after
acute tendon injury, and new vessel length and density has
been shown to peak at 17 days after acute injury [16].
Daily injections of epidermal growth factor have been
shown to increase the extent and organization of granulation tissue [17]. IGF has been shown to increase the synthesis of proteoglycan, collagen, and non-collagen proteins
[18]. Phornphutkul et al. [19] showed that IGF-1 promotes
chondrocyte proliferation and differentiation.

PRP duration of effect
Prior literature has suggested that once platelets are activated by clotting, 70 % of the stored growth factors are
released after 10 min, and almost all stored growth factors

Curr Phys Med Rehabil Rep (2014) 2:1–15

are released within 1 h of injection [1]. The platelets can
then synthesize and secrete growth factors for about
8 days, until the platelets die [1].
Various factors should be weighed when considering the
use of PRP and when reviewing prior research of PRP.
These include platelet concentration, leukocyte count, pH
of the injected substance, use of activators, the total number
of injections given, and the method of delivery and the type
of post-procedure rehabilitation protocol [20]. In particular,
the post-procedure rehabilitation has ranged from activities
as tolerated to full immobilization. A suggested post-rehabilitation program was present in the paper based on the
known healing patterns of most tissues with progressive
loading of the tissues through the various phases following
PRP procedures. This generally allows for full activities at
the 6–8 week time-frame following injection [20].
The components of PRP have also been examined to
assess if certain compositions have a better healing profile.
Dragoo et al. [21] showed that leukocyte-rich PRP had a
greater inflammatory response relative to leukocyte-poor
PRP at post-injection day 5, but there was no difference at
day 14. McCarrel et al. [22] demonstrated that leukocytereduced PRP had decreased levels of tumor necrosis factor
alpha and interleukin 1 beta relative to standard PRP, highconcentration PRP, and concentrated-leukocyte PRP.

Evidence regarding use of PRP for tendinopathy
Basic science
De Mos et al. [23] showed that both platelet-rich clot releasate
(PRCR) and platelet-poor clot releasate (PPCR) increased
tenocyte cell number and collagen production in vitro. In this
study, PRP was ‘‘activated’’ by placing calcium chloride into
the PRP concentrate to induce the platelets to clot and to
release their growth factors. Some limitations of this study are
that the tendons were from young donors, and the fact that this
experiment was performed in vitro and, therefore, may not be
applicable in vivo. Additionally, this PRCR was not autologous, but rather the PRCR was from a different donor source
than the tendons. Wang et al. [24] demonstrated that PRCR
can promote human tenocyte proliferation and promote collagen synthesis. Bosch et al. [25] performed a study in which
they surgically created lesions in the superficial digital flexor
tendons of horses. They then used a commercially available
PRP system, Biomet, to create 3 ml of therapeutic injectate.
Ultrasound guidance was used to place either the PRP or the
control in the lesion. They demonstrated that there was statistically significant improvement in collagen, glycosaminoglycan, and DNA content in the PRP-treated tendons relative
to the controls. In addition, the repair tissue showed higher
strength failure and better collagen organization relative to

the control tendons. One of the limitations of this study was
that the lesion was created artificially by acutely inducing
mechanical damage. This differs from the more clinically
relevant incidence in humans in which repetitive overuse
injury is primarily the etiology for tendon damage [25].
Zhang and Wang [26] showed that PRCR promotes the differentiation of tendon stem cells into active tenocytes. This
experiment was performed in vitro, and used PRP that was
activated with calcium chloride to form the PRCR. These
tenocytes had increased collagen production relative to control cells treated only with autologous serum. Furthermore,
this showed that PRCR did not induce cells to turn into ‘‘nontenocytes’’. This was significant, because it demonstrated that
PRCR would not change tendon cells into non-tendon cells,
potentially exacerbating a tendinopathy. Strengths of this
study included that autologous serum was used on the tendon
stem cells. Limitations of this study include that healthy
tendon stem cells from young rabbits were used, and this may
not be applicable to subjects with older tendons. Additionally,
these experiments were performed in vitro; therefore, the
tendons were not subjected to the mechanical loading that
occurs in vivo [26]. Platelet concentrate was found to
improve Achilles tendon repair callus strength for 3 weeks
after surgical transection in an experimental rat model. This
experiment used heterologous PRCR activated by thrombin.
The PRCR was obtained from one group of rats and was
injected into different rats with surgically induced lesions;
thus, it was not autologous PRCR. Limitations of this study
include the possibility that the measured force that caused
failure of the un-operated tendons may have been underestimated due to the design of the mechanical testing apparatus
[27]. Sadoghi et al. [28] studied whether rotator cuff fibroblasts isolated from human subjects would have dosedependent increased proliferation when exposed to PRP.
They showed that a concentration of platelets five times that
of plasma had an effect on increasing human rotator cuff
fibroblast proliferation, specifically, increasing the DNA to
glycosaminoglycan ratio (the latter being one of the markers
for tendon degeneration). The onefold and five-fold concentrations of PRP had improved DNA to glycosaminoglycan
ratios relative to the ten-fold concentration of PRP. The
limitations of this study include the older age of the patients
(61 years or older), which may have limited both the amount
of growth factors present in the PRP and the regenerative
response of (older) rotator cuff fibroblasts.
Evidence regarding use of PRP for meniscus/cartilage
Ishida et al. [29] demonstrated that PRP had regenerative
effects on meniscal cells in vitro. The PRP was prepared by
doing serial centrifugations at 4 C. Once the PRP was
obtained, it was thawed and then stored at -80 C until ready
for use. Furthermore, in vivo PRP combined with a hydrogel

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had beneficial healing effects on surgically induced meniscal
lesions in a rabbit model. Limitations of this study include
that the lesions were surgically induced, and may therefore
not have similar results in primarily degenerative lesions
[29]. Surgically induced osteochondral defects were treated
in a rabbit model. A polylactic-glycolic acid scaffold was
impregnated with PRP and a thrombin/calcium chloride
solution to activate the PRP. This was then surgically
implanted in the osteochondral defect. Activated PRPimpregnated polylactic glycolic acid improved osteochondral healing relative to a control group in a rabbit model. This
study included the limitation that the osteochondral defect
was surgically induced, and a traumatic or degenerative
lesion may have a different response to this treatment [30].
Van Buul et al. [31] performed a laboratory study in which
they examined whether PRP releasate (PRPr) could decrease
the effect of interleukin-1 on osteoarthritic chondrocytes.
The PRPr was formed by serial centrifugation of whole blood
from healthy donors, and then activated with calcium chloride. PRPr decreased multiple inflammatory effects of IL-1
beta on human osteoarthritic chondrocytes in this in vitro
study. Limitations of this study include that the PRPr was not
autologous, and it is questionable whether these in vitro
effects would occur in vivo. Akeda et al. [32] used PRPr
activated with a thrombin/calcium chloride solution to
examine effects on porcine chondrocytes in vitro. This PRPr
administration to chondrocytes resulted in a statistically
significant increase in collagen synthesis and chondrocyte
DNA relative to chondrocytes treated with platelet-poor
plasma releasate or fetal bovine serum. Additionally, the
chondrocyte cells remained phenotypically stable in the
presence of the PRP. Limitations of this study included the
fact that the chondrocytes were pooled from multiple pigs,
and therefore it was not purely autologous PRPr [32].
Evidence regarding use of PRP for muscle injury
In a mouse model, experimentally induced contusion to the
gastrocnemius muscle was treated with a series of three
injections of either autologous conditioned serum (ACS) or
a series of three injections of saline [33]. Histological
evaluation revealed that there was increased myofiber
diameter regeneration and increased satellite cell activation
in the ACS group compared to the control group [33].

