Sports Medicine
Autologous Chondrocyte Implantation (ACI)
Comprehensive guide to autologous chondrocyte implantation and MACI - two-stage cartilage repair, indications, surgical technique, and outcomes for orthopaedic examination
Reviewed by OrthoVellum Editorial Team
Orthopaedic clinicians and medical editors • Published by OrthoVellum Medical Education Team
High Yield Overview
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI)
Two-Stage Cell Therapy | Hyaline-Like Cartilage | Large Lesions
Over 2cm²Typical lesion size
Two-stageBiopsy then implant
84-90%Good results at 5 years
Type IIHyaline-like collagen
ACI GENERATIONS
First Generation
PatternCells under periosteal flap
TreatmentOriginal technique (Brittberg)
Second Generation
PatternCells under collagen membrane
TreatmentLess hypertrophy than periosteal
Third Generation (MACI)
PatternCells on collagen scaffold
TreatmentMatrix-induced ACI - current standard
Critical Must-Knows
- Two-stage procedure: Biopsy (stage 1) → Cell culture (4-6 weeks) → Implantation (stage 2)
- Hyaline-like cartilage forms, with Type II collagen predominating
- No donor site morbidity unlike OATS (only small biopsy)
- Durable long-term results maintained at 10-20 years
- MACI (third generation) eliminates periosteal hypertrophy issues
Examiner's Pearls
- "MACI = Matrix-induced Autologous Chondrocyte Implantation
- "Cell culture expands 200,000 cells to 12-48 million
- "Periosteal hypertrophy was problem with first-gen ACI
- "Takes 12-18 months for full cartilage maturation
Clinical Imaging
Imaging Gallery
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Critical ACI Exam Points
Two-Stage Procedure
ACI requires two surgeries: Stage 1 harvests cartilage biopsy (200-300mg). Cells cultured for 4-6 weeks to expand. Stage 2 implants expanded cells. This is a key disadvantage vs single-stage OATS.
MACI Advantage
Third-generation MACI uses a collagen scaffold seeded with cells. This eliminates periosteal harvest and reduces hypertrophy complications. MACI is the current standard of care.
Hyaline-Like Repair
ACI produces hyaline-like cartilage with predominantly Type II collagen. Biopsy studies show 80%+ hyaline tissue at 2 years. This is superior to microfracture fibrocartilage.
Long-Term Durability
Unlike microfracture which degrades at 2-5 years, ACI results are durable to 10-20 years. Peterson series showed 84% good/excellent at 20 years follow-up.
ACI vs Other Cartilage Procedures
| Feature | ACI/MACI | Microfracture | OATS |
|---|---|---|---|
| Stages | Two | One | One |
| Cartilage type | Hyaline-like (Type II) | Fibrocartilage (Type I) | Hyaline (Type II) |
| Ideal size | Over 2cm² | Under 2cm² | 1-4cm² |
| Donor morbidity | Minimal (small biopsy) | None | 10-15% |
| Cost | High (cell culture) | Low | Moderate |
Mnemonic
ACIACI - Key Concepts
A
Autologous cells
Patient's own chondrocytes expanded in culture
C
Culture for 4-6 weeks
Cells multiply from 200K to 12-48M
I
Implantation stage 2
Cells injected under membrane or on scaffold
Memory Hook:ACI = your own cells, cultured, then implanted - Autologous, Cultured, Implanted!
Mnemonic
MACIMACI - The Modern Standard
M
Matrix scaffold
Collagen membrane with seeded cells
A
Autologous chondrocytes
Patient's own expanded cells
C
Collagen Type I/III
Bilayer membrane structure
I
Implantation technique
Cut to fit, fibrin glue fixation
Memory Hook:MACI adds Matrix to ACI - cells on a collagen scaffold!
Mnemonic
1-2-3Generations of ACI
1
First: Periosteal flap
Cells under periosteum (hypertrophy risk)
2
Second: Collagen membrane
Cells under Type I/III collagen
3
Third: MACI scaffold
Cells seeded on scaffold - current standard
Memory Hook:ACI evolved 1-2-3: Periosteum → Membrane → Matrix scaffold (MACI)!
Overview and Epidemiology
Why This Topic Matters
ACI/MACI is the gold standard for large cartilage lesions (over 2cm²) where microfracture outcomes are poor and OATS donor capacity is limited. Understanding the generations of ACI, the two-stage nature, and long-term outcomes is essential for examination success.
Indications
- Large lesions over 2cm²
- Failed microfracture or OATS
- Young active patients (under 45)
- Single or multiple focal defects
- Full-thickness cartilage damage (ICRS 3-4)
Contraindications
- Diffuse OA
- Inflammatory arthropathy
- Uncorrected malalignment
- Meniscal deficiency (unless treated)
- Kissing lesions (relative)
- Age over 55 (relative)
Pathophysiology and Mechanisms
Hyaline-Like vs Fibrocartilage
ACI produces hyaline-like cartilage with predominantly Type II collagen and organized matrix structure. Biopsy studies show 80%+ hyaline tissue at 2 years. This is biomechanically superior to the fibrocartilage (Type I collagen) produced by microfracture, explaining the superior long-term durability.
