Application of Platelet-Rich
Plasma to Enhance Tissue Repair
Andrew P. Wroblewski, BS, Hector A. Mejia, MD, and Vonda J. Wright, MD
For over 20 years, autologous blood products such as platelet-rich plasma (PRP) have been
employed as a means to facilitate the healing process in fields such as orthopedics,
dentistry, neurosurgery, cardiothoracic, and maxillofacial surgery. Proponents of this therapy advocate its effectiveness as a safe and natural way to expedite the healing process.
Recent investigations of the specific growth factors present in PRP advocate its promise as
an emerging therapy at the clinical level. However, there exist few controlled trials to
objectively examine the proposed benefits of this therapy. Although some studies demonstrate promising results, the bulk of published data are largely anecdotal and the sample
sizes are small. This article reviews the biological mechanisms by which PRP facilitates
healing as well as the current clinical research that has investigated PRP therapy as a
treatment for musculoskeletal injuries, such as tendonitis, tennis elbow, rotator cuff repair,
Achilles tendon repair, muscle injuries, bone injuries, and anterior cruciate ligament repair.
The increased prevalence of PRP therapy in treating musculoskeletal injuries warrants a
more thorough investigation of its actual benefits if we are to endorse it as an effective
therapy.
Oper Tech Orthop 20:98-105 © 2010 Published by Elsevier Inc.
KEYWORDS autologous blood, growth factors, musculoskeletal injuries, platelet-rich plasma
D
espite a recent explosion of clinical interest in plateletrich plasma (PRP), the concept of harnessing a patient’s
own blood to facilitate healing has existed since the early
1980s.1 PRP contains bioactive elements vital for musculoskeletal tissue healing and has long piqued the interest of
orthopedic surgeons as a source of autologous factors for
augmenting tissue healing. The clinical use of PRP may enable patients to experience shorter recovery times, faster return to play, stronger tissue healing, and perhaps less pain
during recovery. Because of this promise, the clinical use of
PRP has outpaced the basic science research needed to document the mechanism of its healing potential. Simply put,
“Why does PRP seem to make patients heal faster?”
The current answer to this question is still incomplete.
Much of the existing published data on PRP are anecdotal,
with few laboratory studies documenting the content of the
PRP, mechanism of action, or short- and long-term outcomes. Controlled, prospective studies of PRP use in musculoskeletal injuries are necessary to further our understanding
Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA.
Address reprint requests to Vonda J. Wright, MD, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA. E-mail: wrigvj@
upmc.edu
98
1048-6666/10/$-see front matter © 2010 Published by Elsevier Inc.
doi:10.1053/j.oto.2009.10.006
of this therapy and evaluate its efficacy. The purpose of this
chapter is to describe the known characteristics of PRP, review its application in clinical settings, discuss the best procedures for PRP preparation, and to evaluate its use as an
effective therapy in musculoskeletal injuries as a supplemental or stand-alone treatment.
PRP Biochemistry
Platelets are cytoplasmic fragments of megakaryocytes and
play a central role in the complex process of hemostasis. Clot
formation and platelet activation are considered the first
steps of the healing process.2 Within 10 minutes of blood
coagulation, platelets release a burst of proteins from their ␣,
␦, and ␭ granules. These organelles contribute the numerous
biologically active molecules that provide platelets with their
healing properties. The contents of the ␣-granule include
many growth and differentiation factors that are released
upon platelet activation during injury to the vessel wall.3 The
combined effects of these growth factors create an elaborate
autocrine and paracrine process, and therefore may result in
tissue-specific responses. Within an hour of activation, 95%
of the granule’s previously manufactured growth factors will
be secreted. The platelets then sustain production of addi-
Application of PRP for enhancing tissue repair
tional growth factors over the next several days.4 For the
platelets to release this cascade of molecules that contribute
to tissue healing, they must first be activated.