Evidence regarding use of PRP for tendinopathy
Lateral elbow/common extensor origin
Mishra and Pavelko [34] examined a cohort of 20 patients
with chronic lateral epicondylosis that had been refractory
to a standardized physical therapy protocol and who had

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significant and persistent pain for an average of 15 months.
These patients were all considering surgical treatment.
Fifteen patients were given a single PRP injection, and five
were given a single bupivacaine injection. The PRP injectate was produced by serial centrifugation of autologous
whole blood. No activating agent was used, and the PRP
was buffered to physiologic pH using 8.4 % sodium
bicarbonate solution. The tendon was anesthetized with
0.5 ml of bupivacaine with epinephrine. The outcome
measures that they used were a 100-mm visual analog pain
score (0, no pain; 100, worst pain possible) and a modified
Mayo elbow score (best score, 100). At the 8-week followup, the PRP patients had 60 % improvement in symptoms,
and the bupivacaine group had 16 % improvement in their
symptoms. Three of the five control subjects withdrew or
sought other treatments after 8 weeks. At 6 months’ follow-up, the PRP cohort noted 81 % improvement in the
visual analog pain scores. At final follow-up (an average of
25.6 months), the PRP patients reported 93 % pain
reduction. The limitations of this study include the lack of a
randomized control group, and the small number of
patients. The tendon also had a small amount of bupivacaine injected, which can theoretically decrease the efficacy of PRP [35]. It is also important to note that 140
patients were initially evaluated, and only 15 % were
enrolled in the study. This may be viewed as one of the
strengths of this study, as PRP was reserved as a treatment
only for patients with severe tendinopathy that did not
improve with either time or more conservative measures.
Additional strengths include that all patients had also
completed a standardized stretching and strengthening
protocol prior to the injections, and after the injections all
subjects were again given a standardized 4-week stretching
and strengthening program [34].
Peerbooms et al. [36] compared PRP injections to corticosteroid injections in patients with greater than 6 months
of pain from lateral epicondylitis. One hundred patients
were randomized to receive either a PRP injection or a
corticosteroid injection into the extensor tendon of the
symptomatic elbow. The PRP preparation method involved
serial centrifugations, buffering with sodium bicarbonate
8.4 %, and adding 0.5 % bupivacaine with epinephrine to
the injectate. Success was defined as 25 % improvement in
either VAS score or DASH (Disabilities of the arm,
shoulder, and hand) score, without a re-intervention after
1 year. Using the VAS score, 49 % of the corticosteroid
group and 73 % of the PRP group were successful. Using
the DASH score, 51 % of the corticosteroid group and
73 % of the PRP group were successful. There were several strengths of this study. It was double-blind, randomized, and controlled. Patients were excluded if they had a
steroid injection into the tendon within the past 6 months.
The subjects were given a graded post-procedure

Curr Phys Med Rehabil Rep (2014) 2:1–15

rehabilitation including 2 weeks of stretching followed by
2 weeks of eccentric strengthening. The primary outcome
measure, DASH, was a validated upper limb functional
score. Limitations of this study include that the PRP was
combined with a local anesthetic, which may inhibit some
of the beneficial effects of the PRP [35]. Additionally, prior
to the procedure, subjects had been treated with cast
immobilization, a steroid injection, or physiotherapy. All of
the subjects had not definitively undergone a course of
physical therapy and were deemed to have symptoms
recalcitrant to this [36]. This cohort of patients was also
examined at a 2-year follow-up to assess efficacy of the
intervention [37•]. At the 2-year follow-up, with success
defined as 25 % improvement in either VAS score or
DASH score without a re-intervention after 2 years, 65 %
of the PRP group and 35 % of the corticosteroid group had
successful outcomes [37•].
In a prospective, double-blind, randomized trial, 150
patients were randomized to receive either two PRP
injections or two autologous blood injections (ABIs) [38].
Successful outcome was defined as a 25-point improvement on the Patient-Rated Tennis Elbow Evaluation
(PRTEE), which they reported was comparable to other
studies. The authors reported that PRTEE is a well validated 0–100 composite scale measuring pain and physical
function. At the 6-month follow-up, there was a 66 %
success rate in the PRP group and a 72 % success rate in
the ABI group, with no statistically significant difference
between the two groups [34]. Strengths of this study
include that all the patients had already failed a course of
physical therapy including stretching and eccentric
strengthening. They also had a single practitioner who had
15 years of experience and had performed 20,000 ultrasound guided injections perform all the injections. Limitations of this study include that the tendon was bathed in
bupivacaine in both treatment groups, as this can potentially decrease the therapeutic effect [35]. Also, the performing physician was not blinded to the procedure.
Additionally, this study introduces the experiment as
comparing an ABI to a ‘‘moderate yield PRP’’ which they
describe as ‘‘essentially plasma with erythrocytes and
leukocytes removed’’. However, in the methods section,
they describe obtaining the plasma by doing a single centrifugation and then obtaining 1.5 ml from ‘‘the buffy coat
layer’’. In the introduction, they had described the buffy
coat as ‘‘leukocyte-rich, high yield PRP.‘‘ Therefore, one of
these descriptions is inaccurate. Another randomized controlled trial evaluated 28 patients who received either a
single injection of PRP or a single injection of ABI. The
PRP was obtained by performing a single centrifugation of
the whole blood and then the platelet-rich portion was
aspirated. In the analysis of the PRP, they described it as
leukocyte-containing PRP due to histologic analysis

showing leukocytes. Follow-up VAS scores were taken at
6 weeks, 3 months, and 6 months. Changes in VAS scores
and Liverpool elbow scores were used as outcome measures. They report that the Liverpool elbow score evaluates
range of motion, daily activities, and ulnar nerve function.
There was improvement in both groups at all follow-up
assessments. The only statistically significant difference
between the two groups was a larger reduction in pain
score in the PRP group compared to the ABI group at
6 weeks’ follow-up. They did not report any clinically
significant differences in the two groups [39]. Strengths of
this study include that each subject was given a stretching
and eccentric strengthening exercise program one week
after the injection. Limitations of this study include that it
was single-blind, and the patients were aware which
treatment they were receiving. They also explain that the
Liverpool elbow score evaluates elbow range of motion as
well as the ulnar nerve, which is not usually affected in this
condition. They explain that these two components may
hide clinically significant differences.
Krogh et al. [40•] performed a randomized controlled
trial on 60 patients comparing the effects of a blinded
injection of PRP, saline, or glucocorticoid. The primary
outcome measure was a change in pain using the PRTEE
questionnaire at 3 months post-procedure. For pain
assessment, the PRTEE validated for lateral epicondylitis
was applied. The PRP was processed by performing a
single centrifugation cycle on whole blood, and then the
PRP was aspirated. It was then buffered with 8.4 % sodium
bicarbonate solution. They found that pain reduction was
observed in all three groups, and there was no statistically
significant difference between the groups at a 3-month
follow-up [40•]. They also measured the following secondary outcomes: ultrasonographic changes in tendon
thickness and color Doppler activity. They reported that
glucocorticoid was more effective than PRP and saline in
both reducing color Doppler activity as well as reducing
tendon thickness. Limitations of this study include that a
local anesthetic was used in the peritendon, and this may
have decreased the therapeutic effect of the PRP [35]. The
authors describe that the initial primary outcome measure
was going to be the PRTEE at 12 months post-procedure.
However, there was significant drop-out during the study in
all 3 groups, and therefore, the primary outcome was
changed to 3 months post-procedure. They also explained
that 60 % of the subjects in the glucocorticoid group were
not naı̈ve to steroid injection treatment. It was possible that
patients initially treated with glucocorticoid to good effect
would not have been referred for further treatment; therefore, it was not surprising that these subjects failed to have
a successful result the second time they were treated with a
steroid injection. Strengths of this study include that all
participants were given a standard stretching and

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strengthening protocol after the procedure [40•]. A careful
review of this study demonstrates the rapid early effects of
corticosteroid injection over the first 6 weeks following
injection, followed by a progressive decline in efficacy.
This contrasts with the slow improvement slope of the PRP
group. At the 3-month mark, the graphical representation
of the responses demonstrates the PRP group continuing a
downward slope of improvement that intersects the
upward, decreasing benefit of the corticosteroid injection.
This pattern (rapid benefit with regression over time) is a
common finding in reviewing the literature on corticosteroid injections for tendinopathy [41].

