INTRA ARTICULAR GROWTH FACTORS AND CARTILAGE REPAIR

Recoa 2010

Henrique Jones, MD*

Introduction: Intra articular PRP injections, with therapeutic intention of growth

factors action regarding chondral injuries, became a quite frequent procedure,
although its benefits are no longer proved with convincing studies.

Besides some experience, with simply intra articular PRPinjections, the author reserves
this procedure to specific cases of moderate symptomatic osteo arthritis where pain
relieve and functional improving can be, frequently, seen.

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 infomration 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.

• Head of Orthopaedic Surgery of Portuguese Air Force Hospital, Lisbon

The principal experience of the author is the association of Micro fractures with intra
articular PRP in small limited chondral injuries, mostly in sports traumatology:

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, the authors 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. Sixty nine official football players with chronic, limited, (< 3 cm2), chondral
symptomatic Knee lesion, without other relevant pathology, submitted to surgery,
between 2004 and 2007, 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 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 92 % of the cases. To the authors 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.

Sports-related knee chondral injuries, mostly in soccer players, is a common diagnosis

in symptomatic knees, that evolutes with swelling, pain and functional inability. The
chondral lesion in a knee joint is a complicated problem with a difficult solution regarding the
limited intrinsic capacity of hyaline cartilage regeneration and the micro trauma acts like a
predisposed condition for such lesions in soccer players, the same way as a cumulative trauma
disorder. Many surgical techniques have been proposed and, micro fracture is one of the best
known techniques.

This technique was developed by JR Steadman in order to enhance chondral resurfacing by

providing a suitable environment for new tissue formation and taking advantage of the body's
own healing potential. He published in 2001 an article I1I in which micro fracture has been
done in more than 1800 patients. The released marrow elements (including mesenchymal
stem cells, growth factors, and other healing proteins) form a surgically induced super clot that
provides an enriched environment for new tissue formation. The good results and the validity
of this technique were confirmed with the work of Gunnar Knutsen I2I comparing this method
of treatment with Autologous Chondrocyte Implantation. In order to ameliorate the micro
fractures technique results, and based on anterior clinical experience and GF properties, the
authors innovated the application of Platelet derivate Autologous Growth Factors, in situ, after
micro fractures.

About Autologous Growth Factors

Utilizing the patient’s own blood, platelets can be collected, under centrifugal force, into a
highly concentrated formula I3I with parallel concentration of Growth Factors.
Growth factors may enhance current cartilage repair techniques via multiple mechanisms
including recruitment of chondrogenic cells (chemotaxis), stimulation of chondrogenic cell
proliferation (mitogenesis) and enhancement of cartilage matrix synthesis I4I. Two growth
factors that have been studied in cartilage repair are insulin-like growth factor 1(IGF-1) and
platelet derived growth factor (PDGF) but, also, bFGF, EGF, VEGF, TGF-beta and BMP-2 and 7,
showed positive effects on hyaline cartilage. IGF plays a key role in cartilage homeostasis,
balancing proteoglycan synthesis and breakdown. PDGF is a potent mitogenic and chemotactic
factor for all cells of mesenchymal origin, including chondrocytes and mesenchymal stem cells.
Resting zone chondrocytes cultured with PDGF demonstrated increased cell proliferation and
proteoglycan production I5I. Many studies suggest a potential role for these potent biological
regulators of chondrocytes in cartilage repair I6I.

Material and Methods

Between 2004 and 2008, 69 official football players, 61 males and 8 females, with a mean age
of 26.0 (16 – 39) years, with chronic, limited (< 3 cm2), chondral symptomatic lesion of the
knee, without other relevant pathology, were submitted to surgery, by the same surgeon, and
grouped in 3 different series, concerning treatment. The major symptoms were pain, swelling
(SWE) and functional disability (FI), with different incidence between the 3 groups, and the
internal condyle (IC) was the most affected in all 3 groups (Table 2).

