Traumatology, Orthopaedic Surgery

and Sports Medicine

Clinical studies
Clinical studies

JOINT PATHOLOGY

1-Ultrasound-guided platelet-rich plasma injections for the treatment of osteoarthritis of the hip

2-Arthroscopic Treatment and Injection of Plasma Rich in Growth Factors in the Treatment
Femoroacetabular Impingement of the Hip: Results with Two Years of Follow-up

3-Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee
OA: a retrospective cohort study

4-Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on
function and quality of life

5-Comparison of Intra-Articular Injections of Plasma Rich in Growth Factors (PRGF-Endoret) Versus

Durolane Hyaluronic Acid in the Treatment of Patients with Symptomatic Osteoarthritis: A Randomized
Controlled Trial

6-A Randomized Clinical Trial Evaluating Plasma Rich in Growth Factors (PRGF-Endoret) Versus
Hyaluronic Acid in the Short-Term Treatment of Symptomatic Knee Osteoarthritis

7-Combination of Intra-Articular and Intraosseous Injections of Platelet Rich Plasma for Severe Knee
Osteoarthritis: A Pilot Study

8-Plasma Rich in Growth Factors to Treat an Articular Cartilage Avulsion: A Case Report

9-Platelet-Rich Plasma or Hyaluronate in the Management of Osteochondral Lesions of the Talus

10-Arthroscopic management and platelet-rich plasma therapy for avascular necrosis of the hip

11-Intraosseous Infiltration of Platelet-Rich Plasma for Severe Hip Osteoarthritis

SPINE PATHOLOGY

1- Intradical and intra-articular facet infiltrations with plasma rich in growth factors reduce pain in
patients with chronic low back pain
LIGAMENT PATHOLOGY

1-Plasma rich in growth factors (PRGF) as a treatment for high ankle sprain in elite athletes: a
randomized control trial

2-Partial anterior cruciate ligament tears treated with intra ligamentary plasma rich in growth factors

3-Pain in donor site after BTB-ACL reconstruction with PRGF: a randomized trial

4-Magnetic resonance imaging evaluation of patellar tendon graft remodelling after anterior cruciate
ligament reconstruction with or without platelet-rich plasma

5-Aplicación de plasma autólogo rico en factores de crecimiento en cirugía artroscópica

6-Role of Growth Factors in Bone-Tendon-Bone ACL Surgery: Time for Maturation of the ACL Graft and
the Patellar Tendon Donor Site

MUSCLE PATHOLOGY

1-Platelet-Rich Plasma in Muscle and Tendon Healing

TENDON PATHOLOGY

1-PRP in Lateral Elbow Pain

2-Aplicación coadyuvante de plasma rico en factores de crecimiento en rotura bilateral de tendón

cuadricipital

3-Platelet-rich plasma for calcific tendinitis of the shoulder: a case report

4-Management of post-surgical Achilles tendon complications with a preparation rich in growth factors:
A study of two-cases

5-Comparison of Surgically Repaired Achilles Tendon Tears Using Platelet-Rich Fibrin Matrices

6-Surgery of subacromial syndrome with application of Plasma Rich in Growth Factors

BONE PATHOLOGY

1-Delayed union of the clavicle treated with plasma rich in growth factors

2-Nonunions Treated With Autologous Preparation Rich in Growth Factors

NEURAL PATHOLOGY

1-Ultrasound-guided platelet-rich plasma injections for the treatment of common peroneal nerve palsy
associated with multiple ligament injuries of the knee

WOUNDS

1-The use of plasma rich in growth factors (PRGF-Endoret) in the treatment of a severe mal perforant
ulcer in the foot of a person with diabetes

2-Use of Platelet-Rich Plasma to Treat Pressure Ulcers

3-Biological approach for the management of non-healing diabetic foot ulcers

4-Autologous Platelet Gel: Five Cases Illustrating Use on Sickle Cell Disease Ulcers

5-Effectiveness of Autologous Preparation Rich in Growth Factors for the Treatment of Chronic
Cutaneous Ulcers

6-Effectiveness of Autologous Preparation Rich in Growth Factors for the Treatment of Chronic
Cutaneous Ulcers

7-Efficacy and safety of the use of platelet-rich plasma to manage venous ulcers

8-Platelet-Rich Plasma in Skin Ulcer Treatment. A cost-effectiveness analysis

 Rheumatology Advance Access published November 10, 2011
RHEUMATOLOGY

Original article doi:10.1093/rheumatology/ker303

Ultrasound-guided platelet-rich plasma injections

for the treatment of osteoarthritis of the hip
Mikel Sánchez1, Jorge Guadilla1, Nicolás Fiz1 and Isabel Andia2

Abstract
Objective. To assess the safety and symptomatic changes of IA injections of platelet-rich plasma (PRP)
in patients with OA of the hip.
Methods. Forty patients affected by monolateral severe hip OA were included in the study. Each joint
received three IA injections of PRP, which were administered once a week. 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. The visual analogue scale (VAS)
For internal use company and distributors

and Harris hip score subscale for pain were used to verify the results. Secondary end points included
changes in the level of disability of at least 30% and the percentage of positive responders, i.e. the
number of patients that achieved a >30% reduction in pain and disability.
Results. Statistically significant reductions in VAS, WOMAC and Harris hip subscores for pain and func-
tion were reported at 7 weeks and 6 months (P < 0.05). Twenty-three (57.5%) patients reported a clinically
relevant reduction of pain (45%, range 30–71%) as assessed by the WOMAC subscale. Sixteen (40%)
of these patients were classified as excellent responders who showed an early pain reduction at
6–7 weeks, which was sustained at 6 months, and a parallel reduction of disability. Side effects were
negligible and were limited to a sensation of heaviness in the injection site.
Conclusions. This preliminary non-controlled prospective study supported the safety, tolerability and
efficacy of PRP injections for pain relief and improved function in a limited number of patients with OA
of the hip.
Key words: Platelet-rich plasma, Hip, Osteoarthritis, Ultrasound.

Introduction at least slow the development and progression of OA.

For this treatment to be possible, the aetiopathogenic
OA is a syndrome of joint pain and dysfunction that is mechanisms and OA progression that target specific
caused by joint degeneration. OA affects more people tissues require further elucidation. Meanwhile, the admin-
than any other joint disease [1] and has widespread istration of platelet-rich plasma (PRP) has gained attention
economic and social consequences. The hip is a frequent from the scientific and medical communities because of
site for OA, and the prevalence ranges from 7 to 25% in its ability to release a large pool of chemokines, cytokines
Caucasians aged >55 years [2]. The problem is likely and growth factors within the joint capsule [4], which are
intensified by current demographic trends, including the involved in cell signalling and in the stimulation of intrinsic
pandemic of obesity and the higher recreational activity repair mechanisms. IA injections of PRP are currently
levels of our elderly population [3]. Indeed, there is an hypothesized to largely control the activities of different
urgent need for disease-modifying treatments to stop or cell types that target multiple biological processes,
such as apoptosis, extracellular matrix synthesis, the
modulation of angiogenesis and inflammation [5].
1
Unidad de Cirugı́a Artroscópica, UCA ‘Mikel Sánchez’, Clı́nica PRP therapy was first applied after IA knee injury [6]
USP-La Esperanza, Vitoria-Gasteiz, Spain and 2Departamento de and, later, for knee OA [7], because PRP may substitute
Investigación, Osakidetza, Basque Health Service, Zamudio, Vizcaya.
the chondrodestructive environment with high levels of
Submitted 27 April 2011; revised version accepted 19 July 2011.
anabolic and chondroprotective cytokines. PRP-released
Correspondence to: Isabel Andia, Departamento de Investigación,
Osakidetza, Basque Health Service, B Arteaga 107, 48170 Zamudio,
cytokines target the synovium and induce changes in the
Vizcaya. E-mail: [email protected] SF [8, 9]. In the IA milieu, cytokines and growth factors

! The Author 2011. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected] 1
 International Journal of Orthopaedics

Online Submissions: http://www.ghrnet.org/index./ijo/ Int Journal of Orthopaedics 2015 February 23 2(1): 182-187
doi:10.6051/j.issn.2311-5106.2015.02.45-1 ISSN 2311-5106 (Print), ISSN 2313-1462 (Online)

TOPIC HIGHLIGHT

Arthroscopic Treatment and Injection of Plasma Rich in Growth

Factors in the Treatment Femoroacetabular Impingement of
the Hip: Results with Two Years of Follow-up

Roberto Seijas, MD, PhD, Oscar Ares, MD, PhD, Pedro Álvarez-Díaz, MD, Andrea Sallent, MD, Xavier Cuscó, MD,
Robert Tejedor, MS, Ramón Cugat, MD, PhD

Roberto Seijas, Oscar Ares, Pedro Álvarez-Díaz, Xavier Cuscó, of plasma rich in growth factors into the affected hip joint. We
Ramón Cugat, Department of Orthopaedic Surgery, Artroscopia evaluated the results at two years after surgery using general and
GC - Fundación García Cugat, Hospital Quirón Barcelona, Spain speciic validated instruments. Eight patients (7 Tennis 2 and 1 Tennis
Roberto Seijas, Oscar Ares, Pedro Álvarez-Díaz, Xavier Cuscó, 1) underwent a second surgery for total hip replacement within the
Professor, Internacional University of Catalunya, Barcelona, Spain 2-year minimum follow-up. 36 (81.8%) of the 44 patients showed
Pedro Álvarez-Díaz, Ramón Cugat, Catalan Soccer Delegation’s statistically signiicant improvement in pain, stiffness and functional
Health Insurance Company, Spanish Soccer Federation, Barcelona, capacity in evaluation by HOS, WOMAC, mHHS and VAS. This
Spain study showed good results in patients after arthroscopic debridement
Andrea Sallent, Department of Orthopaedic Surgery, Vall d’Hebron of the acetabular rim and femoral neck for femoroacetabular
Hospital, Barcelona, Spain impingement and injection of plasma rich in osteoarthritic hips. This
Robert Tejedor MS, Medicine School, Barcelona University, Bar- surgery in properly selected patients can improve patients’ pain,
celona, Spain stiffness and functional capacity for at least two years after surgery.
Correspondence to: Roberto Seijas, MD, PhD, Department of It is unclear whether the surgery alone or the addition of plasma rich
Orthopaedic Surgery, Fundación García Cugat, Hospital Quirón Bar- in growth factors was responsible for the results. Level of evidence.
celona, Internacional University of Catalunya, Plaza Alfonso Comín Level IV of evidence, therapeutic case series.
5-7, 08023, Barcelona, Spain
Email: [email protected] © 2015 ACT. All rights reserved.
Telephone: +34932172252 Fax: +34932381634
Received: September 13, 2014 Revised: October 26, 2014 Key words: Hip arthroscopy; PRP; Platelet-rich plasma;
Accepted: October 30, 2014 Osteoarthritis; Tennis; Degenerative change
Published online: February 23, 2015
Seijas R, Ares O, Álvarez-Díaz P, Sallent A, Cuscó M, Cugat R.
ABSTRACT Arthroscopic Treatment and Injection of Plasma Rich in Growth
Factors in the Treatment Femoroacetabular Impingement of the
Femoroacetabular impingement has been described as a cause of
Hip: Results with Two Years of Follow-up. International Journal of
injury to the acetabular labrum and degeneration of the hip joint. Orthopaedics 2015; 2(1): 182-187 Available from: URL: http://www.
Surgical treatment is based in correction of the femoral neck ghrnet.org/index.php/ijo/article/view/1047
deformity as well as the prominence of the anterior acetabular rim
by open and arthroscopic techniques. A prospective study performed
between April 2011 and April 2012 with 44 consecutive patients
INTRODUCTION
with osteoarthritic changes of the hip (Tönnis grade 1 and 2) and Femoroacetabular impingement of the hip has been described
symptomatic femoroacetabular impingement underwent arthroscopic as a cause of degeneration of the acetabular labrum and the
debridement of the acetabular rims and femoral neck. During the femoroacetabular joint[1-5]. Several validated instruments can be used
same period of time, 28 patients consecutively underwent hip to measure pain and alteration of functional capacity in activities of
arthroscopy without degenerative changes. All patients had injection daily living and in sports[6], such as SF-36, WOMAC or the more hip-

© 2015 ACT. All rights reserved. 182

 BRIEF PAPER Clinical and Experimental Rheumatology 2008; 26: 00-00

Intra-articular injection of an ABSTRACT biological delivery system of a com-

autologous preparation rich Objective. To obtain preliminary in- plex mixture of bioactive proteins es-
in growth factors for the formation about the effectiveness of sential to natural repair including ana-
treatment of knee OA: intra-articular injections of an autolo- bolic factors for cartilage such as trans-
gous preparation rich in growth factors forming growth factor-β1 (TGF-β1),
a retrospective cohort study
(PRGF) for knee OA treatment to be platelet-derived growth factor (PDGF)
explored further in future studies. and insulin-like growth factor (IGF-I)
M. Sánchez1, E. Anitua2, Methods. We have characterized PRGF (3). The potential of a characterized
J. Azofra1,3, J.J. Aguirre2, treatment by platelet count and con- platelet-derivative, known as “Prepara-
I. Andia2 centration of relevant growth factors tion Rich in Growth Factors” (PRGF),
(TGF-β1, PDGF-AB, VEGF-A; HGF to enhance the limited capacity of car-
1
Unidad de Cirugia Artroscópica “Mikel
and IGF-I) involved in healing mecha- tilage to repair itself (4) encouraged the
Sanchez”, Vitoria, Spain; 2Biotechnology
Institute, BTI IMASD, Vitoria, Spain. nisms. We have performed an observa- idea of treating degenerative joint con-
tional retrospective cohort study using ditions with this autologous prepara-
Mikel Sánchez, MD
Eduardo Anitua, MD hyaluronan injections as a control. tion. Supported by the positive effects
Juan Azofra, MD, PhD Each group included 30 patients with of PRGF in different clinical situations
Joséé Javier Aguirre MD OA of the knee, matched according to involving connective tissues (5-8) and
Isabel Andia, PhD age, sex, body mass index and radio- also in OA synovial cell cultures (9),
The work of this group is partially funded graphic severity. Both treatments were we have hypothesized that the deliv-
by the Basque and Spanish Governments. based on three weekly injections. Clini- ery of a natural mixture of biologi-
cal outcome was examined using the cally active molecules within the joint
For internal use company and distributors

Please address correspondence and

reprint requests to: WOMAC questionnaires prior to treat- compartment is a safe strategy (10) to
Dr. Isabel Andia, Biotechnology Institute, ment and at 5 weeks after treatment. induce positive changes in the joint mi-
c/ Leonardo Da Vinci 14, 01510 Miñano Results. The observed success rates by croenvironment improving the condi-
(Alava), Spain.
week 5 for the pain subscale reached tions of articular tissues.
E-mail. [email protected]
33.4% for the PRGF group and 10% The goal of this preliminary study is to
Received on June 18, 2007; accepted in
revised form on February 6, 2008.
for the hyaluronan group. The differ- explore whether PRGF could be used
ence was attributed exclusively to the for the treatment of OA of the knee. To
© Copyright CLINICAL AND
EXPERIMENTAL RHEUMATOLOGY 2008.
treatment modality, p=0.004. The per- address this issue, a full quantitative
cent reductions in the physical func- characterization of PRGF was carried
Key words: Osteoarthritis, platelets, tion subscale and overall WOMAC at 5 out and a retrospective cohort study
growth factors, hyaluronan, WOMAC. weeks were also associated solely with was performed to test the effectiveness
treatment modality in favour of PRGF, and safety of PRGF. Since intra-articu-
p=0.043 and p= 0.010 respectively. lar hyaluronan (HA) treatments are also
Conclusions. Although these prelimi- included among the therapeutic modali-
nary results need to be evaluated in a ties for knee OA, we were able to study
randomized clinical trial, they provide and compare two groups of patients:
useful information about the safety of those who underwent conventional HA
PRGF and open new perspectives on au- infiltration and those who underwent
tologous treatments for joint diseases. infiltration with PRGF.