Conventionally, bovine thrombin and calcium have been
used for platelet activation. Once activated, the resulting PRP
mixture must be injected immediately, as the subsequent
secretion of the granule contents occurs rapidly. However,
the addition of thrombin and calcium to the platelet mixture
produces a gel that cannot be injected even using a largegauge needle, thus limiting its use in certain surgical procedures. The application of soluble type-I collagen has been
evaluated as an alternative to thrombin and calcium in platelet activation. Activation via type-I collagen produces a less
rapid release of the granule contents, which enable a delayed
administration of PRP. When compared with thrombin activation, the collagen-activated platelets produced equal concentrations of particular growth factors with less clot retraction. The collagen activation technique also permits in vivo
activation that can be administered through a small-gauge
needle. These results suggest that type-I collagen may be an
effective method for platelet activation.5
Current Applications of PRP
Each year, numerous recreational and competitive-level athletes sustain an array of musculoskeletal injuries, which sideline them for significant portions of their season. In the
United States, these injuries account for over 100 million
office visits each year. The ebullience of orthopedic surgeons
over the emergence of PRP as a promising new therapy is due
to its preliminary success in treating tendon, muscle, and
bone injuries. Proponents of PRP believe that it will not only
expedite the healing process but improve the quality of the
damaged tissue as well. The high concentration of growth
factors and cytokines in PRP hint at its promise as a standalone or supplemental treatment for these types of injuries.6
A few of the musculoskeletal injuries that have demonstrated
positive responses to PRP therapy are discussed later in the
text.
Tendonitis
Tendinopathy, or injuries to the tendon, range from acute or
chronic tendonitis to a full-thickness tear. Tendon degeneration has many determinants. The combination of intrinsic
elements, such as age-related decline, and extrinsic elements,
such as acute physical trauma, demonstrate a role as a contributing factor in tendon injury.7 Exposure to fluoroquinolone antibiotics, genetic factors, matrix metalloproteases, and
apoptosis all contribute to tendon injuries.8,9
Tendon healing is a dynamic process that occurs in 3 overlapping phases: inflammation, proliferation, and remodeling.
These phases are mediated by many growth factors that are
believed to act in a series of inter-related signaling pathways.10 In animal models, growth factor expression exhibits a
substantial role in supraspinatus tendon-to-bone healing.11
The concentration of these cytokines is exaggerated in PRP.
This increased concentration is a proposed explanation for
99
the effectiveness of PRP as a viable treatment option for tendon injuries. In vitro, PRP shows promotion of stromal and
mesenchymal stem cell proliferation.12 Other studies demonstrate PRP to reduce macrophage proliferation and interleukin (IL) production within the first 72 hours after exposure.13,14 The ability of PRP to elicit diverse responses from
cells indicates that it may halt excess inflammation while
activating proliferation and maturation. This would inhibit
the fibrous scar tissue healing that accompanies macrophageregulated tendon-to-bone healing.6,15
Tennis Elbow
Chronic elbow epicondylar tendonitis, commonly referred to
as tennis elbow, is often resolved with nonoperative treatment protocols. PRP therapy is currently under investigation
as one of these protocols that would serve as an alternative to
surgical intervention.
In a recent study, patients whose symptoms had not resolved after nonoperative treatment protocol and were considering surgery were subjected to an injection of either buffered PRP or bupivacaine (the control). Patients who received
the PRP treatment demonstrated a 60% improvement in their
visual analog pain scores 8 weeks after the procedure, while
the control group exhibited a 16% improvement. Continued
evaluation showed that the PRP group exhibited an 81%
improvement at 6 months post treatment and a 93% improvement at the final follow-up, 25.6 months post treatment. These results could not be compared with the control
group because 60% of the control subjects either withdrew or
sought other treatments after week 8.16
To endorse PRP injection as an effective alternative to surgical intervention in tennis elbow injuries, controlled, prospective studies with a large sample size are necessary to
evaluate its long-term effectiveness.
Rotator Cuff Repair
The use of PRP as a supplemental therapy in the arthroscopic
repair of a torn rotator cuff tendon may further increase the
patient’s rate of recovery. A pilot study subjected 14 patients
undergoing arthroscopic repair of rotator cuff tears to intraoperative application of autologous PRP with an autologous
thrombin component. The subjects were followed for 24
months postsurgery and evaluated using a pain score (visual
analog scale) and a functional score (UCLA and Constant
scores). All patients recovered passive range of motion within
1 month of treatment. Patients demonstrated a significant
decrease in their outcome measured pain scores at 6, 12, and
24 months. No significant differences between the preoperative and the 1-month postoperative pain scores were witnessed. The UCLA functional scoring increased from a preoperative level of 16.54-32.92 at the final follow-up. There
were no reported complications related to the procedure.17
These results exhibit the application of autologous PRP to be
a safe and stable procedure with no long-term adverse affects.
