Chondral Defect Reconstruction with Hyaluronic Acid
Scaffold (HyaloFast®) and Autologous Bone Marrow
Aspirate Concentrate
...
Articular Hyaline cartilage has a limited

regeneration capacity
In 1743 W.Hunter Stated that :
“from Hippocrates to the p...
Autonomous hyaline cartilage defect regeneration is due
to infiltration of Mesenchimal Stem Cells (MSCs) from the
bone mar...
Articular Cartilage
(Buckwalter et al. 1994)

Composed of:

-Chondrocytes (1-10%)
-Extra-Cellular matrix
• Water (65-80%)
...
Therapeutic Goals of Articular Cartilage
Repair
•

To resolve or at least alleviate the symptoms

•

Ensure the functional...
Treatment procedures
(Nehrer, et al. 2000; Felson, et al., 2000).

Symptomatic procedures
•

Lavage, Shaving, Debridmen , ...
Regenerative Techniques
•

ACI and MACI (Auotologous Cultured Chondrocytes)

•

New one-step techniques with scaffolds+MSC...
ACI and MACI (Auotologous Cultured Chondrocytes )
Transplantation of cultured autologous chondrocytes into the cartilage d...
One-step techniques with scaffolds + MSCs
The use of autologous bone marrow-derived MSCs in the treatment of
osteochondral...
Free MSCs?
Some papers found only a small number of MSCs in the
implant site after 10 days
(5% of the implanted BM-MSCs).
...
MSCs NEED A SCAFFOLD FOR SUPPORT
• To stay and grow at the defect site
• To build a 3D structure of hyaline-like tissue

T...
One-step techniques with scaffolds + MSCs
In order to stabilize the blood clot at the defect site, reasorbable
scaffolds a...
HYAFF 3D-Scaffold

•
•
•
•

13

Non woven felt, 2 mm thick, fiber diameter 10 microns.
Biocompatible
Bioresorbable
Main de...
RESUMING

AUTOLOGOUS CELLS IMPLANT
Knee chondral defects:
• III - IV degree

(According to Outerbridge classification)

• ...
Our case series
•
•
•
•

163 chondral defect of the knee (III-IV degree)
Age range 15-51 y
Defect size
mean age 36 y
• 64 ...
Study

Comparison MACI vs MSCs Implant
Inclusion criteria:

Exclusion criteria:

• Defect: III° - IV° degree

• Arthritis
...
Study

Comparison MACI vs MSCs Implant
Group 1 - 17 cases MACI (Two-step procedure ):
Mean age: 35,8 years (range15-49)
Ge...
Study
MACI Implant Protocol
• 1st surgical step: cartilage biopsy collection

• Chondrocites in vitro expansion, seeding a...
Study

MSCs implant protocol
• Harvest the bone marrow from postero-superior iliac crest,
with the patient in the lateral ...
Study
MSCs Implantation: Arthoscopic Technique
Study
MSCs Implantation: Large troclear defect
Study
Post-operative Rehabilitation
KEY POINTS
Immobilization: first 24 hours
Control Passive Motion (CPM): after 24 hours...
Follow up evaluations
Clinical evaluations:
•IKDC subjective: pre-op, 5 months, 10 months
•Tegner score: 10 months follow ...
Clinical Results

Summary of MACI case series –
Group 1

Patient . Age

Follow-up

IKDC (pre-op) IKDC (5 m)

IKDC (10 m)

...
Clinical Results

Summary of MSCs + scaffold case series Group 2

Patient Age

Follow-up IKDC (pre-op)

IKDC (5 m)

IKDC (...
MRI Results
Uniform post-operative NMR evolution :
• 3 months: subchondral bone edema important

3M

MSCs implant

• 6 mon...
MRI Results
24 months: there is a slight remodeling of 'subchondral bone,
that means a cartilage still in the remodeling p...
MRI Results

A

MSCs implant

B

MACI

C

MSCs implant

3M

E

MSCs implant

FF

24 M

D

MACI

12 M

MACI

G MSCs implant...
MACI 2nd look

MSCs 2nd look

SECOND LOOK 24 MONTHS

SECOND LOOK 6 MONTHS

D
Conclusions
On the basis of the results of this ongoing study, MSCs
implantation via one-step regeneration procedure at
pr...
BEWARE!!!
!!