Introduction Patients and methods

The treatment of osteoarthritis (OA) in- Patients
cludes a wide spectrum of approaches The study was designed as an observa-
but at present, with the exception of tional retrospective cohort study using
surgery, these approaches are merely HA as a control. All patients signed a
palliative. Current research efforts to- detailed informed consent. The study
wards the testing of protein biothera- was conducted following the ICH
peutics for restoring the metabolic GPC guidelines. Patients were diag-
balance within the capsular joint are in nosed according to the American Col-
progress (1). Although the therapeutic lege of Rheumatology criteria (11).
use of anabolic and anti-catabolic fac- Radiographic severity was assessed
tors appears promising, developing by anterio-posterior weight bearing
controllable approaches for delivery radiographs scored for Ahlbäck. Idi-
represent a major challenge (2). opathic and secondary post-traumatic
Autologous platelet-rich fibrin (pre- and mechanical OA were included.
Competing interests: none declared. pared from platelet-rich plasma) is a OA secondary to joint inflammatory

174
Arch Orthop Trauma Surg. 2011 Mar;131(3)311-7
Arch Orthop Trauma Surg
DOI 10.1007/s00402-010-1167-3

ORTHOPAEDIC SURGERY

InWltration of plasma rich in growth factors for osteoarthritis

of the knee short-term eVects on function and quality of life
Ana Wang-Saegusa · Ramón Cugat ·
Oscar Ares · Roberto Seijas · Xavier Cuscó ·
Montserrat Garcia-Balletbó

Received: 18 May 2010

 Springer-Verlag 2010

Abstract Results Statistically signiWcant diVerences (P < 0.0001)

Purpose Osteoarthritis (OA) is a highly prevalent, between pre-treatment and follow-up values were found for
chronic, degenerative condition that generates a high pain, stiVness and functional capacity in the WOMAC
expense. Alternative and co-adjuvant therapies to improve Index; pain and total score, distance and daily life activities
the quality of life and physical function of aVected patients in the Lequesne Index; the VAS pain score; and the SF-36
are currently being sought. physical health domain. There were no adverse eVects
Methods A total of 808 patients with knee pathology were related to PRGF inWltration.
treated with PRGF (plasma rich in growth factors), 312 of Conclusion At 6 months following intra-articular inWltration
them with OA of the knee (Outerbridge grades I–IV) and of PRGF in patients with OA of the knee, improvements in
symptoms of >3 months duration met the inclusion criteria function and quality of life were documented by OA-speciWc
and were evaluated to obtain a sample of 261 patients, 109 and general clinical assessment instruments. These favourable
women and 152 men, with an average age of 48.39. Three Wndings point to consider PRGF as a therapy for OA.
intra-articular injections of autologous PRGF were admin-
istered at 2-week intervals in outpatient surgery. The pro- Keywords Osteoarthritis · Chondropathy ·
cess of obtaining PRGF was carried out following the Platelet-rich plasma · PRP
Anitua Technique. Participants were asked to Wll out a
questionnaire with personal data and the following assess-
ment instruments: VAS, SF-36, WOMAC Index and Introduction
Lequesne Index before the Wrst inWltration of PRGF and
6 months after the last inWltration. Osteoarthritis (OA) is a highly prevalent, chronic, degener-
ative illness, the most frequent cause of pain and a major
cause of disability and dependence, which generates a high
expense. Currently, there is no curative treatment for OA.
This research was funded by Fundación García Cugat. The therapy used may be a conservative approach or surgery
A. Wang-Saegusa · M. Garcia-Balletbó
and varies depending on the aVected joint. Non-steroidal
Regenerative Medicine Department, Fundación García Cugat, anti-inXammatory drugs (NSAIDs) have been the main
Hospital Quirón Barcelona, Barcelona, Spain pharmacological OA treatment, but the elderly have a high
risk of showing side eVects. Studies show that 5 IA injections
R. Cugat · O. Ares · R. Seijas (&) · X. Cuscó
Orthopaedic Surgery Department, Fundación García Cugat,
of hyaluronic acid (HA) produce an extended symptomatic
Hospital Quirón Barcelona, ISAKOS Approved Teaching Center, improvement in patients with OA [17].
Pza. Alfonso Comín 5-7, 08023 Barcelona, Spain In the past, arthritis therapy did not taken into account,
e-mail: [email protected] the true causes and underlying pathogenic mechanisms of
R. Cugat
the condition, focusing mainly on treating the symptoms,
Spanish Soccer Federation, rather than interfering with the progression of cartilage
Catalonian Soccer Players Insurance Company, Catalonia, Spain damage. This approach is now changing [15] with the

123
 Comparison of Intra-Articular Injections of Plasma Rich in
Growth Factors (PRGF-Endoret) Versus Durolane Hyaluronic
Acid in the Treatment of Patients With Symptomatic
Osteoarthritis: A Randomized Controlled Trial
Víctor Vaquerizo, M.D., Miguel Ángel Plasencia, Ph.D., Ignacio Arribas, Ph.D.,
Roberto Seijas, M.D., Sabino Padilla, Ph.D., Gorka Orive, Ph.D., and
Eduardo Anitua, M.D., D.D.S., Ph.D.
For internal use company and distributors

Purpose: The purpose of this study was to compare the efficacy and safety in a randomized, clinical trial of 3 injections of
PRGF-Endoret (BTI Biotechnology Institute, Vitoria, Spain) versus one single intra-articular injection of Durolane hya-
luronic acid (HA) (Q-MED AB, Uppsala, Sweden) as a treatment for reducing symptoms in patients with knee osteo-
arthritis (OA). Methods: Ninety-six patients with symptomatic knee OA were randomly assigned to receive PRGF-
Endoret (3 injections on a weekly basis) or one infiltration with Durolane HA. The primary outcome measures were
a 30% decrease and a 50% decrease in the summed score for the pain, physical function, and stiffness subscales of the
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne scores from baseline to weeks
24 and 48. The percentage of OMERACT-OARSI (Outcome Measures for Rheumatology Committee and Osteoarthritis
Research Society International Standing Committee for Clinical Trials Response Criteria Initiative) responders was also
documented. As secondary outcomes, pain, stiffness, and physical function by use of the WOMAC and the Lequesne
score were considered and overall safety of the injection themselves. Results: The mean age of the patients was 63.6
years. Treatment with PRGF-Endoret was significantly more efficient than treatment with Durolane HA in reducing knee
pain and stiffness and improving physical function in patients with knee OA. The rate of response to PRGF-Endoret was
significantly higher than the rate of response to HA for all the scores including pain, stiffness, and physical function on the
WOMAC, Lequesne index, and OMERACT-OARSI responders at 24 and 48 weeks. Adverse events were mild and evenly
distributed between the groups. Conclusions: Our findings show that PRGF-Endoret is safe and significantly superior to
Durolane HA in primary and secondary efficacy analysis both at 24 and 48 weeks; provides a significant clinical
improvement, reducing patients’ pain and improving joint stiffness and physical function with respect to basal levels in
patients with knee OA; and should be considered in the treatment of patients with knee OA. Level of Evidence: Level I,
multicenter randomized controlled clinical trial.

From the Departments of Orthopaedic Surgery (V.V., M.Á.P.) and Clinical

Analysis (I.A.), Príncipe de Asturias University Hospital, Alcalá de Henares;
Orthopaedic Surgery Department, Fundación García Cugat, Hospital Quirón
O steoarthritis (OA) of the knee can have a devas-
tating impact on a patient’s quality of life and
increase the cost to society due to loss of work, early
Barcelona (R.S.), Barcelona; and BTI Biotechnology Institute ImasD (S.P., retirement, and arthroplasty.1,2 The incidence of the
G.O., E.A.), Vitoria, Spain. disease is influenced by typical demographic parame-
Supported by the Biomedical Research Foundation of Príncipe de Asturias
ters of developed countries including aging population
University Hospital and Ministry of Health, Social Policy and Equality of
Spain. The authors report the following source of funding: V.V., M.Á.P., I.A., and the epidemic of obesity.3,4 Despite the societal and
R.S., G.O., and E.A. receive support from BTI. health care burden, there are no medical treatments
Received January 30, 2013; accepted July 10, 2013. that alter the course of the disease. The current thera-
Address correspondence to Víctor Vaquerizo, M.D., Department of Ortho- peutic approaches focus on preventing or at least
paedic Surgery, Príncipe de Asturias University Hospital, Carretera Alcalá-
delaying the structural and functional changes of OA.5
Meco s/n 28805, Alcalá de Henares, Spain. E-mail: [email protected]
Ó 2013 by the Arthroscopy Association of North America The development and progression of OA are now
0749-8063/1387/$36.00 believed to involve inflammation even in the early
http://dx.doi.org/10.1016/j.arthro.2013.07.264 stages of the disease. There is a clear relation between

Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 29, No 10 (October), 2013: pp 1635-1643 1635
 A Randomized Clinical Trial Evaluating Plasma Rich in Growth
Factors (PRGF-Endoret) Versus Hyaluronic Acid in the
Short-Term Treatment of Symptomatic Knee Osteoarthritis

Mikel Sánchez, Ph.D., Nicolás Fiz, Ph.D., Juan Azofra, Ph.D., Jaime Usabiaga, Ph.D.,
Enmanuel Aduriz Recalde, Ph.D., Antonio Garcia Gutierrez, Ph.D., Javier Albillos, Ph.D.,
Ramón Gárate, Ph.D., Jose Javier Aguirre, Sabino Padilla, Ph.D.,
Gorka Orive, Ph.D., and Eduardo Anitua, M.D., D.D.S., Ph.D.

Purpose: This multicenter, double-blind clinical trial evaluated and compared the efficacy and safety
For internal use company and distributors

of PRGF-Endoret (BTI Biotechnology Institute, Vitoria-Gasteiz, Spain), an autologous biological

therapy for regenerative purposes, versus hyaluronic acid (HA) as a short-term treatment for knee
pain from osteoarthritis. Methods: We randomly assigned 176 patients with symptomatic knee
osteoarthritis to receive infiltrations with PRGF-Endoret or with HA (3 injections on a weekly basis).
The primary outcome measure was a 50% decrease in knee pain from baseline to week 24. As
secondary outcomes, we also assessed pain, stiffness, and physical function using the Western
Ontario and McMaster Universities Osteoarthritis Index; the rate of response using the criteria of the
Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International
Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and
safety. Results: The mean age of the patients was 59.8 years, and 52% were women. Compared with
the rate of response to HA, the rate of response to PRGF-Endoret was 14.1 percentage points higher
(95% confidence interval, 0.5 to 27.6; P ⫽ .044). Regarding the secondary outcome measures, the
rate of response to PRGF-Endoret was higher in all cases, although no significant differences were
reached. Adverse events were mild and evenly distributed between the groups. Conclusions: Plasma
rich in growth factors showed superior short-term results when compared with HA in a randomized
controlled trial, with a comparable safety profile, in alleviating symptoms of mild to moderate
osteoarthritis of the knee. Level of Evidence: Level I, randomized controlled multicenter trial.

O steoarthritis (OA) is an heterogeneous disease

that affects the structures of the joints. It has
become one of the most common painful conditions
affecting adults and the most frequent cause of mo-
bility disability in the United States and Europe.1 The
incidence of OA is rising, influenced by the aging
population and the epidemic of obesity.2 Recent esti-
mates suggest that symptomatic knee OA affects 13%
of persons aged 60 years or older and a total of 20
From Unidad Cirugía Artroscópica (USP Clínica la Esperanza)
(M.S., N.F., J. Azofra), Vitoria, Spain; Hospital Donostia (J.U., E. million Americans, a number that is expected to dou-
Aduriz, A.G.), San Sebastián-Donostia, Spain; Policlínica Guipúzcoa ble over the next 2 decades.3
(J. Albillos, R.G.), San Sebastián-Donostia, Spain; and BTI Biotech- Unfortunately, there are currently no agents available
nology Institute (J.J.A., S.P., G.O., E. Anitua), Vitoria, Spain.
The authors report that they have no conflicts of interest in the that can halt OA progression and reverse any existing
authorship and publication of this article. damage. Analgesics and nonsteroidal anti-inflammatory
Received December 30, 2011; accepted May 24, 2012.
Address correspondence to Eduardo Anitua, M.D., D.D.S., drugs (NSAIDs) have suboptimal effectiveness, and
Ph.D., Instituto Eduardo Anitua, c/Jose Maria Cagigal 19 (01007), there are some concerns regarding their safety, in light of
Vitoria, Spain. E-mail: [email protected] the well-described gastrointestinal and cardiorenal side
© 2012 by the Arthroscopy Association of North America
0749-8063/11876/$36.00 effects.4 Current therapeutic approaches focus on devel-
http://dx.doi.org/10.1016/j.arthro.2012.05.011 oping less invasive procedures and applying them earlier

1070 Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 28, No 8 (August), 2012: pp 1070-1078
Hindawi Publishing Corporation
BioMed Research International
Volume 2016, Article ID 4868613, 10 pages
http://dx.doi.org/10.1155/2016/4868613

Clinical Study
Combination of Intra-Articular and Intraosseous
Injections of Platelet Rich Plasma for Severe Knee
Osteoarthritis: A Pilot Study

Mikel Sánchez,1 Diego Delgado,2 Pello Sánchez,2 Emma Muiños-López,3

Bruno Paiva,4 Froilán Granero-Moltó,3,5 Felipe Prósper,3,6 Orlando Pompei,1
Juan Carlos Pérez,1 Juan Azofra,1 Sabino Padilla,7 and Nicolás Fiz1
1
Arthroscopic Surgery Unit, Hospital Vithas San Jose, C/Beato Tomás de Zumarraga 10, 01008 Vitoria-Gasteiz, Spain
2
Arthroscopic Surgery Unit Research, Hospital Vithas San Jose, C/Beato Tomás de Zumarraga 10, 01008 Vitoria-Gasteiz, Spain
3
Cell herapy Area, Clı́nica Universidad de Navarra, Avenida de Pı́o XII 36, 31008 Pamplona, Spain
4
Center for Applied Medical Research, Avenida de Pı́o XII 55, 31008 Pamplona, Spain
5
Orthopaedic Surgery and Traumatology Department, Clı́nica Universidad de Navarra, Avenida de Pı́o XII 36, 31008 Pamplona, Spain
6
Hematology Department, Clı́nica Universidad de Navarra, Avenida de Pı́o XII 36, 31008 Pamplona, Spain
7
Fundacion Eduardo Anitua, C/Jose Marı́a Cagigal 19, 01007 Vitoria-Gasteiz, Spain

Correspondence should be addressed to Mikel Sánchez; [email protected]

Received 26 February 2016; Revised 3 June 2016; Accepted 6 June 2016

Academic Editor: Magali Cucchiarini

Copyright © 2016 Mikel Sánchez et al. his is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

he aim of this study was to assess a novel approach to treating severe knee osteoarthritis by targeting synovial membrane, supericial
articular cartilage, synovial luid, and subchondral bone by combining intra-articular injections and intraosseous iniltrations of
platelet rich plasma. We explored a new strategy consisting of intraosseous iniltrations of platelet rich plasma into the subchondral
bone in combination with the conventional intra-articular injection in order to tackle several knee joint tissues simultaneously.
We assessed the clinical outcomes through osteoarthritis outcome score (KOOS) and the inlammatory response by quantifying
mesenchymal stem cells in synovial luid. here was a signiicant pain reduction in the KOOS from baseline (61.55 ± 14.11) to week
24 (74.60 ± 19.19), ater treatment (� = 0.008), in the secondary outcomes (symptoms, � = 0.004; ADL, � = 0.022; sport/rec.,
� = 0.017; QOL, � = 0.012), as well as VAS score (� < 0.001) and Lequesne Index (� = 0.008). he presence of mesenchymal
stem cells in synovial luid and colony-forming cells one week ater treatment decreased substantially from 7.98 ± 8.21 MSC/�L to
4.04 ± 5.36 MSC/�L (� = 0.019) and from 601.75 ± 312.30 to 139.19 ± 123.61 (� = 0.012), respectively. Intra-articular injections
combined with intraosseous iniltrations of platelet rich plasma reduce pain and mesenchymal stem cells in synovial luid, besides
signiicantly improving knee joint function in patients with severe knee osteoarthritis. his trial is registered on EudraCT with the
number 2013-003982-32.

1. Introduction synovial membrane (SM), which produces synovial luid

(SF), and subchondral bone (SB), both endowed with heat
Knee osteoarthritis (KOA) is a mechanically induced, receptors, chemoreceptors, and mechanoreceptors. Nocicep-
cytokine and enzyme-mediated disorder comprising difer- tive stimuli, coming from a microenvironment undergoing
ent phases and phenotypes, with pain as the clinical hallmark nonphysiological mechanical loading and/or proinlamma-
of the disease [1]. his diarthrodial joint is a complex tory cytokines and damage-associated molecular patterns
biological system where articular cartilage (AC), an aneural (DAMPS), might initially lead to peripheral and eventually
and avascular tissue, lies functionally sandwiched between both peripheral and neuropathic pain traits by mechanisms
two highly vascularized and innervated tissues, namely, yet to be fully identiied [2–4]. Moreover, the aggression
 Plasma Rich in Growth Factors to Treat an
Articular Cartilage Avulsion: A Case Report
MIKEL SÁNCHEZ1, JUAN AZOFRA1, EDUARDO ANITUA2, ISABEL ANDÍA3, SABINO PADILLA4,
JUANMA SANTISTEBAN4, and IÑIGO MUJIKA4
1
Arthroscopic Surgery Unit, USP-La Esperanza Clinic, Vitoria-Gasteiz, Basque Country, SPAIN; 2B.T.I. Biotechnology
Institute, Vitoria-Gasteiz, Basque Country, SPAIN; 3Department of Neurochemistry Research, Osakidetza–Basque Health
Service, Zamudio, Basque Country, SPAIN; and 4Department of Research and Development, Medical Services, Athletic
Club of Bilbao, Basque Country, SPAIN

ABSTRACT
SÁNCHEZ, M., J. AZOFRA, E. ANITUA, I. ANDÍA, S. PADILLA, J. SANTISTEBAN, and I. MUJIKA. Plasma Rich in Growth
Factors to Treat an Articular Cartilage Avulsion: A Case Report. Med. Sci. Sports Exerc., Vol. 35, No. 10, pp. 1648 –1652, 2003.
Introduction: The application of an autologous plasma rich in growth factors is beneficial in restoring connective tissues, as shown by clinical
evidence in oral surgery and more recently in arthroscopic anterior cruciate ligament reconstruction and two cases of ruptured Achilles tendon
in professional athletes. This is attributed to the slow delivery of growth factors from harvested platelets that have been activated by
endogenous thrombin promoted by the addition of calcium chloride. Purpose: This case report describes a new application of this therapy
For internal use company and distributors

in the arthroscopic treatment of a large, nontraumatic avulsion of articular cartilage in the knee of an adolescent soccer player. Methods: After
arthroscopic reattachment of the large (⬎2 cm) loose chondral body in its crater in the medial femoral condyle, autologous plasma rich in
growth factors was injected into the area between the crater and the fixed fragment. Results and Conclusion: Despite the extremely poor
prognosis of the case, complete articular cartilage healing was considerably accelerated, and the functional outcome was excellent, allowing
a rapid resumption of symptom-free athletic activity. This technique opens new perspectives for human tissue regeneration. Key Words:
PRGF, KNEE ARTHROSCOPY, TISSUE REGENERATION, FUNCTIONAL RECOVERY

