PRP in muscle and tendon injuries

1. PRP in muscle and tendon
injuries
Lars Engebretsen MD, PhD
Professor and Chair Department of
Orthopaedic Surgery, U of Oslo

2. Disclosures 2013
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Consultant
n Arthrex equipment development
Fellowship grants
n Smith and Nephew
n Arthrex
Editor and Editorial board
n BJSM
n JBJS (am)
n SJMSS
n KSSTA
n
n
Research grants
n Smith & Nephew
n Fin-Ceramica
n TBF-Tissue Engineering
n Biomet
Competitive grants
n Norwegian NIH
n AOSSM
n FIFA
n IOC
n NIH
n Health South East Norway
n Department of Culture
Norway

3. Been in Sports Traumatology as a
clinician researcher since 1984
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Cochair of the Oslo Sports Trauma Research Center
Chief of the Orthopedic Department at the
University of Oslo
Consultant at the Norwegian Olympic Center
Head of three research groups in Cartilage, Knee
ligaments and Injury Prevention
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Head of Scientific activities in the IOC
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Past President of ESSKA
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Editor of BJSM IPHP
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Deputy Editor JBJS (Am)

4. This lecture will discuss:
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Why is PRP hot?
Proof of concept?
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Role in tendon, ligament, muscle and cartilage
Procedure- dose- frequency
White cells ?
Local anesthesia ?
Antiinflammatories ?
Adverse effects ?
Anti doping regulations
Summary

5. IOC Consensus statements
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Sports Nutrition (2003)
Sex Reassignment in Sports (2003)
Sudden Cardiovascular Death in Sports (2004)
Training the Elite Child Athlete (2005)
Female Athlete Triad (2005)
Sexual Harassment & Abuse in Sport (2006)
Molecular Basis of Connective Tissue and Muscle Injuries in Sport (2007)
Non-contact ACL Injury in the Female Athlete (2008)
Concussion in Sport (2008)
Asthma in Elite Athletes (2008)
Fasting in Sports (2009)
Periodic Health Evaluation of Elite Athletes (2009)
Age Determination in High-Level Young Athletes (2009)
Sports Nutrition (2010)
Functional Hyper-Androgenism and Sport (2010)
The Use of Platelet-Rich Plasma in Sports Medicine (2010)
Fitness and Health in Young People through Physical Activity and Sport (2011)
Thermoregulatory and altitude challenges in the high-level athlete (2011)

7. Did PRP win it?
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Hines Ward
Pittsburgh Steelers
wide receiver
Super Bowl XLIII Feb
2009
Pittsburgh Steelers
versus Ravens

11. Sandeep Patel MD AJSM 2013

12. PRP: what does it contain?

13. Comparison of mean cell counts
amongMajor commercial PRP systems

15. Not all PRPs are the same
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Leukocytes (white blood cells)
n Platelet concentration
n Platelet activation
Andia et al. Expert Opin Biol Ther.
2010 Oct;10(10):1415-26
Jia et al. Oper Tech Sports Med. 2011

16. Differences in PRP Systems
Competitor 1
Competitor 2
PRGFTM
Types of PRP
L-PRP1
P-PRP2
P-PRP
Input Blood
Volume
30-55ml3
9ml4
Variable (9ml per
tube)
Centrifuge
Protocol
3200rpm
(1100g) for
15min1
1500rpm
(400g) for
5min2
580g for 8min
PRP Yield
3-6ml3
2-3ml4
2ml of F2 per tube
Platelet
Enrichment
Factor
2.07 ± 1.11
1.3x2
2.3 ± 0.6
Leukocyte
Concentration
[103/ul]
34.4 ± 13.61
0.68 ± 0.422
0.7±0.7
Is Scaffold
Forming
Activator
Included in the
Kit?
No
No
Yes
3
1Castillo
et al. Am J Sports Med. 2011 Feb; 39(2): 266-71
2Sundman et al. Am J Sports Med. 2011 Oct;39(10):2135-40
Data available at: http://www.biomet.com/biologics/information/pdf/BBI0003.0.pdf
4 Data
Available at: https://www.arthrex.com/innovations/index.cfm?adid=28