Achilles tendon
In 2010, de Vos et al. [42] published a double-blind, randomized, placebo-controlled trial that was performed on a
group of 54 patients. They used the Victorian Institute of
Sports Assessment-Achilles (VISA-A) as a primary outcome measure. The authors reported that this is a validated
questionnaire specifically designed for evaluating outcomes in Achilles tendinopathy. Achilles tendinopathy was
treated with eccentric strengthening exercises and either a
PRP injection or a saline injection. The PRP was prepared
by performing a single centrifugation, and then the injectate was buffered with 8.4 % sodium bicarbonate. This
study showed improvement in both groups, but there was
not a statistically significant difference between the saline
group and the PRP group [42]. Strengths of this study
include the design being double-blinded, randomized, and
controlled. Additionally, all subjects were given a standard
post-procedure rehabilitation protocol. The same physician
performed all the injections. A significant limitation of this
study was their exclusion criteria. They specifically
excluded any patient who had previously completed a
heavy load eccentric exercise program. Therefore, this
injection was performed on patients naı̈ve to eccentric
strengthening exercises. This goes against a common recommendation that PRP treatment be performed in tendinopathy cases that are recalcitrant to an eccentric
strengthening protocol. In their conclusion, the authors
recommend that PRP treatment not be used in chronic midportion Achilles tendinopathy. In line with their experimental design, it may be more accurate to not recommend
PRP treatment in Achilles chronic mid-portion tendinopathy in patients that are naı̈ve to eccentric strengthening
exercises. Ultrasonographic tendon evaluation of the same
group of subjects showed no statistically significant differences in tendon structure or neovascularization in the
PRP group compared to the saline injection group [43].
One-year follow-up of the same group of subjects did not
show statistically significant differences in VISA-A score

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or ultrasonographic appearance of the PRP group compared
to the saline injection group [44•]. It is also noteworthy that
significant improvement occurred in both groups in this
study, and therefore, what lead to those improvements (the
needling itself, the injectate, and/or the eccentric exercise
program) is not clear from this study.

Patellar tendon
In a cohort study of 20 male athletes with a mean history of
20.7 months of patellar tendon pain, a series of 3 PRP
injections to treat patellar tendinopathy was performed to
assess the efficacy of this treatment for this condition [45].
They described that the primary purpose of the study was
to explore PRP for the treatment of chronic patellar tendinosis, and to specifically assess adverse events of subjects
before and after treatment. The secondary purpose was to
measure the results of the treatment. The blood went
through two serial centrifugations, and then the PRP was
aspirated. Before each injection, the PRP was mixed with
calcium chloride to activate the platelets. After the first
injection, the patients were allowed to use non-steroidal
anti-inflammatory drugs (NSAIDS) for somewhere
between 24 h up until the second injection. The exact
amount of time for which NSAIDS were permitted was not
clear in the paper. After the second injection, stretching and
mild activities were suggested. After the third injection,
participants were encouraged to begin a strengthening
program. After 1 month they were advised to return to
activities as tolerated. The outcome measures used were
Tegner, EQ-VAS, and SF-36. The mean clinically significant difference was set at 15 points. At 6 months’ followup, all parameters of the SF-36 demonstrated both statistically and clinically significant improvement. The EQVAS was also reported to demonstrate statistically significant improvement. The Tegner score assessment was
described to show a statistically significant improvement in
the patients. They further report that most of the men
returned to the sport with a lower score than their score
prior to their injury. However, the score of most of these
men was not statistically significantly different than their
score prior to their injuries. The strength of this study as
reported was that they did achieve their purpose, which was
to evaluate the safety of their protocol. There were several
limitations to this study. They described the purpose as
primarily looking for adverse events, and therefore the
results of the treatment were only a secondary purpose.
This was a cohort study, and therefore no control group
was present. They allowed the patients to use NSAIDS for
an inexact period of time for pain control between the first
and second injections, which could have inhibited some of
the therapeutic effect. The patients had tried a variety of

Curr Phys Med Rehabil Rep (2014) 2:1–15

treatments prior to these injections, but none of these prior
treatments was common to all the participants. This protocol also involved a series of three PRP injections. These
injections can be several hundred dollars each, and the cost
of three injections may be prohibitive to a large portion of
patients [45].
Filardo et al. [46] performed a cohort control study in
order to assess the therapeutic effect of three PRP injections in patients with chronic tendinopathy. They compared
a group of 15 patients who received a series of 3 PRP
injections for patellar tendinopathy to a group of 16
patients treated primarily with physical therapy. The blood
was put through two serial centrifugations, and then the
PRP was aspirated. The PRP was mixed with calcium
chloride prior to injection in order to activate the platelets.
They reported that Tegner, EQ-VAS, and pain scale were
used as outcome measures. The authors did not specifically
explain how they chose to use these particular outcome
measures. At 6-month follow-up, there was not a difference
in EQ-VAS or pain scale between the two groups. The
authors did report that the PRP group did achieve a greater
improvement in sport activity level relative to the control
group. This study had several limitations. The control
group had not had a course of physical therapy prior to
their intervention; thus, the two groups had a different preintervention treatment regimen. Furthermore, the study was
neither blinded nor randomized [46].
De Almeida et al. [47] discussed that sports injuries
have heterogeneity of lesions, which makes it difficult to
compare efficacy of treatments in prospective randomized
trials. They also reviewed basic science literature that
showed PRP improved the mechanical properties of a
rabbit’s patellar tendon after resection of its central portion
[48]. Therefore, they used the patellar tendon harvest site
as an experimental model to assess the effect of PRP on
patellar tendon healing in humans in a prospective, randomized, evaluator-blinded study. The primary outcome
was magnetic resonance imaging (MRI) assessment of
patellar tendon harvest site healing. Secondary outcomes
were functional and clinical evaluations of ACL reconstruction with a patellar tendon graft to examine whether
adding PRP to the harvest site affects the clinical and
functional outcomes of the procedure. PRP was obtained
by using a cell separator with a specific kit for platelet
apheresis in the operating room simultaneously with ACL
reconstruction. Calcium chloride was added to one of the
vials of PRP to activate the platelets. With regards to the
primary outcome, PRP treatment to the patellar tendon
harvest site for ACL graft harvesting showed a smaller
tendon gap at 6 months relative to a control group [47]. On
the Tegner questionnaire, both groups had worse results.
When comparing the questionnaire scores of the two
groups, there was no statistically significant difference.

Notably in this study, due to the method of obtaining PRP,
30–50 ml of PRP was obtained for each patient. There
were several strengths of this study. A single surgeon
performed all the procedures. There was a standard defect
in the central portion of the patellar tendon, therefore the
authors could compare patellar tendon harvest site healing
after a standardized and well-established procedure. A
single musculoskeletal trained radiologist performed all the
blinded MRI evaluations. All subjects followed the same
rehabilitation protocol. Limitations of this study included
that post-procedure analgesic medications included ketoprofen, and this may have blunted the therapeutic efficacy
of the PRP [35]. Additionally, the surgeon performing the
procedures was not blinded to the two treatment groups.
A randomized controlled trial of 46 athletes compared
the treatment of patellar tendinopathy with either 2 PRP
injections or 3 sessions of focused extra-corporeal shock
wave (ECSW) therapy [49•]. The PRP was obtained by
performing a single centrifugation of whole blood, and the
PRP was then collected and stored until ready for injection.
The outcome measures were the Victorian Institute of
Sports Assessment–Patella (VISA-P) questionnaire, the
pain visual analog scale (VAS) during five single-legged
squats on the affected knee, and a modified Blazina scale.
The authors report VISA-P is the only published clinical
scale validated for patellar tendinopathy. Using the VISA-P
scale, there was statistically significant improvement in the
PRP group relative to the ECSW group at 6 months (PRP—
I86.7 [SD = 14.2], ECSW—73.7 [19.9], P = 0.014) and at
12 months (PRP—91.3 [SD = 9.9], ECSW—77.6 [19.9],
P = 0.026) [49•]. At 6- and 12-month follow-ups, there was
a greater improvement in VAS scores after 5 single-legged
squats in the PRP group compared to the ECSW group. At a
12-month follow-up, there was also a greater improvement
in the modified Blazina scale in the PRP group relative to
the ECSW group. Strengths of this study include that the
same physician performed all the procedures. They also
avoided the use of anesthetics in both treatment groups.
Limitations of this study include that the patients were not
blinded to the intervention, and it was not placebo-controlled. It is possible that awareness of the treatment
modality may have had some effect on the patients’ perception of their response to the treatment.
In the multi-center, retrospective study by Mautner et al.
[50], the patellar tendon was found to be the most difficult to
treat, with greater than 50 % or more improvement noted in
only 59 % of patients treated for chronic patellar tendinopathy.

