1 ORTHOBIOLOGICS CLASSIFICATIONS 2019

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The use of platelet-rich plasma (PRP) in ortho-
paedic practice has grown exponentially over the 
last decade.1-3 PRP can be defined as any autolo-
gous blood preparation in which the platelets have 
been concentrated to levels exceeding that in the 
whole blood from the same patient. These thera-
pies aim to deliver proregenerative growth factors 
(GFs) and cytokines, which are released from a 
concentrated pool of degranulating platelets, to 
the site of pathology. GFs released by platelets 
have been demonstrated to perform proregenera-
tive functions in vitro, including promoting stem 
and progenitor cell proliferation and recruitment, 
modulating inflammatory responses, and stim-
ulating angiogenesis.4,5 The rationale for using 
platelets is to augment or accelerate healing in 
many musculoskeletal conditions. The autologous 
nature, favourable safety profile, and simplicity of 
production of PRP makes it an appealing approach 
to treatment. PRP preparations vary considerably, 
and the optimal preparation for treating different 
musculoskeletal conditions remains unknown. 
Overall, the clinical use of PRP has greatly out-
paced the evidence supporting its application.5,6
The heterogeneity of the processing methods 
used to prepare PRP, as well as the lack of reporting 
of even basic characteristics and compositions of 
these preparations, is a key barrier to understand-
ing PRP’s clinical effects. The vast majority of 
clinical studies evaluating PRP preparations have 
not provided sufficient information to allow inter-
pretation or replication of protocols.7 This makes 
interpretation of outcomes difficult and makes 
comparison between studies almost impossible.
At present, there is no all-encompassing and 
universally accepted system to allow classification 
of PRP and other autologous blood preparations. 
An ideal classification should be simple to use, 
should be reproducible, and should focus on char-
acteristics that are relevant to the prognosis and 
therapeutic decision-making. Although numer-
ous classification systems for PRP formulations 
have been proposed, none has achieved univer-
sal acceptance.8-13 In this annotation, we outline 
existing systems used to classify preparations of 
PRP, highlighting the need for a standardized uni-
versal nomenclature and classification system for 
blood-derived products.
Existing PRP classifications systems. Dohan 
Ehrenfest classification (2009): with appreciation 
that different components of PRP preparation may 
influence therapeutic effect, Dohan Ehrenfest et 
al8 proposed a classification that separated prod-
ucts using two basic parameters: the presence or 
absence of leucocytes, and the fibrin architecture 
(Table I).8-13 This separation resulted in four main 
PRP subtypes. 1) Pure PRP, or leucocyte-poor 
PRP: preparations with no or low leucocyte lev-
els and with a low-density fibrin network after 
activation. The PRP products in this group can be 
used as liquid solutions or in an activated gel form. 
2) Leucocyte-rich and PRP: preparations with ele-
vated values of leucocytes and with a low-density 
fibrin network after activation. The PRP products 
in this group can also be used as liquid solutions 
or in an activated gel form. 3) Pure platelet-rich 
fibrin, or leucocyte-poor platelet-rich fibrin: prepa-
rations with no or low leucocyte levels and with a 
 ANNOTATION
Classification systems for platelet-rich plasma
L. A. Rossi, 
I. R. Murray, 
C. R. Chu, 
G. F. Muschler, 
S. A. Rodeo, 
N. S. Piuzzi
From Cleveland 
Clinic, Cleveland, 
Ohio, United States
Correspondence should be 
sent to N. S. Piuzzi; email: 
piuzzin@ccf.org
©2019 The British Editorial 
Society of Bone & Joint Surgery 
doi:10.1302/0301-620X.101B8.
BJJ-2019-0037.R1 $2.00
Bone Joint J 
2019;101-B:891–896.
There is good scientific rationale to support the use of growth factors to promote 
musculoskeletal tissue regeneration. However, the clinical effectiveness of platelet-rich 
plasma (PRP) and other blood-derived products has yet to be proven. Characterization 
and reporting of PRP preparation protocols utilized in clinical trials for the treatment of 
musculoskeletal disease is highly inconsistent, and the majority of studies do not provide 
sufficient information to allow the protocols to be reproduced. Furthermore, the reporting 
of blood-derived products in orthopaedics is limited by the multiple PRP classification 
systems available, which makes comparison of results between studies challenging. 
