INTRA ARTICULAR GROWTH FACTORS AND CARTILAGE REPAIR
HENRIQUE JONES – PORTUGUESE AIR FORCE HOSPITAL - LISBON
www.henriquejones.pt
John Hunter - 1743
Hippocrates – 400 BC
“Bone, cartilage, nerve, or the prepucewhen divided, are not regenerated, nordo the parts reunite.”
“From Hippocrates to the present age, it isuniversally allowed that ulcerated cartilageis a troublesome thing and that, oncedestroyed, it is not repaired. “
ANABOLICS
CATABOLICS
CARTILAGE BALANCE
THE MAIN PROBLEM OF CARTILAGE – CHONDROCYTE DISEASE
Growth Factor Skeletal Muscle Hyaline Cartilage Meniscus Ligament Bone
IGF-1 + + + + +
bFGF + + + + +
NGF + - -
PDGF - - +
EGF - + + +
TGF-alpha - + -
TGF-beta + + + + +
BMP-2 + + +
+ = positive effect; - = no or negative effect; blank = not testedIGF-1 = insulin-like growth factor-1; bFGF = basic fibroblast growth factor; NGF = nerve growth factor; PDGF = platelet-derived growth factor; EGF = epidermal growth factor;TGF = transforming growth factor; BMP-2 = bone morphogenetic protein-2
GROWTH FACTORS ACTION IN TISSUES
Hyaline Cartilage
+
+
+
+
+
PRP* (ng/ml)
PDGF 133 - 250
TGF beta 170 - 470
VEGF 1-7
EGF 0.47
IGF-1 60 -100
GROWTH FACTORS CONCENTRATION IN PRP
* From diferent studies
Intra-articular injection of an autologous preparation rich in growth factors for the treatment of knee
OA: a retrospective cohort study.
Sánchez M, Anitua E, Azofra J, Aguirre JJ, Andia I.
Unidad de Cirugia Artroscópica "Mikel Sanchez", Vitoria, Spain. 2008 Sep-Oct;26(5):910-3.Clin Exp Reumathology
CONCLUSIONS: Although these preliminary results need to be evaluated in a randomized clinical trial, they provide
useful information about the safety of PRGF and open new perspectives on autologous treatments for joint diseases.
BioDrugs. 2005;19(6):355-62. Novel biological approaches to the intra-articular treatment of osteoarthritis.
Evans CH. Center for Molecular Orthopaedics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Alternatively, instead of injecting a heterogeneous, incompletely characterized mixture of native molecules into the
joint, it is possible to inject recombinant growth factors and cytokine antagonists. None of these are in routine clinical
use, but promising preliminary human trials have been performed with insulin-like growth factor-1 and the interleukin-
1 receptor antagonist. It is possible that sustained intra-articular production of such factors could be achieved by
gene transfer. Although gene therapy for osteoarthritis is not yet a clinical reality, the first human trial should begin
next year.
Ann Rheum Dis 1994;53:593-600 doi:10.1136/ard.53.9.593
Research Article
In vivo protection against interleukin-1-induced articular cartilage damage by transforming growth factor-beta 1: age-
related differences.
H M van Beuningen, P M van der Kraan, O J Arntz, W B van den Berg
CONCLUSIONS--TGF-beta 1 aggravates IL-1 induced knee joint inflammation, but counteracts the deleterious effects
of IL-1 on articular cartilage proteoglycan synthesis and content. The data indicate that TGF-beta 1 could play an
important part in articular cartilage restoration after IL-1 induced proteoglycan depletion.
Autologous Plasma Rich in Growth Factors (PRGF) Treating the Symptomatic Knee OA
Verified by Biotechnology Institute IMASD, February 2010
First Received: October 30, 2008 Last Updated: February 2, 2010 History of Changes
PurposeThe purpose of this study is to evaluate the efficacy and safety of PRGF infiltrations in the treatment of knee osteoarthritis.