A
vulsions of articular cartilage are not uncommon inflammatory cells. These factors stimulate cell prolifera-
among athletically active children and adolescents. tion, migration, differentiation, and matrix synthesis and can
As in cases of osteochondritis dissecans, the medial affect chondrocyte metabolism, chondrogenesis, and im-
femoral condyle of the knee joint is the most commonly prove cartilage healing in vivo (7,9,10,14,17,18,26).
affected area, and although the etiology of this condition Growth factors could therefore be considered suitable
remains speculative, repetitive microtrauma is considered to tools to enhance cartilage repair. However, the most appro-
be associated with it (1,12,22,25). Patients with open distal priate way to use these growth factors is not known. Our
femoral physis usually have a more favorable prognosis for work is based on the use of an autologous plasma rich in
healing with nonoperative treatment, but not all lesions in growth factors (PRGF) obtained from the patient’s own
the skeletally immature patient heal without operative in- blood by means of a simple procedure. Our hypothesis is
tervention, and surgical treatment is indicated for detached that the presence of PRGF in the surgical site accelerates the
lesions (2,8,12,20,27). Given its lack of blood supply, lym- regeneration of local tissues by a mechanism that repro-
phatic drainage, or neural elements, articular cartilage pos- duces the initial physiological steps of tissue repair: upon
sesses a limited capability to regenerate after significant activation, platelets aggregate producing a clot, and secrete
mechanical destruction of the cells and collagen scaffold a variety of cytokines, including adhesive proteins and
(6,7,18). Recent reports in animal models suggest that the growth factors such as platelet-derived growth factor
process of cartilage healing in vivo may be improved by (PDGF), transforming growth factor beta (TGF-␤), vascular
growth factors, which are small proteins synthesized both by endothelial growth factor (VEGF), basic fibroblast growth
local cells at the injury site and by infiltrated blood-borne factor (bFGF), insulin-like growth factor I (IGF-I), and
epidermal growth factor (EGF). These substances act on
local cells inducing specific responses.
Address for correspondence: Iñigo Mujika, Ph.D., Mediplan Sport S.L., Until now, autologous PRGF has been shown to enhance
Obdulio López de Uralde 4, bajo, 01008 Vitoria–Gasteiz, Basque Country, and accelerate soft tissue repair and bone regeneration in the
Spain; E-mail: [email protected]. preparation of future sites for dental implants (3,4), and to
Submitted for publication December 2002. enhance postsurgery healing and remodeling of anterior
Accepted for publication June 2003.
cruciate ligament grafts (23) and ruptured Achilles tendons
0195-9131/03/3510-1648 in professional athletes (unpublished observations). These
MEDICINE & SCIENCE IN SPORTS & EXERCISE® successful clinical results, along with the above-mentioned
Copyright © 2003 by the American College of Sports Medicine observations from animal models, provided a rationale for
DOI: 10.1249/01.MSS.0000089344.44434.50 the application of PRGF in a case of arthroscopically treated
1648
Platelet-Rich Plasma or Hyaluronate
in the Management of Osteochondral
Lesions of the Talus
Omer Mei-Dan,*y MD, Michael R. Carmont,z FRCS(Tr&Orth), Lior Laver,y MD,
Gideon Mann,y§ MD, Nicola Maffulli,|| MD, MS, PhD, FRCS(Orth), and Meir Nyska,y MD
Investigation performed at Department of Orthopedic Surgery,
Meir University Hospital, Kfar-Saba, Israel

Background: Nonoperative options for osteochondral lesions (OCLs) of the talar dome are limited, and currently, there is a lack of
scientific evidence to guide management.
Purpose: To evaluate the short-term efficacy and safety of platelet-rich plasma (PRP) compared with hyaluronic acid (HA) in
reducing pain and disability caused by OCLs of the ankle.
Study Design: Randomized controlled trial; Level of evidence, 2.
Methods: Thirty-two patients aged 18 to 60 years were allocated to a treatment by intra-articular injections of either HA (group 1)
or PRP (plasma rich in growth factors [PRGF] technique, group 2) for OCLs of the talus. Thirty OCLs, 15 per arm, received 3 con-
secutive intra-articular therapeutic injections and were followed for 28 weeks. The efficacy of the injections in reducing pain and
improving function was assessed at each visit using the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot
Scale (AHFS); a visual analog scale (VAS) for pain, stiffness, and function; and the subjective global function score.
Results: The majority of patients were men (n = 23; 79%). The AHFS score improved from 66 and 68 to 78 and 92 in groups 1 and 2,
respectively, from baseline to week 28 (P \ .0001), favoring PRP (P \ .05). Mean VAS scores (1 = asymptomatic, 10 = severe symp-
toms) 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 \ .0001), favoring PRP (P \ .05 for stiffness, P \ .01 for function, P . .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 \ .01 in favor of PRP).
Conclusion: Osteochondral lesions of the ankle treated with intra-articular injections of PRP and HA resulted in a decrease in pain
scores and an increase in function for at least 6 months, with minimal adverse events. Platelet-rich plasma treatment led to a sig-
nificantly better outcome than HA.
Keywords: osteochondritis dissecans; osteochondral lesion; ankle; platelet-rich plasma; PRP; hyaluronic acid

Osteochondral lesions (OCLs) of the talus are relatively patients; and occur most commonly in the young popula-
uncommon and involve injury to cartilage and subchondral tion.37,42 The cause of OCL of the talus may include
bone.41 Osteochondral lesions occur most frequently in the trauma, ischemia, abnormal ossification, or genetic predis-
knee, elbow, and ankle; are more likely to affect male position.12,41 Although trauma is probably the most likely
cause of OCL of the ankle, repetitive microtrauma may
also be a contributing factor.19 Sports-related injuries
*Address correspondence to Omer Mei-Dan, MD, Department of causing inversion, forced dorsiflexion, plantar flexion, or
Orthopedic Surgery, Meir University Hospital, 59 Tchernichovsky Street, lateral rotation of the tibia may lead to traumatic lesions.10
Kfar-Saba, Israel (e-mail: [email protected]).
y
Department of Orthopedic Surgery, Meir University Hospital, Kfar-
These lesions may either heal spontaneously or progress to
Saba, Israel. give chronic symptoms of deep joint pain, worse on weight-
z
Princess Royal Hospital, Telford, United Kingdom. bearing and exercise.42 Lesions may also develop subchon-
§
Ribstein Center for Sport Medicine Sciences and Research, Wingate dral cystic change or detach, forming intra-articular loose
Institute, Netanya, Israel.
|| bodies.41,42 Catching, stiffness, and joint swelling may
Queen Mary University of London, Centre for Sports and Exercise
Medicine, Barts and The London School of Medicine and Dentistry, also be reported. Because articular cartilage is aneural,
Mile End Hospital, London, United Kingdom. the pain is thought to arise from the subchondral bone
The authors declared that they have no conflicts of interest in the beneath the OCL defect and may be caused by high fluid
authorship and publication of this contribution. pressure during weightbearing.41
The prognosis for OCL of the talus varies according to
The American Journal of Sports Medicine, Vol. 40, No. 3
DOI: 10.1177/0363546511431238 a patient’s age at the time of lesion development. Lesions
Ó 2012 The Author(s) identified during childhood and adolescence tend to heal

534
 Knee Surg Sports Traumatol Arthrosc (2012) 20:393–398
DOI 10.1007/s00167-011-1587-9

HIP

Arthroscopic management and platelet-rich plasma therapy

for avascular necrosis of the hip
Jorge Guadilla • Nicolas Fiz • Isabel Andia •

Mikel Sánchez

Received: 24 February 2011 / Accepted: 14 June 2011 / Published online: 22 June 2011
! Springer-Verlag 2011

Abstract Introduction
Purpose The purpose is to describe a noninvasive
For internal use company and distributors

arthroscopic procedure as an alternative to open surgery for During the last decade, the management of hip pathologies
avascular necrosis of the hip. has progressed toward earlier and less invasive approaches
Methods Patients with grade I or IIA avascular necrosis due to outstanding advances in both diagnostic magnetic
of the hip are treated by core decompression performed by resonance imaging (MRI) and arthroscopy. Likewise,
drilling under fluoroscopic guidance. Liquid platelet-rich improved understanding of healing mechanisms and
plasma (PRP) is delivered through a trocar, saturating the platelet-rich plasma (PRP) therapies has provided oppor-
necrotic area. In more severe conditions, the necrotic bone tunities for combining mechanical and biological concepts
is decompressed and debrided, through a cortical window to treat compromised clinical conditions such as avascular
at the head–neck junction. A composite graft made of necrosis (AVN) of the femoral head. Because AVN typi-
autologous bone and PRP is delivered by impactation cally presents in young patients and most often progresses
through the core decompression track. Fibrin membranes to collapse [8] and arthritic changes, any intervention for
are applied to enhance healing of the head–neck window joint preservation should be considered in order to avoid
and arthroscopic portals. Platelet-rich plasma is infiltrated hip replacement.
in the central compartment. Avascular necrosis is not a specific disease; rather, it is
Results This arthroscopic approach aids in making diag- the final common pathway of various pathological pro-
nosis of the labrum and articular cartilage and permits cesses. The treatment is independent of causative factors—
intra-operative treatment decisions. Visual control permits idiopathic conditions, high stress trauma, high-dose corti-
the precise localization and treatment for the necrotic area costeroid administration, or alcohol abuse—that activate
allowing cartilage integrity to be preserved. the biological process. However, the choice of treatment is
Conclusions Arthroscopic management of avascular dictated by the stage of the disease and the size of the
necrosis of the femoral head is viable and has significant lesion, which are stratified by various classification systems
advantages. Clinical studies should justify the theoretical based on MRI and radiography [15]. Although commonly
additional benefits of this approach. treated with open hip surgery, in view of the morbidity and
risks associated with such surgery, referral to less invasive
Keywords Avascular necrosis ! Hip ! Arthroscopy ! arthroscopic procedures enhanced with PRP therapies
Core decompression ! Bone graft ! Platelet-rich plasma might be an effective approach to slow and possibly
reverse the effects of AVN.
An arthroscopic approach, for early intervention of
AVN at Pennsylvania stages I-IIA-C, is described [21].
J. Guadilla ! N. Fiz ! I. Andia (&) ! M. Sánchez Diagnosis and treatment for necrosis and associated
Unidad de Cirugı́a Artroscópica, UCA
pathologies are performed by arthroscopic access to both
‘‘Mikel Sánchez’’, Clı́nica USP-La Esperanza,
c/La Esperanza 3, 01002 Vitoria-Gasteiz, Spain the central compartment and necrotic area using approa-
e-mail: [email protected] ches consistent with current practice [14]. Additionally, the

123
Technical Note

Intraosseous Infiltration of Platelet-Rich Plasma for

Severe Hip Osteoarthritis
Nicolás Fiz, M.D., Juan Carlos Pérez, M.D., Jorge Guadilla, M.D., Ane Garate, Ph.D.,
Pello Sánchez, M.Sc., Sabino Padilla, M.D., Ph.D., Diego Delgado, Ph.D., and
Mikel Sánchez, M.D.

Abstract: This work describes a technique of platelet-rich plasma (PRP) infiltration for the treatment of severe hip
osteoarthritis (OA). Although the results achieved with intra-articular infiltrations of PRP are promising, they may be
insufficient in the long-term for severe hip OA. The technique consists of a combined intra-articular and intraosseous
infiltration of PRP to reach all joint tissues, especially the subchondral bone, and hence facilitate a greater distribution of
PRP. Diagnosis is based on clinical and radiographic findings, and patients with grade III OA according to the Tönnis scale,
as well as patients who have not responded to conventional treatment, are considered candidates for this technique. After
an ultrasound-guided intra-articular PRP infiltration is performed, 2 intraosseous infiltrations are conducted with a
fluoroscope; the first injection is applied into the acetabulum and the second into the femoral head. However, this
technique presents more difficulty than the conventional administration, so it is necessary to consider several aspects
described in this work.

A fter osteoarthritis (OA) of the knee, the hip ranks

as the second most affected joint, with a high
prevalence in patients older than 50 years. Although
In an attempt to improve present-day treatments,
techniques based on regenerative medicine have been
introduced using intra-articular infiltrations of platelet-
OA is not a life-threatening condition, the severity of rich plasma (PRP).3-5 This biological therapy uses the
this disease lies in the continuous pain and functional patient’s own blood to obtain a product in which
impairment that patients undergo, undermining their platelets are found at higher concentrations than in
quality of life. Formerly, the basic theory to understand blood and mainly convey fibrin and growth factors as
and deal with this disease was cartilage loss. Including effectors. PRP-based therapies have broken into the
oral drug treatment and intra-articular injections of clinical practice of many medical specialties, especially
hyaluronic acid and steroids, the conservative treat- the field of orthopaedics and sports medicine; proof of
ments used to date have merely relieved the symptoms this are the increasing studies for pathologies such as
but do not stop or slow the natural course of the dis- OA, tendinopathy, or ligamentous injuries.6 In the case
ease. As a result, total hip replacement is often the only of PRP use in OA, growth factors have inductive and
solution for patients with hip OA.1,2 protective effects on chondrocyte and anti-
inflammatory action, restoring joint homeostasis.7
Although the results achieved thus far are promising
and many patients will undoubtedly benefit from these
cutting-edge interventions, treatments are still focused
From the Arthroscopic Surgery Unit (N.F., J.C.P., J.G., M.S.) and on cartilage as the main therapeutic target and they
Advanced Biological Therapy Unit (A.G., P.S., D.D., M.S.), Hospital Vithas may be insufficient in the long-term for severe hip OA.
San Jose; and Biotechnology Institute (S.P.), Vitoria-Gasteiz, Spain.
Currently, cartilage loss is not considered the key
The authors report the following potential conflict of interest or source of
funding: S.P. receives support from Biotechnology Institute (BTI). pathologic process that triggers OA. Rather, the initiating
Received October 9, 2016; accepted February 15, 2017. factor seems to be the result of a malfunction present in
Address correspondence to Diego Delgado, Ph.D., Advanced Biological the whole joint, including all tissues crucial for main-
Therapy Unit, Hospital Vithas San Jose, Vitoria-Gasteiz, C/Beato Tomás de taining articular homeostasis. Subchondral bone is
Zumárraga 10, 01008 Vitoria-Gasteiz, Spain. E-mail: diego.delgado@
identified as the starting place for pathologic changes,
ucatrauma.com
Ó 2017 by the Arthroscopy Association of North America and cartilage is the victim of this process. Lesions in this
2212-6287/16970/$36.00 tissue lead inevitably to the onset of OA if they are not
http://dx.doi.org/10.1016/j.eats.2017.02.014 properly treated.7 By means of the technique described

Arthroscopy Techniques, Vol -, No - (Month), 2017: pp e1-e5 e1

[PDF Purchased from http://www.jcvjs.com on Monday, November 28, 2016]abce

Original Article

Intradiscal and intra‑articular facet iniltrations with plasma

rich in growth factors reduce pain in patients with chronic
low back pain
ABSTRACT
Context: Low back pain (LBP) is a complex and disabling condition, and its treatment becomes a challenge.
Aims: The aim of our study was to assess the clinical outcome of plasma rich in growth factors (PRGF‑Endoret) iniltrations (one
intradiscal, one intra‑articular facet, and one transforaminal epidural injection) under luoroscopic guidance‑control in patients
with chronic LBP. PRGF‑Endoret which has been shown to be an eficient treatment to reduce joint pain.
Settings and Design: The study was designed as an observational retrospective pilot study. Eighty-six patients with a
history of chronic LBP and degenerative disease of the lumbar spine who met inclusion and exclusion criteria were recruited
between December 2010 and January 2012.
Subjects and Methods: One intradiscal, one intra-articular facet, and one transforaminal epidural injection of PRGF-Endoret
under luoroscopic guidance‑control were carried out in 86 patients with chronic LBP in the operating theater setting.
Statistical Analysis Used: Descriptive statistics were performed using absolute and relative frequency distributions for
qualitative variables and mean values and standard deviations for quantitative variables. The nonparametric Friedman
statistical test was used to determine the possible differences between baseline and different follow-up time points on pain
reduction after treatment.
Results: Pain assessment was determined using a visual analog scale (VAS) at the irst visit before (baseline) and after the
procedure at 1, 3, and 6 months. The pain reduction after the PRGF‑Endoret injections showed a statistically signiicant drop
from 8.4 ± 1.1 before the treatment to 4 ± 2.6, 1.7 ± 2.3, and 0.8 ± 1.7 at 1, 3, and 6 months after the treatment, respectively,
with respect to all the time evaluations (P < 0.0001) except for the pain reduction between the 3rd and 6th month whose
signiication was lower (P < 0.05). The analysis of the VAS over time showed that at the end point of the study (6 months),
91% of patients showed an excellent score, 8.1% showed a moderate improvement, and 1.2% were in the ineficient score.
Conclusions: Fluoroscopy‑guided iniltrations of intervertebral discs and facet joints with PRGF in patients with chronic LBP
resulted in signiicant pain reduction assessed by VAS.

