Resorbable meniscus scaffold for the treatment of partial meniscal tear or meniscal loss

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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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Presenters Financial Disclosure

• No potential 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

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Tibial Plateau Load Transmission
a
d
b
c
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(a) Intact meniscus (b) partial meniscectomy
(c) scaffold implanted knee (d) fully
meniscectomized knee
Ovine Model (HSS)
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Current Standard of Care
Biomechanical Cadaver Study

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  Partial Meniscectomy
• Mechanical imbalance
• in the knee joint
• 
  Addresses symptoms only

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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

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The Optimum Material
An Optimized Design
A new vascularized and functional meniscus
Results in
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THE IRREPARABLE MENISCUS

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i Ghadially FN, Lalonde JM, Wedge JH
(1983)136773-791. ii King D. (1936) J Bone
Joint Surg 181069-1076.
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The Actifit concept
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Tissue regeneration through vascular ingrowth and
cellular infiltration from the synovium and the
meniscal rim
Partial meniscectomy
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) lt 35 kg/m2
• Axial alignment
• ICRS classification 3
• Full understanding of importance to adhere to
  rehabilitation program

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• Safety and Efficacy Study

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Study Centers

• NAME
• 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
• Adverse event profile (ongoing)
• Gross examination at 12 months relook
• Device stability and cartilage score on MRI (3,
  6, and 12 months)
• Performance
• Tissue ingrowth
• Dynamic Contrast Enhanced MRI (3 months)
• Tissue Biopsy (12 months)
• Efficacy
• Pain
• VAS (Baseline, 1 week, 3, 6,12 months)
• Functionality
• IKDC, KOOS, Lysholm (Baseline, 3, 6, 12 months)

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Study Population

• 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)

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Baseline characteristics
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
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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

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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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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 permeability1, 2
• Increase in SI in the first 3 minutes can only be
  explained by the presence of blood vessels

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Imaging Findings

• 1 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 Findings

• 3 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 Findings

• 3 Months
• In 32 out of 48 subjects complete filling of the
  meniscal defect was observed.
• 17 subjects had slight (lt33) external
  displacement and 10 had moderate (gt33, lt66))
  external displacement of the body of the scaffold
  meniscus.

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Imaging Findings

• 12 Months
• In all subjects tissue gain was achieved with
  complete fill of the meniscal lesion in 10 out of
  33 subjects.

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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 Findings

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

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

• 12 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.

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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

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• 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 MRI

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Conclusion
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Actifit is a safe, novel solution for the
treatment of irreparable, partial, meniscal
defects
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