17. Why should it work?

18. AUTOLOGOUS PLATELETS CAN BE A SOURCE OF
GROWTH FACTORS FOR HEALING AND
TISSUE REGENERATION
Platelet-Rich Plasma
is the outcome of a
centrifugation of
autologous blood.
Contains a high
concentration of
platelets
(4-8 times)

19. PLATELETS
Role in
HAEMOSTASIS
Growth Factors
RELEASE
Ø Promote tissue repair
Ø Influence the reactivity of vascular and other
blood cells in angiogenesis and inflammation

20. Where are the GFs?

21. Platelet activation
§ Activation
§ exposed collagen, damage or thrombin
§ Dramatic morphological change
§ Adhesion, spreading, aggregation,
activation of other platelets and clot
retraction
§ Alpha Granule release
§ 200-500 nm, ~50 to 80 per platelet
§ Over 30 bioactive proteins, with
roles in haemostasis and tissue
healing.
Harrison and Cramer 1993
0.5 µm

22. Platelet granule release
Alpha granules migrate
to platelet periphery (a),
where the plasma
membrane blebs (b),
and ruptures (c) Loss of
electron density with
rupture
Polasek J. Lysosomal concept of platelet secretion - revisited. Eur J Haematol 1989. Suppl 50; Vol 43.

23. SOURCES
ROLE
PRP
(multiplication factor)
Platelets
Blood
Initial control of haemorrhage, release GF
3-8
PDGF
Platelets
Stimulates cell replication, angiogenesis, mitogen for fibroblasts
5-29
VEGF
Platelets
Angiogenesis
6-52,7
TGF-β
Platelets
Increase chondrocyte expression, induce Chondrogenic differentiation
of MSCS, enhance matrix deposition, decrease the suppressive effects
of inflammatory mediators IL-1 on proteglycans synthesis in cartilage
3,5-27
FGF
Platelets
Stimulates proliferation of myoblasts, angiogenesis
Detected
EGF
Platelets
Proliferation of mesencymal and epithelial cells, Potentiation other GF
3
HGF
Plasma
Angiogenesis, mitogen for endothelial cells, anti-fibrotic
No increase from baseline
IGF-1
Plasma
Stimultes myoblasts and fibroblasts, mediator in growth and repair of
skeletal muscle
No increase from baseline
EGF: epidermal growth factors, HGF: hepatocyte growth factor, IGF-1: insuline-like growth factor, PDGF: platelet-derived growth factor, TGF-b: transforming
growth factor beta, VEGF: vascular endothelial growth factor, FGF: fibroblasts growth factor

26. Does ACP/PRP increase human
tendon, bone, cartilage and muscle
cell proliferation
Mazzocca et al UCon

27. Local anesthesia and cortison has a
harmfull effect on proliferation of
tenocytes
Mazzocca et al UCon

28. Does repeated dosage help?
Mazzocca et al U Con

29. Where and when is the
action?
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Cook and Purdam
BJSM 2009
Reactive
tendinopathy?
Tendon dysrepair?
Degenerative
tendinopathy?