Several attempts have been made to characterize and classify PRP; however, no consensus 
has been reached, and there is lack of a comprehensive and validated classification. 
In this annotation, we outline existing systems used to classify preparations of PRP, 
highlighting their advantages and limitations. There remains a need for standardized 
universal nomenclature to describe biological therapies, as well as a comprehensive and 
reproducible classification system for autologous blood-derived products.
Cite this article: Bone Joint J 2019;101-B:891–896.
892 L. A. ROssI, I. R. MURRAy, C. R. CHU, G. F. MUsCHLER, s. A. ROdEO, N. s. PIUzzI 
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high-density fibrin network. Products from this group only exist 
in a strongly activated gel form and cannot be injected as a liq-
uid solution. 4) Leucocyte-rich and platelet-rich fibrin: prepara-
tions with elevated values of leucocytes and with a high-density 
fibrin network. They only exist in a strongly activated gel form. 
Although this classification is simple, quantitative values are 
lacking.
PAW classification (2012): DeLong et al9 described the plate-
let, activation, white blood cells (WBCs), or ‘PAW’, system, 
which is based on three components: 1) the absolute number of 
platelets; 2) the manner in which platelet activation occurs; and 
3) the presence or absence of WBCs (Table I). Additionally, the 
importance of precise determination of neutrophil levels was 
emphasized, and the authors incorporated a subcategory for 
neutrophil count. The three main parameters were described as: 
1) platelet concentration, measured in platelets per millilitre and 
categorized as P1 (≤ baseline), P2 (> baseline to 750 000 cells/
μl), P3 (> 750 000 to 1 250 000 cells/μl), and P4 (> 1 250 000 
cells/μl); 2) total WBC content, identified as either above or 
below/equal to baseline levels, with α (above) added if neu-
trophils were included in the buffy coat or β (below) added if 
neutrophils were filtered out; and 3) activation method. Endog-
enous activation was not given a designation. However, if an 
exogenous external activator was used, it was documented with 
an ‘X’. This classification ensures a more accurate and defini-
tive reporting of the concentration of platelets (number of plate-
lets per millilitre) but leucocytes remain described as a binary 
measure (above or below/equal to baseline levels).
Mishra’s classification (2012): Similarly to DeLong et al9, 
Mishra et al10 also published a classification based in platelet 
concentration, the presence or absence of WBCs in the PRP, 
and the use of agonists to activate PRP (Table I). However, the 
authors classified the variables in a different way to DeLong 
et al,9 identifying four types of PRP: 1) type 1 contains an 
increased concentration of platelets and WBCs over baseline, 
and is not activated by an exogenous activator such as throm-
bin or calcium; 2) type 2 contains both increased platelets and 
WBCs and is activated with thrombin and or calcium; 3) type 3 
Table I. Summary of published classifications for platelet-rich plasma (PRP)
Study Classification Method Spin Platelet 
concentration
RBC WBC 
(neutrophils)
Activation Image 
guided
Purity Efficiency
Dohan 
Ehrenfest 
et al8 (2009) 
Pure PRP: 1 
spin 
(leucocyte-rich 
PRP, Pure PRF, 
leucocyte-rich 
PRF)
NR NR NR NR NR NR NR NR
DeLong 
et al9 
(2012) 
PAW NR NR P1: ≤ baseline 
levels; P2: 
>baseline to 
750 000; P3: 
> 750 000 to 
1 250 000; P4: 
> 1 250 000
NR A: above base-
line; B: below or 
equal to base-
line (α: above 
baseline; β: 
below or equal 
to baseline)
X: exogenous NR NR NR
Mishra 
et al10 
(2012) 
NR NR A: ≥ 5-fold basal 
(types 1 and 
2); B: 
< 5-fold basal 
(types 3 and 4)
NR NR Activated: 
(types 2 to 4); 
not activated: 
(types 1 to 3)
NR NR NR
Mautner 
et al11 
(2012) 
PLRA NR NR Total number 
injected = 
volume × 
(platelets × ml)
NR Leucocyte 
present: +ve; 
leucocyte ab-
sent: -ve (% of 
neutrophils)
Yes/No NR NR NR
Magalon 
et al12 
(2016)
DEPA NR NR Dose = platelet × 
volume injected; 
A: very high 
dose (> 5 billion 
platelets); B: 
high dose (3 to 5 
billion platelets); 
C: medium dose 
(1 to 3 billion 
platelets); D: low 
dose (< 1 billion 
platelets)
See 
purity