Outerbridge classification I7I was used to classify the severity of the injury (table 1). The first
group of 23 players (Group 1 – MF+AGF) was treated with micro fractures associated with PRP
(autologous growth factors) using the GPS II (Gravitational Platelet Separation System) for
platelets separation and the injuries were mostly grade II and III. The second group (Group 2 –
MF) was treated with micro fractures, alone, and the severity of injuries was mostly grade I
and II. The third group (Group 3 – AB), grade I and II, limited injuries were treated only by
abrasoplasty. The objectives of this work were to demonstrate, using an adequate sore scale,
the validity of the arthroscopic micro fracture ( MF ) treatment in combination with autologous
growth factors ( AGF ) for knee chondral lesions in soccer players. All the players had an x-ray
(some of them had an MRI) study before surgery and we utilised the CDSS ( Chondral Defect
Scoring Scale) as chosen study to analyse the subjective and objective results I8I

Groups Group 1 Micro-Fractures Group 2 Micro- Group 3 Abrasoplasty

OUTERBRIDGE CLASSIFICATION (MF)+Aut.Growth Factors Fractures (MF) (AB)
Severity of chondral injury (AGF)
GRADE I 1 6 9
GRADE II 10 15 14
GRADE III 8 2 0
GRADE IV 4 0 0
Table 1 – Severity of chondral injury (Outerbridge Classification) for the 3 groups

We begin with multiple perforations with 3-4 mm diameter and 6 - 8 mm deep, using our own
awls (Fig. 1). The difficulty of PRP application, in micro-fractures site, during arthroscopic
procedure, took us to a new application technique, named by the authors the “multi-needle
application technique”, in which we reference the micro fracture site with multiple 14 or 16
mm catheters, allowing the individual injection of PRP in each individual micro fracture hole
(Fig. 2).

Fig. 1 – The micro fracture awls utilised

Some of instilled PRP will stay in articular space which, is probed, to have a positive effect on
post operative pain, swelling and range of motion.

A B

C
Fig. 2 - The multi – needle application technique. A Catheter`s angulations in order to reach
the throclear injury. B The arthroscopic image of multiple catheters. C The extra articular
image of the technique.

Statistical analysis

Statistical analyses were performed using software SPSS (versions 14.0 and 16.0). The
statistical significance levels used were 1% and 5%.

An exploratory analysis was first used. Means, standard deviations and confidence intervals at
a 95% confidence interval were calculated for CDSS, in each period and separately for each
group one of the three groups.

Imagiolog examinations

The results of x-ray, and in some cases MRI, show a better defect image, according with clinical
improvement (Fig 3)
 A B

Fig. 6 - X-ray evolution of one of the study cases. A Before surgery B After 18 months

Discussion

According with treatment options, regarding severity of the cases, the results were, globally
good or very good in clinical and return to competition aspects (Fig 4). The multiple
comparative tests applied detected differences between group 1 and both groups 2 and 3.
Thus, group 1 registered a CDSS evolution, on an average, significantly superior to groups 2 e 3
registered evolutions.

A B

Fig. 7 - A Treatment options according to severity B Results regarding sports activity

Different statistics methodologies applied are complementary and show corroborative results
between them. Group 1 distinguishes itself clearly from the other two groups. Group 1
(MF+AGF) registers CDSS mean values, before treatment, below the other two groups.
Nevertheless, regarding mean CDSS 18 months after treatment, Group 1 inversely shows
superior values in relation with the other two groups. All the groups show an increase in CDSS
mean values over time, but CDSS progress in group 1 is much higher than the ingrowths for the
other two groups. 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.

Conclusions

Despite the insufficiency of this study, still in progress regarding sample characteristics and
number of patients, it seems that, based on clinical findings ( CDSS) and imaging studies 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. The introduction of complementary AGF to the technique of MF seems to improve
the percentage of good results comparing with other groups, and literature, on MF alone. The
statistical data analysis, applying several complementary methodologies, show that MF
associated with GF presents a better CDSS evolution than the other groups of treatment. In
cases of, Outerbridge grade I e II symptomatic, limited, lesions, the treatment could be the
traditional Abrasoplasty and/or Micro fractures, alone, but , mostly in grade II, the association
of AGF gives a better prognosis and is highly recommended . In cases of, Outerbridge grade III,
and even IV, symptomatic, limited lesions the treatment should be Micro fractures in
association with PRP (Autologous Growth Factors).

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