In order to be effective in joint tissue regeneration, MSCs seem to need a
scaffold for :
•Improving bone ma...
www.marcospoliti.com
Dottore Marco Spoliti ortopedico, Cellule mesenchimali, difetto condrale Ricostruzione con Acido Ialuronico e midollo osse...
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Dottore Marco Spoliti ortopedico, Cellule mesenchimali, difetto condrale Ricostruzione con Acido Ialuronico e midollo osseo autologo Aspirare Concentrate

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il dottor Spoliti Ortopedico illustra come curare con le Cellule mesenchimali, difetto condrale Ricostruzione con Acido Ialuronico e midollo osseo autologo Aspirare Concentrate

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Dottore Marco Spoliti ortopedico, Cellule mesenchimali, difetto condrale Ricostruzione con Acido Ialuronico e midollo osseo autologo Aspirare Concentrate

  1. 1. Chondral Defect Reconstruction with Hyaluronic Acid Scaffold (HyaloFast®) and Autologous Bone Marrow Aspirate Concentrate M. Spoliti M.D., F.R. Rossetti M.D. San Camillo Hospital – Rome, ITALY 9/6/13 Satellite Symposium, Izmir Turkey 1
  2. 2. Articular Hyaline cartilage has a limited regeneration capacity In 1743 W.Hunter Stated that : “from Hippocrates to the present age, it is universally allowed that ulcerated cartilage is a troublesome thing and that when destroyed, it is not recovered”
  3. 3. Autonomous hyaline cartilage defect regeneration is due to infiltration of Mesenchimal Stem Cells (MSCs) from the bone marrow , through perforation/microfracturing the subchondral bone. Unfortunately the reparative tissue consists of fibrocartilage. This newly formed and less resistant tissue, could have a breakdown expecially in young active competitive patients. Minas & Nehrer 1997, Shapiro 1993 To produce cartilage of BETTER QUALITY, as yet unidentified FAVOURABLE CONDITIONS MUST BE CREATED. REPAIR OF LARGE FULL-THICKNESS ARTICULAR CARTILAGE DEFECTS IN THE RABBIT THE EFFECTS OF JOINT DISTRACTION AND AUTOLOGOUS BONE-MARROW-DERIVED MESENCHYMAL CELL TRANSPLANTATION T Yanai et Al , JBJS Br 2005
  4. 4. Articular Cartilage (Buckwalter et al. 1994) Composed of: -Chondrocytes (1-10%) -Extra-Cellular matrix • Water (65-80%) • Collagen (90-95% of type II) • Proteoglycans • Other matrix proteins and lipids P.Motta” La Sapienza” University Rome It is avascular, alymphatic, and aneural, nutrition through diffusion from the synovial fluid. Its lack of vascularity, high extracellular matrix to cell ratio, and lack of progenitor cells, leads to its limited capacity to self-repair injuries. 3
  5. 5. Therapeutic Goals of Articular Cartilage Repair • To resolve or at least alleviate the symptoms • Ensure the functional recovery of the movement • Restore the integrity of the articular surface • Prevent further deterioration of the tissue (Jackson, Scheer et al., 2001) The final goal should be to produce a repair tissue that has the same functional and mechanical properties of the original hyaline articular cartilage to prevent osteoarthritis.
  6. 6. Treatment procedures (Nehrer, et al. 2000; Felson, et al., 2000). Symptomatic procedures • Lavage, Shaving, Debridmen , Abrasion arthroplasty Biological restoration: tissue repair/regeneration based on cells or living tissues Repair procedures • • • • Subchondral drilling Microfracture Osteochondral transplantation (OCT) Periosteal or perichondral grafting Regenerative procedures • Autologous chondrocyte transplantation (ACT) • One-step mesenchymal stem cells techniques (MSCs)
  7. 7. Regenerative Techniques • ACI and MACI (Auotologous Cultured Chondrocytes) • New one-step techniques with scaffolds+MSC The goal of these techniques is to restore the articular surface with a newlyformed hyaline-like tissue having physical, biomechanical and durability properties as similar as possible to the native cartilage. 7
  8. 8. ACI and MACI (Auotologous Cultured Chondrocytes ) Transplantation of cultured autologous chondrocytes into the cartilage defects to regenerate hyaline articular cartilage. Two-step technique: 1st surgery: arthroscopic biopsy collection 2nd surgery: arthroscopic graft implantation Good clinical results at long term follow up, but… Disavantages: • two surgeries • high costs • Graft not immediatly available ACI 1st generation MACI 2nd generation
