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Autologous
Chondrocyte
Transplantation
Dr. Babloo
Chondral Injuries
Commonly these injuries heal by scar tissue formation :
- Arthroscopic Debridement :
- Arthroscopic lavage
- Subchondral drilling
- Microfracture Marrow stimulation techniques
- Abrasion arthroplasty
to induce the growth of fibrocartilage into the
chondral defect.
Treatment options
Stages of ACI healing
Healing process has several stages. They
include the
• proliferative stage (0 to 6 weeks),
• the transition stage (7 to 12 weeks), and
• a remodeling and maturation stage which
occurs over a prolonged period (13 weeks to
3 years)
Proliferative stage
• During this stage, a primitive cell response
occurs with tissue fill of the defect and poor
integration to underlying bone or adjacent
cartilage.
• Mostly type I and some type II collagen is
produced.
• The tissue is soft and jelly-like and easily
damaged
Transition phase
• This marks the production of type II collagen framework
and the early production of proteoglycans.
• The proteoglycans, which form the matrix, help imbibe
water to give cartilage its viscoelastic properties.
• The tissue is not yet firm or well integrated and has the
consistency of a firm gelatin.
• It is milkable when probed with an arthroscopic nerve
hook, indicating incomplete integration to underlying
bone
Stage of remodeling and maturation
• The matrix proteins cross-link and stabilize
in large aggregates.
• The collagen framework reorganizes so as
to integrate into the subchondral bone and
form arcades of Benninghoff.
• Usually by 4 to 6 months, the tissue has
firmed up to a putty-like consistency and is
integrated to the underlying bone
• At this stage, patients experience good
symptom relief
• During this stage excessive activity may
cause repair tissue degeneration or
continued improvement in remodeling
• Hence, the concept of a time course of
healing is critical during the rehabilitation
phase of ACT
Indications for ACT
• Symptomatic full-thickness chondral injury of
the femoral articular surface (femoral weight-
bearing condyles and sulcus or trochlea) in a
physiologically young (<45 years) patient
who is compliant with the rehabilitation
protocol
• osteochondritis dissecans (OCD)
• Results of chondral injuries of the patella
and tibia (improved in 70% to 80% of
patients) are not as consistently high as
those of the femoral weight-bearing condyles
and trochlea (85% to 90% improved)
• ACT is not FDA approved as a treatment for
OA, that is, bipolar chondral injuries with
radiographic weight-bearing joint space loss
Pre-requisites for surgery
• Appropriate biomechanical alignment
• Ligamentous stability
• Range of motion
Not recommended for patients who have :
• an unstable knee
• in children
• in any joint other than knee.
Clinical examination
• Assessing subtle PF maltracking is important
because this may become more pronounced
and symptomatic after arthrotomy, which
may adversely affect the treatment outcome
of a trochlea or patellar ACT
• Assessment of predisposing factors for
cartilage injury and degeneration may affect
the prognostic outcome.
• These may include cruciate ligament
insufficiency, genu varus or valgus, obesity,
bone deficiency (AVN, OCD, and degenerative
or ganglion bone cysts), inflammatory
arthropathy, and familial osteoarthropathy
• These must be assessed so that they may be
either corrected in a staged or concomitant
fashion with ACT
Investigations
Wt bearing xray and skyline views
• Evidence of joint space narrowing 50% with
osteophyte formation, subchondral bony
sclerosis or cyst formation eliminates
patients from treatment (ie, if bone on bone
changes are present)
MRI
MRI scanning, while helpful for soft-tissue
evaluation of meniscal or ligamentous injury as
well as assessment of bone bruises and
osteonecrosis, does not have a high sensitivity
and specificity (75% to 93%) for determining the
extent of a chondral injury or subtle
chondromalacia changes.
The gold standard for determining whether a
symptomatic patient is a candidate for ACT
are normal radiographs, accompanied by an
arthroscopic assessment showing focal
pathology
A’scopy and Cartilage Biopsy
• Extent of lesion, Menisci, AP length of lesion
• Quality and thickness of the surrounding
articular cartilage will determine whether
healthy cartilage will be available for
periosteal suturing or a non-contained
chondral injury will require suturing through
synovium or small drill holes through the
bone.
• The most commonly chosen site for biopsy
is the superior medial edge of the trochlea
• Superior lateral femoral condyle
• lateral intercondylar notch
• superior transverse trochlea margin adjacent
to the supracondylar synovium
• Approximately 200 to 300 mg of articular
cartilage (approximately 5 mm wide and 1
cm long) is required for enzymatic digestion
for cell culturing.
• This contains approximately 2 to 3 lakh cells,
which may be enzymatically digested and
grown to approximately 120 lakh cells per
0.4 mL of culture media per implantation vial.