See purity (NR) Activated; 
not activated
NR % of platelets 
in the PRP 
compared with 
RBC and WBC: 
A: very pure 
(> 90%); B: pure 
(70% to 90%); 
C: heterogeneous 
(30% to 70%); 
D: whole blood 
(< 30%)
% of platelets 
recovered in 
the PRP from 
the blood: 
A: high (> 90%); 
B: medium 
(70% to 90%); 
C: low (30% to 
70%); D: poor 
(< 30%)
Lana 
et al13 
(2017)
MARSPILL H or M 1 
spin; 
2 
spin
Folds basal; PL 2 
to 3; PL 4 to 6; PL 
6 to 8; PL 8 to 10
Rich: > 15 
fold basal; 
Poor: < 15 
fold basal
Rich: > baseline; 
poor: < baseline 
(NR)
A+: activated; 
A-: not 
activated; 
light 
activation (L)
G+: 
guided; 
G-: not 
guided
NR NR
RBC, red blood cells; WBC, white blood cells; PRF, platelet-rich fibrin; NR, not reported; PAW, platelets, activation, WBCs; PLRA, Platelet count, 
 leucocyte content, RBC content, activation; DEPA, dose, efficiency, purity, activation; MARSPILL, method, activation, RBCs, spin, platelet number, 
image guided, leucocyte concentration, light activation; H or M, handmade or machine; spin, number of spins utilized in the PRP preparation
 CLAssIFICATION sysTEMs FOR PLATELET-RICH PLAsMA 893
VOL. 101-B, No. 8, AUGUST 2019
contains only an increased concentration of platelets with-
out any WBCs and is not activated prior to application; and 
4) type 4 contains only an increased platelet concentration and 
is activated with thrombin and/or calcium. Subtype A contains 
an increased platelet concentration at or above five times base-
line. Subtype B contains an increased platelet concentration 
less than five times baseline. Nevertheless, the three preceding 
classifications do not take into account the final volume of the 
preparation delivered.
In 2015, Mautner et al11 highlighted the potential detrimental 
effects of red blood cells (RBCs) on PRP activity due to their 
chondrotoxic and proinflammatory effects, recommending that 
the presence or absence of RBCs in PRP preparations should be 
reported. Consequently, they established a PRP classification 
system called platelet, leucocyte, RBCs, and activation (PLRA) 
classification (Table I). The authors emphasized the importance 
of describing the platelet count (absolute number/μl), leucocyte 
content (as positive or negative), percentage of neutrophils, 
RBC content (as positive or negative), and activation (yes or no 
for exogenous activation).
DEPA classification (2016): In 2016, Magalon et al12 intro-
duced two new concepts that had not been addressed by the 
previous classifications. First, the authors stressed the impor-
tance of the efficiency of production of the PRP, which corre-
sponds to the proportion of the platelets recovered in the PRP 
from the blood. Second, the authors emphasized the importance 
of reporting the purity of the obtained PRP. They defined purity 
as the relative composition of platelets, leucocytes, and RBCs 
in the obtained PRP. The Magalon classification is called dose 
of platelet, efficiency, purity, and activation (DEPA; Table I). 
The four main parameters are described as follows: 1) dose is 
calculated by multiplying the number of platelets in PRP by the 
obtained volume of PRP, classifying from A (> 5 billion plate-
lets) to D (< 1 billion platelets); 2) efficiency corresponds to the 
proportion of platelet recovery from whole blood, ranging from 
A (> 90%) to D (< 30%); 3) purity corresponds to the propor-
tion of platelets in the PRP compared with RBC and leucocytes 
varying from A (> 90% platelets in relation to other cell types) 
to D (< 30%); and 4) activation related to exogenous activation.
MARSPILL Classification (2017): Finally, Lana et al13 estab-
lished a PRP classification system called MARSPILL (method, 
activation, red blood cells, spin, platelets, image guidance, 
leucocytes, and light activation; Table I). In this system, the 
authors recommend taking into account four variables that they 
considered relevant that were not included in previous classi-
fications. Specifically, they propose to include: 1) whether the 
PRP is prepared in an automated manner or manually; 2) the 
number of spins that are performed during PRP preparation; 
3) whether image guidance is used in order to identify the cor-
rect site of application; and 4) if photoactivation was applied 
to the PRP.