Although the patients demonstrated marked improvement
after surgery, the small sample size and lack of a control
A.P. Wroblewski, H.A. Mejia, and V.J. Wright
100
group make it difficult to ascertain the benefits of this technique compared with surgery as the sole treatment.
In another study, platelet-leukocyte–rich plasma was prepared from a whole unit of blood and used to produce platelet-leukocyte gel (PLG). The gel is similar to PRP in that it
exhibits concentrations of platelets and leukocytes well above
baseline levels. PLG was applied to patients undergoing open
subacromial decompression to investigate its role in postoperative recovery. Compared with controls, the PLG group
evidenced decreased pain scores, took less pain medication,
and demonstrated an improved range of motion in the recovery process. The results of this study indicate that PLG is an
effective agent in the return to full function after shoulder
surgery.18
Achilles Tendon Repair
In a retrospective study of Achilles tendon repairs, athletes
treated with surgery and PRP therapy recovered range of
motion earlier than the control groups, which received surgery alone. The PRP group also demonstrated no wound
complications and returned to training activities faster than
the controls. In addition, this study investigated the quality of
the repaired tendon by measuring the cross-sectional area
of the tendon using ultrasound. This is an aspect of the healing process that is often overlooked when investigating the
effectiveness of PRP therapies. The ultrasounds of the PRP
group showed tendons with a smaller cross-sectional area
than those of the control group.19 In animal models, the use
of PRP in Achilles tendon repairs displayed a greater maturation in tendon callus. Mechanical stimulation of the repaired
tendons revealed an increased force to failure and ultimate
stress in those treated with PRP. This increase is believed to
be attributed to the benefits of PRP during the early phases of
the healing process, which allows mechanical stimulation to
proceed at an earlier time, driving the growth of new tendon
at a faster rate than the control groups.20,21
Muscle Injuries
Muscle injuries in sports may result from a blow, strain, or
sometimes a laceration. They are most prevalent in sports
that include physical contact, sprinting, or jumping. They
usually occur after an eccentric contraction, resulting in an
injury at the musculotendinous junction.22 Similar to tendon
healing, muscle healing occurs in an arrangement of overlapping steps. The sequence of these steps is inflammation, proliferation, and remodeling, and they are regulated by growth
factors and cell-to-cell interactions. Local vascularity and regeneration of intramuscular nerve branches are integral to
the muscle healing process. PRP therapy has been shown to
enhance both of these processes.23,24 Ultimately, the rate of
recovery for any patient will be dependent on their own
biology as well as the prescribed treatments. Standard procedure for treatment of these types of injuries follows the RICE
acronym (Rest Ice Compression Elevation) and a gradual
return to resistance exercise. Nonsteroidal anti-inflammatory
drugs are typically used to alleviate pain as part of the recovery process. However, recent research suggests that they may
obstruct the healing properties of the muscle tissue by inhibiting the fusion of the myogenic precursor cells.25 The importance of growth factors to the muscle healing process is evident through the large concentrations of cytokines found in
healing tissue. Particular growth factors can enhance not only
muscle regeneration after injury but muscle force as well.26
The inflammatory phase of muscle healing is governed by
growth factors, macrophages, and products of the cyclooxygenase-2 pathway. Investigations of the interaction between
transforming growth factor (TGF) ␤ and prostaglandin E2
molecules suggest a negative feedback loop that controls the
level of fibrosis formed during the healing process.27
A group of elite athletes subjected to a form of PRP therapy
that uses ultrasound-guided injection displayed an expedited
functional restoration by returning to full function in half of
the expected time. They also lacked any evidence of excessive
fibrosis. This treatment requires further investigation to validate its use in treating muscle injuries.6
Bone
Overall, success of PRP as a clinical treatment after orthopedic trauma is debatable. Most studies evaluating its use in
bone repair are in oral and craniofacial surgery. A clinical
study exploring the application of autologous fibrin to cancellous bone during mandibular reconstruction evidenced