Rotator cuff tendinopathy
Bergeson et al. [51] performed an observational cohort
study on 16 patients with at-risk arthroscopic rotator cuff

123

repairs to determine the effect of platelet-rich fibrin matrix
(PRFM) augmentation on healing rates and functional
outcome scores. They used an algorithm to determine
patients with a rotator cuff tear that was at risk for a re-tear.
They used a retrospective control group of 21 patients that
had been operated on by the same group of surgeons performing the PRP-augmented repair. The PRFM was created by performing serial centrifugations on autologous
whole blood. The second centrifugation was done with
calcium chloride added, in order to initiate the fibrin clotting cascade. Several functional outcome scales were used
to assess functional improvement in the two groups. These
included the American Shoulder and Elbow Surgeons
system (ASES), the Constant system, the University of
California at Los Angeles (UCLA) system, the Western
Ontario Rotator Cuff Index (WORC), and Single Assessment Numeric Evaluation (SANE). There was no statistically detectable difference between the PRFM group and
the retrospective control group with respect to postoperative functional scores. MRIs were also performed at 1 year
post-surgery in all patients except three. The percentage of
re-tears in the PRFM group was 56 %, and in the historical
control group was 38 %. This difference reached statistical
significance (P = 0.024). Weaknesses of this study include
no randomization and the inherent selection bias due to the
use of an historical control group. There was heterogeneity
of repair technique, which may have also influenced the
results. The mean follow-up time for the PRFM group
functional scores was 13 months, and the mean follow-up
time for the historical control group functional scores was
27 months, which also may have introduced bias.
Rodeo et al. [52] performed a randomized trial on 79
patients undergoing surgical repair of full-thickness rotator
cuff tears. Forty patients received the experimental treatment, which was surgical repair augmented with PRFM,
and 39 patients received surgical repair without augmentation. The primary outcome measure was ultrasonographic
evidence of postoperative tendon healing at 6 and
12 weeks. Secondary outcomes included standardized
shoulder outcome scales and strength measurements. The
standard postoperative rehabilitation regimen was prescribed in all patients. The authors report that the PRFM
was made intra-operatively by obtaining peripheral venous
blood at the start of the case. They report that they used a
second centrifugation and added calcium chloride during
this step in order to activate the fibrin-clotting cascade. At
6 weeks, 30 of 36 (83 %) rotator cuff tendons were intact
in the control group, and 28 of 34 (82.4 %) rotator cuff
tendons were intact in the PRFM group (P = 0.913). At
12 weeks, 25 of 31 (80.6 %) rotator cuff tendons were
intact in the control group, compared with 24 of 36
(66.7 %) in the PRFM group (P = 0.198). Strengths of this
study included that the evaluating sonographer was blinded

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to which treatment each patient received. Weaknesses of
this study include that the surgeons performing the procedure were not blinded to which patients were receiving the
PRFM augmentation. The follow-up points were also relatively soon after the surgery.
In a prospective cohort study, 42 patients had arthroscopic repair of full-thickness rotator cuff tears, either with
or without PRP to augment the surgery [53]. The patients
made the decision whether or not they wanted to have PRP
used. The PRP was obtained by using a plateletpheresis
system with a leukoreduction set. In order to form a gel,
calcium gluconate was added to the PRP. After the medial
row of sutures were threaded, the PRP gel was applied. The
outcome assessments included pain, ROM, strength, and
functional scores and overall satisfaction at periodic
intervals up to 16 months. Several functional scales were
used: American Shoulder and Elbow Surgeons system, the
Constant system, the University of California at Los
Angeles (UCLA) system, the Disabilities of the Arm,
Shoulder and Hand (DASH) system, the Simple Shoulder
test, and the SPADI. The majority of functional scores
showed no significant difference at any of the follow-up
time periods, with the exception of the 3-month follow-up.
At this point, the ASES score, the Constant score, and the
SPADI score showed increased functional improvement in
the control group. Additionally, the authors commented
that the PRP group had a lower re-tear rate—26.7 %
compared to 41.2 %; however, they report that this was not
statistically significant. Strengths of this study include the
standardization of the PRP gel. The authors report that they
focused on two factors to obtain meaningful results—
standardization of PRP production and the reproducible
application of PRP. They obtained this by using a plateletpheresis system instead of a desktop system. They also
used a gel because they felt that an injection might be
diluted or washed out during an arthroscopic procedure due
to the nature of the procedure. All subjects had the same
postoperative protocol—shoulders were immobilized for
4–6 weeks using an abduction brace. They gradually progressed to short arc range of motion, then passive range of
motion and then active assisted range of motion. Patients
returned to sports after 6–9 months according to individual
recovery. The weaknesses of this study include lack of
randomization, a larger proportion of large and massive
tears in the PRP group, and an arbitrary volume, concentration, and activation level for the PRP.
Kesikburun et al. [54•] performed a randomized controlled trial on 40 patients with rotator cuff tendinosis or
partial thickness rotator cuff tears. The patients received
either a single PRP injection or a single saline injection.
The PRP was obtained by performing a single centrifugation on whole blood, and then separating out the PRP. The
primary outcome measure was the Western Ontario Rotator

Curr Phys Med Rehabil Rep (2014) 2:1–15

Cuff Index (WORC). The authors reported the WORC is a
valid and reliable disease-specific, quality of life selfassessment measurement tool for rotator cuff disease. The
authors attempted to detect a clinically relevant difference
of 17 % in the WORC score between the 2 groups. This
study demonstrated no statistically significant differences
in the WORC score between the two treatment groups in
follow-ups at weeks 3, 6, 12, and 24, or at one year [54•].
Strengths of this study include that it was double-blinded,
and the clinician performing the injection, the patient, and
the evaluator were blinded as to which injection the patient
received. A single clinician performed all the injections.
All patients underwent the same post-procedure rehabilitation protocol. The patients were told to avoid NSAIDS
after the procedure. Limitations of this study include that
the rotator cuff was anesthetized with lidocaine prior to
either injection, which may decrease the therapeutic effect
of the PRP [35].
Rha et al. [55•] performed a prospective randomized,
double-blind, controlled study in 39 patients with rotator
cuff tendinosis or partial-thickness tears. They compared
the effects of two serial PRP injections that were performed
4 weeks apart to two serial dry needling procedures performed 4 weeks apart. The PRP was obtained by performing two serial centrifugations on autologous whole blood.
SPADI was the main outcome measurement. Follow-up
evaluations were performed at several intervals up to
6 months after the second injection. Acetaminophen and
hydrocodone were used for post-procedure pain control.
After the second injection, they found that at 2-week follow-up, at 3-month follow-up, and at 6-month follow-up,
the PRP treated group had statistically detectable
improvement relative to the dry needling group, using the
SPADI [48]. They did not specifically address the clinical
significance of the statistically detectable improvement in
the overall SPADI score. However, they did also perform a
separate analysis of the total pain score subset of SPADI
score between the two groups, and the total disability score
subset of SPADI score between the two groups. The authors
note that there was no statistically detectable difference
between the two groups at any time point when comparing
the total pain score subset and total disability score subset.
Strengths of the study include that the patients were blinded
as to which treatment they received. Weaknesses of this
study include that the physician performing the procedure
was not blinded as to which injectate he was using. Due to
this fact, the study was not technically double-blind,
because this presents the possibility of bias from the proceduralist, which may have affected the outcomes. There
was also a 25 % drop-out rate in this study by the end of the
6-month follow-up period, which may bias the results. The
authors do not describe a specific standardized rehabilitation protocol for all subjects in the methods section.