Therefore, the parameters in this classification are described 
as follows. 1) Method: whether preparation was automated, 
by machine (M), or handmade (H). 2) Activation: whether 
PRP is activated (A+) or not (A-). 3) RBCs: rich (RBC-R) or 
poor (RBC-P), with poor classified as a reduction of approxi-
mately 15-fold compared with baseline. 4) Spin: whether one 
(SP1) or two (SP2) spins are used during the PRP preparation. 
5) Platelet concentration: categories of PL two- to three-fold, 
PL four- to six-fold, PL six- to eight-fold, and PL eight- to ten-
fold over baseline. 6) Image guided: guided (G+) or not guided 
(G-). 7) Leucocytes: leucocyte-rich PRP (Lc-R) or leucocyte 
poor- PRP (Lc-P) depending on whether the concentration of 
leucocytes is higher or lower than baseline value, respectively. 
8) Light activation: light activated (L+) or not (L-).
However, the relevance of image guidance and light acti-
vation are unknown. It is acknowledged that placement in a 
certain anatomical location (e.g. hip) would be dependent on 
image guidance, and limited evidence for photoactivation of 
PRP exists for the nonsurgical management of osteoarthritis of 
the knee.14
Barriers to uptake of existing systems. There are a number of 
potential explanations why none of these systems have achieved 
universal acceptance or widespread use. The complexity and 
inherent variability of biological preparations of PRPs pre-
cludes a comprehensive listing of all constituents within a clas-
sification system or communication tool. However, researchers 
or clinicians may feel that the current systems do not account 
for variability in preparations described, nor do they represent 
the raw data variables from blood components. As such, they 
do not wish to categorize their own PRP preparations together 
with previously published preparations that may have produced 
unfavourable results. In addition to PRP, there are a growing 
number of autologous blood preparations being proposed for 
musculoskeletal applications that do not contain concentrated 
platelets.15 These include platelet lysate, autologous protein 
solution, autologous conditioned serum, and platelet- poor 
plasma. It is crucial for future classification systems to encom-
pass all autologous blood preparations.
There are logistical and financial barriers due to the cost and 
complexity associated with cell and biochemical analysis that 
might explain why some variables have not been included in 
the classifications systems. Nonetheless, a comprehensive and 
granularly structured system is required to allow classification 
based on similar predefined characteristics. Without such a 
system, access to information in an efficient and timely man-
ner is limited, which jeopardizes the advancement of the field.
Urgent need for consensus on the classification and com-
munication of autologous bloodproducts. Blood-derived 
products, including PRP, are now widely used to treat a range 
of musculoskeletal pathologies, despite a lack of robust evi-
dence to support efficacy.1,16-23 This popularity has been fuelled 
by a lack of efficacious non-surgical options to treat some 
musculoskeletal pathologies combined with the ease of use, 
perceived safety, and commercial enthusiasm.2,24 In response 
to growing clinical use of biological therapies, the Amer-
ican Academy of Orthopaedic Surgeons (AAOS) recently 
convened a collaborative symposium that aimed to identify 
strategies to facilitate high-quality research into autologous 
products and encourage the responsible and evidence-based 
use of these therapies.2
Numerous basic science and animal studies support the 
notion that targeted preparations of PRP may have favoura-
ble effects on the healing process of various musculoskele-
tal tissue types.25-29 Given these positive findings, it is easy 
to understand the interest in treatment with PRP. However, in 
894 L. A. ROssI, I. R. MURRAy, C. R. CHU, G. F. MUsCHLER, s. A. ROdEO, N. s. PIUzzI 
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the rush to clinical translation, numerous clinical trials have 
been performed without full characterization of PRP attrib-
utes nor optimization of preparations.5-7,30 Even though the 
basic science data supporting the potential beneficial effects 
of GFs in augmenting connective tissue healing are promising, 
the clinical benefits of using PRP have not been universally 
achieved.5,6 A critical analysis of the PRP literature suggests 
two primary reasons for the absence of alignment between the 
expectation derived from basic science and clinical reality. 