radiographic consolidation in half the time of the control
group. The accelerated consolidation witnessed was attributed to enhanced osteoconduction of the osteocomponent
cells in the graft by the fibrin network, which formed from
the concentration of platelets.28 As a result, dentists have
developed a procedure where platelet-rich material is combined with autograft, allograft, demineralized bone matrix,
and other materials to fill blemishes in the mandible and
cranium.29 In cases where PRP has been used in spinal fusion
it has exhibited positive results, with all patients obtaining
union.30 In another study, callus formation was witnessed
between 34 and 47 days in 3 patients during osteogenesis
distraction when treated with a mixture of PRP and bone
marrow cells. The role of PRP in the increased distraction and
speedy bone formation is inconclusive, as it was used in
combination with another osteoconductive substance.31
In a study that investigated the use of PRP in treating
fractures of the foot and ankle, the concentration of plateletderived growth factor (PDGF) and TGF␤ in the hematoma of
24 patients was measured. Seven of these fractures had failed
to unite. They demonstrated no trace of PDGF and TGF␤
proteins upon examination. Revision operations were performed and PRP was applied to the nonunions. Those subjected to this treatment exhibited radiographic union at an
average of 8.5 weeks.32
Anterior Cruciate Ligament
Although PRP is hypothesized to be an effective treatment for
improving the biomechanics of anterior cruciate ligament
(ACL) repair, recent studies of animal models have demonstrated conflicting results. Bilateral suture repair of ACL in
pigs, with one side receiving suture repair, and the other side
Application of PRP for enhancing tissue repair
receiving suture repair and PRP application, yielded imperfect results. No significant differences in anteroposterior knee
laxity at 30° and 60°, maximum tensile load, or linear stiffness were discovered at 14 weeks after suture repair.33 Studies of ACL grafts enhanced by collagen-platelet composite in
goats exhibited similar findings. In the group that received
ACL reconstruction alone, the average increase in anteroposterior knee laxity at 30° was 40% greater than the collagenplatelet-composite–treated group. At 60°, the average increase was 30%, favoring the control group. In regard to
structural differences, no significant changes were witnessed.34 These findings emphasize the need for further research on the perceived benefits of PRP at the clinical level.
Biological Properties of PRP
Basic science research is essential to elucidate the proposed
benefits of this therapy at the molecular level. Currently,
much of its promise is attributed to the intrinsic properties of
its growth factors. It is important to note that growth factors
are not the only elements present in significant concentrations in PRP, as proteins of the cytokine and chemokine
families are known to be present in varying concentrations as
well. The elements identified in PRP include TGF␤, vascular
endothelial growth factor (VEGF), platelet-derived endothelial growth factor, epidermal growth factor, insulin-like
growth factor, platelet factor 4, IL-1, platelet-derived angiogenesis factor, epithelial cell growth factor, osteocalcin, osteonectin, thrombospondin-1, fibrinogen, fibronectin, and
vitronectin. The concentrations of these various growth factors increase linearly as platelet concentration increases.3,35
The network of activated growth factors induces intracellular
signaling pathways that lead to the production of proteins
essential to the regenerative processes, such as cell proliferation, matrix formation, osteoid production, and collagen synthesis.36 Cell types that are involved in the healing process,
such as osteoblasts, fibroblasts, epithelial cells, endothelial
cells, and adult mesenchymal stem cells reveal the presence
of membrane receptors that are specific for certain growth
factors. Furthermore, when cytokines are released they bind
to the transmembrane receptors on the surface of local or
circulating cells. This supports the proposed role of growth
factors as integral components in activating soft-tissue healing and bone regeneration.2,37 Simply put, at the time of
injury, the platelets arrive via the capillaries and are activated,
releasing their granule contents into the wound site. This
influx of growth factors and proteins play an active role in
synthesizing the necessary components for the regenerative
process and may also play a paracrine role by recruiting other
cells to the wound site.