Platelet-rich plasma: intra-articular knee injections produced favorable results on
degenerative cartilage lesions Journal Knee Surgery, Sports Traumatology, Arthroscopy
Volume 18, Number 4 / April, 2010
Elizaveta Kon1 , Roberto Buda2 , Giuseppe Filardo1 , Alessandro Di Martino1 ,
Antonio Timoncini2 , Annarita Cenacchi3 , Pier Maria Fornasari3 ,
Sandro Giannini2 and Maurilio Marcacci1 Volume 18, Number 4 / April, 2010
Conclusion: PRP injections is safe and may be useful for the treatment of early
degenerative articular pathology of the knee – pain, function, quality of life.
The Journal of Bone and Joint Surgery (American) 86:455-464 (2004)
© 2004 The Journal of Bone and Joint Surgery, Inc.
Autologous Chondrocyte Implantation Compared with Microfracture in the Knee . A Randomized Trial
Gunnar Knutsen, MD1, Lars Engebretsen, MD, PhD2, Tom C. Ludvigsen, MD2,
Jon Olav Drogset, MD3,Torbjørn Grøntvedt,MD, PhD3, Eirik Solheim, MD, PhD4,
Torbjørn Strand, MD4, Sally Roberts, PhD5, Vidar Isaksen, MD1 and
Oddmund Johansen, MD, PhD1
Conclusions: Both methods had acceptable short-term clinical results. There was no significant difference in macroscopic or histological results between the two treatment groups and no association between the histological findings and the clinical outcome at the two-year time-point.
Autologous chondrocyte implantation versus microfracture for knee cartilage injury: a prospective randomized trial, with 2-year follow-up .Dieter Van Assche, Filip Staes, Danny Van Caspel, Johan Vanlauwe, Johan Bellemans, Daniel B. Saris and Frank P. Luyten KSSTA Volume 18, Number 4 / April, 2010
� The therapeutic role of micro fractures in small chondral defects is universally recognised regarding the intention of releasing marrow elements, including stem cells, growth factors and other healing proteins, creating a special environment for a new tissue formation.
�With this in mind, we thought of an additional external help to the healing process, with the addition of Platelet Rich Plasma, to micro fractures site, utilizing a new technique of reference and, PRP, application – the multi needle technique.
MF + GFMULTI
CATETERS
PERSONNALTHECNIQUE
Sixty nine official football players with chronic, limited, (< 3 cm2), chondral symptomatic Knee lesion,
without other relevant pathology, submitted to surgery, between 2004 and 2008, grouped in 3 different
series, concerning treatment. The first group was treated by micro fractures in association with PRP
(Group 1 – MF+AGF), the second group was treated with micro fractures alone (Group 2 – MF), and the
third group was treated by abrasoplasthy (Group 3 – AB).