Multi-tendon tendinopathy studies
In a retrospective cross-sectional survey, Mautner et al.
[50] assessed the results of 325 patients who received
ultrasound-guided PRP injections for tendinopathy that was
refractory to conventional management. Only 180 patients
that were contacted answered the survey. The primary
outcome measurement was the perceived improvement in
symptoms at least 6 months after the PRP injection(s). This
perception was quantified using the following Likert scale:
‘‘Not at all,’’ ‘‘Slightly,’’ ‘‘Moderately,’’ ‘‘Mostly,’’ and
‘‘Completely’’. The primary outcome measurement
(improvement in symptoms) was analyzed by calculating a
global average for all tendons, average improvement for
each of the most commonly treated tendon groups, and
average improvement according to the number of injections received. Secondary outcome measurements were the
following: perceived change in VAS before and after the
procedure (from 0 for no pain to 10 for worst pain),
functional pain after the procedure using the Nirschl Pain
Phase Scale for overuse injuries, and overall satisfaction
with the PRP procedure (quantified with the following
Likert scale: ’’Completely Dissatisfied,‘‘ ’’Mostly Dissatisfied,‘‘ ’’Somewhat Dissatisfied,‘‘ ’’No Difference,‘‘
’’Somewhat Satisfied,‘‘ ’’Mostly Satisfied,‘‘ and ’’Completely Satisfied‘‘). 82 % of patients that responded at
1 year or greater post-procedure recorded a moderate-tocomplete resolution of symptoms (C50 % improvement).
The three most common tendons treated were the insertion
of the common extensor tendon at the lateral epicondyle,
the Achilles, and the patellar tendons. 93 % of patients who
received a lateral epicondyle injection, 100 % of patients
who received an Achilles injection, and 59 % of patients
who received a patellar tendon injection reported moderate
to complete resolution of symptoms (C50 % improvement). Over 80 % of patients that received an injection in
the rotator cuff, hamstring, gluteus medius or the common
flexor tendon at the medial epicondyle reported C50 %
improvement. 60 % of patients received only one injection;
30 % received two injections, and 10 % received three or
more injections. There was an average reduction in VAS of
74 % noted. Strengths of this study include that it represents the largest database of patients treated with PRP for
tendinopathy that has been published at the time of its
publication. Weaknesses of this study include that all the
patients had not uniformly attempted and failed an eccentric strengthening therapeutic exercise program prior to
having the PRP procedure performed. Rather, the authors
state that the inclusion criteria was a diagnosis of tendinopathy for [6 months that had not resolved with conventional
treatments,
including
oral
medications,
physiotherapeutic modalities, and eccentric exercises
(those that involve slow, controlled lengthening of the

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muscle/tendon unit), among others. This is further accentuated by the fact that the authors document that the
patients must have completed a rehabilitation program that
included eccentric exercises no earlier than 4 weeks after
the procedure. This description makes it difficult to determine what portion of improvement was from the PRP
injection versus from the eccentric exercise rehabilitation
that they completed after the injection. This is especially
true given that they had not necessarily completed an
eccentric exercise program prior to the PRP injection,
based on the inclusion criteria described. Only 55 % of the
patients that were contacted responded to the survey, which
introduces selection bias as a possible confounder. The
study collected retrospective data, which results in recall
bias, does not control for confounding factors, and limits
the type of questions that can be asked.
In a two-part study, Finoff et al. examined 41 subjects
who first received a single ultrasound-guided percutaneous
needle tenotomy and PRP injection. In the second part of
the study, a diagnostic musculoskeletal ultrasound examination was performed on the tendon that was treated with
PRP [56]. The PRP used for the first part of the study was
obtained by processing autologous whole blood in one of
two different types of platelet concentrating devices. The
PRP was buffered with 8.4 % sodium bicarbonate prior to
being injected into the tendinopathic lesion. After the
injection, all patients were given the same progressive stepwise rehabilitation protocol. The outcomes of primary
interest included clinical outcomes (pain severity [including average, worst, and best], functional limitations, and
satisfaction) and tendon morphology (thickness, length of
tendinopathy, echotexture, and extent of neovascularization). They report that a 3-point or greater improvement in
pain or function was considered clinically significant,
because a Cochrane review suggested that the placebo
effect on pain was approximately 24 mm (24 %) on a
100-mm VAS for pain [57].
They found that the mean time to maximum improvement was 4 months. The mean functional improvement
was 68 %, and the mean ‘‘worst-pain’’ improvement was
58 %. There was an 84 % improvement in echotexture, and
83 % of the patients were satisfied with their outcome [56].
Strengths of the study include that all subjects completed
the standardized post-procedure rehabilitation protocol.
Strict inclusion and exclusion criteria were used when
selecting patients for the procedure, which reduced the
heterogeneity of the patient population. Only two providers
performed the procedures, thus reducing interoperator
variability of the procedure. Weaknesses of this study
include that all the patients had not definitively performed
an eccentric strengthening protocol, but rather eccentric
strengthening was reported to be performed ‘‘where
applicable’’. 2 ml of 1 % lidocaine was used to anesthetize

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the tendon prior to the tenotomy and PRP injection, which
may have blunted the therapeutic effect [35]. There was not
a control group. It was also a retrospective study, which
can be subject to a variety of biases.

Evidence regarding use of PRP for ligament injuries
Anterior cruciate ligament (ACL)
There is little research regarding the role of PRP for most
ligament injuries, including the ACL. Murray et al. [58]
showed that placement of a collagen-PRP scaffold in a
central ACL defect in pigs, at the time of surgical repair,
was able to promote ACL healing both histologically and
biomechanically at a 4-week follow-up.
In a Level 1 study Silva, KSSTA 2009 noted that PRP
did not accelerate healing of autologous HS ACL reconstruction as assessed by MRI [59].
In a Level III, case–control study of anterior cruciate
ligament reconstruction, there was noted improved ligamentization of tendon grafts treated with an endogenous
preparation rich in growth factors [60].
Ulnar collateral injury of the elbow
In a prospective cohort study, 34 athletes with MRI-confirmed partial tears of the ulnar collateral ligament were
treated with a single PRP injection under ultrasound
guidance [61]. The investigators found that 30 of 34 athletes (88 %) had returned to the same level of play without
any complaints with an average follow-up of 70 weeks.
The average time to return to play was 12 weeks (range
10–15 weeks). The average KJOC score improved from 46
to 93 (P \ 0.0001). The average DASH score improved
from 21 to 1 (P \ 0.0001). DASH questionnaire improved
from 69 to 3 (P \ 0.0001). Medial elbow joint space
opening with valgus stress decreased from 28 to 20 mm at
final follow-up (P \ 0.0001). The difference in medial
elbow joint space opening (stressed vs. non-stressed)
decreased from 7 to 2.5 mm at final follow-up
(P \ 0.0001). One player had persistent UCL insufficiency
and required ligament reconstruction 31 weeks after
injection [61].

