Intra articular Growth Factors and Cartilage Repair. Henrique Jones

8/6/2019 Intra articular Growth Factors and Cartilage Repair. Henrique Jones

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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.

Snchez M, Anitua E, Azofra J, Aguirre JJ, Andia I.

Unidad de Cirugia Artroscpica "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. [email protected]

Alternatively, instead of injecting a heterogeneous, incompletely characterizedmixture 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


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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


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authors innovated the application of Platelet derivate Autologous Growth Factors, in situ, after

micro fractures.

About Autologous Growth Factors

Utilizing the patients own blood, platelets can be collected, under centrifugal force, into ahighly 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 chemotacticfactor for all cells of mesenchymal origin, including chondrocytes and mesenchymal stem cells.

Resting zone chondrocytes cultured with PDGF demonstrated increased cell proliferation andproteoglycan production I5I.Many studies suggest a potential role for these potent biologicalregulators 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

OUTERBRIDGE CLASSIFICATION

Severity of chondral injury

Group 1 Micro-Fractures

(MF)+Aut.Growth Factors

(AGF)

Group 2 Micro-

Fractures (MF)

Group 3 Abrasoplasty

(AB)

GRADE I 1 6 9

GRADE II 10 15 14


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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


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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)


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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 CDSSmean values over time, but CDSS progress in group 1 is much higher than the ingrowths for the


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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


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Intra articular Growth Factors and Cartilage Repair. Henrique Jones

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