• After in-vitro expansion of cells 3 to 5 weeks
later, a suitable number and volume of cells
(usually one vial per each 4 to 6 sq cm
defect) will be grown to accommodate the
defect size required
• Can be stored upto 2 years
Implantation of Autologous Chondrocytes
Open implantation include arthrotomy, defect
preparation, periosteum procurement from
the tibia or femur, periosteum fixation,
periosteum water-tight integrity testing,
autologous or allogeneic fibrin glue sealant,
chondrocyte implantation and wound closure
MACI
• Matrix induced ACI
• Cultured chondrocytes seeded in bilayered
typeI/III collagen membrane
• Implanted using fibrin glue
Rehabilitation goals
● Aggressive ROM exercises to enhance
chondrocyte regeneration and decrease the
likelihood of intraarticular adhesions
●Touch-weight bearing for 6 wks and full by 12
weeks to prevent periosteal overload and central
degeneration or delamination of a weight bearing
graft
● Isometric and gentle functional muscle exercises to
regain muscle tone and prevent atrophy
• CPM is instituted as soon as cell attachment
has occurred, usually 6 hours after surgery
• This is utilized for approximately 6 to 8 hours
daily for up to 6 weeks after surgery
• Initially it is used for a range of 0° to 40°
maximum. CPM from 40° to 70° is not
recommended because maximal PF contact
forces occur in this range.
• CPM for defects of trochlear defects is less
vigorous
• The remainder of the motion is obtained by
the patient dangling a leg over the edge of
the bed to regain further motion
• On average, it takes 4 to 4 1/2 months for
patients to discard their supports and walk
comfortably
• Running is not permitted until graft hardness
becomes similar to adjacent cartilage, which
takes approximately 9 to 12 months
• Kneeling and squatting are not permitted
until 12 to 18 months after surgery
• Osteochondritis dissecans may take 18 to
24 months.
Advantages
• Can produce hyaline-like cartilage.
• Can fill defects regardless of size with functional repair
tissue.
• Moderate to large defects that have failed previous
intervention.
• Repair tissue which matures, rather than deteriorates
over time.
• Expected outcome
• Return to previous level of functioning
Disadvantages
• More invasive
• Expense
• Longer recovery
• Overall failure rate is at present quoted as
being 10%.
Complications
• Incomplete periosteal graft incorporation to host
cartilage and hypertrophic graft edge response.
• Clinically, this usually manifests as a
proliferative hypertrophic periosteal healing
response between 3 and 7 months after surgery
• Intra-articular adhesions with resultant stiffness
are uncommon
• Post-op hematoma, hypertrophic synovitis
Autologous chondrocyte implantation

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Autologous chondrocyte implantation

  • 2. Chondral Injuries Commonly these injuries heal by scar tissue formation :
  • 3. - Arthroscopic Debridement : - Arthroscopic lavage - Subchondral drilling - Microfracture Marrow stimulation techniques - Abrasion arthroplasty to induce the growth of fibrocartilage into the chondral defect. Treatment options
  • 4. Stages of ACI healing Healing process has several stages. They include the • proliferative stage (0 to 6 weeks), • the transition stage (7 to 12 weeks), and • a remodeling and maturation stage which occurs over a prolonged period (13 weeks to 3 years)
  • 5. Proliferative stage • During this stage, a primitive cell response occurs with tissue fill of the defect and poor integration to underlying bone or adjacent cartilage. • Mostly type I and some type II collagen is produced. • The tissue is soft and jelly-like and easily damaged
  • 6. Transition phase • This marks the production of type II collagen framework and the early production of proteoglycans. • The proteoglycans, which form the matrix, help imbibe water to give cartilage its viscoelastic properties. • The tissue is not yet firm or well integrated and has the consistency of a firm gelatin. • It is milkable when probed with an arthroscopic nerve hook, indicating incomplete integration to underlying bone
  • 7. Stage of remodeling and maturation • The matrix proteins cross-link and stabilize in large aggregates. • The collagen framework reorganizes so as to integrate into the subchondral bone and form arcades of Benninghoff. • Usually by 4 to 6 months, the tissue has firmed up to a putty-like consistency and is integrated to the underlying bone
  • 8. • At this stage, patients experience good symptom relief • During this stage excessive activity may cause repair tissue degeneration or continued improvement in remodeling • Hence, the concept of a time course of healing is critical during the rehabilitation phase of ACT
  • 9. Indications for ACT • Symptomatic full-thickness chondral injury of the femoral articular surface (femoral weight- bearing condyles and sulcus or trochlea) in a physiologically young (<45 years) patient who is compliant with the rehabilitation protocol • osteochondritis dissecans (OCD)
  • 10. • Results of chondral injuries of the patella and tibia (improved in 70% to 80% of patients) are not as consistently high as those of the femoral weight-bearing condyles and trochlea (85% to 90% improved) • ACT is not FDA approved as a treatment for OA, that is, bipolar chondral injuries with radiographic weight-bearing joint space loss
  • 11. Pre-requisites for surgery • Appropriate biomechanical alignment • Ligamentous stability • Range of motion
  • 12. Not recommended for patients who have : • an unstable knee • in children • in any joint other than knee.
