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Resorbable meniscus scaffold for the treatment of

partial meniscal tear or meniscal loss

P.Djian, P.Beaufils, J Bellemans, P.Colombet, R Cugat, H Laprell, P.Neyret, H Paessler, E.Servien,

R.Verdonk, P. Verdonk

JOFDOF Martinique les trois ilets 2010

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No potential financial disclosure

Presenters Financial Disclosure

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Introduction

• The potential detrimental outcome following partial meniscectomy has been well establish

• Symposium SFA 1995 : – 95 Partial meniscectomies – F.U : 11.5 ± 1.2 Y– 45 % arthrosis

• Symposium SFA 2008– 47 partial meniscectomies– FU : 22.5 Years– 100 % arthrosis 3

a b c d

(a): Intact meniscus (b): partial meniscectomy (c): scaffold implanted knee (d): fully meniscectomized knee

Tibial Plateau Load Transmission*

*Ovine Model (HSS)7

Current Standard of Care

Partial Meniscectomy

Mechanical imbalance

in the knee joint

Addresses symptoms only

Biomechanical Cadaver Study

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THE SPORT SURGEONS NEED:

• A means to replace lost tissue and to reinforce remaining tissue post meniscectomy

• Ideal Product Requirements:

– Biocompatible

– Timely biodegradation

– Promotes blood vessel and tissue ingrowth

– Provides chondroprotection

– Easy to insert and suture arthroscopically

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THE ORTEQ SOLUTION

The Optimum Material

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An Optimized Design

Results in:A new vascularized and functional meniscus

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[i] Ghadially FN, Lalonde JM, Wedge JH (1983);136:773-791.[ii] King D. (1936) J Bone Joint Surg 18:1069-1076.

THE IRREPARABLE MENISCUS

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The Actifit™ concept

Partial meniscectomy Tissue regeneration through

vascular ingrowth and cellular

infiltration from the synovium and

the meniscal rim

Regenerated tissue next to

meniscal tissue

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Dimensions and shape based on human meniscus

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INDICATION• Irreparable medial or lateral partial meniscal tear

• Intact rim

• Anterior and posterior horn present

• Stable knee joint or stabilization procedure within 12 weeks

• (BMI) < 35 kg/m2

• Axial alignment

• ICRS classification ≤ 3

• Full understanding of importance to adhere to rehabilitation

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SURGICAL TECHNIQUE:

• Debride the damage

• Measure defect

• Cut the scaffold

• Insert into defect

• Suture in place

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Safety and Efficacy Study

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Study CentersNAME• Prof R Verdonk• Dr P Beaufils• Prof P Neyret• Dr H Paessler• Dr R Cugat• Dr P Colombet• Dr H Laprell• Dr P Djian• Prof J Bellemans

AFFILIATION• University Hospital Gent• Centre Hospitalier de Versailles• Centre Livet de Lyon• Atos Praxisklinik Heidelberg• Hospital Quirón de Barcelona• Clinique de Merignac-Bordeaux• Lubinus Clinicum of Kiel• Institut Nollet Paris• University Hospital Pellenberg

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OBJECTIVES– Safety

o Adverse event profile (ongoing)o Gross examination at 12 months relooko Device stability and cartilage score on MRI (3, 6, and 12

months)– Performanceo Tissue ingrowth

• Dynamic Contrast Enhanced MRI (3 months)• Tissue Biopsy (12 months)

– Efficacyo Pain

• VAS (Baseline, 1 week, 3, 6,12 months)o Functionality

• IKDC, KOOS, Lysholm (Baseline, 3, 6, 12 months)

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Study Population

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Enrolment : March 2007- April 2008

Enrolled: 52 subjects (34 M / 18 L)

Withdrawn before 3 month follow-up:1 post-operative infection

Major protocol violations: 8 subjects (5 M / 3 L)of which 3 withdrawn (2 M / 1 L)

Baseline characteristics

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Medial Lateral

N = 34 N = 18

Age (years)

Mean ± SD: 33.4 ± 9.4 25.8 ± 8.5

Sex (n)

Male: 25 (73.5%) 14 (77.8%)

Female: 9 (26.5%) 4 (22.2%)

Longitudinal length (mm)

Mean ± SD: 48.8 ± 10.4 43.9 ±8.6

Previous surgeries on index knee*

No previous surgery on index knee 2 ( 3.8%)

One previous surgery on index meniscus 34 (65.4%)

Two previous surgeries on index meniscus 12 (23.1%)

* Missing data on 4 subjects

Baseline characteristics

Safety No Serious Adverse Device Events Six Serious Adverse Event:

Subject number Description of SAE

01‑002* Allograft transplantation / investigational device removal

01‑005* Medical device removal

01-013 Cartilage graft

01‑023* Knee arthroplasty / investigational device removal

06‑001 Myocardial infarction

07‑004 Post operative infection with investigational device removal

* Subjects 01-002, 01-005 and 01-023 did not fulfill the inclusion criteria and were considered protocol violators.

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Safety AE profile similar to that reported in the literature

for meniscal surgery and meniscal implants.

Overall, 29 (55.8%) subjects reported an AE (20 M / 9 L)

Majority of AEs were mild or moderate in intensity.

7 subjects experienced AEs considered probably or possibly related to the device.

22 subjects experienced AEs considered related to the meniscus repair procedure.