Key words: Chronic low back pain; ibrin matrix; plasma rich in growth factors; platelet‑rich plasma; visual analog scale.

Introduction F r a iK r ruiE ar iA a1u2

Barcelona Traumatology Institute, Mataró, Eduardo Anitua 1

Low back pain (LBP) is a complex, personal experience Foundation for Biomedical Research, 2BTI‑Biotechnology
encompassing multidimensional phenomena such as Institute, Vitoria, Spain
physiologic, sensory, affective, cognitive, behavioral, and
Addressiforicorrespondence: Dr. Eduardo Anitua,
sociocultural effects.[1] This endemic condition leads to Jose Maria Cagigal Kalea, 19, 01007 Vitoria‑Gasteiz, Álava, Spain.
disability with current estimates of 632 million people E‑mail: [email protected]
affected worldwide.[2] Although in most patients LBP is
This is an open access article distributed under the terms of the Creative Commons
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For reprints contact: repri ts@ edk ow. o

DOI:
How to cite this article: Kirchner F, Anitua E. Intradiscal and intra articular
10.4103/0974-8237.193260 facet iniltrations with plasma rich in growth factors reduce pain in patients
with chronic low back pain. J Craniovert Jun Spine 2016;7:250-6.

250 © 2016 Journal of Craniovertebral Junction and Spine | Published by Wolters Kluwer - Medknow
Knee Surg Sports Traumatol Arthrosc
DOI 10.1007/s00167-014-3119-x

ANKLE

Plasma rich in growth factors (PRGF) as a treatment for high

ankle sprain in elite athletes: a randomized control trial
Lior Laver • Michael R. Carmont • Mark O. McConkey •

Ezequiel Palmanovich • Eyal Yaacobi • Gideon Mann •

Meir Nyska • Eugene Kots • Omer Mei-Dan

Received: 16 September 2013 / Accepted: 3 June 2014

Ó Springer-Verlag Berlin Heidelberg 2014

Abstract external rotation, and larger neutral tibia–fibula distance on

Purpose Syndesmotic sprains are uncommon injuries that ultrasound. Early diagnosis and treatment lead to shorter
require prolonged recovery. The influence of ultrasound- RTP, with 40.8 (±8.9) and 59.6 (±12.0) days for the PRP
guided injections of platelet-rich plasma (PRP) into the and control groups, respectively (p = 0.006). Significantly
injured antero-inferior tibio-fibular ligaments (AITFL) in less residual pain upon return to activity was found in the
athletes on return to play (RTP) and dynamic stability was PRP group; five patients (62.5 %) in the control group
studied. returned to play with minor discomfort versus one patient
Methods Sixteen elite athletes with AITFL tears were in the treatment group (12.5 %). One patient in the control
randomized to a treatment group receiving injections of group had continuous pain and disability and subsequently
PRP or to a control group. All patients followed an iden- underwent syndesmosis reconstruction.
tical rehabilitation protocol and RTP criteria. Patients were Conclusions Athletes suffering from high ankle sprains
prospectively evaluated for clinical ability to return to full benefit from ultrasound-guided PRP injections with a
activity and residual pain. Dynamic ultrasound examina- shorter RTP, re-stabilization of the syndesmosis joint and
tions were performed at initial examination and at 6 weeks less long-term residual pain.
post-injury to demonstrate re-stabilization of the syndes- Level of evidence II.
mosis joint and correlation with subjective outcome.
Results All patients presented with a tear to the AITFL Keywords Syndesmosis
Injections
Platelet-rich
with dynamic syndesmosis instability in dorsiflexion– plasma
Ultrasound
Return to play

L. Laver (&)
E. Palmanovich
E. Yaacobi
G. Mann
G. Mann

M. Nyska Ribstein Center for Sport Medicine Sciences and Research,
Department of Orthopaedic Surgery, Sports Medicine Unit, Wingate Institute, Netanya, Israel
‘‘Meir’’ Medical Center, The Sackler School of Medicine
(Tel-Aviv University), Kfar-Saba, Israel E. Kots
e-mail: [email protected] Department of Radiology, Sports Medicine Unit, ‘‘Meir’’
Medical Center, Kfar-Saba, Israel
L. Laver
Division of Sports Medicine, Department of Orthopaedic O. Mei-Dan
Surgery, Duke University, Durham, NC, USA Department of Sports Medicine, University of Colorado
Hospitals, Boulder, CO, USA
M. R. Carmont
Department of Trauma and Orthopaedic Surgery, Princess Royal
Hospital, Telford, Shropshire, UK

M. O. McConkey
Pacific Orthopaedics and Sports Medicine, North Vancouver,
BC, Canada

123
 Online Submissions: http://www.wjgnet.com/esps/ World J Orthop 2014 July 18; 5(3): 373-378
Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx ISSN 2218-5836 (online)
doi:10.5312/wjo.v5.i3.373 © 2014 Baishideng Publishing Group Inc. All rights reserved.

RETROSPECTIVE STUDY

Partial anterior cruciate ligament tears treated with

intraligamentary plasma rich in growth factors

Roberto Seijas, Oscar Ares, Xavier Cuscó, Pedro Álvarez, Gilbert Steinbacher, Ramón Cugat

Roberto Seijas, Oscar Ares, Xavier Cuscó, Pedro Álvarez, level 9. The time between the injury and the time of
Ramón Cugat, Department of Orthopaedic Surgery, Fundación surgery was 5.78 wk (SD 1.57). In total, 81.75% (16/19)
García Cugat, Hospital Quirón Barcelona, 08023 Barcelona, returned to the same pre-injury level of sport activity
Spain (Tegner 9-10). 17 males and 2 females were treated.
Roberto Seijas, Oscar Ares, Anatomy Department, Universitat The rate of associated injury was 68.42% meniscal le-
Internacional de Catalunya, 08023 Barcelona, Spain
sions and 26.31% cartilage lesions. The KT-1000 values
Oscar Ares, Pedro Álvarez, Orthopedic and Trauma Surgery,
Universitat Internacional de Catalunya, 08023 Barcelona, Spain were normalized in all operated cases. One patient was
Pedro Álvarez, Gilbert Steinbacher, Ramón Cugat, Mutuali- not able to return to sport due to the extent of their
tat Catalana de Futbolistes of Spanish Soccer Federation, 08023 cartilage lesions. The 15 patients with Tegner activity
Barcelona, Spain level 9 returned to play at an average of 16.20 wk (SD
Author contributions: Cugat R designed research; Cugat R, 1.44) while the 3 patients with Tegner activity level 10
Cuscó X, Steinbacher G, Álvarez P, Ares O and Seijas R per- did so in 12.33 wk (SD 1.11).
formed research; Seijas R analyzed data; Ares O and Seijas R
wrote the paper. CONCLUSION: With one remaining intact bundle the
Correspondence to: Roberto Seijas, MD, PhD, Department of application of PRGF-Endoret in instability cases due to
Orthopaedic Surgery, Fundación García Cugat, Hospital Quirón
partial ACL tear showed high return to sport rates at
Barcelona, Plaza Alfonso Comín 5-7, 08023 Barcelona,
Spain. [email protected] pre- injury level in professional football players.
Telephone: +34-93-2172252 Fax: +34-93-2381634
Received: December 25, 2013 Revised: February 15, 2014 © 2014 Baishideng Publishing Group Inc. All rights reserved.
Accepted: April 16, 2014
Published online: July 18, 2014 Key words: Anterior cruciate ligament; Plasma rich in
growth factors; Platelet-rich plasma; Partial tears ante-
rior cruciate ligament; Platelet-rich plasma

Abstract Core tip: The treatment with plasma rich in growth

factors during an arthroscopy in cases of partial tears
AIM: To evaluate the effect of the application of plasma rich of ACL in soccer players could provide a restoration of
in growth factors (PRGF)-Endoret to the remaining intact function of the knee and return to play rates to pre in-
bundle in partial anterior cruciate ligament (ACL) tears. jury levels in less than 4 mo.

METHODS: A retrospective review of the rate of return

to play in football players treated with the application of Seijas R, Ares O, Cuscó X, Álvarez P, Steinbacher G, Cugat R.
PRGF-Endoret in the remaining intact bundle in partial Partial anterior cruciate ligament tears treated with intraligamentary
ACL injuries that underwent surgery for knee instability. plasma rich in growth factors. World J Orthop 2014; 5(3): 373-378
Patients with knee instability requiring revision surgery Available from: URL: http://www.wjgnet.com/2218-5836/full/v5/
for remnant ACL were selected. PRGF was applied in i3/373.htm DOI: http://dx.doi.org/10.5312/wjo.v5.i3.373
the wider part of posterolateral bundle and the time it
took patients to return to their full sporting activities at
the same level before the injury was evaluated.

RESULTS: A total of 19 patients were reviewed. Three INTRODUCTION

had a Tegner activity level of 10 and the remaining 16 Anterior cruciate ligament (ACL) tears are common in

WJO|www.wjgnet.com 373 July 18, 2014|Volume 5|Issue 3|

Arch Orthop Trauma Surg (2016) 136:829–835
DOI 10.1007/s00402-016-2458-0

ARTHROSCOPY AND SPORTS MEDICINE

Pain in donor site after BTB-ACL reconstruction with PRGF:

a randomized trial
Roberto Seijas1 • Xavier Cuscó1 • Andrea Sallent2 • Iván Serra3 • Oscar Ares1,4 •

Ramón Cugat1

Received: 3 October 2015 / Published online: 4 May 2016

Ó Springer-Verlag Berlin Heidelberg 2016

Abstract Introduction
Introduction Anterior cruciate ligament (ACL) tears are
highly incident injuries in young athletes within our work Knee injuries define a significant group of sports patholo-
area. The use of the patellar graft, despite being the treat- gies and include one of the most severe injuries for ath-
ment of choice, presents post-operative problems such as letes, the anterior cruciate ligament (ACL), which accounts
anterior knee pain, which limits its use and leads to pref- for 50 % of these injuries [1]. In the United States alone, it
erence being taken for alternative grafts. Our aim was to is estimated that 50,000 patients undergo surgery every
evaluate if the application of PRGF reduces anterior knee year due to this lesion [2].
pain in donor site in BTB-ACL reconstruction. ACL rupture renders the athlete absolutely incapable of
Materials and Methods 43 patients were included in the playing soccer due to the knee instability that this rupture
double-blinded and randomized clinical trial comparing entails. Thus, soccer players who suffer from ACL injuries
two patient groups who underwent ACL reconstruction frequently undergo surgery to advance their return to play [2].
using patellar tendon graft, comparing anterior knee pain The bone-patellar tendon-bone ligament (patellar graft)
with and without the application of PRGF at the donor site is a widely used autograft for this type of surgery [1].
after harvesting the graft. Results: The PRGF group Donor site complications include anterior knee pain,
showed decreased donor site pain in comparison to the ranging from 4 to 60 % [3]. The central third of the patellar
control group, with significant differences in the first two ligament, with tibial and patellar bone blocks, is used as an
months of follow-up. ACL, also called ‘‘patellar graft’’ or ‘‘bone -tendon-bone’’
Conclusion The application of PRGF decreased donor site (BTB). Anterior knee pain within BTB-ACL reconstruc-
pain compared to the control group. tion could be improved by adhering to contemporary
recovery precepts, thereby reducing post-operative anterior
Keywords BTB-ACL reconstruction
Anterior knee pain
knee pain at the harvest site. There is an existent rela-
Plasma rich in growth factors
Patellar graft tionship between donor site defect healing time and ante-
rior knee pain, leading to a rise in the use of alternatives
due to donor site pain after patellar tendon graft harvest [4].
The empty space or gap left in place after graft harvest
& Roberto Seijas
[email protected]
has been defined as the cause of persistent discomfort and
pain at the donor site for several months, even at rest [4].
1
Orthopaedic Surgery, Artroscopia G.C., Fundación Garcı́a- However, the usefulness of BTB graft for ACL injuries has
Cugat, Hospital Quirón Barcelona, Universitat Internacional previously been studied [5].
de Catalunya Pza, Alfonso Comı́n 5-7, 08023 Barcelona,
Spain
Autologous plasma rich in growth factors (PRGFÒ)
2
allows for a new possibility in the preventive treatment of
Hospital Vall d’Hebrón, Barcelona, Spain
these complications. PRGF are biologically enhanced
3
Veterinarian Surgery University of Valencia, Valencia, Spain peptides, which have been shown to accelerate tissue repair
4
Hospital Clı́nic Barcelona, Barcelona, Spain [6–8]. Several studies have observed accelerated

123
Journal of Orthopaedic Surgery 2013;21(1):10-4

Magnetic resonance imaging evaluation

of patellar tendon graft remodelling after
anterior cruciate ligament reconstruction with
or without platelet-rich plasma
Roberto Seijas, Oscar Ares, Jordi Catala, Pedro Alvarez-Diaz, Xavier Cusco, Ramon Cugat
Instituto de Ortopedia y Traumatologia, Fundacion García Cugat Hospital Quiron Barcelona, Spain

12 (p=0.354).
conclusion. PRP enabled faster remodelling of
ABSTRACT patellar tendon grafts.

purpose. To evaluate the stages of patellar tendon Key words: anterior cruciate ligament reconstruction;
graft remodelling using magnetic resonance imaging patellar ligament; platelet-rich plasma; transplantation,
(MRI) after anterior cruciate ligament (ACL) autologous
reconstruction with or without platelet-rich plasma
(PRP) injection.
Methods. 98 patients aged 18 to 65 years with introduction
complete rupture of the ACL were randomised to
undergo reconstruction with the autologous patellar Anterior cruciate ligament (ACL) tears are usually
tendon grafts with or without PRP injection. For treated surgically if the rupture is complete or
the PRP group, 8 ml of PRP was obtained in the causes knee instability. The use of an autologous
surgery room and was percutaneously injected into patellar tendon graft is a controversial but recognised
the suprapatellar joint after portal suture. MRI was treatment for athletes.1 Platelet-rich plasma (PRP)
obtained at months 4, 6, and 12. Remodelling stages or plasma rich in growth factors (PRGF) has been
of the grafts were classiied as hypointense, mildly approved in the US and European Community
hyperintense, moderately hyperintense, severely for promotion of tissue regeneration in bone,
hyperintense, and diffusely hyperintense by a cartilage, ligaments, and tendons in vitro, in vivo,
radiologist blinded to treatment allocation. and in humans.2–8 The remodelling process of the
results. More patients in the PRP group than graft takes about one year and correlates with its
controls attained higher stages of remodelling at homogeneity on magnetic resonance imaging (MRI)
month 4 (p=0.003), month 6 (p=0.0001), and month and its tension.9 Remodelling stages can be classiied

Address correspondence and reprint requests to: Roberto Seijas, Orthopedic Surgery, Fundación García Cugat Hospital Quiron
Barcelona, Pza Alfonso Comín 5-7 Planta-1, Hospital Quiron, 08023, Barcelona, Spain. Email: [email protected]
 Aplicación฀de฀plasma฀autólogo฀
rico฀en฀factores฀de฀crecimiento฀
en฀cirugía฀artroscópica
M.฀Sánchez(1),฀J.฀Azofra(1),฀B.฀Aizpurúa(1),฀
R.฀Elorriaga(1),฀E.฀Anitua(2),฀I.฀Andía(3)
(1)Unidad฀de฀Cirugía฀Artroscópica.฀
Clínica฀USP฀La฀Esperanza.฀Vitoria-Gasteiz.
(2)Biotechnology฀Institute฀(BTI).฀Vitoria-Gasteiz.
(3)Dpto.฀Investigación฀Neuroquímica.฀Osakidetza-Servicio฀Vasco฀de฀Salud.

Correspondencia:฀
D.฀Juan฀Azofra
For internal use company and distributors

Unidad฀de฀Cirugía฀Artroscópica
Clínica฀USP฀La฀Esperanza
01002฀Vitoria-Gasteiz
e-mail:฀juan.azofra@cle,uspeurope.com

La฀utilización฀de฀plasma฀autólogo฀rico฀en฀factores฀ Use฀of฀autologous฀plasma฀rich฀in฀growth฀fac-
de฀crecimiento฀(PRGF),฀tiene฀como฀objetivo฀me- tors฀ in฀ arthroscopic฀ surgery.฀ The฀ application฀
jorar฀la฀evolución฀quirúrgica,฀reforzando฀y฀poten- of฀ an฀ autologous฀ plasma฀ rich฀ in฀ growth฀ factors฀
ciando฀el฀proceso฀de฀reparación฀fisiológica,฀ade- (PRGF),฀ is฀ beneficial฀ in฀ restoring฀ connective฀
más฀de฀permitir฀una฀regeneración฀más฀rápida฀y฀de฀ tissues฀through฀the฀enhancement฀and฀accelera-
mayor฀calidad฀en฀los฀tejidos฀conjuntivos฀dañados.฀ tion฀of฀the฀healing฀process.฀This฀is฀achieved฀by฀
Se฀ describe฀ el฀ método฀ de฀ aplicación฀ de฀ PRGF฀ creating฀conditions฀that฀allowed฀natural฀healing฀
en฀ la฀ cirugía฀ artroscópica฀ de฀ las฀ plastias฀ del฀ to฀proceed.฀The฀procedure฀for฀the฀application฀of฀
ligamento฀cruzado฀ anterior.฀ Se฀compara฀ la฀evo- PRGF฀during฀the฀reconstruction฀of฀the฀anterior฀
lución฀clínica฀en฀50฀plastias฀realizadas฀sin฀PRGF฀ cruciate฀ ligament฀ (ACL)฀ is฀ described.฀ Clinical฀
y฀50฀plastias฀aplicando฀PRGF.฀Cuando฀se฀utiliza฀ outcome฀following฀ACL฀reconstruction,฀with฀and฀
PRGF,฀asociado฀a฀la฀cirugía,฀฀las฀complicaciones฀ without฀ PRGF,฀ was฀ evaluated.฀ Postoperative฀
postoperatorias฀ y฀ los฀ signos฀ inflamatorios฀ son฀ complications฀ and฀ inflammation฀ are฀ reduced;฀
menores,฀se฀acelera฀la฀cicatrización฀de฀las฀heri- healing฀and฀remodeling฀rates฀of฀the฀autologous฀
das฀y฀la฀integración฀de฀la฀plastia.฀La฀utilización฀de฀ tendon฀graft฀are฀improved฀with฀the฀use฀of฀PRGF.฀
PRGF฀no฀implica฀ningún฀riesgo฀ni฀complicación฀ It฀has฀not฀got฀risks฀and฀the฀benefits฀for฀the฀pa-
para฀el฀paciente,฀y฀los฀beneficios฀de฀su฀aplicación฀ tient฀are฀enormous.
son฀considerables.