  9. 9. One-step techniques with scaffolds + MSCs The use of autologous bone marrow-derived MSCs in the treatment of osteochondral lesions, represents an opportunity allowing, at the same time: •the restoration of both cartilage and sub-chondral bone tissues •AVOID A TWO-STEP surgical procedure (less invasive, lower cost) The source of autologous MSCs can be: 1.bone marrow from subchondral bone at the lesion site (microfracture) 2.bone marrow aspirate, collected from the iliac crest, concentrated or not and then applied on the defect site. A limitation is that MSCs are simply released (1) or applicated (2) into the joint, rather then being contained at the site of the defect.
  10. 10. Free MSCs? Some papers found only a small number of MSCs in the implant site after 10 days (5% of the implanted BM-MSCs). Guest DJ, Smith MR, Allen WR. Equine embryonic stem-like cells and mesenchymal stromal cells have different survival rates and migration patterns following their injection into damaged superficial digital flexor tendon. Equine Vet J 2010
  11. 11. MSCs NEED A SCAFFOLD FOR SUPPORT • To stay and grow at the defect site • To build a 3D structure of hyaline-like tissue The goal is the appropriate scaffold
  12. 12. One-step techniques with scaffolds + MSCs In order to stabilize the blood clot at the defect site, reasorbable scaffolds are developed to enhance cartilage regeneration The Ideal Scaffold • • • • • • • • Resistant (Arthroscopic implant) Tridimensional Absorbing Allowing good cellular adhesion Enhancing MSCs proliferation Biodegradable Biocompatible Promoting cell differentiation towards chondrogenetic and/or osteogenic phenotype • Handful
  13. 13. HYAFF 3D-Scaffold • • • • 13 Non woven felt, 2 mm thick, fiber diameter 10 microns. Biocompatible Bioresorbable Main degradation product: Hyaluronic Acid
  14. 14. RESUMING AUTOLOGOUS CELLS IMPLANT Knee chondral defects: • III - IV degree (According to Outerbridge classification) • area > 1-5 cm2 MACI vs BM - derived MSCs • 2-steps surgery • Single step surgery • High costs • Less expensive procedure • No bony defect regeneration • Bony regeneration • Good results • Results (?) • Hyaline like cartilage
  15. 15. Our case series • • • • 163 chondral defect of the knee (III-IV degree) Age range 15-51 y Defect size mean age 36 y • 64 < 1 cm2 Last 4 years • 99 >1 -5 cm2 • • • 39 MACI 17 MSCs 43 microfractures + HialoFast >1 -5 cm2 • • 51 microfractures 13 OATs < 1 cm2
  16. 16. Study Comparison MACI vs MSCs Implant Inclusion criteria: Exclusion criteria: • Defect: III° - IV° degree • Arthritis • Width: 1- 5 cm 2 • Scheletrical malalignement • Age range: 15-50 years old • ACL-PCL tear • Patellar instability • Kissing lesions
  17. 17. Study Comparison MACI vs MSCs Implant Group 1 - 17 cases MACI (Two-step procedure ): Mean age: 35,8 years (range15-49) Gender: 10 M + 7 F Defect location: 2 patella ,1 tib.plateau ,5 lat. condyle, 9 med. condyle Mean follow-up time: 30,5 months (range 3 months to 4 years) Defect Size: 6 Pts >1/= 2 9 Pts >2 =3 2 Pts >3 Group 2 - 15 cases (BMAC)+ Hyalofast: Mean age: 31,9 anni (range19-42) Gender: 11 M + 4 F Defect location: 2 patella, 2 lateral condyle, 5 medial condyle, 2 troclea Mean follow-up time: 10,1 months (range 5 to 26 months) Defect Size: 3 Pts >1/= 2 7 Pts >2 =3 2 Pts >5
  18. 18. Study MACI Implant Protocol • 1st surgical step: cartilage biopsy collection • Chondrocites in vitro expansion, seeding and culture on 3D HA matrix (Hyalograft C autograft). • 2nd surgical step: arthroscopic graft implantation
  19. 19. Study MSCs implant protocol • Harvest the bone marrow from postero-superior iliac crest, with the patient in the lateral decubitus (60 mL of bone marow). • Process the collected bone marrow directly in the operating room by removing erythrocytes and plasma by a cell separator-concentrator consisting of a centrifuge and a disposable double chamber. • At the end of a 15 min centrifugation cycle, 7 mL of concentrate containing nucleated cells (stem cells, monocytes, lymphocytes, and other bone marrow resident cells) are retrieved in the anterior chamber. • 3ml/cm2 of BMAC can be loaded onto the scaffold together with the PRP gel and thrombin; the matrix, due to its hydrophilic properties, allows the homogeneous distribution of the concentrate fluid rapidly. •The pre-loaded scaffold arthroscopic technique can be implanted by