One reason may be the heterogeneity in the PRP preparation 
protocols and the final composition of the PRP delivered. Var-
iations in the volume of whole blood taken, the platelet recov-
ery efficacy, the final volume of plasma in which the platelets 
are suspended, the presence or absence of WBCs, and the 
addition of exogenous activators to induce fibrin formation 
can all affect the character and potential efficacy of the final 
PRP product.31-37 When analyzing the PRP preparation pro-
tocols and PRP composition utilized in clinical trials for the 
treatment of musculoskeletal diseases, only 10% of the stud-
ies provided comprehensive reporting that included a clear 
description of the preparation protocol that could be used to 
repeat the method by subsequent investigators.7 Furthermore, 
only 16% of the studies provided quantitative metrics on the 
composition of the PRP final product. Even within a given 
PRP separation technique, a high degree of inter- and intrasu-
bject variability in the composition of PRP exists, which must 
be addressed for improved reporting.38 This will contribute 
to the inconsistency of results reported in the literature. It is 
essential that a precise and stepwise description of the PRP 
preparation protocol is provided to allow comparison among 
studies and enable reproducibility.
Nevertheless, even if the PRP preparation protocol is 
clearly described, and if detailed quantitative metrics on 
the composition of the final product is provided, there is an 
additional key challenge, namely to communicate autologous 
blood preparations effectively using standardized nomencla-
ture. There is a wide spectrum of PRP preparation protocols 
and formulations used in the different studies, all grouped 
under the term ‘PRP’.3,16-23 Therefore, the success or failure of 
a specific PRP product is not necessarily predictive of all PRP 
preparations. As shown, in the last six years, five different 
classifications were described.9-13 To our knowledge, no evi-
dence-based classification guidelines specifying the optimal 
PRP preparation have been reported for different musculo-
skeletal disorders. A classification that accurately character-
izes the specific preparation of PRP will enable correlation 
with validated outcome assessment tools in studies exploring 
specific indications.
Which factors should be considered in a future consensus- 
based classification?. A future consensus classification on 
PRP should incorporate complete information from the final 
PRP delivered to allow standardized comparison between 
studies. Such a classification will have to incorporate a quan-
titative approach to reporting on all main components of PRP 
while staying simple and practical. Therefore, the authors 
feel that three essential factors that need to be represented 
are: 1) platelets; 2) WBCs and percentage of neutrophils; and 
3) RBCs. Furthermore, concentration and dose of PRP has 
to be recorded to document total number of the components 
delivered.
We believe that platelet number should be reported as plate-
let concentration (platelet number per millilitre), along with 
the volume of PRP delivered. We do not recommend reporting 
the platelet concentration as a multiple of the baseline because 
the baseline platelet count can vary significantly between 
patients.
WBCs should also be reported as concentration, and WBC 
differential should be reported when possible. Leucocyte con-
centrations have a strong influence on the growth factor and 
cytokines delivered to the target tissue.39 Given the multifunc-
tional roles of WBCs, it is possible that WBCs levels in PRP, 
or specific WBC subtypes, may be beneficial in specific mus-
culoskeletal conditions (such as chronic tendinopathy),40 while 
being detrimental in other others (such as osteoarthritis or acute 
muscle strain).17,41 It is likely that the need to include WBCs in 
the PRP preparation will vary by indication, and the WBC con-
centration should be documented. We believe that only charac-
terizing WBCs as above or below the baseline is insufficient. 
The concentration of leucocytes above the baseline can vary 
markedly and this will probably influence clinical outcomes.39 
Regarding WBC differential, and especially neutrophils, we 
believe that they should be measured and reported as a percent-
age of total WBCs.
Concerning RBCs, basic science studies have showed that 
they can adversely affect platelet function by altering local pH 
and promoting inflammation.37,42 Furthermore, blood-derived 
proinflammatory cytokines trigger chondrocytes and induce 
the production of cartilage-degrading proteases causing chon-
drocyte death. Additional clinical studies are needed to deter-
mine the clinical effects of different concentrations of RBCs on 
inflammation and wound healing. In the meantime, we recom-
mend that the dose of RBCs should be documented in the same 
way as platelets and WBCs.