Evidence regarding use of PRP for joint and cartilage
damage
Knee joint
In an uncontrolled, prospective preliminary study, 14
patients with primary or secondary knee OA received intra-

Curr Phys Med Rehabil Rep (2014) 2:1–15

articular PRP injections at 4-week intervals for three total
injections [62]. Several outcome measures were used,
including the Brittberg–Peterson Visual Analog Pain,
Activities, and Expectations Score, which included a
10-mm VAS with resting, walking and with the knee in a
bent position; and the five subscale Knee Injury and
Osteoarthritis Outcome Score. The Brittberg–Peterson
scale showed statistically significant overall improvement
with respect to resting pain, moving pain, and bent knee
pain (P \ 0.05). At one-year follow-up, eight of the
patients indicated that they achieved their individual goal
with the injection; three patients indicated the pain was the
same, and two patients indicated the knee pain had
worsened.
A cohort of 100 patients with degenerative knee cartilage lesions received a series of 3 PRP injections administered at 21-day intervals [63]. The outcome measures
used were the International Knee Documentation Committee (IKDC) and EuroQol VAS (EQ VAS). There was a
statistically significant improvement in both outcome
measures from baseline to 6-month and baseline to
12-month follow-up (P \ 0.0005). The results significantly
worsened from 6 to 12 months, although the results at
12 months were still significantly higher with respect to
baseline (P \ 0.0005). There was a statistically significant
improvement in the IKDC score at 6-month follow-up.
Poorer outcomes were associated with older age, more
severe grade of osteoarthritis, and higher body mass index.
In a prospective cohort study, twenty patients with early
knee osteoarthritis received a single PRP injection [64].
Fifteen of the patients had clinical assessments at baseline,
1 week, and 1, 3, 6 and 12 months. They also had MRIs at
1 year. VAS scores and Western Ontario McMaster Universities Arthritis Index (WOMAC) scores were used as
outcome measures. There was a statistically significant
56.2 % (P \ 0.001) reduction in mean baseline VAS pain
scores at 6 months, and a 58.9 % reduction in mean VAS
pain scores (P = 0.001) at 1 year [55]. The overall scores
also improved significantly at 6 months by 45.1 %
(P = 0.003) and at 12 months by 56.2 % (P = 0.002).
In a prospective cohort study, 65 patients with knee OA
were treated with a single PRP intra-articular knee injection [65]. VAS and IKDC scores were used as outcome
measures. Overall, the average VAS score improved from
7.4 before the procedure to 5.0, 4.5, and 4.2 for 1, 3, and
6 months after procedure, respectively. However, the
clinical symptoms tended to deteriorate to 4.7 and 5.0 for
9 months and 1 year, respectively. On average, patients
reported relapse of knee pain at an average of 8.8 months
after the procedure. The mean IKDC score changed from
54.1 before the procedure to 53.9 at 1 month post-procedure, 61.6 at 6 months post-procedure, and 50.3 at 1 year
post-procedure. There was a shortened time to the re-onset

of pain according to KL grade (P = 0.037). If PFJ
degeneration occurred, the pain returned at 7.9 months on
average; if FPJ was not present, pain returned at an average
of 10.2 months, and this was reported to be statistically
significant (P = 0.038). There was also the suggestion that
at greater age, the clinical effect was attenuated.
Gobbi et al. [66] examined a 50-patient case series (25
patients with a prior operative intervention for a cartilage
lesion and 25 patients with surgically naı̈ve knees) who
were given two intra-articular knee PRP injections to treat
knee OA. The primary outcome measure was the IKDC.
All patients showed significant improvement in all scores
at 6 and 12 months (P \ 0.01) and returned to previous
activities, including recreational sports.
In a prospective comparative study, 150 patients were
divided to receive either 3 autologous PRP injections, 3
high molecular weight HA (HWHA) injections, or 3 low
molecular weight HA injections (LWHA) [67]. All injections were given at 2-week intervals. IKDC and EQ VAS
scales were used for outcome measures. A statistically
significant improvement in all clinical scores from baseline
evaluation to the 2- and 6-month follow-up evaluations was
observed in all treatment groups. There was a higher
number of satisfied patients in the PRP group (82 % in PRP
group, 64 % in LWHA group and 66 % in the HWHA
group; P = 0.04). The analysis at the 6-month follow-up,
the primary outcome of the study, showed better IKDC
results in the PRP group compared with the LW HA group
(P = 0.003), as well as compared with patients treated
with HW HA (P = 0.005). EQ VAS also showed greater
improvement in the PRP group compared to the other two
groups (PRP vs. LWHA, P = 0.001; PRP vs. HWHA,
P = 0.002). There were overall worst results in patients
aged over 50 years: at 6 months of follow-up, IKDC
evaluation showed lower scores in older patients in the
PRP group (P = 0.004), as well as in the LW HA group
(P = 0.003) and HW HA group (P = 0.003). More severe
degeneration was also associated with worse outcomes in
all three groups.
Spaková et al. [68] performed a prospective cohort/
control study in which 120 patients received either three
PRP intra-articular knee injections or three hyaluronic acid
(HA) injections [68]. Outcome measures included the
Western Ontario and McMaster Universities Osteoarthritis
Index (WOMAC) and the 11-point pain intensity numeric
rating scale (NRS). At 3- and 6-month follow-ups, the PRP
group showed statistically significant improvement compared to the HA group in both outcome measures
(P \ 0.01 in both outcome measures). In the PRP group,
the mean score of the WOMAC improved from 38.76
(SD = 16.50) at baseline to 14.35 (SD = 14.18) at
3-month follow-up and to 18.85 (SD = 14.09) at 6-month
follow-up. The mean score of the 11-point pain intensity

123

NRS was 5.27 (SD = 1.87) at baseline, 2.06 (SD = 2.02)
at 3-month follow-up, and 2.69 (SD = 1.86) at 6-month
follow-up. In the HA group, the WOMAC improved from
43.21 (SD = 13.70) to 26.17 (SD = 17.47) at 3-month
follow-up and to 30.90 (SD = 16.57) at 6-month follow
up. The mean score of the NRS was 6.02 (SD = 1.77) at
baseline, 3.98 (SD = 2.27) at 3-month follow-up, and 4.3
(SD = 2.07) at 6-month follow-up.
In an observational retrospective cohort/control study,
Sánchez et al. [69] examined 30 patients who received 3
weekly injections of an autologous preparation rich in
growth factors, and 30 patients received 3 weekly injections of HA. WOMAC was measured at baseline and at
5-week follow-up. The observed success rates by week 5
for the pain subscale reached 33.4 % for the autologous
preparations rich in growth factors (PRGF) group and 10 %
for the hyaluronan group (P = 0.004).
A randomized controlled trial of 120 patients compared
two groups who received either 4 weekly PRP injections or 4
weekly HA injections [70•]. The WOMAC score was the
primary outcome measure. At week 24, the PRP group had
continuous improvement, whereas the subjects treated with
HA showed a sharp worsening. The mean WOMAC score was
36.5 in the ACP group (range 5–76; SD = 617.9) and 65.1 in
the HA group (range 41–82; SD = 610.6) (P \ 0.001). The
PRP group also had better functional scores at 4 and 12 weeks
follow-up compared to the HA group (P \ 0.001 and
P \ 0.001, respectively). A statistically significant difference
between grade III gonarthrosis treated with ACP and that
treated with HA was observed at week 12 as well as at week
24, with a noticeable improvement that was greater in the
patients treated with ACP (P \ 0.001). Other than the historical use of viscosupplement injections in a series of 3
weekly injections, the rationale for performing PRP injections
in either 3 or 4 weekly injections is not substantiated by basic
science or clinical practice.
Hip joint
Sánchez et al. [71] examined 40 patients with severe unilateral hip OA who each received a series of 3 intra-articular
hip PRP injections. The primary end point was meaningful
pain relief, which was described as a reduction in pain
intensity of at least 30 % from baseline levels as evaluated
by the WOMAC subscale at 6 months post-treatment. There
was a significant reduction in the WOMAC pain scores over
the 6 to 7-week (W = 438 P = 0.00047) and 6-month
periods (W = 516, P = 0.00607).
Ankle joint
Mei-Dan et al. [72] assessed the efficacy of using PRP for
non-invasive management of osteochondral lesions (OCL)