PDGF is a multiple mitogen that has been found in macrophages, endothelial cells, monocytes, fibroblasts, bone matrix, and ␣-granules of the platelets. The principal activities of
PDGF include angiogenesis, macrophage activation, proliferative activity on fibroblasts, and chemotaxis for fibroblasts
and collagen synthesis.38-40 It is recognized as a factor in bone
metabolism by enhancing osteoblast replication and bone
collagen degradation.41 PDGF is present in 3 isoforms: ␣␣,
101
␤␤, and ␣␤. Although the reason for these 3 isoforms is
unclear, differential binding by various receptor cells is a
proposed solution.42 This would imply that PDGF exhibits a
dual nature, acting as both a stimulator and suppressor of
osseous and soft-tissue repair.43
TGF␤ is a bone morphogenetic protein.44 Studies of TGF␤
reveal its role in simulating matrix production by bone cells
and possibly its influence on the nature of the matrix.45 It is a
key factor in the promotion of the proliferative activity of
fibroblasts, as well as the synthesis of type-I collagen and
fibronectin. TGF␤ can promote differentiation or proliferation of osteoblast cell types while suppressing the development of osteoclast precursors. These findings suggest that
while a player in both processes, TGF␤ favors bone formation over bone resorption.39,46,47 Three isoforms of TGB␤ are
identified: ␤1, ␤2, and ␤3.48
Insulin-like growth factor-1 plays a role in the metabolism
of numerous cell types. It is chemotactic for fibroblasts and
enhances the synthesis of proteins.49 By stimulating the proliferation and differentiation of osteoblasts, it is able to promote bone formation.50,51
Platelet-derived endothelial growth factor enhances epidermal regeneration. It promotes the proliferation of keratinocytes and dermal fibroblasts to activate wound healing. Its
presence augments the concentration and effects of other
growth factors.52
Platelet factor 4 is released from the ␣-granules of platelets
and is proposed to play a partial role in the influx of neutrophils into the wound site. It operates as a chemoattractant for
fibroblasts and mediates the effects of heparin-like molecules
to increase blood clotting.53,54
VEGF is a signaling protein that is a member of the cytosine-knot growth factor family. Its role in vasculogenesis
and angiogenesis showcase its importance to the healing process.55 VEGF increases microvascular permeability and acts
as a vasodilator, processes imperative to tissue healing. In
vitro studies demonstrate the stimulation of cell migration
and mitogenesis in endothelial cells by VEGF.53,55
Epidermal growth factor binds to a corresponding cell surface receptor with high affinity. This stimulates the expression of genes that induce DNA synthesis and cell proliferation.56
A summary of these growth factors, their role in the healing process, and their relative concentration in a sample of
PRP are presented in Table 1.
The Role of Dense Granules
Although the ␣-granules are commonly recognized as the
major contributors to the cascade of bioactive elements released from the platelets, it is important not to overlook the
effects of the dense granules. The dense granules of platelets
contain adenosine, serotonin, histamine, and calcium, the
combination of which exhibit effects on the different stages of
tissue repair.
Adenosine is a nucleoside that is involved in many cellular
processes. It acts as a primary cytoprotective agent that represses
tissue damage. In the inflammatory process that accompanies
A.P. Wroblewski, H.A. Mejia, and V.J. Wright
102
Table 1 Effect of the Growth Factors Produced by Platelets, and Their Average Concentrations in Platelet-Rich Plasma (PRP)
Growth
Factor
PDGF
TGF␤
IGF-I
PDEGF
PDAF
PF-4
EGF
VEGF
PRP Concentration
(SD)
Effect
Macrophage activation and angiogenesis
Fibroblast chemotaxis and proliferative activity
Enhances collagen synthesis
Enhances the proliferation of bone cells
Enhances the proliferative activity of fibroblasts
Stimulates biosynthesis of type I collagen and fibronectin
Induces deposition of bone matrix
Inhibits osteoclast formation and bone resorption
Chemotactic for fibroblasts and stimulates protein synthesis
Enhances bone formation by proliferation and differentiation of osteoblasts
Promotes wound healing by stimulating the proliferation of keratinocytes
and dermal fibroblasts
Induces vascularization by stimulating vascular endothelial cells
Stimulates the initial influx of neutrophils into wounds
A chemoattractant for fibroblasts
A potent antiheparin agent
Cellular proliferation
Differentiation of epithelial cells
Angiogenesis
Migration and mitosis of endothelial cells
Creation of blood vessel lumen
Creates fenestrations
Chemotactic for macrophages and granulocytes
Vasodilation (indirectly by release of nitrous oxide)
␣␤ 117.5 ng/mL (63.4)
␤␤ 9.9 ng/mL (7.5)
␤1: 169.9 ng/mL (84.5)
␤2: 0.4 ng/mL (0.3)