Palabras฀ clave:฀ Artroscopia฀ de฀ rodilla,฀ recons- Key฀words:฀Knee฀arthroscopy,฀ACL฀reconstruc-

trucción฀del฀ligamento฀cruzado฀anterior,฀factores฀ tion,฀growth฀factors.
de฀crecimiento.

567

E
12
n฀ la฀ actualidad,฀ los฀ avances฀ en฀
las฀diferentes฀especialidades฀de฀la฀
medicina฀se฀deben฀al฀esfuerzo฀y฀a฀
la฀participación฀de฀distintas฀ramas฀de฀la฀ciencia:฀
bioingeniería,฀ informática,฀ química,฀ biología฀ y฀
medicina.฀ De฀ esta฀ colaboración฀ entre฀ discipli-

Cuadernos฀de฀Artroscopia,฀Vol.฀10,฀fasc.฀1,฀nº฀19.฀Abril฀2003,฀págs.฀12-19
 International Journal of Orthopaedics

Online Submissions: http://www.ghrnet.org/index./ijo/ Int Journal of Orthopaedics 2015 February 23 2(1): 196-201
doi:10.6051/j.issn.2311-5106.2015.02.45-4 ISSN 2311-5106 (Print), ISSN 2313-1462 (Online)

TOPIC HIGHLIGHT

Role of Growth Factors in Bone-Tendon-Bone ACL Surgery:

Time for Maturation of the ACL Graft and the Patellar
Tendon Donor Site

Roberto Seijas, MD, PhD, Oscar Ares, MD, PhD, Jordi Català, Xavier Cuscó, MD, Pedro Álvarez, MD, Montserrat
García-Balletbó, Ramón Cugat, MD, PhD

Roberto Seijas, Oscar Ares, Xavier Cuscó, Pedro Álvarez, of maturation at several time schedules. Another group of patients
Ramón Cugat, Department of Orthopaedic Surgery, Fundación (40) were divided into with the same characteristics but assessing the
García Cugat, Quirón Hospital, Barcelona, Spain donor site with ultrasounds.
Roberto Seijas, Oscar Ares, Professor in Anatomy Department. RESULTS: In the irst group study, The MRI showed statistically
Internacional University of Catalunya, Barcelona, Spain different maturation grade at 4 months and at 6 months. Once they
Oscar Ares, Pedro Álvarez, Profesor in Orthopaedic and Trauma reached the year no signiicant differences (p=0.354) between both
Surgery. Internacional University of Catalunya, Barcelona, Spain groups were observed. The second study groups were composed
Montserrat García-Balletbó, Department of Regenerative Mede- of 23 and 19 patients, who underwent ACL surgery with and
cine, Fundación García Cugat. Quirón Hospital, Barcelona, Spain without PRGF-Endoret® at the donor site. The PRGF group showed
Pedro Álvarez, Ramón Cugat, Catalan Soccer Delegation’s signiicantly increased maturation speed at 4th postoperative month.
Health Insurance Company, Spanish Soccer Federation, Barce- DISCUSSION: The results show that the use of PRGF-Endoret®
lona, Spain significantly accelerates the processes of maturation of both
Jordi Català, Medical Director Alomar Centers, Barcelone, Spain anatomical regions.
Correspondence to: Roberto Seijas, MD, PhD, Department of
Orthopaedic Surgery, Fundación García Cugat, Quirón Hospital, © 2015 ACT. All rights reserved.
Barcelona, Internacional University of Catalunya, Plaza Alfonso
Comín 5-7, 08023 Barcelona, Spain Key words: ACL; Knee; Platelet-rich plasma; PRGF
Email: [email protected]
Telephone: +34932172252 Fax: +34932381634 Seijas R, Ares O, Cuscó X, Álvarez P, García-Balletbó M, Cugat R.
Received: September 13, 2014 Revised: October 11, 2014 Role of Growth Factors in Bone-Tendon-Bone ACL Surgery: Time
Accepted: October 15, 2014 for Maturation of the ACL Graft and the Patellar Tendon Donor Site.
Published online: February 23, 2015 International Journal of Orthopaedics 2015; 2(1): 196-201 Available
from: URL: http://www.ghrnet.org/index.php/ijo/article/view/1050

ABSTRACT
INTRODUCTION
AIM: Anterior Cruciate Ligament surgery can be complemented
with biological treatments, including plasma rich in growth factors, Knee injury is common in sports. Anterior Cruciate Ligament (ACL)
which have been demonstrated by numerous authors to accelerate the injury is one of the most frequent, reaching 70% and typically
process of tendon maturation. Studies both in vitro and in animals, with an indirect injury mechanism of deceleration-rotation without
including human studies have shown improved results in ligament contact[1]. In the United States, 50,000 patients require ACL surgery
strength and structure, as well as earlier ACL graft maturation. We annually[2-4].
present the results of two studies on maturation with the use of The majority of these injuries are sports related and affect patients
PRGF-Endoret®. ACL graft and donor site. between 15 and 45 years old with 47% taking place during the
METHODS: 100 soccer players were randomly divided into two decade from 30 to 40 years old[1]. It is estimated that one ACL tear
groups, group A received a dose of PRGF-Endoret while the other occurs every 1,500 hours of sports practice, including sports such as
one was used as a control. MRI was performed to assess the grade soccer, basketball, rugby and skiing, which is equivalent to one injury

© 2015 ACT. All rights reserved. 196

 Platelet-Rich Plasma in Muscle and Tendon Healing
Mikel Sánchez, MD,* Javier Albillos, MD,† Francisco Angulo, MD,‡
Juanma Santisteban, MD,‡ and Isabel Andia, PhD§

Platelet-rich plasma (PRP) products represent advanced regenerative therapies for acute
and chronic muscle and for tendon injuries because they can exploit the regenerative
capabilities of the musculoskeletal system. PRP injections are used in clinical practice, but
there is a need to evaluate the claims made about PRP therapies. Herein, we review current
published clinical studies and focus on PRP formulations and application procedures. This
article also describes the authors’ clinical experience with PRP therapy in muscle and
tendon conditions during the past decade. Treatment effects and the primary conclusions
of clinical studies may be affected by procedures of PRP administration, and estimates of
PRP treatment effect may deviate from its true value. To better define the conditions of
clinical trials, we need to know more about the differences not only between PRP formu-
For internal use company and distributors

lations but also among technical procedures in surgery and injection protocols, including
applied volumes, target areas to treat, treatment schedules, and patient selection criteria.
Oper Tech Orthop 22:16-24 © 2012 Elsevier Inc. All rights reserved.

KEYWORDS healing, injuries, muscle, platelet-rich plasma, tendinopathy, tendon

S oft-tissue disorders, including muscle, tendon, ligament,

and joint capsular injuries, represent more than 50% of
all the musculoskeletal injuries reported each year in the
cated since 2003,3 and is a promising, innovative technology
that can address diverse musculoskeletal conditions. The
straightforward preparation protocols (minimally manipu-
United States.1 Primary care studies have shown that 16% of lated blood products) and the biosafety and versatility of PRP
the general population suffers from shoulder pain, and elbow preparations have stimulated translational research and in-
tendinopathy affects 1%-2% of the population. In 2002, an terest among both the scientific and medical communities,
estimated US $15.8 billion in total health care expenditures and have widened PRP applications to several musculoskel-
was used for the medical management of these injuries.2 The etal problems.4 Several disciplines, including surgery, regen-
importance of this problem is substantial and represents a erative biology, and medicine, have converged toward the
significant burden to society in terms of health care re- development of various PRP products suitable for harnessing
sources, personal disability, and activity restriction. the known regenerative capabilities of the musculoskeletal
Platelet-rich plasma (PRP) technology represents an ad- system. However, despite intensive research, there is a gap in
vanced regenerative therapy for acute and chronic injuries, the basic knowledge necessary5 to ascertain the best PRP
and it is commonly used for the repair, reconstruction, or product for each clinical problem, as well as the guidelines
supplementation of a recipient’s tissues. The management of for clinical applications.
musculoskeletal injuries with PRP therapies has been advo- These regenerative medical products pose novel chal-
lenges that may have significant bearing on the different PRP
formulations and how application procedures are developed.
*Unidad de Terapia Biológica, UTB and Unidad de Cirugía Artroscópica, There is preliminary evidence to suggest a link between PRP
UCA Clínica USP-La, Esperanza, c/o La Esperanza 3, 01002 Vitoria- formulation (number of platelets, balance between platelet-
Gasteiz, Spain.
†Unidad de Terapia Biológica, UTB, Policlínica Gipuzkoa, Paseo Miramón
secreted and plasma proteins, mechanism of plasma activa-
174, 20,014 Donostia-San Sebastián, Spain. tion) and/or application procedures (ie, number of doses,
‡Unidad de Terapia Biológica, UTB and Servicios Médicos Athletic Club de volume, activation, and injection procedures) and clinical
Bilbao, 48196 Lezama, Vizcaya, Spain. effect.6,7 Some relevant concepts are needed to understand
§Instituto de Investigación BIOCRUCES, Osakidetza, Basque Health Ser- why the formulations and procedures for PRP application
vice, Pza Cruces s/n, 48903 Barakaldo, Vizcaya, Spain.
Address reprint requests to Isabel Andia, PhD, Instituto de Investigación
should be carefully analyzed. First, these products combine
BIOCRUCES, Osakidetza, Basque Health Service, Pza Cruces s/n, 48903 at least 3 established product paradigms: pharmaceuticals
Barakaldo, Vizcaya, Spain. E-mail: [email protected] (biologically active substances), grafts (platelets and leuko-

16 1048-6666/12/$-see front matter © 2012 Elsevier Inc. All rights reserved.

doi:10.1053/j.oto.2011.11.003
 PRP in Lateral Elbow Pain
10
Jorge Guadilla, Emilio Lopez-Vidriero,
Rosa Lopez-Vidriero, Sabino Padilla,
Diego Delgado, Rafael Arriaza, and Mikel Sanchez

10.1 Introduction The most used term is “lateral epicondylitis”

and was previously considered to be a tendinitis,
The lateral elbow pain has been named differ- arising as inflammation of the tendon [5–7].
ently along the years. However, the current consensus is that
Lateral epicondylitis was first described in the microtrauma from excessive and repetitive use of
medical literature by Runge in 1873 [1]. the forearm extensors initiates a degenerative
The term “tennis elbow” appeared ten years process with a paucity of inflammatory cells.
later and remained since its initial description by Therefore, histologically it is said to be more a
Major who in 1883 described the “lawn tennis tendinosis (epicondylosis) than a tendinitis [8–10].
arm” [2]. However, there is a last years’ trend that estab-
Nevertheless, it is known that less than 10 % lishes that inflammation plays a role in general
of patients consulting for this condition are actu- tendinopathy more than suspected. Thus, degen-
ally tennis or racquet sport players [3]. eration (osis) and inflammation (itis) could both
Also called “lateral elbow pain” or “chronic be involved in the origin and progression of ten-
lateral elbow pain,” this term is wide enough to dinopathies triggered by stressful stimuli such as
include different clinical conditions. In the litera- mechanical stress present in the lateral epicondy-
ture other names as “lateral epicondylalgia,” litis [11, 12].
“shooter’s elbow,” or “archer’s elbow” can be The condition which is going to be described
found to describe conditions that have in com- along this chapter is an enthesopathy of the lat-
mon the lateral elbow pain [4]. eral epicondyle, and the most commonly affected
muscle is the extensor carpi radialis brevis
(ECRB) [13].
J. Guadilla • S. Padilla • D. Delgado • M. Sanchez In the remainder of this chapter, the term lat-
Unidad de Cirugia Artroscopica, VItoria, Spain eral epicondylitis (LE) is going to be used.
E. Lopez-Vidriero, MD, PhD (*)
Chief of Traumatology, Department at Ibermutuamur
Sevilla, ISMEC. International Sports Medicine Clinic,
Arjona 10. Bajo, Sevilla 41001, Spain
10.2 Incidence and Related Sports
e-mail: [email protected]
Tendon injuries, both acute and chronic (or tendi-
R. Lopez-Vidriero
ISMEC. International Sports Medicine Clinic, nopathy), affect the quality of life, increase the
Arjona 10. Bajo, Sevilla 41001, Spain costs of health care, and lead to stop sporting
R. Arriaza activities of a quite high amount of patients and
Arriaza Asociados, La Coruña, Spain sport professionals.

© ESSKA 2016 109

L.A. Pederzini et al. (eds.), Elbow and Sport, DOI 10.1007/978-3-662-48742-6_10
 Acta Ortopédica Mexicana 2014; 28(5): Sep.-Oct: 310-314

Caso clínico

Aplicación coadyuvante de plasma rico en factores de crecimiento en rotura

bilateral de tendón cuadricipital
Galán M,* Seijas R,* Ares O,* Cuscó X,* Rius M,* Cugat R*
Hospital Quirón Barcelona, Barcelona, España

RESUMEN. Antecedentes: Las roturas bilatera- ABSTRACT. Background: Bilateral quadriceps

les de tendones cuadricipitales son enfermedades tendon tears are infrequent conditions. Surgical
de muy baja frecuencia. Las reparaciones quirúr- repairs are the most appropriate treatments and
gicas suelen ser los tratamientos más adecuados y they involve several months of recovery. Meth-
exigen tiempos de recuperación de varios meses. ods: We report the case of a patient with bilateral
Métodos: Presentamos el caso de un paciente con quadriceps tendon tear resulting from low energy
rotura bilateral de tendones cuadricipitales tras trauma. He was treated with surgical transpatel-
un traumatismo de baja energía, que fue tratado lar suturing reinforced with plasma rich in growth
mediante sutura transpatelar quirúrgica refor- factors (PRGF-Endoret). Results: Short-term re-
zada con plasma rico en factores de crecimiento sults showed functional and radiological recovery
(PRGF-Endoret). Resultados: Los resultados a at the two-months follow-up. The use of PRGF to-
corto plazo evidenciaron una recuperación funcio- gether with usual surgery may contribute to early
nal y mediante imagen en poco más de dos meses. rehabilitation.
Conclusiones: La utilización de PRGF asociado a
la cirugía habitual puede ayudar a la realización
de una rehabilitación precoz.

Palabras clave: rodilla, traumatismo de tendo- Key words: knee, tendon injuries, growth fac-
nes, factores de crecimiento, plasma. tors, plasma.

Introducción peculiaridades del caso que presentamos son varias al tra-

tarse de un varón sin patología de base que, tras un trauma-
Las roturas unilaterales del tendón del cuádriceps son tismo de baja energía, sufre una rotura bilateral de ambos
lesiones comunes que están bien documentadas.1 Sin em- tendones cuadricipitales. Se realizó tratamiento quirúrgico
bargo, la rotura bilateral de ambos tendones cuadricipitales de las lesiones junto con inyección de plasma rico en fac-
es una lesión poco común. Generalmente, ésta ocurre por tores de crecimiento intraoperatoriamente, evidenciándose
una caída por las escaleras o se presenta de forma espontá- continuidad ecográfica completa de los tendones a los dos
nea.2 Steiner y Palmer3 describieron el primer caso de rotura meses y medio de la cirugía. Para esa fecha, el paciente
bilateral de tendón cuadricipital en 1949 y hasta 2009, hay ya se encontraba con una funcionalidad completa y había
recogidos sólo 70 casos en la literatura inglesa. retomado sus actividades de la vida diaria. El resultado tan
Históricamente este tipo de lesión se presentaba más satisfactorio y la pronta recuperación del paciente de las
comúnmente en hombres mayores de 50 años.4,5 Sin em- lesiones pueden haber sido favorecidos por el uso de la
www.medigraphic.org.mx
bargo, los últimos casos documentados se presentaban en
individuos más jóvenes con enfermedades crónicas.4,6 Las
terapia con factores de crecimiento derivados de plaquetas.
Por tanto, puede que las terapias biológicas en este tipo de

* Consultor Ortopédico, Fundación García Cugat.