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of the talardome. They performed a randomized controlled
trial on 30 OCLs. The patients were randomized to receive
three consecutive injections of either HA or PRP. The
follow-up points were at 4, 12, and 28 weeks. The primary
outcome measures were VAS scale and Ankle Hindfoot
Scale (AHFS). Both groups were reported to have significant improvement at all follow-up points compared to
baseline. The AHFS score improved from 66 and 68 to 78
and 92 in groups 1 and 2, respectively, from baseline to
week 28 (P \ 0.0001), favoring PRP (P \ 0.05). Mean
VAS scores (1 = asymptomatic, 10 = severe symptoms)
decreased for pain (group 1: 5.6 to 3.1; group 2 :4.1 to 0.9),
stiffness (group 1: 5.1 to 2.9; group 2: 5.0 to 0.8), and
function (group 1: 5.8 to 3.5; group 2: 4.7 to 0.8) from
baseline to week 28 (P \ 0.0001), favoring PRP (P \ 0.05
for stiffness, P \ 0.01 for function, P \ 0.05 for pain).
Subjective global function scores, reported on a scale from
0 to 100 (with 100 representing healthy, preinjury function)
improved from 56 and 58 at baseline to 73 and 91 by week
28 for groups 1 and 2, respectively (P \ 0.01 in favor of
PRP). The authors concluded that the group receiving the
PRP treatment had a significantly greater improvement
compared to the group receiving the HA treatment.
Muscle injury
At the Second World Congress on Regenerative Medicine
in 2005, a poster was presented describing the treatment of
20 professional athletes with muscle injury [73]. Based on
the severity of the injury, the athletes were treated with 1–3
injections of PRGF. Swelling and pain were reduced, and
functional capabilities were fully restored in half the
expected recovery time. Ultrasonographic images showed
full regenerated muscle tissue after treatment, and fibrosis
did not appear in any of the treated cases. This differs from
the normal pattern of muscle recovery following a muscle
strain, which generally includes disruption of the normal
architecture of the muscle fibers followed by muscle
regeneration; this is often associated with muscle fibrosis.
Depending on the severity of the injury, recovery can take
as long as 4–6 weeks, with return to sport participation
taking even longer.

Conclusions
There is evolving evidence for the efficacy of PRP for a
variety of musculoskeletal conditions. The best studies
have been performed in chronic tendinopathy, with positive
results noted for chronic lateral epicondylosis. There has
been mixed evidence in other tendons, in particular the
Achilles tendon, where in a randomized, controlled study
PRP was found to be no better than a saline injection. PRP

Curr Phys Med Rehabil Rep (2014) 2:1–15

does not appear to provide additive benefit in conjunction
with rotator cuff repair. There is good and increasing evidence for the efficacy of PRP (in reducing pain and
improving daily function) in osteoarthritis of the knee and
limited but increasing evidence for other joints. PRP
injections appear to have superior efficacy to HA injections. PRP use appears to be effective in the treatment of
partial tears of ulnar collateral injury of the elbow in
baseball pitchers, but this is based on a single study. Its
efficacy for other ligament injuries and muscle tears has not
been proven. There are various factors that must be
addressed when considering the use of PRP, and when
reviewing prior research of PRP, which include platelet
concentration, leukocyte count, pH of the injected substance, use of activators, the total number of injections
given, the method of delivery, and perhaps most importantly, the type of post-procedure rehabilitation protocol.
Compliance with Ethics Guidelines
Conflict of Interest G. A. Malanga declares no conflicts of interest.
M. Goldin declares no conflicts of interest.
Human and Animal Rights and Informed Consent This article
does not contain any studies with human or animal subjects
performed by any of the authors.

References
Papers of particular interest, published recently, have been
highlighted as:
• Of importance
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13
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21. Dragoo JL, Braun HJ, Durham JL, et al. Comparison of the acute
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26. Zhang J, Wang JH-C. Platelet-rich plasma releasate promotes
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27. Aspenberg P, Virchenko O. Platelet concentrate injection
improves Achilles tendon repair in rats. Acta Orthop Scand.
2004;75(1):93–9.

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14
28. Sadoghi P, Lohberger B, Aigner B, et al. Effect of platelet-rich
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1249–53.
29. Ishida K, Kuroda R, Miwa M, et al. The regenerative effects of
platelet-rich plasma on meniscal cells in vitro and its in vivo
application with biodegradable gelatin hydrogel. Tissue Eng.
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30. Sun Y, Feng Y, Zhang CQ, et al. The regenerative effect of
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31. Van Buul GM, Koevoet WLM, Kops N, et al. Platelet-rich
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32. Akeda K, An HS, Okuma M, et al. Platelet-rich plasma stimulates
porcine articular chondrocyte proliferation and matrix biosynthesis. Osteoarthr Cartil. 2006;14(12):1272–80.
33. Wright-Carpenter T, Opolon P, Appell HJ, et al. Treatment of
muscle injuries by local administration of autologous conditioned
serum: animal experiments using a muscle contusion model. Int J
Sports Med. 2004;25(8):582–7.
34. Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with
buffered platelet-rich plasma. Am J Sports Med. 2006;34(11):
1774–8.
35. Carofino B, Chowaniec DM, McCarthy MB, et al. Corticosteroids
and local anesthetics decrease positive effects of platelet-rich
plasma: an in vitro study on human tendon cells. Arthroscopy.
2012;28(5):711–9.
36. Peerbooms JC, Sluimer J, Bruijn DJ, et al. Positive effect of an
autologous platelet concentrate in lateral epicondylitis in a double-blind, randomized, controlled trial: platelet-rich plasma versus corticosteroid injection with a 1-year follow-up. Am J Sports
Med. 2010;38(2):255–62.
37. • Gosens T, Peerbooms JC, van Laar W, et al. Ongoing positive
effect of platelet-rich plasma versus corticosteroid injection in
lateral epicondylitis: a double-blind randomized controlled trial
with 2-year follow-up. Am J Sports Med. 2011;39(6):1200–8.
The authors report that with success being defined as a 25%
improvement in either VAS score or DASH score and no reintervention at 2-year follow-up, 65 % of the PRP group and 35
% of the corticosteroid group had successful outcomes. This is an
important clinical response that warrants recognition by practitioners who treat patients with lateral epicondylitis.
38. Creaney L, Wallace A, Curtis M, et al. Growth factor-based
therapies provide additional benefit beyond physical therapy in
resistant elbow tendinopathy: a prospective, single-blind, randomised trial of autologous blood injections versus platelet-rich
plasma injections. Br J Sport Med. 2011;45(12):966–71.
39. Thanasas C, Papadimitriou G, Charalambidis C, et al. Plateletrich plasma versus autologous whole blood for the treatment of
chronic lateral elbow epicondylitis: a randomized controlled
clinical trial. Am J Sports Med. 2011;39(10):2130–4.
40. • Krogh TP, Fredberg U, Stengaard-Pedersen K, et al. Treatment
of lateral epicondylitis with platelet-rich plasma, glucocorticoid,
or saline: a randomized, double-blind, placebo-controlled trial.
Am J Sports Med. 2013;41(3):625–35. The authors report that
pain reduction was observed in all 3 groups, and there was no
statistically significant difference in the primary outcome measure- Patient-Rated Tennis Elbow Evaluation (PRTEE) between
the groups receiving either a PRP injection, saline injection, or
corticosteroid injection at 3-month follow-up.36 It is important
for providers who treat lateral epicondylitis to know of studies
that refute PRP efficacy in addition to studies that support PRP
efficacy.
41. Coombes BK, Bisset L, Vicenzino B. Efficacy and safety of
corticosteroid injections and other injections for management of

123

Curr Phys Med Rehabil Rep (2014) 2:1–15

42.

43.

44.

45.

46.

47.

48.

49.

50.

51.

52.

53.

54.