Histological Comparison
| Feature | ACI/MACI (Hyaline-like) | Microfracture (Fibrocartilage) |
|---|---|---|
| Dominant collagen | Type II (80%+) | Type I |
| Proteoglycans | Organized | Disorganized |
| Cell arrangement | Columnar | Random |
| Integration | Variable | Fibrous |
| Long-term stability | Maintained 10-20 years | Degrades 2-5 years |
Cell Culture Process
- Harvest: 200-300mg cartilage biopsy
- Enzymatic digestion: Release chondrocytes
- Expansion: 4-6 weeks in culture
- Result: 12-48 million cells
- Matrix: MACI = cells seeded on collagen
Maturation Timeline
- 3 months: Soft cartilage repair tissue
- 6 months: Increasing firmness
- 12 months: Near-normal stiffness
- 18-24 months: Full maturation
- Rehabilitation reflects this timeline
Classification Systems
Evolution of ACI Techniques
| Generation | Technique | Advantages | Disadvantages |
|---|---|---|---|
| First (P-ACI) | Cells under periosteal flap | Original technique, proven long-term | Periosteal hypertrophy (30%), second incision for periosteum |
| Second (C-ACI) | Cells under collagen membrane | No periosteal harvest, less hypertrophy | Still requires watertight suturing |
| Third (MACI) | Cells seeded on collagen scaffold | No suturing needed, fibrin glue fixation, less invasive | Higher cost, requires adequate cell adherence |
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MACI is Current Standard
MACI (third-generation) is now the standard of care. The collagen scaffold is seeded with cells in the lab, delivered as a ready-to-implant product. This eliminates periosteal harvest, reduces hypertrophy, and allows minimally invasive implantation with fibrin glue.
Clinical Assessment
History
- Prior cartilage surgery (failed microfracture/OATS)
- Symptom duration and progression
- Mechanical symptoms (catching, locking)
- Activity level and sport demands
- Willingness for two surgeries and extended rehab
Examination
- Effusion - common with cartilage damage
- Tenderness - localized to compartment
- Crepitus - may indicate damage
- Alignment - assess for malalignment
- Ligament/meniscal integrity
Patient Selection
ACI requires significant patient commitment: two surgeries, 4-6 week wait for cell culture, and 12-18 month rehabilitation. Ensure patient understands and is prepared for this timeline. Non-compliant patients are poor candidates.
Investigations
Investigation Protocol
First LineX-rays
Weight-bearing AP, lateral, Rosenberg, skyline. Assess alignment, joint space, OA changes. Rule out diffuse disease.
EssentialMRI
Cartilage sequences for lesion mapping. Size, location, depth. Subchondral bone status. Associated meniscal/ligament pathology.
If NeededAlignment Films
Full-length standing films if malalignment suspected. Plan osteotomy if significant deviation.
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MRI for ACI Planning
MRI helps identify all cartilage lesions for treatment planning. Unlike OATS (limited by donor), ACI can address multiple lesions simultaneously. Identify any lesion that needs treatment and plan to address at implantation.
Management Algorithm
📊 Management Algorithm
Click to expand
When to Choose ACI/MACI
Ideal candidates:
- Lesion over 2cm² (especially over 4cm²)
- Failed prior microfracture or OATS
- Multiple lesions
- Good subchondral bone (no significant loss)
- Motivated, compliant patient
- Age under 45-50
Alternative treatments:
- Under 2cm²: Consider microfracture first
- 1-4cm²: OATS reasonable single-stage option
- Bone loss present: OCA may be better
- OCA unavailable: ACI good for large lesions
This framework guides appropriate treatment selection based on lesion and patient characteristics.
Pre-operative Planning
Pre-operative Steps
InitialStage 1 Planning
Confirm indication for ACI. Plan biopsy location (non-weight-bearing area). Coordinate with cell laboratory. Patient counseling about timeline.
4-6 weeksCell Culture Period
Cells expanded in specialized laboratory. Patient rehab from biopsy (usually minimal). Plan stage 2 surgery date.
Pre-implantStage 2 Planning
Confirm cell culture successful. Plan implantation approach. Prepare MACI scaffold or membrane. Fibrin glue available.
Biopsy Site Selection
The biopsy for cell harvest should be taken from a non-weight-bearing area with healthy cartilage. Common sites include the superior margin of the intercondylar notch, the superomedial trochlear margin, or the peripheral edge of the lesion itself.
Surgical Technique
Stage 1: Cartilage Harvest
Biopsy Procedure
Step 1Approach
Arthroscopic or mini-open approach. Locate biopsy site (non-weight-bearing, healthy cartilage).
Step 2Harvest
Use curette or gouge to harvest 200-300mg of full-thickness cartilage. Typical size: 2-3 pieces, 4-5mm each.
Step 3Storage
Place in specialized transport medium. Send to cell culture laboratory. Cells must remain viable during transport.