84.2 ng/mL (23.6)
470 pg/mL (320)
0.189 nmol/mL (0.07)
51 pmol/L (5)
76-854 pg/mL
Abbreviations: PDGF, platelet-derived growth factor; TGF, transforming growth factor; IGF, insulin-like growth factor; PDEGF, plateletderived endothelial growth factor; PDAF, platelet-derived angiogenesis factor; PF-4, platelet factor 4; EGF, endothelial growth factor; VEGF,
vascular endothelial growth factor. Reprinted with permission.57
diabetic nephropathy, the activation of the adenosine receptor
demonstrates an anti-inflammatory response.58 Laboratory
studies show the topical application of adenosine A2A receptor agonists to diabetic foot wounds to yield more rapid
wound closure by amplifying the salutary functions of inflammatory cells, endothelial cells and fibroblasts.59 Adenosine can upregulate IL-10 production by immunostimulated
macrophages.60 In addition, macrophage activation by adenosine yields proinflammatory cytokines, IL-1, and IL-18.61
Serotonin is a monoamine neurotransmitter and displays
many observed effects relative to inflammation and healing.6
Its effect in augmenting capillary permeability is proposed to
exceed those of histamine.62 It increases fibroblast proliferation, and macrophage cells have receptors sensitive to the
hormone. Studies of the effects of this hormone on macrophage function advocate its position as a mediator at sites of
inflammation by suppressing interferon-␥–induced 1a expression. Serotonin’s suppression of this expression is concentration-dependent and is much more potent than the related compounds dopamine, histamine, and tryptamine.63
Histamine is a biogenic amine that is used during the local
immune response and is a strong activator of macrophages. It
is released at the time of injury and acts as a vasodilator. In
addition, it augments the permeability of the microvascular
system of capillaries and venules through the contraction of
the epithelial cells and the expulsion of the fenestrated diaphragms blocking gaps in the epithelial lining.64 This increase in permeability is imperative to the tissue healing pro-
cess because it affords inflammatory and immune cells more
access to the site of injury.53
Calcium functions as a key component in tissue repair
through keratinocyte proliferation and differentiation. Calcium is necessary for skin fibroblasts, although keratinocytes
are not as responsive to its effects. In the bone remodeling
phase, calcium could be a necessary component for epidermal cell migration and regeneration. Overall, calcium plays a
critical role in wound management, and is proposed to demonstrate a crucial role when delivered to the wound site by
the dense granules.65
Methods of PRP Preparation
PRP is defined as a volume of the plasma fraction of autologous blood with a platelet concentration above baseline.29
Plasma with a platelet concentration of approximately
1,407,640 ␮L, or 5 times greater than the platelet count in
normal blood, is the suggested working concentration for
PRP therapy. The relative ease of PRP preparation has led to a
variety of available commercial systems, each of which operate through different techniques and yield varying platelet
concentrations. In implant dentistry, a field where PRP use is
becoming increasingly common, 4 commercial systems are
commonly used for the preparation of PRP in clinical settings. These include SMart-PReP autologous platelet-concentrate system (Harvest Technologies Corporation, Plymouth,
MA), Platelet Concentrate Collection System (3i Implant In-
Application of PRP for enhancing tissue repair
novations, Palm Beach Gardens, FL), Curasan PRP Kit
(Curasan, Pharma, GmbH AG, Lindigstrab, Germany), and
Ace Platelet Concentration System (Ace Surgical Supply
Company, Brockton, MA). Although these 4 systems are currently the most used systems, various other commercial systems are available for use.66 The Arthrex Autologous Conditioned Plasma Double Syringe System is specifically designed
to extract PRP for a patient’s peripheral blood while eliminating the need for a second centrifugation step. The 3 techniques commonly used to prepare PRP through these systems
are the gravitational platelet sequestration (GPS), the standard cell separator technique, and autologous selective filtration technology (plateletpheresis). Factors such as force and
duration of centrifugation must be considered to ensure the
reproducibility of a particular method, as they may lead to
differences in the obtained platelet concentration. It is suggested that studies that display conflicting evidence of the
proposed benefits of PRP may be the result of an insufficient
platelet concentration.37
GPS is the most common and effective technique used in
PRP preparation. It uses a centrifuge system to separate anticoagulated blood into distinct layers: the plasma, the buffy
coat, and the red blood cells. The volume of PRP that results