Dirección para correspondencia:

María Galán Gómez-Obregón
Plaza Alfonso Comín 5-7 Planta-1,
Hospital Quirón, CP 08023, Barcelona, España.
E-mail: [email protected]

Este artículo puede ser consultado en versión completa en http://www.medigraphic.com/actaortopedica

310
Journal of Orthopaedic Surgery 2012;20(1):126-30

Platelet-rich plasma for calciic tendinitis of the

shoulder: a case report
Roberto Seijas, Oscar Ares, Pedro Alvarez, Xavier Cusco, Montserrat Garcia-Balletbo, Ramon Cugat
Fundacion Garcia Cugat, Hospital Quiron, Barcelona, Spain

calcium is deposited in the rotator cuff tendons,

especially the supraspinatus tendon, often causing
ABSTRACT acute pain. This cell-mediated process can be chronic
in nature, but is usually self-limiting. Tendinopathy
We report a 44-year-old woman with calciic tendinitis of the supraspinatus tendon usually develops in the
of the shoulder treated with platelet-rich plasma ‘critical area’ between 1.25 and 2.5 cm proximal to the
injection. Prior to this, she had no improvement insertion site,1,2 owing to vascularisation deicits when
of the symptoms after 6 weeks of ultrasound the arm is in abduction.2–6 The rotator cuff tendons,
treatment, Codman exercises, and anti-inlammatory particularly the deepest portion of the supraspinatus,
treatment. Platelet-rich plasma was injected into the undergo a transient irrigation deiciency,.
subacromial area 3 times at 2-week intervals. She Non-operative management remains the
had progressive improvement of pain after 2 weeks, treatment of choice, with a success rate of up to 90%.
and was asymptomatic at week 6. The patient then When conservative measures fail, needle puncture
underwent the previous protocol of rehabilitation. or surgical removal, mainly by arthroscopy, may be
At the one-year follow-up, the patient was pain-free indicated. Acromioplasty should not be performed
and had complete resolution of calciic tendinitis. The without radiographic signs of impingement. If a
patient had regained full range of movement and had large rotator cuff defect is found after removal of
resumed all her activities. the calciic deposit, the defect should be sutured to
prevent progression of the cuff tear and to promote
Key words: platelet-rich plasma; tendinopathy healing.
Treatments for calciic tendinitis entail
introduction physical therapy, kinesitherapy, application of
ultrasound, extracorporeal shock wave therapy, and
Calciic tendinitis of the shoulder occurs when corticosteroids injection. Platelet-rich plasma has

Address correspondence and reprint requests to: Dr Roberto Seijas, Fundacion García Cugat, Hospital Quiron, Plaza Alfons Comín
5-7 08023 Barcelona, Catalunya, Spain. E-mail: [email protected]
 Injury Extra 40 (2009) 11–15

Contents lists available at ScienceDirect

Injury Extra
journal homepage: www.elsevier.com/locate/inext

Case report

Management of post-surgical Achilles tendon complications with a preparation

rich in growth factors: A study of two-cases
Mikel Sánchez a, Eduardo Anitua b, Alejandro Cole c, Alejandra Da Silva c,
Juan Azofra a, Isabel Andia b,*
a
Unidad de Cirugı´a Artroscópica ‘‘Mikel Sánchez’’, Clı´nica USP-La Esperanza, Vitoria-Gasteiz, Spain
b
BTI Biotechnology Institute, c/Leonardo Da Vinci 14, Vitoria-Gasteiz, Spain
c
Private Practice, c/Montevideo 1178-1‘‘A’’ CP1019, Buenos Aires, Argentina
For internal use company and distributors

A R T I C L E I N F O

Article history:
Accepted 26 September 2008

1. Introduction management of acute Achilles tendon rupture. To our knowledge,

this is the first article reporting the use of platelet-rich prepara-
The incidence of Achilles tendon ruptures is rising among active tions in severe complications after primary Achilles repair. The
individuals regardless of age. Although operative reconstruction is biosafety, versatility and ease of preparation of platelet-based
a standard approach to rupture care, it is accompanied by a non- formulations in combination with our promising clinical results
trivial risk of complications.11 Overall, open repair is specially moved us to share our experience in hopes of inspiring awareness
indicated for active people since it re-establishes fiber continuity, and further investigation of this novel therapeutic option.
reducing re-rupture risk and improving long-term functional
outcome.16 When post-surgical complications arise, their manage- 2. Patients and methods
ment is demanding, particularly in extensively diseased tendons.
Although relatively infrequent, deep infection along with tendon 2.1. Case presentation
necrosis can be a devastating complication requiring repeated
surgery. Determining optimal treatment for this entity is a 2.1.1. Case #1
significant challenge to the orthopaedic surgeon.14,17 A 52-year-old male recreational athlete with a history of
The emergence of platelet-rich technologies has created new Achilles tendinopathy and acute Achilles rupture at the calcaneous
therapeutic opportunities by combining an understanding of the insertion was referred to our institution post-surgical therapy. He
biology of tendon injury and repair with surgical principles.6,22 Our reported difficulty walking, impairment of ankle plantar flexion
group is investigating the use of the versatile autologous and sharp pain at the posterior aspect of his left ankle to superficial
preparation termed preparation rich in growth factors (PRGF) in calcaneus palpation. Clinical evaluation disclosed a wound fistula
different medical conditions.3,21 PRGF has been shown to enhance in the distal region of the surgical scar, and a defect was palpated
and accelerate soft tissue repair in cutaneous ulcers,6 to improve around the prominent superior tuberosity of the calcaneous.
bone repair in oral implantology7 and non-unions in orthopae- Complementary axial computerised tomography, magnetic reso-
dics,23 to ameliorate intra-articular conditions in select osteoar- nance imaging and histology confirmed active osteomyelitis,
thritis (OA) patients22 and to enhance soft tissue healing and interstitial tears and the presence of necrotic areas all along the
remodeling in anterior cruciate ligament (ACL) reconstructive entire length of the Achilles tendon (Fig. 1A). Microbial cultures
surgery as well as ruptured Achilles tendons in professional ascertained the presence of Klebsiella both in tendon and
athletes.20,23 calcaneus bone, prompting intravenous ciprofloxacin for 1 week
This report describes PRGF-assisted management of major and oral ciprofloxacin treatment for 2 more weeks.
complications in two recreational athletes after initial surgical
2.1.2. Case #2
A 62-year-old male mountain medicine physician and profes-
* Corresponding author. Tel.: +34 945 297030; fax: +34 945 297031. sional mountaineer with asymptomatic degenerative tendino-
E-mail address: [email protected] (I. Andia). pathy (Fig. 1B) who had been previously operated on at our

1572-3461/$ – see front matter ß 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.injury.2008.09.017
Comparison of Surgically Repaired
Achilles Tendon Tears Using Platelet-Rich
Fibrin Matrices
Mikel Sánchez,* MD, Eduardo Anitua,† MD, DDS, Juan Azofra,* MD, Isabel Andía,† PhD,
Sabino Padilla,‡ MD, PhD, and Iñigo Mujika,‡§ PhD
From the *Arthroscopic Surgery Unit, USP–La Esperanza Clinic, Vitoria-Gasteiz, Basque
†
Country, Spain, the BTI Biotechnology Institute, Vitoria-Gasteiz, Basque Country, Spain,
‡
and the Department of Research and Development, Medical Services, Athletic Club Bilbao,
Basque Country, Spain

Background: Platelet-rich fibrin matrices release a natural mixture of growth factors that play central roles in the complex
processes of tendon healing.
Hypothesis: Application of autologous platelet-rich matrices during Achilles tendon surgery may promote healing and functional
recovery.
Study Design: Case-control study and descriptive laboratory study; Level of evidence, 3.
Methods: Twelve athletes underwent open suture repair after complete Achilles tendon tear. Open suture repair in conjunction with
a preparation rich in growth factors (PRGF) was performed in 6 athletes and retrospectively compared with a matched group that
followed conventional surgical procedure. The outcomes were evaluated on the basis of range of motion, functional recovery, and
complications. Achilles tendons were examined by ultrasound at 50 ± 11 months in retrospective controls and 32 ± 10 months in
the PRGF group. In the laboratory portion of the study, PRGF treatment was characterized by the number of platelets and concen-
tration of insulin (IGF-I), transformed (TGF-β1), platelet-derived (PDGF-AB), vascular endothelial (VEGF), hepatocyte (HGF), and epi-
dermal (EGF) growth factors in patients affected by musculoskeletal traumatic injuries.
Results: Athletes receiving PRGF recovered their range of motion earlier (7 ± 2 weeks vs 11 ± 3 weeks, P = .025), showed no wound
complication, and took less time to take up gentle running (11 ± 1 weeks vs 18 ± 3 weeks, P = .042) and to resume training activi-
ties (14 ± 0.8 weeks vs 21 ± 3 weeks, P = .004). The cross-sectional area of the PRGF-treated tendons increased less (t = 3.44,
P = .009). TGF-β1 (74.99 ± 32.84 ng/mL), PDGF-AB (35.62 ± 14.57 ng/mL), VEGF (383.9 ± 374.9 pg/mL), EGF (481.5 ± 187.5 pg/mL),
and HGF (593.87 ± 155.76 pg/mL) significantly correlated with the number of platelets (677 ± 217 platelets/µL, P < .05).
Conclusion: The operative management of tendons combined with the application of autologous PRGF may present new possi-
bilities for enhanced healing and functional recovery. This needs to be evaluated in a randomized clinical trial.
Keywords: sports; platelets; growth factors; surgical repair; Achilles tendon

Epidemiologic reports indicate that rupture of the Achilles incidence in modern society, especially among athletes.16,17
tendon has become a common problem with an increasing Because of its limited blood supply and slow cell turnover, the
ruptured Achilles tendon heals slowly, often requiring surgical
treatment and several months for full recovery of functional
§
Address correspondence to Iñigo Mujika, PhD, Athletic Club Bilbao, capacities. Tendon healing is a complex process that involves
Sports Facilities, Garaioltza 147, Lezama, Bizkaia, Spain (e-mail: inigo
several stages, including angiogenesis, cell proliferation, and
.mujika@ euskalnet.net).
One or more of the authors has declared a potential conflict of interest: the deposition of extracellular matrix. These stages are fol-
Eduardo Anitua is the scientific director and Isabel Andía is the research lowed by remodeling and maturation, during which the heal-
director of a company that commercializes a system for obtaining ing tendon should ultimately regain its mechanical strength.
a platelet-rich preparation. Healing is promoted in particular by certain growth fac-
The American Journal of Sports Medicine, Vol. 35, No. 2
tors acting directly on target cells present in the injured
DOI: 10.1177/0363546506294078 site. In animal models, upregulated temporal expression of
© 2007 American Orthopaedic Society for Sports Medicine some growth factors and their receptors has been reported

245
Original Article
Surgery of subacromial syndrome with
application of plasma rich in growth factors
A Jiménez-Martín, J. Angulo-Gutiérrez, J. González-Herranz, J. M. Rodriguez-De La Cueva,
J. Lara-Bullón, R. Vázquez-García

AbstrAct
Background: Our objective was to evaluate clinical recovery of patients with subacromial
syndrome, after administering them plasma rich in growth factors (PRGF) by means of the Orthopaedic Surgery and Traumatology
Constant, University of California Los Angeles (UCLA) and Dissabilities of Arm, Shoulder and Service, University Hospital Nuestra
Señora de Valme, Seville, Spain
Hand (DASH) tests.
Materials and Methods: Prospective cohort study involving two groups — group A, treated with Address for correspondence:
PRGF (52 patients); and group B, without PRGF treatment (79 patients). We analyzed the clinical Dr. Antonio Jiménez-Martín,
2Urb. Al-Alba, C/ Brisa, no. 10, D.
situation preoperatively (time 1), at 1 month (time 2) and after rehabilitation (time 3). Sevilla, Spain.
Results: We considered 131 patients (71.2% were men, with median age of 53.7 years). E-mail: [email protected]
Different approaches were used — traditional (62.5%), mini-open (22.5%) and arthroscopic (15%), DOI: 10.4103/0973-6042.57932
without signiicant differences (P= .71). We observed improvement in the Constant test results
at time 2 (59.8 ± 11.5 points in group A vs. 13.2 ± 7.1 points in group B; P < .05) and at time 3
(79.3 ± 11.6 points in group A vs. 59.7 ± 20.1 points in group B; P < .05). We found improvement
in the UCLA test results at time 2 (23.2 ± 5.8 points in group A vs. 4.72 ± 1.1 points in group B;
P < .05) and at time 3 (32.1 ± 5.3 points in group A vs. 22.1 ± 7.35 points in group B; P < .05). We
also observed improvement in the DASH test results at time 2 (45.2 ± 17.2 points in group A vs.
118.3 ± 7.6 points in group B, P < .05) and at time 3 (37.3 ± 12.6 points in group A vs. 69 ± 25.7
points in group B). Time of rehabilitation reduced signiicantly: 2.53 months in group A vs. 4.96
months in group B (P < .05). No signiicant differences were observed in surgical times: 88 minutes
(group A) vs. 97 minutes (group B).
Conclusion: In our experience, PRGF should be indicated in subacromial syndrome and cuff
involvement, as shown by the improvement in our results in terms of better results of tests,
reduction in rehabilitation time and no increase in operation time.

Key words: Acromioplasty, constant, cuff, DASH, PRGF, subacromial syndrome, UCLA

INTRODUCTION these lesions by direct application of plasma rich in growth

factors.
Subacromial syndrome is a very frequent pathology in our
society, with a prevalence of 47% of population, from 5% to maTeRIalS aND meTHODS
80% in patients of over 80 years of age.[1]
Our objective was to evaluate the clinical effectiveness of
Pathophysiology of the inlammatory process in subacromial PRGF in subacromial syndrome. We used numerical values of
syndrome has been studied by authors such as Kasperk[2] and the validated Constant,[4] UCLA[5] and DASH[6] tests. We also
Sakai.[3] However, there are no studies on biological repair of measured inluence of PRGF application on rehabilitation time

Please cite this article as: Jiménez-Martín A, Angulo-Gutiérrez J, González-Herranz J, La Cueva JMR, Lara-Bullón J, Vázquez-García R. Surgery of subacromial syndrome with application of plasma
rich in growth factors. Int J Shoulder Surg 2009,3:2:28-33.

♦ Int J Shoulder Surg - April-June 2009 / Volume 3 / Issue 2 28

 Acta Orthop. Belg., 2010, 76, 689-693 CASE REPORT

Delayed union of the clavicle treated with

plasma rich in growth factors
Roberto SEijAS, Romen Y. SAntAnA-SuáREz, Montserrat GARCíA-BAllEtBó,
Xavier CuSCó, Oscar ARES, Ramón CuGAt

From Hospital Quirón, Barcelona, Spain

Nonunion is an uncommon complication of fracture using various techniques, among which the most
of the clavicle ; it is usually treated surgically. The use common is intramedullary fixation or rigid internal
of biological treatments in this type of condition is fixation with plates (7).
increasingly more common because of their ease of Fracture nonunion occurs when the normal bio-
application. Plasma rich in growth factors (PRGF) logical healing processes of the bone cease, such that
has been used in delayed healing and in nonunion of
solid healing will not occur without further treat-
fractures. We report a case of delayed union fracture
of the clavicle in which biological treatment was cho-
ment. in these situations, careful assessment of the
sen before considering surgery. Three percutaneous mechanical and biological factors contributing to the
injections of PRGF, one every 2 weeks, were delivered cause of nonunion can be used to direct treatment
into the delayed union site. The autologous PGRF (8,11,15,20). Several crucial elements should be con-
used was obtained through the patented PRGF® sidered, for example, whether the nonunion is septic
system. Three months after the final dose, computed or aseptic (25) and whether it is hypertrophic, with an
tomography study showed healing of the bone. The intact vascular supply, or atrophic, with little callus
patient regained complete mobility of the shoulder and an avascular and nonviable nonunion site. the
without pain. Currently she is able to carry out all the latter is thought to be associated with a deficient bio-
normal life activities and experiences no pain. logical process and may warrant the application of
advanced biological technologies (2,24).
Key words : platelet-rich plasma ; nonunion ; clavicle
fracture.

■ Roberto Seijas, MD, Consultant.

INTRODUCTION ■ Romen Y. Santana-Suárez, MD, Resident.
Montserrat García-Balletbó, MD, PhD, Senior consultant.
the clavicle is the most commonly fractured bone ■ Xavier Cuscó, MD, Senior Consultant.
■ Oscar Ares, MD, PhD, Consultant.
in the body, accounting for 5% to 10% of all fractures
■ Ramón Cugat, MD, PhD, Senior Consultant, Professor
(5,19). the reported incidence of nonunion is only Department of Orthopaedic Surgery and Traumatology
0.1% to 0.8% (17,19). When nonunion occurs, how- Fundación García Cugat, Hospital Quirón, Barcelona,
ever, it can pose a difficult problem, causing pain and Spain.
functional impairment of shoulder function (12,23). Correspondence : Dr. Roberto Seijas, Fundación García
the resulting deformity or callus may cause com- Cugat – Hospital Quiron Barcelona, pza. Alfonso Comín 5-7,
planta 1, 08023 Barcelona, Spain.
pression of the brachial plexus or subclavian artery E-mail : [email protected]
(23,32). Management of patients with symptomatic © 2010, Acta Orthopædica Belgica.
nonunion of the clavicle usually consists of surgery

No benefits or funds were received in support of this study Acta Orthopædica Belgica, Vol. 76 - 5 - 2010
 ORIGINAL ARTICLE

Nonunions Treated With Autologous Preparation

Rich in Growth Factors
Mikel Sanchez, MD,* Eduardo Anitua, DDS, MD,† Ramon Cugat, MD,‡ Juan Azofra, MD,*
Jorge Guadilla, MD,* Roberto Seijas, MD,‡ and Isabel Andia, PhD†

Key Words: bone graft, fracture fixation, growth factors, nonunion,

Objectives: To evaluate the clinical safety and efficacy of using platelets, percutaneous injection
a biologic technology known as preparation rich in growth factors
(PRGF) for the treatment of nonhypertrophic nonunion. (J Orthop Trauma 2009;23:52–59)

Design: The design of the study was a retrospective case series.