  • 13. Clinical examination • Assessing subtle PF maltracking is important because this may become more pronounced and symptomatic after arthrotomy, which may adversely affect the treatment outcome of a trochlea or patellar ACT • Assessment of predisposing factors for cartilage injury and degeneration may affect the prognostic outcome.
  • 14. • These may include cruciate ligament insufficiency, genu varus or valgus, obesity, bone deficiency (AVN, OCD, and degenerative or ganglion bone cysts), inflammatory arthropathy, and familial osteoarthropathy • These must be assessed so that they may be either corrected in a staged or concomitant fashion with ACT
  • 15. Investigations Wt bearing xray and skyline views • Evidence of joint space narrowing 50% with osteophyte formation, subchondral bony sclerosis or cyst formation eliminates patients from treatment (ie, if bone on bone changes are present)
  • 16. MRI MRI scanning, while helpful for soft-tissue evaluation of meniscal or ligamentous injury as well as assessment of bone bruises and osteonecrosis, does not have a high sensitivity and specificity (75% to 93%) for determining the extent of a chondral injury or subtle chondromalacia changes.
  • 17. The gold standard for determining whether a symptomatic patient is a candidate for ACT are normal radiographs, accompanied by an arthroscopic assessment showing focal pathology
  • 18. A’scopy and Cartilage Biopsy • Extent of lesion, Menisci, AP length of lesion • Quality and thickness of the surrounding articular cartilage will determine whether healthy cartilage will be available for periosteal suturing or a non-contained chondral injury will require suturing through synovium or small drill holes through the bone.
  • 19. • The most commonly chosen site for biopsy is the superior medial edge of the trochlea • Superior lateral femoral condyle • lateral intercondylar notch • superior transverse trochlea margin adjacent to the supracondylar synovium
  • 20. • Approximately 200 to 300 mg of articular cartilage (approximately 5 mm wide and 1 cm long) is required for enzymatic digestion for cell culturing. • This contains approximately 2 to 3 lakh cells, which may be enzymatically digested and grown to approximately 120 lakh cells per 0.4 mL of culture media per implantation vial.
  • 21. • After in-vitro expansion of cells 3 to 5 weeks later, a suitable number and volume of cells (usually one vial per each 4 to 6 sq cm defect) will be grown to accommodate the defect size required • Can be stored upto 2 years
  • 22. Implantation of Autologous Chondrocytes Open implantation include arthrotomy, defect preparation, periosteum procurement from the tibia or femur, periosteum fixation, periosteum water-tight integrity testing, autologous or allogeneic fibrin glue sealant, chondrocyte implantation and wound closure
  • 23. MACI • Matrix induced ACI • Cultured chondrocytes seeded in bilayered typeI/III collagen membrane • Implanted using fibrin glue
  • 24. Rehabilitation goals ● Aggressive ROM exercises to enhance chondrocyte regeneration and decrease the likelihood of intraarticular adhesions ●Touch-weight bearing for 6 wks and full by 12 weeks to prevent periosteal overload and central degeneration or delamination of a weight bearing graft ● Isometric and gentle functional muscle exercises to regain muscle tone and prevent atrophy
  • 25. • CPM is instituted as soon as cell attachment has occurred, usually 6 hours after surgery • This is utilized for approximately 6 to 8 hours daily for up to 6 weeks after surgery • Initially it is used for a range of 0° to 40° maximum. CPM from 40° to 70° is not recommended because maximal PF contact forces occur in this range.
  • 26. • CPM for defects of trochlear defects is less vigorous • The remainder of the motion is obtained by the patient dangling a leg over the edge of the bed to regain further motion • On average, it takes 4 to 4 1/2 months for patients to discard their supports and walk comfortably
  • 27. • Running is not permitted until graft hardness becomes similar to adjacent cartilage, which takes approximately 9 to 12 months • Kneeling and squatting are not permitted until 12 to 18 months after surgery • Osteochondritis dissecans may take 18 to 24 months.
  • 28. Advantages • Can produce hyaline-like cartilage. • Can fill defects regardless of size with functional repair tissue. • Moderate to large defects that have failed previous intervention. • Repair tissue which matures, rather than deteriorates over time. • Expected outcome • Return to previous level of functioning
  • 29. Disadvantages • More invasive • Expense • Longer recovery • Overall failure rate is at present quoted as being 10%.
  • 30. Complications • Incomplete periosteal graft incorporation to host cartilage and hypertrophic graft edge response. • Clinically, this usually manifests as a proliferative hypertrophic periosteal healing response between 3 and 7 months after surgery • Intra-articular adhesions with resultant stiffness are uncommon • Post-op hematoma, hypertrophic synovitis