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Results

• Clinical data :– KOOS Score– IKDC Score– VAS – Lysholm score

• Anatomic control– Relook at one year post-op

• Biopsie and histological control

– MRI 1 week, 3 MO, 6 MO, 12 MO• Special interest for vascularization 2

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Clinical Data : Efficacy

3 Months data available for 51 subjects

6 Months data available for 51 subjects

12 Months data available for 50 subjects

18 Months data available for 30 subjects

Parameters:

VAS

KOOS

IKDC

Lysholm score

*p=0.007

22.9 point change in mean VAS from baseline*

Efficacy at 12 Months

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Efficacy at 12 Months

24.8 point change in mean IKDC from baseline*

*p=0.0012

22.4 point change in mean Lysholm from baseline*

*p=0.0036

Efficacy at 12 Months

KOOS Symptoms

*p=0.0371

13.4 point change in mean KOOS Symptoms from baseline*

Efficacy at 12 Months

*p=0.0117

16.7 point change in mean KOOS Pain from baseline*

Efficacy at 12 Months

*p=0.0197

16.2 point change in mean KOOS Daily Living from baseline*

Efficacy at 12 Months

*p=0.0020

30.7 point change in mean KOOS sports from baseline*

Efficacy at 12 Months

*p=0.0143

21.9 point change in mean KOOS quality of life from baseline*

Efficacy at 12 Months

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Anatomical results

• Relook at 1 year FU– Biopsie and histological evaluation

– 27 biopsies samples• No signs of necrosis or cells death• Biocompatibility• Successful tissue ingrowth• No loose fragments of scaffold

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Relooks

L-M 8001

Photos courtesy of Dr Djian, Paris, France

Relooks

R-L 1016

Photos courtesy of Professor R Verdonk, Ghent, Belgium

Relooks

9003

Photos courtesy of Professor Bellemans, Leuven, Belgium

Histology Results

Biopsy from center of free inner edge

N= 27

Histology Results

Fibrous capsule (C)

layer 1: vascular, hyper cellular

layer 2: avascular, transition zone

layer 3: avascular, hypo cellular

Fibrous capsule

layer 1: vascular, hyper cellular

layer 2: avascular, transition zone

layer 3: avascular, hypo cellular

Histology Results

CD 34 IHC (200x) showing capsule, formation of vessel “sprouts” (arrows) in layer 1

Capsule and Layer 1

Histology Results

Histology Results

Sirius Red stain (400x) Layer 2 fibroblasts (short arrow) and fibrochondroblastic-like cells

(long arrow)

Layer 2

Histology Results

H&E staining : chondroblast like cells in layer 3

Layer 3

Histology Results

Immunohistochemistry (400x) with positive cartilage marker S100

Layer 3

Imaging Protocol Anatomic MR imaging at 1 week, 3, 12 and 24

months post-implantation

Dynamic Contrast Enhanced MRI (DCE-MRI) at

3 months Imaging in first 3 minutes after IV gadolinium injection

Influx of gadolinium causes increase in the signal Intensity

(SI) of a tissue

Signal enhancement is primarily determined by

vascularization, but also by perfusion rate and capillary

permeability[1, 2]

Increase in SI in the first 3 minutes can only be explained

by the presence of blood vessels

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Imaging Findings1 Week

No loosening of sutures or tears of the

scaffold were found.

All scaffolds had a normal position of

the posterior horn.

Some mild or moderate extrusion of

the body of the scaffold was observed.

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Imaging Findings3 Months

Increased enhancement observed in the peripheral half of the scaffold,

and thus evidence of tissue ingrowth into the scaffold in 36/42 (85.7%)

subjects with DCE-MRI at 3 months post-implantation.

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Imaging Findings3 Months

In 32 out of 48 subjects complete filling of the meniscal defect was observed.

17 subjects had slight (<33%) external displacement and 10 had moderate (>33%, <66%)) external displacement of the body of the scaffold meniscus.

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Imaging Findings12 Months In all subjects tissue gain was achieved with complete fill of the

meniscal lesion in 10 out of 33 subjects.

Complete filling of the meniscal defect at 12 months in subject with an autologous osteochondral plug transfer to repair a pre-study osteochondral defect overlying the scaffold.

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Imaging Findings12 Months

3/33 subjects had improved cartilage scores in the index compartment.

Filling of cartilage defect in the area overlying the tissue populated scaffold.

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Imaging Findings12 Months 3/33 subjects had a deteriorated cartilage scores in the index compartment.

Of these, two had generalized deterioration of the knee and one had developed a focal defect in an area not in direct contact with the scaffold.

Focal defect in area not adjacent to scaffold

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Discussion

• No comparative data

• Need to augmente the F.U.

• Cartilage status 15 years F.U

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Discussion

• Prospective study

• Clinical data and safety evaluation

• Anatomical evaluation with relook and biopsies

• MRI and vascularization 50

• Safe– No SADEs– Biocompatible

• Vital cell populations in all biopsies

• Promotes ingrowth of meniscus like tissue in 85.7% – Meniscus like morphology in biopsies– Positive staining for chondroblasts

• Effective– Significant improvements of pain and functionality

• Easy to use– Sizing, cutting, positioning, suturing

– Visible on MRI44

Conclusion

Actifit™ is a safe, novel solution

for the treatment of

irreparable, partial, meniscal

defects45