from the GPS technique is approximately 10% of the total
volume of whole blood drawn. A 12-minute spin at a speed of
3200 rpm with a flat-bottomed, 60 mL plastic centrifuge tube
produces a PRP volume of approximately 5 mL.53 In dentistry, the ACE Double-Centrifugation System has been compared to the Nahita single-centrifugation system to elucidate
the differences in the obtained PRP. Analysis of the platelet
concentration yields of the 2 methods revealed 336% for the
double-centrifugation system and 227% for the single-centrifugation system. Although the double-centrifugation system produces higher platelet concentrations, the range of
values achieved is much higher. Ultrastructural analysis of
the 2 samples by transmission electron microscopy reveals
changes in PRP structure for the double-centrifugation
method. This method was also more susceptible to slight
errors during the preparation process.67
Standard cell separators typically operate on a full unit of
blood, usually through a continuous-flow centrifuge bowl or
a continuous-flow disk separation technique and use both
fast and slow spins.68 This will generally yield platelet concentrations 2-4 times higher than baseline levels.69 There
exists a discontinuous technique that can produce a platelet
count 5 times greater than baseline, while returning the red
blood cells and some of the plasma to the patient to maintain
the volume of the circulating blood.70,71 Compact office systems exist, which can yield approximately 6 mL of PRP from
a starting blood volume of 45-60 mL. A blood sample this
small would eliminate the need for reinfusion.72,73 However,
a disadvantage of this technique is that it differs widely in the
concentration of the available platelets accumulated, ranging
from 30% to 85%, or 2 to 8 times baseline.68,73
Plateletpheresis uses a disposable proprietary filter to capture the platelets from whole blood. The captured platelets
are collected to produce PRP. This method does not require a
centrifuge. It produces a blood fraction with platelet and
103
growth factor concentrations similar to those of the centrifuge methods.74
Discussion
Numerous athletes across all levels of competitiveness are
sidelined by musculoskeletal injuries each year. Advancements in medicine demand less invasive therapies and faster
recovery times for athletes suffering from these injuries. To
continue to offer these patients the best treatments available,
we must investigate all leads in search of promising new
therapies. Currently, the major avenues being explored are
stem cells, gene therapy, and autologous or bioengineered
cytokines. However, these therapies are not yet ready for
widespread clinical use. Because PRP is prepared from the
patient’s own blood, the risk of experiencing complications is
minimal. Preparation of PRP is quick, simple, and relatively
inexpensive. In addition, it can work with a range of different
cell types. All these factors exhibit PRP’s potential as an ideal
biological therapy. More thorough clinical investigation of
PRP is necessary in controlled, prospective, randomized
studies to determine its effectiveness in treating musculoskeletal injuries. Types of injuries where PRP has shown the most
promise are tears of the Achilles, patellar, quadriceps, or
rotator cuff tendons.
Another area requiring further investigation is the effect of
PRP on different locations within a tissue. For example, tissues, such as tendon comprise 3 overlapping zones: the myotendinous junction, the midsubstance, and the osseotendinous junction.6 Each of these zones may exhibit different
effects when exposed to PRP. Such differential effects can be
studied individually using ultrasound-guided injections of
PRP. The dosage and type of PRP may also contribute to the
effectiveness of the treatment. It is suggested that studies that
failed to demonstrate the benefits of PRP therapy may have
used an insufficient dose or concentration of PRP. Rehabilitation procedures specific to PRP therapy should be designed
to facilitate the patient’s recovery proceeding injection to
maximize the effectiveness of this treatment. For example,
the benefits of PRP may be augmented if the patient performs
a series of gentle exercises to load the tendon before injection.
This would contrast traditional rehabilitation methods after
surgical treatments, but could display positive results.
In summary, PRP may be a promising treatment option for
musculoskeletal injuries. Preliminary research has expanded
our knowledge of PRP at the molecular level, although its
effectiveness as a clinical therapy is not yet proven. Prospective randomized trials are necessary to determine the efficacy
of PRP therapy in all musculoskeletal injuries. The results of
these studies will outline future use of this therapy as a viable
treatment option.
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