30. Consider a
patient with
Achilles tendon
pain as just one
example

39. The heel drop stimulates
integrins to flip and this triggers
signaling pathways and PRP
acts??????

40. The heel drop stimulates
integrins to flip and this triggers
signaling pathways

41. The heel drop stimulates
integrins to flip and this triggers
signaling pathways

42. The heel drop stimulates
integrins to flip and this triggers
signaling pathways

43. The heel drop stimulates
integrins to flip and this triggers
signaling pathways

44. The heel drop stimulates
integrins to flip and this triggers
signaling pathways

45. The nucleus is signaled to
create mRNA and PRP acts?

46. The nucleus is signaled to
create mRNA

47. The nucleus is signaled to
create mRNA
Gene transcription and PRP
acts?

48. The nucleus is signaled to
create mRNA

49. The nucleus is signaled to
create mRNA

50. The nucleus is signaled to
create mRNA

51. Ribosomes create protein
Ribosomes

52. Ribosomes create protein
Ribosomes

53. Collagen extrudes from matrix
Ribosomes

54. Collagen extrudes from matrix

57. Collagen is repaired

60. Recent studies:

62. Recent RCT in OA:

63. Knee OA:

65. CASE: PATELLAR TENDON LESION
RMN BASAL
RMN AT 6 M F U
Male, 25 y, D LEAGUE SOCCER PLAYER
3y of pain and limited function, bilateral, previous surgery
RETURNED AT PREVIOUS ACTIVITY LEVEL AT 4 MONTHS

66. PRP IN TENDON PATOLOGY
TREATMENT
ü PROMISSING RESULTS IN ATHLETES
ü TREATMENT OF FAILED CASES
ü HAVE TO BE COMBINED WITH
PHYSICAL THERAPY
ü RANDOMIZED STUDIES ARE NEEDED

67. Tendinopathy: Effect?

68. PRP and muscles

70. AFTER TREATMENT
ü Restricted activity for 24 hours
ü No use of non-steroidal medication.
ü Mild activities with bike or mild exercises in pool

75. Use ultrasound guided injections!

77. This lecture will teach you:
n
n
Why is PRP hot?
Proof of concept?
n
n
n
n
n
n
n
n
Role in tendon, ligament, muscle and cartilage
Procedure- dose- frequency
White cells ?
Local anesthesia ?
Antiinflammatories ?
Adverse effects ?
Anti doping regulations
Summary

78. Adverse effects?
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So far no serious side
effects reported
A case report on DVT in
November 2010 and a
comment on being aware
of this possibility

79. This lecture will teach you:
n
n
Why is PRP hot?
Proof of concept?
n
n
n
n
n
n
n
n
Role in tendon, ligament, muscle and cartilage
Procedure- dose- frequency
White cells ?
Local anesthesia ?
Antiinflammatories ?
Adverse effects ?
Anti doping regulations
Summary

80. PRP from a regulatory viewpoint:
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Autologous blood
No agreement on procurement (degree of
centrifugation, white cells?)
Principally no difference in mechanism on
muscle, tendon and ligaments
No indication that PRP has any effect in
healthy tissue

88. Where does it belong?…
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Exercises for rehabilitation
Strength training
Aligning tissue with stretching
Manual therapy
NSAIDs, cortisone
Hyaluronic acid, PRP
Surgery
PRP?

94. Intratendinous
injections
of
autologous
conditioned
plasma,
or
platelet
rich
plasma
with
or
without
WBC
enrichment
for
patellar
tendinopathy
A
mul&-­‐centre,
double-­‐blind,
randomized
controlled
trial
*Alex
Sco*1,
*Kim
Harmon2,
Roald
Bahr3,
Lars
Engebretsen3,
Robert
LaPrade4
1.
Department
of
Physical
Therapy,
University
of
BriJsh
Columbia,
Canada
2.
Departments
of
Family
PracJce,
Orthopaedics
and
Sports
Medicine,
University
of
Washington,
USA
3.
Oslo
Trauma
Research
Centre,
Norway
4.
Steadman
Clinic,
Vail,
USA

95. EBM: Definition
Integrate current “best evidence”
from clinical research
with individual clinical expertise
and patient preferences
in making decisions about the care of individual patients
Rosenberg W & Donald A. BMJ 1995; 310:1122-6

96. The Oslo Sports Trauma Research Center
has been established at
the Norwegian School of Sport Sciences
through generous grants from the Royal Norwegian Ministry of
Culture, the South-Eastern Norway Regional Health Authority,
the International Olympic Committee, the Norwegian Olympic
Committee & Confederation of Sport, and Norsk Tipping AS