Lars Engebretsen MD, PhD Professor and Chair Department of Orthopaedic Surgery, U of Oslo
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This document provides disclosures for Lars Engebretsen, who will be giving a lecture on PRP in muscle and tendon injuries. It lists that Engebretsen has received consulting fees, fellowship and research grants, and serves on editorial boards for several journals. He has extensive experience in sports traumatology and currently holds leadership roles in several research centers and organizations. The lecture will discuss why PRP is popular, its potential roles in tendon, ligament, muscle and cartilage, injection procedures, the role of white blood cells, adverse effects, anti-doping regulations, and provide a summary.
![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](https://image.slidesharecdn.com/3-131014055438-phpapp01/85/Lars-Engebretsen-MD-PhD-Professor-and-Chair-Department-of-Orthopaedic-Surgery-U-of-Oslo-16-320.jpg)
Lars Engebretsen MD, PhD Professor and Chair Department of Orthopaedic Surgery, U of Oslo
- 1. PRP in muscle and tendon injuries Lars Engebretsen MD, PhD Professor and Chair Department of Orthopaedic Surgery, U of Oslo
- 2. Disclosures 2013 n n n 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 n n n n 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 n Head of Scientific activities in the IOC n Past President of ESSKA n Editor of BJSM IPHP n Deputy Editor JBJS (Am)
- 4. This lecture will discuss: 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
- 5. IOC Consensus statements • • • • • • • • • • • • • • • • • 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? n n n n 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 n 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? n n n n 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
- 53. Collagen extrudes from matrix Ribosomes
- 54. Collagen extrudes from matrix
- 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
- 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? n n 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: n n n n 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?… n n n n n n n 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