55.

tendinopathy: a systematic review of randomised controlled trials. Lancet. 2010;376(9754):1751–67.
De Vos RJ, Weir A, Van Schie HTM, et al. Platelet-rich plasma
injection for chronic Achilles tendinopathy. JAMA. 2010;303(2):
144–9.
De Vos RJ, Weir A, Tol JL, et al. No effects of PRP on ultrasonographic tendon structure and neovascularisation in chronic
midportion Achilles tendinopathy. Br J Sport Med. 2011;45(5):
387–92.
• De Jonge S, de Vos RJ, Weir A, et al. One-year follow-up of
platelet-rich plasma treatment in chronic Achilles tendinopathy: a
double-blind randomized placebo-controlled trial. Am J Sport
Med. 2011;39(8):1623–29. The authors report that there was not
statistically significant difference in VISA (Victorian Institute of
Sport Assessment) score or ultrasonographic appearance of the
PRP group compared to the saline injection group at 1 year
follow-up. It is important for providers who treat Achilles tendinopathy to know studies that refute PRP efficacy in addition to
studies that support PRP efficacy.
Kon E, Filardo G, Delcogliano M, et al. Platelet-rich plasma new
clinical application: a pilot study for treatment of jumper’s knee.
Injury. 2009;40(6):598–603.
Filardo G, Kon E, Della Villa S, et al. Use of platelet-rich plasma
for the treatment of refractory jumper’s knee. Int Orthop.
2010;34(6):909–15.
De Almeida AM, Demange MK, Sobrado MF, et al. Patellar
tendon healing with platelet-rich plasma: a prospective, randomized, controlled trial. Am J Sports Med. 2012;40(6):1282–8.
Lyras DN, Kazakos K, Verettas D, et al. The effect of plateletrich plasma gel in the early phase of patellar tendon healing. Arch
Orthop Trauma Surg. 2009;129(11):1577–82.
• Vetrano M, Castorina A, Vulpiani MC, et al. Platelet-rich plasma
versus focused shock waves in the treatment of jumper’s knee in
athletes. Am J Sports Med. 2013;41(4):795–803. The authors
report that there was statistically significant improvement in the
PRP group relative to the ECSW group at 6 month and 12 month
follow-up using the VISA-P as an outcome measure. This is
important to know for providers that treat patellar tendinopathy.
Mautner K, Colberg RE, Malanga G, et al. Outcomes after
ultrasound-guided platelet-rich plasma injections for chronic
tendinopathy: a multicenter retrospective review. PM R.
2013;5(3):169–75.
Bergeson AG, Tashjian RZ, Greis PE, et al. Effects of plateletrich fibrin matrix on repair integrity of at-risk rotator cuff tears.
Am J Sports Med. 2012;40(2):286–93.
Rodeo Sa, Delos D, Williams RJ, et al. The effect of platelet-rich
fibrin matrix on rotator cuff tendon healing: a prospective, randomized clinical study. Am J Sports Med. 2012;40(6):1234–41.
Jo CH, Kim JE, Yoon KS, et al. Does platelet-rich plasma
accelerate recovery after rotator cuff repair? A prospective cohort
study. Am J Sports Med. 2011;39(10):2082–90.
• Kesikburun S, Tan AK, Yilmaz B, et al. Platelet-rich plasma
Injections in the treatment of chronic rotator cuff tendinopathy: a
randomized controlled trial with 1-year follow-up. Am J Sports
Med. 2013;41(11):2609-16. The authors report that in patients
who received a single PRP injection or a single saline injection
for partial thickness rotator cuff tears or rotator cuff tendinopathy, there were no statistically significant differences in the
WORC score between the two treatment groups at 3-week, 6week, 12-week, 24-week or 1-year follow-up. It is important for
practitioners who treat these conditions to be aware of this study
that demonstrates no efficacy of a single PRP injection treatment.
• Rha D, Park G-Y, Kim Y-K, et al. Comparison of the therapeutic effects of ultrasound-guided platelet-rich plasma injection
and dry needling in rotator cuff disease: a randomized controlled
trial. Clin Rehabil. 2013;27(2):113–22. The authors report that

Curr Phys Med Rehabil Rep (2014) 2:1–15

56.

57.
58.

59.

60.

61.

62.

63.

64.

65.

patients with rotator cuff tendinosis or partial thickness tears
treated with 2 serial PRP injections had statistically significant
improvement relative to patients treated with 2 serial dry needling procedures at 2-week follow-up, at 3-month follow-up and
at 6-month follow-up using the Shoulder Pain and Disability
Index. It is important for providers who treat rotator cuff tendinopathy or partial thickness rotator cuff tears to be aware that
2 serial injections have demonstrated efficacy.
Finnoff JT, Fowler SP, Lai JK, et al. Treatment of chronic tendinopathy with ultrasound-guided needle tenotomy and plateletrich plasma injection. PM R. 2011;3(10):900–11.
Hróbjartsson A, Gøtzsche PC. Placebo interventions for all clinical conditions. Cochrane database Syst Rev. 2010;1:CD003974.
Murray MM, Spindler KP, Devin C, et al. Use of a collagenplatelet rich plasma scaffold to stimulate healing of a central
defect in the canine ACL. J Orthop Res. 2006;24(4):820–30.
Silva A, Sampaio R. Anatomic ACL reconstruction: does the
platelet-rich plasma accelerate tendon healing? Knee Surg Sports
Traumatol Arthrosc. 2009;17(6):676–82.
Sánchez M, Anitua E, Azofra J, et al. Ligamentization of tendon
grafts treated with an endogenous preparation rich in growth factors:
gross morphology and histology. Arthroscopy. 2010;26(4):470–80.
Podesta L, Crow SA, Volkmer D, et al. Treatment of partial ulnar
collateral ligament tears in the elbow with platelet-rich plasma.
Am J Sports Med. 2013;41(7):1689–94.
Sampson S, Reed M, Silvers H, et al. Injection of platelet-rich
plasma in patients with primary and secondary knee osteoarthritis:
a pilot study. Am J Phys Med Rehabil. 2010;89(12):961–9.
Kon E, Buda R, Filardo G, et al. Platelet-rich plasma: intraarticular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc.
2010;18(4):472–9.
Halpern B, Chaudhury S, Rodeo Sa, et al. Clinical and MRI
outcomes after platelet-rich plasma treatment for knee osteoarthritis. Clin J Sport Med. 2013;23(3):238–9.
Jang S-J, Kim J-D, Cha S–S. Platelet-rich plasma (PRP) injections as an effective treatment for early osteoarthritis. Eur J
Orthop Surg Traumatol. 2013;23(5):573–80.

15
66. Gobbi A, Karnatzikos G, Mahajan V, et al. Platelet-rich plasma
treatment in symptomatic patients with knee osteoarthritis: preliminary results in a group of active patients. Sports Health.
2012;4(2):162–72.
67. Kon E, Mandelbaum B, Buda R, et al. Platelet-rich plasma intraarticular injection versus hyaluronic acid viscosupplementation as
treatments for cartilage pathology: from early degeneration to
osteoarthritis. Arthroscopy. 2011;27(11):1490–501.
68. Spaková T, Rosocha J, Lacko M, et al. Treatment of knee joint
osteoarthritis with autologous platelet-rich plasma in comparison
with hyaluronic acid. Am J Phys Med Rehabil. 2012;91(5):411–7.
69. Sánchez M, Anitua E, Azofra J, et al. Intra-articular injection of
an autologous preparation rich in growth factors for the treatment
of knee OA: a retrospective cohort study. Clin Exp Rheumatol.
2008;26(5):910–3.
70. • Cerza F, Carnı̀ S, Carcangiu A, et al. Comparison between
hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med.
2012;40(12):2822–7. The authors report that patients who
received 4 weekly PRP injections had statistically significant
increased improvement in WOMAC score at week 24 relative to
patients who received 4 weekly hyaluronic acid (HA) injections.61 There was also a statistically significant difference
between grade III gonarthrosis treated with ACP and that treated
with HA at week 12 and at week 24, with a noticeable
improvement that was greater in the patients treated with ACP
(P \ 0.001). This improvement with 4 serial PRP injections
relative to 4 HA injections is important to know for practitioners
to treat patients with knee arthritis.
71. Sánchez M, Guadilla J, Fiz N, et al. Ultrasound-guided plateletrich plasma injections for the treatment of osteoarthritis of the
hip. Rheumatology (Oxford). 2012;51(1):144–50.
72. Mei-Dan O, Carmont MR, Laver L, et al. Platelet-rich plasma or
hyaluronate in the management of osteochondral lesions of the
talus. Am J Sports Med. 2012;40(3):534–41.
73. Sanchez M, Anitua E, Andia I. Application of autologous growth
factors on skeletal muscle healing. In: 2nd world congress on
regenerative medicine. Poster presentation; 2005. p. 1.

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