INTRODUCTION
Setting: The private practice was in 2 centers. Nonunion of fractures occurs when the normal biologic
healing processes of bone cease, such that solid healing will
For internal use company and distributors

Patients: There were 15 patients with a total of 16 aseptic non- not occur without further treatment. In these situations,
unions, 12 diaphyseal and 4 supracondylar, diagnosed as nonhyper- a careful assessment of the mechanical and biologic factors
trophic. The mean time since prior surgical treatment was 21 months contributing to the cause of nonunions can be used to direct
(9–46 months). treatment.1–2 Several crucial elements should be considered,
Intervention: Supracondylar and diaphyseal nonunions followed for example, whether the nonunion is septic or aseptic3 and
surgical fixation with condylar plating or intramedullary nailing, whether it is hypertrophic, with an intact vascular supply, or
whereas a composite biomaterial created by mixing PRGF with bone atrophic, with little callus and an avascular and nonviable
allograft was applied. The area was then covered with autologous fibrin nonunion site. The latter is thought to be associated with
membranes. Stable nonunions were treated with repeated percutaneous a deficient biologic process and may require the application of
injections of PRGF; this minimally invasive procedure was also advanced biologic technologies.
applied if delayed healing was suspected after surgical treatment. The last few years have seen critical developments in
platelet-rich therapies as biologic systems for growth factor
Main Outcome Measurements: Radiographic union using release and tissue engineering. All these emerging technol-
radiographic views was taken in 2 planes. Clinical outcome evaluated ogies commonly use or release bioactive proteins at localized
pain, motion at the fracture site upon manual stress testing, and orthopaedic sites. The easy preparation of protocols, biosafety,
recovery of range of motion. and versatility of platelet-rich preparations and their reduced
cost have encouraged their therapeutic use for the stimulation
Results: All nonunions treated operatively healed after a single of tissue healing and bone regeneration. Preparation rich in
procedure, even though additional PRGF had to be injected in
growth factors (PRGF) is a standardized and well-characterized
2 patients. Two of 3 stable nonunions achieved healing only after
platelet-rich preparation that has shown its versatility and
repeated percutaneous PRGF injections. The mean time from surgery
efficacy in several medical areas.4–9 The bioactivity of PRGF is
and/or PRGF application to union was 4.9 months (2–8 months).
based on the progressive and balanced release of a pool of
Complications associated with the described procedure were not
proteins and growth factors, such as platelet-derived growth
observed.
factor (PDGF), transforming growth factor-b1 (TGF-b1), and
Conclusion: This study, although uncontrolled, shows that PRGF insulin-like growth factor, known to stimulate fracture
technology is clinically safe and can enhance the healing of healing.10–12 In the present report, we describe the use of
nonhypertrophic nonunions. PRGF for nonunion treatment, namely, enhanced bone grafting
that can be achieved by creating a composite biomaterial
Accepted for publication September 30, 2008. comprising PRGF and bone allograft13; in addition, fibrin
From the *Unidad de Cirugia Artroscópica UCA, Clı́nica USP-La Esperanza, membranes can be used to favor epithelialization, although
Vitoria, Spain; †Biotechnology Institute, BTI IMASD, Minano, Alava,
Spain; and ‡Instituto de Traumatologı́a Quiron, Hospital Quiron, Pza liquid PRGF can be injected when additional delivery of GFs is
Alfonso Comin, Barcelona, Spain. required or less invasive procedures are indicated for stable
Supported by the Basque and Spanish Governments. nonunion. The present study retrospectively analyzes the
Marketing approval: Preparation rich in growth factors are licensed by the efficacy and biosafety of PRGF technology in 15 patients
European Regulatory Agency as a class III medical device, Directive
93/42/EEC (EC Certificate G1 05 03 43180 006). Preparation rich in
treated for nonhypertrophic nonunions of long bones.
growth factors are indicated on the area of oral surgery and treatment of
skin ulcers and musculoskeletal injuries.
Reprints: Isabel Andia, PhD, BTI IMASD, Leonardo Da Vinci 14, 01510
PATIENTS AND METHODS
Minano, Alava, Spain (e-mail: [email protected]). The study group was identified from a larger group of 32
Copyright Ó 2008 by Lippincott Williams & Wilkins consecutive patients with nonunion treated at 2 private medical

52 J Orthop Trauma  Volume 23, Number 1, January 2009

Knee Surg Sports Traumatol Arthrosc
DOI 10.1007/s00167-013-2479-y

KNEE

Ultrasound-guided platelet-rich plasma injections

for the treatment of common peroneal nerve palsy associated
with multiple ligament injuries of the knee
M. Sánchez • T. Yoshioka • M. Ortega •

D. Delgado • E. Anitua

Received: 22 November 2012 / Accepted: 11 March 2013

Ó Springer-Verlag Berlin Heidelberg 2013

Abstract infiltrations of PRGF were started using ultrasound guid-

Purpose Peroneal nerve palsy in traumatic knee disloca- ance. The therapeutic effect was assessed by electromy-
tions associated with multiple ligament injuries is common. ography (EMG), echogenicity of the peroneal nerve under
Several surgical approaches are described for this lesion ultrasound (US) and manual muscle testing.
with less-than-optimal outcomes. The present case repre- Results Twenty-one months after the first injection, not
sents the application of plasma rich in growth factors complete but partial useful recovery is obtained. He is
(PRGF) technology for the treatment of peroneal nerve satisfied with walking and running without orthosis. Sen-
palsy with drop foot. This technology has already been sitivity demonstrates almost full recovery in the peroneal
proven its therapeutic potential for various musculoskeletal nerve distribution area. EMG controls show complete
disorders. Based on these results, we hypothesized that reinnervation for the peroneus longus and a better rein-
PRGF could stimulate the healing process of traumatic nervation for the tibialis anterior muscle, compared with
peroneal nerve palsy with drop foot. previous examinations.
Methods The patient was a healthy 28-year-old man. He Conclusion Plasma rich in growth factors (PRGF) infil-
suffered peroneal nerve palsy with drop foot after multiple trations could enhance healing process of peroneal nerve
ligament injuries of the knee. PRGF was prepared palsy with drop foot. This case report demonstrates the
according to the manufactured instruction. Eleven months therapeutic potential of this technology for traumatic
after the trauma with severe axonotmesis, serial intraneural peripheral nerve palsy and the usefulness of US-guided
PRGF.
Level of evidence V.
M. Sánchez
T. Yoshioka
Arthroscopic Surgery Unit, UCA ‘‘Mikel Sánchez’’, USP-La
Keywords Plasma rich in growth factors
Platelet-rich
Esperanza Clinic, La Esperanza 3, 01002 Vitoria-Gasteiz, Spain
e-mail: [email protected] plasma
Drop foot
Common peroneal nerve palsy
Knee

Ultrasound-guided injection
T. Yoshioka (&)
Rehabilitation Medicine Service, University of Tsukuba
Hospital, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
e-mail: [email protected] Introduction

M. Ortega Peroneal nerve injury in traumatic knee dislocations

Clinical Neurophysiology Unit, Galdakao-Usánsolo Hospital,
associated with multiple ligament injuries is quite common
Bilbao, Spain
[25, 28]; in fact, most studies have reported an incidence of
D. Delgado 25–36 % of peroneal nerve palsy in these types of lesions
UCA RESEARCH, USP-La Esperanza Clinic, [14, 18, 20]. Clinically, these patients present mainly with
Vitoria-Gasteiz, Spain
a drop foot accompanied by pain and a sensory deficit on
E. Anitua the anterolateral skin of the leg. Recovery of ankle dorsi-
Foundation Eduardo Anitua, Vitoria-Gasteiz, Spain flexion is likely in more than 80 % of cases when the nerve

123
 diabetes research and clinical practice 93 (2011) e65–e67

Contents lists available at ScienceDirect

Diabetes Research
and Clinical Practice
journ al h ome pa ge : www .elsevier.co m/lo cate/diabres

Brief report

The use of plasma rich in growth factors (PRGF-Endoret)

in the treatment of a severe mal perforant ulcer
in the foot of a person with diabetes

Beatriz Orcajo a,*, Francisco Muruzabal b, Marı́a Concepción Isasmendi a,

Nerea Gutierrez a, Mikel Sánchez c, Gorka Orive b, Eduardo Anitua b
a
Clinica Juber, Plaza San Antón 4, 01002 Vitoria, Spain
b
Instituto Eduardo Anitua, c/Jose Maria Cajigal 19, 10005 Vitoria, Spain
c
Unidad de Cirugı́a Artroscópica ‘‘Mikel Sánchez’’, c/La Esperanza, 01005 Vitoria, Spain

article info abstract

Article history: A 71 year old person with diabetes with a severe mal perforant ulcer in the right foot was
Received 17 December 2010 treated twice with autologous plasma-rich in growth factors (PRGF) obtained from her own
Accepted 4 April 2011 blood. After PRGF treatment the severe mal perforant ulcer completely healed in 10 weeks.
Published on line 5 May 2011 # 2011 Elsevier Ireland Ltd. All rights reserved.

Keywords:
Diabetic foot ulcers
Plasma rich in growth factors
Platelet rich plasma
Mal perforant ulcer

The management of a mal perforant ulcer is difficult, time-

1. Introduction consuming, expensive and resource intensive requiring wound
care treatments, offloading, and dedicated monitoring [4].
In some people with diabetes injuries caused by weight We report the use of autologous proteins and fibrin
bearing remain painless due to the presence of poor material obtained from plasma rich in growth factors (PRGF-
vascularity and impaired sensation resulting from sensory Endoret) technology as a novel approach for the management
neuropathy. Continued weight bearing and pressure of of mal perforant ulcers. PRGF consists of a limited volume of
keratotic lesions on the underlying dermis eventually cause plasma enriched in platelets that is easily obtained from the
necrosis and ulceration [1]. Approximately 15–20% of people patient and which has potent wound healing and tissue
with diabetes may develop a foot ulcer during their lifetime [2]. regenerative potential together with an anti-inflammatory
Ulcers are the leading cause of amputation in the United States activity [5–7]. Apart from releasing a wide range of biologically
and the second leading cause of hospitalization of people with active proteins, PRGF enables the development of a biocom-
diabetes [3]. patible fibrin material, which acts as a biological membrane

* Corresponding author. Tel.: +34 945257862; fax: +34 945160657.

E-mail address: [email protected] (B. Orcajo).
Abbreviations: PRGF, plasma rich in growth factors; F1, fraction 1; F2, fraction 2; F3, fraction 3.
0168-8227/$ – see front matter # 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.diabres.2011.04.008
 J Wound Ostomy Continence Nurs. 2013;40(2):198-202.
Published by Lippincott Williams & Wilkins

CHALLENGES IN PRACTICE

Use of Platelet-Rich Plasma to Treat

Pressure Ulcers
A Case Study
Javier Ramos-Torrecillas 䡲 E. De Luna-Bertos 䡲 O. García-Martínez 䡲 L. Díaz-Rodríguez 䡲 C. Ruiz

her right heel that exhibited no signs of healing despite

■ ABSTRACT topical therapy applied over a 4-month period. Her medi-
BACKGROUND: Pressure ulcers (PUs) are prevalent and chronic cal history included Alzheimer-type cognitive deteriora-
wounds that require significant time to heal and the search tion, arterial hypertension, and obesity (body weight ⫽ 95
for new treatments to reduce healing time is ongoing. We kg, 209 pounds). The patient spent long periods of time in
describe our experience with platelet-rich plasma to facilitate bed with her heel on the bed. Despite repositioning every
PU healing. 2 hours, the wound failed to heal. Topical treatment of her
CASE: An 86-year-old woman residing in a long-term care facility PU included polyurethane foam dressings with hydrogel
developed a grade III PU on her right heel that exhibited no signs and collagenase for enzymatic debridement. She had no
of healing despite topical therapy over a 4-month period. Her PU dietary restrictions, walked with difficulty, and was depen-
was treated with platelet-rich plasma generated from her own dent for daily life activities. She was scored as being at
blood, with a follow-up every 3 days for a period of 8 weeks. medium risk on the Mini Nutritional Assessment Scale
and Braden Scale. At the time of treatment, the PU had a
CONCLUSIONS: The platelet-rich plasma-treated PU closed com-
surface area of 7.5 cm2 and contained granulation tissue.
pletely at 54 days. We found platelet-rich plasma easy to apply
The periwound skin was free from moisture-associated
and inexpensive. Additional research is needed to evaluate the
skin damage.4 The progression of the ulcer was followed
efficacy of this intervention in patients with nonhealing PUs.
by using the Pressure Ulcer Scale for Healing.5 Ethical
KEY WORDS: Platelet-rich plasma, Ulcer, Sore, PRP, Chronic wound,
approval was granted by the Local Nursing Home Ethics
Tissue regeneration. Committee, informed consent was obtained, and the pro-
■ Introduction cedure was conducted according to the Declaration of
Helsinki.
Pressure ulcers (PU) pose a daily challenge to nursing pro- On day 0, we extracted 20 mL of peripheral blood with
fessionals throughout the world. The EPUAP (European 3.8% sodium citrate that acted as an anticoagulant. The
Pressure Ulcer Advisory Panel) defines PU as skin lesions of sample was centrifuged and the technique of Anitua6 was
ischemic etiology that affect the integrity of the skin and applied to obtain PRP, which was then activated with 10%
underlying tissues; they are produced by prolonged pres- calcium chloride (Braun Medical, Barcelona, Spain). The
sure or friction between an internal and external hard
surface.1 Their severity ranges from a slight skin reddening
䡲 J. Ramos-Torrecillas, MSN, MSC, Department of Nursing, School of
to the impairment of deeper tissues, including muscle and Health Sciences, University of Granada, Granada, Spain.
even bone.2 The high cost and human suffering associated 䡲 E. De Luna-Bertos, MSN, PhD, Department of Nursing, School of
with PU have led nursing professionals to seek novel strat- Health Sciences, University of Granada, Granada, Spain.
egies to reduce healing time and associated hospital stays.3 䡲 O. García-Martínez, DDS, PhD, Department of Nursing, School of
The objective of this case study was to determine the Health Sciences, University of Granada, Granada, Spain.
feasibility of platelet-rich plasma (PRP) for treatment and 䡲 L. Díaz-Rodríguez, MSN, PhD, Department of Nursing, School of
Health Sciences, University of Granada, Granada, Spain.
of a nonhealing PU in a frail, elder patient with multiple
䡲 C. Ruiz, PhD, Professor, Department of Nursing, School of Health
comorbid conditions. Sciences, and Institute of Neuroscience, University of Granada,
Granada, Spain.
The authors declare no conflict of interest.
■ Case Correspondence: Javier Ramos Torrecillas, Facultad de Ciencias de
An 86-year-old woman living in a residential home for the la Salud, Avda. de Madrid s/n, 18971, Granada, Spain ([email protected]).
elderly developed a grade III PU (EPUAP classification1) on DOI: 10.1097/WON.0b013e318280018c

198 J WOCN ■ March/April 2013 Copyright © 2013 by the Wound, Ostomy and Continence Nurses Society™

Copyright © 2013 Wound, Ostomy and Continence Nurses Society™. Unauthorized reproduction of this article is prohibited.
Journal of Tissue Viability (2016) --, -e-

www.elsevier.com/locate/jtv

Case report

Biological approach for the management

of non-healing diabetic foot ulcers
Elena Perez-Zabala a, Andima Basterretxea a,
Ainara Larrazabal a, Karmele Perez-del-Pecho a,
Eva Rubio-Azpeitia b, Isabel Andia b,*

a
Hospital-at-Home Department, Cruces University Hospital, OSI, Pza Cruces S/N, 48903
Barakaldo, Spain
b
BioCruces Health Research Institute, Cruces University Hospital, Pza Cruces S/N,
48903 Barakaldo, Spain

KEYWORDS Abstract Objective: To show an approach to profit of the main components of

Diabetic foot ulcer; platelet rich plasma (PRP), i.e. the signaling proteins, and the fibrin scaffold and
Platelet rich plasma; discuss the intervention within TIME (Tissue, Inflammation/Infection, Moisture,
Fibrosis; Edges) framework.
Growth factors; Methods: Two patients with diabetic foot ulcers are treated with both liquid and
Cytokines gelled PRP, and the rationale for the PRP intervention is described herein. Autolo-
gous blood is withdrawn and, PRP is separated by single spinning and activated with
CaCl2 prior to application. PRP is injected in an activated liquid form, i.e. freshly
activated, before coagulation, within the wound edges. In fibrotic tissue PRP is
introduced performing a needling procedure. In addition, PRP, clotted ex-vivo, is
applied in the wound bed as a primary dressing.
Results: Both patients responded positively to PRP intervention. Case 1 healed af-
ter five weekly PRP applications. Case 2 healed after eight weekly PRP applications.
Patient satisfaction was high in both cases. The procedure had no complications, is
well tolerated and easy to perform in any medical setting.
Conclusion: PRP intervention is safe and if associated with correct tissue debride-
ment and preparation of the host tissue it may help to decrease the burden of

* Corresponding author.
E-mail addresses: Mariaelena.perezzabala@osakidetza.
e us (E. Per ez -Z aba l a ), An d im a . b ast e r r e t xea o z ami z@
osakidetza.eus (A. Basterretxea), Ainara.larrazabalarbaiza@
osakidetza.eus (A. Larrazabal), Karmele.perezdelpecho@
osakidetza.eus (K. Perez-del-Pecho), Eva.rubioazpeitia@
osakidetza.eus (E. Rubio-Azpeitia), iandia2010@hotmail.
com, [email protected] (I. Andia).

http://dx.doi.org/10.1016/j.jtv.2016.03.003
0965-206X/ª 2016 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Perez-Zabala E et al., Biological approach for the management of non-healing diabetic foot
ulcers, Journal of Tissue Viability (2016), http://dx.doi.org/10.1016/j.jtv.2016.03.003
534979
research-article2014
IJLXXX10.1177/1534734614534979The International Journal of Lower Extremity WoundsGilli et al

Clinical and Translational Research

The International Journal of Lower
Extremity Wounds
Autologous Platelet Gel: Five Cases 1–7
© The Author(s) 2014
Illustrating Use on Sickle Cell Disease Ulcers Reprints and permissions:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/1534734614534979
ijl.sagepub.com

Simone C. O. Gilli, MD, PhD1, Suely A. do Valle Oliveira1,

and Sara T. Olalla Saad, MD, PhD1

Abstract
Leg ulcers represent a particularly disabling complication in patients with sickle cell disease (SCD). Platelet gel (PG) is a
novel therapeutic strategy used for accelerating wound healing of a wide range of tissues through the continuous release
of platelet growth factors. Here, we describe the use of PG preparation according to Anitua’s PRGF (preparations rich in
growth factors) protocol for treating chronic nonhealing ulcers in patients with SCD. A positive response occurred in 3
patients with an area reduction of 85.7% to 100%, which occurred within 7 to 10 weeks, and a 35.2% and 20.5% of area
reduction in 2 other patients, who however, had large ulcers. After calcium chloride addition, the platelet-rich plasmas
demonstrated enhanced platelet-derived growth factors–BB (P < .001), transforming growth factor-β1 (P = .015), vascular
endothelial growth factors (P = .03), and hepatocyte growth factors (nonsignificant) secretion. Furthermore, calcium
chloride addition induced a significant decrease in platelet number (P = .0134) and there was no leukocyte detection in
the PG product. These results demonstrate that PG treatment might impact the healing of leg ulcers in sickle cell disease,
especially in patients with small ulcers.