  20. 20. Study MSCs Implantation: Arthoscopic Technique
  21. 21. Study MSCs Implantation: Large troclear defect
  22. 22. Study Post-operative Rehabilitation KEY POINTS Immobilization: first 24 hours Control Passive Motion (CPM): after 24 hours, for 4 weeks Joint Loading: not allowed for about 6 weeks. 6th-10th week: gradual recovery of the joint loading and of the step Back to Sports: Low impact : from 4th month (swimming, cycling) High impact : from 10th month (running, soccer, tennis, etc…)
  23. 23. Follow up evaluations Clinical evaluations: •IKDC subjective: pre-op, 5 months, 10 months •Tegner score: 10 months follow up •MRI assesment: •all patients underwent MRI evaluation at 3- 6 -12 - 24 months •Cartilage repair evaluations: 3 Pts group 1 and 3 Pts group 2 2° look arthroscopy with biopsy and histology
  24. 24. Clinical Results Summary of MACI case series – Group 1 Patient . Age Follow-up IKDC (pre-op) IKDC (5 m) IKDC (10 m) B.B. S.A. P.F. P.M. D.D. V.M L.D. P.M. P.L. C.E. P.A. G.R. B.B. M.S. A.G. M.G. D.S. 4Y 9M 3Y 2Y 2Y 10 M 1Y 1Y 4Y 2Y 4Y 4Y 4Y 3Y 2Y 11M 1Y 32 53 25 35 30 27 36 35 23 41 33 31 40 25 19 17 51 88 90 75 84 98 80 83 80 49 95 88 74 89 85 87 77 65 35 48 46 23 15 42 34 44 49 21 47 45 37 23 24 49 28 90 95 70 84 89 85 85 76 45 90 74 51 73 80 85 80 75 IKDC pre - op: 32,5 Poor IKDC post- op 5 m: 78,5 Excel. IKDC post- op 10 m: 81,6 Excel. Tegner score (10 m) 7 7 5 9 9 7 9 7 4 8 6 5 5 7 9 6 4 TEGNER post op 10 m: 6.7
  25. 25. Clinical Results Summary of MSCs + scaffold case series Group 2 Patient Age Follow-up IKDC (pre-op) IKDC (5 m) IKDC (10 m) Tegner score (10 m) B.A. B.B. C.M S.L. R.V. P.M. T.G. M.D R.M S.G. M.L N.V. G.O. F.O. M.N. 2Y 18 M 1Y 1Y 2Y 10 M 11 M 18 M 2Y 10 M 3Y 1Y 16 M 17 M 15 M 85 88 90 45 73 85 74 72 90 85 93 91 72 77 84 89 76 95 55 75 88 85 83 90 80 87 65 77 81 76 28 42 22 40 35 25 27 33 29 41 32 19 42 39 25 25 35 30 27 36 35 23 41 33 31 40 25 29 27 45 IKDC pre - op: 32,1 9 7 8 4 6 6 6 7 9 7 8 7 6 7 7 Poor IKDC post- op 5 m: 80,2 Excel. IKDC post- op 10 m: 80,1 Excel. TEGNER post op 10 m: 7
  26. 26. MRI Results Uniform post-operative NMR evolution : • 3 months: subchondral bone edema important 3M MSCs implant • 6 months: substantial reduction in subchondral edema • 12 months: disappearance of edema 6 M MSCs implant • In the following assessment, we have found the coverage of the areas of chondropathy with integrity and restoration of the articular surface of the joint lining
  27. 27. MRI Results 24 months: there is a slight remodeling of 'subchondral bone, that means a cartilage still in the remodeling process. (in agreement with the results of Marcacci 2005). MACI MACI MSCs implant
  28. 28. MRI Results A MSCs implant B MACI C MSCs implant 3M E MSCs implant FF 24 M D MACI 12 M MACI G MSCs implant H 3Y MACI
  29. 29. MACI 2nd look MSCs 2nd look SECOND LOOK 24 MONTHS SECOND LOOK 6 MONTHS D
  30. 30. Conclusions On the basis of the results of this ongoing study, MSCs implantation via one-step regeneration procedure at present is a viable and lower cost alternative compared to two step techniques. With confirmed long-term results, one-step technique could eventually replace autologous chondrocyte implantation. Furthermore, the use of MSCs implantation allows us to treat via a "one-step“ technique associated lesions, such as meniscal or ligament tears .
  31. 31. BEWARE!!! !! In order to be effective in joint tissue regeneration, MSCs seem to need a scaffold for : •Improving bone marrow handling •Favouring cells attachment and organization at the lesion site •Stimulating MSCs differentiation into chondrocytes and proper reorganization of the osteochondral compartment Some PRP gel can add a supplement of growth factors to stimulate cell differentiation and optimize implant stability. The lack of a guide and containment in situ (osteo-chondral defect) leads the potential of these cells to a "wild” regeneration pattern.
  32. 32. www.marcospoliti.com

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