Most authors have included activation in their classifi-
cations.10-13 Platelet activation, and subsequent release of 
cytokines and GFs, can be initiated by a number of meth-
ods such as shear forces caused by fluid flow, contact with a 
variety of materials including fibrillar collagen and basement 
membranes of cells, and thrombin.27,43 Once the PRP is acti-
vated, a fibrin network will begin to form and plasma will 
begin to solidify to create a fibrin clot or membrane. Some 
PRP preparation techniques advocate the activation of plate-
lets, with thrombin and/or calcium chloride (CaCl2), before 
PRP delivery to guarantee that the bioactive factors contained 
in the α granules will be secreted and readily available. In 
contrast, opponents of using activators suggest that natural 
activation via interaction with the patient’s own collagen is 
a superior route.44 When activated, platelets begin secreting 
their GFs immediately.45 Approximately 70% of these GFs are 
secreted within the first ten minutes after activation; within an 
hour almost 100% have been secreted.45 Although activation 
changes the properties of PRP, the biological consequences 
of exogenous activation of PRP on tissue healing have yet to 
be delineated. We recommend that if PRP is activated exog-
enously, this should be part of the classification of the final 
PRP product.CLAssIFICATION sysTEMs FOR PLATELET-RICH PLAsMA 895
VOL. 101-B, No. 8, AUGUST 2019
Finally, guidance on the reporting of relevant parameters 
describing preparation protocol of PRP might also need to be 
included in the methods section of every study to allow repro-
ducibility. Some of the parameters that might be suggested 
includes type of anticoagulant, preparation technique (includ-
ing spin rate and/or g-forces and duration), and make and model 
of the centrifuge.
Take home message
- At present, there is no all-encompassing and universally ac-
cepted system to allow classification of platelet-rich plasma 
(PRP) and other autologous blood preparations.
- An ideal classification should be simple to use, should be reproducible, 
and should focus on characteristics that are relevant to the prognosis and 
therapeutic decision making.
- A future consensus classification on PRP should incorporate complete 
information from the final PRP delivered to allow standardized compar-
ison between studies. Such a classification will have to incorporate a 
quantitative approach to reporting: 1) platelets; 2) white blood cells and 
percentage of neutrophils; and 3) red blood cells. Furthermore, concen-
tration and dose of PRP has to be recorded to document total number of 
the components delivered.
Twitter
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Follow G. F. Muschler @MuschlerMd
Follow N. S. Piuzzi @nspiuzzi
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Author information:
L. A. Rossi, MD, Attending Orthopaedic Surgeon, Department of Orthopaedic 
Surgery, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
I. R. Murray, MD, PhD, Wellcome Trust Clinical Lecturer in Musculoskeletal 
Regeneration, Resident in Orthopaedic Surgery, Royal Infirmary of Edinburgh, 
University of Edinburgh, Edinburgh, UK; Clinical Lecturer and Specialty Registrar 
in Orthopaedic, Department of Trauma and Orthopaedics, University of 
 Edinburgh, Edinburgh, UK..
C. R. Chu, MD, Professor and Vice Chair Research, Department of Orthopedic 
Surgery, Stanford University, Stanford, California, USA; Director of the Joint 
Preservation Center and Chief of Sports Medicine, VA Palo Alto, Palo Alto, 
California, USA.
G. F. Muschler, MD, Professor of Orthopaedic Surgery, Director of the Joint 
Preservation Center, and Director of the Regenerative Medicine Laboratory, 
Cleveland Clinic, Cleveland, Ohio, USA.
S. A. Rodeo, MD, Co-Chief Emeritus, Sports Medicine and Shoulder Service 
and Co-Director, Tissue Engineering, Regeneration, and Repair Program, 
Hospital for Special Surgery, New York, New York, USA; Professor, Orthopaedic 
Surgery, Weill Medical College of Cornell University, New York, New York, 
USA; Attending Orthopaedic Surgeon, The Hospital for Special Surgery, 
New York, New York, USA; Head Team Physician, New York Giants Football, 
New York, New York, USA.
N. S. Piuzzi, MD, Attending Orthopaedic Surgeon – Center for Adult 
Reconstructive Surgery, Cleveland Clinic, Cleveland, Ohio, USA; Associate 
Investigator, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Author contributions:
L. A. Rossi: Acquired, analyzed, and interpreted the data, Drafted and critically 
revised the manuscript.
I. R. Murray: Analyzed and interpreted the data, Drafted and critically revised 
the manuscript.
C. R. Chu: Critically revised the manuscript.
G. F. Muschler: Critically revised the manuscript.
S. A. Rodeo: Critically revised the manuscript.
N. S. Piuzzi: Conceptualized and designed the study, Acquired, analyzed, and 
interpreted the data, Drafted and critically revised the manuscript.
Funding statement:
No benefits in any form have been received or will be received from a 
 commercial party related directly or indirectly to the subject of this article.
This article was primary edited by G. Scott.