Keywords
platelet gel, ulcers, sickle cell disease, healing

Sickle cell disease (SCD) has many clinical manifestations, ulcers may heal within a few months. Persistent leg ulcers
among them, leg ulcers are relatively common and can be however, may require some specific treatment modalities
disabling. This complication is most common in sickle cell and the success or failure of these measures is merely anec-
anemia (homozygosity for HBB glu6val; HbSS) and less dotal with no controlled clinical trial to identify the best
common in HbSC or HbS-β thalassemia. The exact mecha- management approach.
nism for the occurrence of sickle leg ulcers has not yet Topical growth factor products are typically used as
been fully explained. However, mechanical obstruction by adjuvant treatments along with the standard care for treat-
dense sickled red cells, venous incompetence, bacterial ment of diabetic foot ulceration with successful results.4-6
infections, abnormal autonomic control with excessive Clinical evidence suggests that platelet gel (PG), prepared
vasoconstriction, in situ thrombosis, anemia with a decrease by platelet activation of platelet-rich plasma (PRP) por-
in oxygen carrying capacity, and decreased nitric oxide tion,7,8 could have beneficial therapeutic effects on hard and
bioavailability leading to impaired endothelial function, soft tissue healing because of the contents of growth factors
have all been proposed as potential contributing factors,1,2 stored in the platelets.
which most likely play a major role in the etiopathogenesis Blood platelets have a major role in the initiation of cuta-
of leg ulcers. Minniti et al3 evaluated the microcirculation neous wound healing; adhering, aggregating, and releasing
of lower extremity ulcers and demonstrated highest blood numerous growth factors, adhesive molecules, and lipids
flow probably related with inflammation, cutaneous vaso- that regulate migration, proliferation, and functions of
dilatation, venostasis, and in situ thrombosis. They con-
cluded that leg ulcers in sickle cell disease may be an 1
University of Campinas–UNICAMP, INCT do Sangue, Campinas, São
end-organ complication with endothelial dysfunction and Paulo, Brazil
with a higher frequency in these individuals than in the
Corresponding Author:
general population.3 Simone C. O. Gilli, University of Campinas, Rua Carlos Chagas, 480,
The treatment used for leg ulcers wound care includes Campinas, São Paulo 13083-878, Brazil.
wet to dry dressings and with regular treatment, many small Email: [email protected]
Effectiveness of Autologous Preparation Rich in Growth Factors
for the Treatment of Chronic Cutaneous Ulcers
Eduardo Anitua,1 José J. Aguirre,1 Jaime Algorta,2 Eduardo Ayerdi,3 Ana I. Cabezas,4
Gorka Orive,1 Isabel Andia1*
1
Biotechnology Institute, Vitoria, Spain
2
Fundación LEIA, Hospital Txagorritxu, Vitoria, Spain
3
Service of Traumatology, Hospital Txagorritxu, Vitoria, Spain
4
Service of Vascular Surgery, Hospital Txagorritxu, Vitoria, Spain

Received 2 November 2006; revised 5 March 2007; accepted 3 May 2007

Published online 26 June 2007 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.b.30886

Abstract: Autologous Preparation Rich in Growth Factors (PRGF), a small volume of

plasma enriched in platelets, is a novel therapeutic strategy for the acceleration of the wound
healing of a wide range of tissues because of the continuous release of multiple growth factors,
including PDGF-AB, TGF-b1, IGF-I, HGF, VEGF-A, and EGF. In this article, we have
characterized the PRGF preparation and designed a randomized open-label controlled pilot
trial to evaluate the effectiveness of PRGF in the treatment of chronic cutaneous ulcers.
Results showed that at 8 weeks, the mean percentage of surface healed in the PRGF group was
72.94% 6 22.25% whereas it was 21.48% 6 33.56% in the control group (p < 0.05). These
results, with the limitations of a pilot study, suggest that topical application of PRGF is more
effective than standard therapy in helping a chronic ulcer to heal. ' 2007 Wiley Periodicals, Inc. J
Biomed Mater Res Part B: Appl Biomater 84B: 415–421, 2008

Keywords: chronic cutaneous ulcers; platelet; growth factors; PRGF; randomized trial

INTRODUCTION in chronic venous ulcers with the resultant failure of comple-

tion of the healing process.4,5
Cutaneous ulceration is a common clinical problem rising The dynamic and efficient process of wound healing
with the increasing median age of the population. The Euro- involves a complex dynamic series of events, including
pean Union allocates 2% of the yearly health budget to hemostasia, inflammation, granulation tissue formation, epi-
wound care1 and it is estimated that in the United States the thelialization, neovascularisation, collagen synthesis, and
costs related to the care of patients with pressure ulcers is wound contraction. Blood platelets have a major role in ini-
over $1.3 billion per year.2 Absence of healing is not uncom- tiation of cutaneous wound healing. They adhere, aggregate,
mon when predisposing factors, such as rheumatism, diabe- and release numerous growth factors, adhesive molecules,
tes, peripheral vascular disease, or previous scars are and lipids that regulate the migration, proliferation, and
present. In fact some comorbid conditions could be related functions of keratinocytes, fibroblasts, and endothelial cells.
to a deficiency of growth factors, such as platelet-derived Some of the stored growth factors essential for wound repair
growth factor (PDGF), epithelial growth factor (EGF), vas- include PDGF, transformed growth factor (TGF-b), VEGF,
cular endothelial growth factor (VEGF) in the ulcer site, basic fibroblast growth factor, EGF, type-I insulin-like
resulting in the impairment of the healing process.3 Addi- growth factor (IGF-I), and hepatocyte growth factor
tionally, matrix metalloproteinases (MMP’s) have also been (HGF).6–10 In fact, the potential therapeutic effects of some
implicated with excessive extracellular matrix degradation of these growth factors in promoting wound healing has
been reported.11,12 The key roles of growth factors in wound
healing has stimulated significant research efforts aiming to
test different platelet-derived products as therapeutic treat-
Correspondence to: I. Andia (e-mail: [email protected]) ments to improve wound healing and to accelerate the clo-
Presented in part at the XIX Congress of the Spanish Society of Clinical Pharma-
cology, October 28–30, 2004, Santander and the V National Symposium on Pressure sure of chronic wounds. Technology has evolved since the
Ulcers and Chronic Wounds, November 11–13, 2004, Oviedo, Spain. first applications of this concept. Initially a liquid product
' 2007 Wiley Periodicals, Inc. containing autologous platelet secreted molecules was
415
03-Aguirre_. 20/04/15 12:46 Pagina 13

Original article

Efficacy and safety of plasma rich in growth factors

in the treatment of venous ulcers: a randomized
clinical trial controlled with conventional treatment

li
na
José Javier Aguirre1,3 events were assessed at each visit.
Eduardo Anitua3 Results. At 8 weeks, the mean percentage of
Silvia Francisco1 healed surface in the PRGF group was 81.8% ±

io
Ana Isabel Cabezas2 9.3% versus 23.9% ± 0.8% in the control group (p<
Gorka Orive3,4,5 0.001); five ulcers in the experimental group hea-
Jaime Algorta1,6 led completely; patients percentage with more

az
than 40% healing in the PRGF group was 100%
versus 0% in the control group (p<0.001). Estimat-
1 Clinical Trials Unit. University Hospital of Alava ed healing time was 9.6 ± 1.2 weeks in the PRGF
(HUA), Vitoria, Spain group and 23.7 ± 1.2 weeks in the control group
(p<0.001).

rn
2 Department of Vascular Surgery, University Hospital

of Alava (HUA), Vitoria, Spain Conclusions. The PRGF can be an effective and
3 Eduardo Anitua Foundation, Vitoria, Spain safe treatment for leg ulcers.
4 NanoBioCel Group, Laboratory of Pharmaceutics,

te
University of the Basque Country, School of Pharma- KEY WORDS:
cy, Vitoria, Spain
5 Biomedical Research Networking Center in Bioengi-

Introduction
neering, Biomaterials and Nanomedicine (CIBER-
In
BBN), Vitoria, Spain
6 University of the Basque Country Skin ulcers are a significant health problem nowadays
due to their high prevalence (1) and their repercus-
sions in the state of health of those who suffer them.
ni
Address for correspondence: The consequences of skin ulcers also associated with
Gorka Orive, MD, PhD a decreased quality of life for patients and caregivers,
Eduardo Anitua Foundation thus and to a high consumption of resources for the
io

Vitoria, Spain. C/ Jose María Cagigal, 19 health system (2).

01007 Vitoria, Spain Chronic ulcers are typically wounds which do not fol-
E-mail: [email protected] low a normal repair process, therefore causing them
iz

to bring to a standstill in some of the healing stages

and so not reaching to restore the anatomical and
Summary functional integrity of the injured tissue. This imbal-
Ed

ance seems to be in connection with the increase of

Background. Skin ulcers are a significant health some pro-inflammatory cytokines, the decrease of
problem nowadays due to their high prevalence other growth factors by the action of proteases, a de-
and their repercussions in the state of health of crease in cell mitogenic activity and an alteration in
those who suffer them, the use of autologous the collagen and extracellular matrix deposit. These
platelet rich plasma may be effective for this changes disturb cell proliferation and protein synthe-
IC

pathology, due to the capability of the platelets to sis leading to an increased cell apoptosis (3).
store and secrete signaling proteins essential for Plasma rich in growth factors (PRGF) is an autologous
the correct development of the healing process biological therapy obtained from patient’s blood by
Objective. To evaluate the efficacy and safety of which it is possible to obtain different formulations with
C

plasma rich in growth factors (PRGF) in the treat- therapeutic potential. The biological basis of this ther-
ment of venous ulcers. apy involves on the one hand the release of a pool of
Methods. We randomly assigned 23 patients to re- biologically active proteins (especially growth factors),
ceive PRGF infiltrations or conventional treatment and on the other hand to provide fibronectin and ad-
hesive proteins like fibrin and vitronectin, thus acting
©

for 8 weeks. The primary outcome was the com-

parison of the recovered surface between treat- as sealing molecules capable of forming a dynamic
ment groups. Secondary outcomes were the num- scaffold which facilitates epithelial migration in the le-
ber of healed ulcers at the end of the follow-up pe- sion (4).
riod, patients percentage with more than 40% The present study is to our knowledge the first one fo-
healing and the estimated time until complete cusing on evaluating the efficacy and safety of PRGF
wound healing. Safety assessment, nature, onset, in the treatment of skin ulcers secondary to chronic
duration, severity, and outcome of all adverse venous insufficiency.

Clinical Dermatology 2015; 3 (1): 13-20 13

 ACCEPTED MANUSCRIPT
EFFICACY AND SAFETY OF THE USE OF PLATELET-RICH PLASMA TO
MANAGE VENOUS ULCERS

ABSTRACT
Objectives: The aim of this study was to analyse the efficacy and safety of using platelet
rich in growth factor (PRGF) as a local treatment for venous ulcers.
Methods: In a clinical trial 102 venous ulcers (58 patients) were randomly assigned to

PT
the study group (application of PRGF) or the control group (standard cure with saline).
For both groups the healed area was calculated before and after the follow up period

RI
(twenty-four weeks). The Kundin method was used to calculate the healed area (Area =
Length × Width × 0.785). Pain was measured at the start and end of treatment as a

C
secondary variable for each group by record obtained by means of self-evaluation visual
analogue scale.

US
Results: The average percentage healed area in the platelet rich plasma group was 67.7±
41.54 compared to 11.17±24.4 in the control group (P=0.001). Similarly, in the
AN
experimental group a significant reduction in pain occurred on the scale (P=0.001). No
adverse effects were observed in either of the two treatment groups.
M

Conclusions: The study results reveal that application of plasma rich in platelets is an
effective and safe method to speed up healing and reduce pain in venous ulcers.
D

Keywords: efficacy of platelet rich in growth factor, platelet gel, platelet-rich plasma,
TE

venous chronic disease, venous chronic wounds

C EP
AC

1
 ORIGINAL RESEARCH

Platelet-Rich Plasma in Skin Ulcer

Treatment
Raquel Cobos Campos, Pharm1; Naiara Parraza Diez, Pharm,
PhD1; Felipe Aizpuru Barandiaran, MD, PhD1,2,3

WOUNDS 2013;25(9):256-262 Abstract: Introduction. Chronic vascular ulcers are associated with a high
use of resources. Conventional treatment consists of wound cleansing, ne-
From the 1Health Research Unit crotic tissue debridement, prevention, diagnosis, and, if necessary, treat-
of Álava, Basque Health Service, ment of infection and dressing application; although conventional treat-
Álava, Spain; 2Network Center ment has limited effectiveness with wound healing (around 15-30%).8-11
for Biomedical Research in Platelet-rich plasma, used in various fields of medicine, improves chronic
Epidemiology and Public Health, vascular ulcer results, but is more expensive. Methods. A cost-effective-
Granada, Spain; 3University of the ness analysis was performed using a 48-week period comparing platelet-
Basque Country, Álava, Spain rich plasma with standard care. A meta-analysis of papers identified by a
literature search was done. Results. A combined measure of effectiveness
Address correspondence to: at 12 weeks for each treatment option was calculated and served as the
Felipe Aizpuru Barandiaran, MD, PhD basis for estimating the probability of healing at 48 weeks with a Markov
José Achótegui s/n model. Conclusions. The probability of healing and associated costs were
01009 Vitoria-Gasteiz 56% and €5224 using platelet-rich plasma and 31% and €5133 with
Álava, Spain usual care. The incremental cost that must be assumed to achieve ad-
Felipeesteban.aizpurubarandiaran@ ditional healing with platelet-rich plasma is €364.
osakidetza.net
Key words: varicose ulcers, skin ulcers, platelet-rich plasma, cost-benefit
Disclosure: The authors disclose analysis
no financial or other conflicts of
interest.

C
hronic vascular ulcers require multidisciplinary management that is as-
sociated with a high use of resources, especially in primary care. It is esti-
mated that in Western countries 1% of adults will have a chronic vascular
ulcer at some stage in their lives, the prevalence being 1.3 to 3 individuals out
of 1000.1 In Spain, according to the first national study on leg ulcers carried out
between 2002 and 2003, the prevalence of vascular ulcers was found to be 1.65
per 1000.2
Vascular ulcers can be arterial, venous, or both, with the most common eti-
ology being venous and representing 80%-90% of all vascular ulcers.3,4 Venous
ulcers tend to be persistent—among patients with venous ulcers, 30% have a
> 5-year history of this condition and an estimated 72% rate of recurrence.5,6 The
conventional treatment of vascular ulcers consists mainly of wound cleansing;
debridement of necrotic tissue; prevention; diagnosis; and, if necessary, treatment
of infection and application of dressings.7 The effectiveness of the conventional
treatment is still relatively low, around 15%-30%.8-11,22 Moreover, the mean dura-
tion of skin ulcers is approximately 1 year, indicating the seriousness of the prob-
lem for many patients, given the associated pain and disability.
The use of platelet-rich plasma (PRP) and plasma rich in growth factors
256 WOUNDS® www.woundsresearch.com

Campos_0913.indd 256 9/5/13 12:47 PM