THE STUDY
Subjective (60)
Pain (20)
20 -none
15 -mild, activity related
10 -moderate, activity related
5 -unable to perform sports
0 -pain at rest
Swelling (10)
10 - none
5 - sports / activity related
0 - with ADL’s
Objective (40)
Range of Motion (10)
10 - full ROM compared to opposite knee
5 - lacks 5-10 degrees flexion and/or
extension
0 - lacks > 10 degrees flexion and/or
extension
Ability to Perform Knee Bends (10)
10 - without difficulty
5 - mild discomfort
0 – unable
Ability to perform sport / work (20)
10 - no restrictions
5 - mild decrease in performance
0 - unable to compete / work at same level
Locking
10 - none
0 - intermittent locking
Effusion (10)
10 - none
5 - mild
0 - moderate to severe
Pain with Varus / Valgus stress on ROM (10)
10 - none
5 - mild
0 - moderate to severe
CHONDRAL DEFECT SCORING SCALE ( CDSS )
COMPARATIVE STUDY RESULTS : 3 ATHLETS SERIES
3 SERIES CHARACTERISTICS
SERIES SÉRIE 1 MF+MC
SÉRIE 2MF
SÉRIE 3ABRASATION
AGE (MEDIA) 25.2 28.6 24.2
MAJORSYMPTOMS
PAIN / SWE/FI PAIN/FI/SWE PAIN/FI/SWE
CDSS BEFORE (MEDIA)
55 65 68
CDSS +/- 18 MONTHS( MEDIA)
85 80 83
SEX 21M – 2W 19 M – 4 W 20M-3W
LOCATION IC 19-EC3-PAT1
IC19-EC4 IC18-EC5
COMPARATIVE STUDY : 3 ATHLETS TREATMENT SERIES
BEFORE SURGERY 1 YEAR AFTER SURGERY
EVOLUTION 1 YEAR AFTER SURGERY
1 YEAR AFTER SURGERY
FOOTBALL WITHOUT COMPLAINS OR LIMITATIONS
CARLA , 15 YEARS OLD ( PAIN + SWELLING + FUNCTION DISABILITY)
3.5 MONTHS
RESULTS
�The injuries were classified according Outerbridge classification and the results were validated with Chondral Defect Scoring Scale(CDSS), clinical and imagiologic evaluation.
�The present study demonstrates that the micro fractures associated with PRP (Autologous Growth Factors) had mean CDSS scores at 18 months significantly (p<0.01) better than the other two groups, although the mean values, before treatment, were above the other two groups. The clinical and imagiologic findings show a good or very good evolution with return to competition, the same level, in 91 % of the cases.
�To the author these results confirm the positive effects, and better results, regarding literature, with the association of Autologous Growth Factors to the, well known, technique of micro fractures.
DISCUSSION
� In cases of, Outerbridge grade I e II symptomatic, limited, lesions, the tratament could be the tradicional Abrasationplasty and/or Microfractures, alone, but , mostly in grade II, the association of GF gives a better prognosis and is hightly recomended .
� In cases of, Outerbridge grade , III, and even IV, symptomatic, limited lesions the treatment should be Microfractures in association with PRP ( Growth Factors ).
� The association of GF in the MF thecnique seems to show better results, mostly in grade III injuries, comparing, isolated MF as shown, in this and other, authors studies.
RECOMMENDATIONS
CONCLUSIONS OF THIS STUDY
� Despite all the insufficiencycies of this study, it seems that, based on clinical findings, imaging studies and clinical evidence, that MF is a reasonable first approach treatment of limited chondral defects ( degenerative or traumatic ), even for football players.
� Return to competition it possible in an average of 3.5 to 4 months.
� More follow up, experience and comparative studies must be achieved.
� This technique does not exclude future procedures.
� The introduction of complementary GF to the technique of MF seems to improve the percentage of good results comparing with existing literature on MF alone.
� Cost effective; technically feasible ; supportive clinical data
� Does not reliably produce hyaline cartilage
� We still go on following this players and further results will come soon.
– Facilitate the natural reparación capacity– Replacement of injuried cartílago with tissues or cells that can generate matrix
• Limitations– Experimental thecniques– Hight costs– Confiability– Versatility- Understanding sub-chondral bone
– To obtain cells and tissues, implants, that answer a to local stimulation with diferentation in mature quality chondrocytes
– Production of integrated extracelular cartilaginousmatrix– Reproduction in diferent clinical scenaries
THE PRESENT AND THE FUTURE
Recently we apply Mesofol as selant. We begin now covering with fibrine glue and collagen membrane.
“It should be clear that cartilage does not yield its secrets easily and
that inducing cartilage to heal is not simple. The tissue is difficult to
work with, injuries to joint surface, whether traumatic or degenerative,
are unforgiving, and the progression to osteoarthritis is sometimes so
slow that we delude ourselves into thinking we are doing better than we
are. It is important, however, to keep trying." Henri Mankin
THANKS FOR YOUR ATTENTION!
The author declares no conflit of interests
in this presentation!