INTRA ARTICULAR GROWTH FACTORS

AND CARTILAGE REPAIR

www.henriquejones.pt

HENRIQUE JONES – PORTUGUESE AIR FORCE HOSPITAL - LISBON

 “Bone, cartilage, nerve, or the prepuce
when divided, are not regenerated, nor
do the parts reunite.”

Hippocrates – 400 BC

“From Hippocrates to the present age, it is

universally allowed that ulcerated cartilage
is a troublesome thing and that, once
destroyed, it is not repaired. “

John Hunter - 1743

 CARTILAGE BALANCE

ANABOLICS
CATABOLICS

THE MAIN PROBLEM OF CARTILAGE – CHONDROCYTE DISEASE

 GROWTH FACTORS ACTION IN TISSUES

Growth Factor Skeletal Muscle Hyaline

Hyaline Cartilage
Cartilage Meniscus Ligament Bone
IGF-1 + +
+ + + +

bFGF + + + + +
+
NGF + - -

PDGF - - +

EGF - + + + +

TGF-alpha - + -

TGF-beta + ++ + + +

BMP-2 ++ + +

+ = positive effect; - = no or negative effect; blank = not tested

IGF-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 CONCENTRATION IN
PRP
PRP* (ng/ml)

PDGF 133 - 250

TGF beta 170 - 470
VEGF 1-7
EGF 0.47
IGF-1 60 -100

* 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.
cevans@rics.bwh.harvard.edu

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

Purpose
The 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 + GF
MULTI
CATETERS

PERSONNAL
THECNIQUE
 THE STUDY

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).
Subjective (60)
CHONDRAL DEFECT SCORING SCALE ( CDSS )
Pain (20)
20 -none Ability to perform sport / work (20)
15 -mild, activity related 10 - no restrictions
10 -moderate, activity related 5 - mild decrease in performance
5 -unable to perform sports 0 - unable to compete / work at same level
0 -pain at rest
Swelling (10) Locking
10 - none 10 - none
5 - sports / activity related 0 - intermittent locking
0 - with ADL’s

Objective (40)
Range of Motion (10) Effusion (10)
10 - full ROM compared to opposite knee 10 - none
5 - lacks 5-10 degrees flexion and/or 5 - mild
extension 0 - moderate to severe
0 - lacks > 10 degrees flexion and/or
extension
Ability to Perform Knee Bends (10) Pain with Varus / Valgus stress on ROM (10)
10 - without difficulty 10 - none
5 - mild discomfort 5 - mild
0 – unable 0 - moderate to severe
COMPARATIVE STUDY RESULTS : 3 ATHLETS SERIES
COMPARATIVE STUDY : 3 ATHLETS TREATMENT SERIES

3 SERIES CHARACTERISTICS

SERIES SÉRIE 1 SÉRIE 2 SÉRIE 3

MF+MC MF ABRASATION
AGE (MEDIA) 25.2 28.6 24.2
MAJOR PAIN / SWE/FI PAIN/FI/SWE PAIN/FI/SWE
SYMPTOMS
CDSS BEFORE 55 65 68
(MEDIA)
CDSS +/- 18 85 80 83
MONTHS
( MEDIA)
SEX 21M – 2W 19 M – 4 W 20M-3W
LOCATION IC 19-EC3- IC19-EC4 IC18-EC5
PAT1
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
 DISCUSSION

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.
 RECOMMENDATIONS

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.
 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.
 THE PRESENT AND THE FUTURE

– Facilitate the natural

reparación capacity – To obtain cells and
– Replacement of tissues, implants, that
injuried cartílago with answer a to local
tissues or cells that can stimulation with
generate matrix diferentation in mature
quality chondrocytes
• Limitations
– Experimental – Production of
thecniques integrated extracelular
– Hight costs cartilaginous
– Confiability matrix
– Versatility – Reproduction in
- Understanding sub- diferent clinical
chondral bone scenaries
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

The author declares no conflit of interests

in this presentation!

THANKS FOR YOUR ATTENTION!