Step 4Assessment
Assess the cartilage lesion(s). Measure size for implantation planning. Identify any additional pathology.
Stage 1 is a relatively minor procedure. Patients typically recover quickly and await cell culture completion.
Complications
| Complication | Incidence | Risk Factors | Prevention/Management |
|---|---|---|---|
| Graft hypertrophy | 5-20% (higher first-gen) | Periosteal ACI | Use MACI, debride if symptomatic |
| Graft failure | 5-10% | Malalignment, poor technique | Address alignment, meticulous surgery |
| Delamination | 5% | Trauma, early loading | Protected rehab, gradual return |
| Arthrofibrosis | 5% | Prolonged immobilization | Early ROM protocol |
| Infection | Under 1% | Standard surgical risks | Sterile technique |
Graft Hypertrophy
First-generation ACI with periosteal flap had 20-30% hypertrophy rates requiring secondary debridement. MACI has significantly reduced this complication. If hypertrophy occurs, arthroscopic debridement is usually effective.
Postoperative Care and Rehabilitation
Weight-Bearing Protocol
Progression
Touch weight-bearingWeeks 0-6
Toe-touch only with crutches. Brace for protection. Allows early cartilage maturation without load.
Partial weight-bearingWeeks 6-12
Progressive weight-bearing 25% to 75%. Wean brace. Crutches until comfortable.
Full weight-bearingWeeks 12-16
Full weight-bearing without aids. No impact activities. Low-load exercises.
Cartilage Maturation
ACI cartilage takes 12-18 months to fully mature. Early in healing, the tissue is soft and vulnerable. Weight-bearing and activity progression reflects this maturation timeline - slower than OATS or microfracture.
Outcomes and Prognosis
Long-term Outcomes
| Study | Follow-up | Good/Excellent | Key Finding |
|---|---|---|---|
| Peterson (Brittberg) | 20 years | 84% | Original ACI series, durable results |
| Minas series | 10 years | 75% | Salvage cases included |
| STAR trial | 5 years | ACI superior to MFx | RCT evidence for ACI |
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Superior to Microfracture Long-term
The STAR trial (RCT) showed ACI superior to microfracture at 5 years. While microfracture results deteriorate at 2-5 years, ACI maintains improvement. For larger lesions, this difference is even more pronounced.
Evidence Base and Key Trials
Peterson 20-Year Follow-up
Peterson L, Vasiliadis HS, Brittberg M, et al • AJSM (2010)
Key Findings:
- 84% good/excellent at 20 years
- Durability of first-generation ACI confirmed
- Results maintained long-term without deterioration
- Originally described by Brittberg 1994
Clinical Implication: ACI provides durable long-term results, supporting its use in young patients who need lasting cartilage repair.
Limitation: First-generation technique, single center.
STAR Trial - ACI vs Microfracture
Saris DB, Vanlauwe J, Victor J, et al • AJSM (2014)
Key Findings:
- ACI superior to microfracture at 5 years
- Microfracture results declined after 2 years
- ACI maintained improvement
- Treatment failure higher in microfracture group
Clinical Implication: RCT evidence supports ACI over microfracture for larger lesions, especially long-term.
Limitation: High dropout rate at 5 years, heterogeneous lesion sizes.
MACI vs ACI
Basad E, Ishaque B, Bachmann G, et al • KSSTA (2010)
Key Findings:
- MACI equivalent clinical outcomes to periosteal ACI
- Significantly less hypertrophy with MACI
- Less re-operation rate with MACI
- Simpler surgical technique
Clinical Implication: MACI preferred over first-gen ACI due to reduced complications with equivalent efficacy.
Limitation: Relatively short follow-up for long-term durability comparison.
ACI for Failed Prior Surgery
Minas T, Gomoll AH, et al • CORR (2009)
Key Findings:
- ACI effective after failed microfracture
- Slightly lower success than primary ACI
- Subchondral bone changes may affect outcomes
- Revision ACI also possible
Clinical Implication: ACI remains viable after failed microfracture, though primary treatment may be preferable if ACI is ultimately planned.
Limitation: Retrospective comparison.
Return to Sport After ACI
Mithoefer K, Della Villa S, et al • AJSM (2009)
Key Findings:
- 71% returned to sports
- 55% returned to competitive level
- Larger lesions had lower return rates
- Younger patients had better outcomes
Clinical Implication: Counsel patients that return to high-level sport is not guaranteed but majority return to some activity.
Limitation: Heterogeneous patient populations and sport levels.
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
VIVA SCENARIOStandard
Scenario 1: Failed Microfracture (~2-3 min)
EXAMINER
"A 32-year-old female athlete has persistent symptoms 2 years after microfracture for a 3cm² medial femoral condyle lesion. MRI shows incomplete fill with subchondral changes. What are your options?"
EXCEPTIONAL ANSWER
This is a failed microfracture with a lesion size that was probably too large for microfracture to begin with (3cm² exceeds optimal size of under 2cm²).
For a 3cm² lesion after failed microfracture, my options are:
**First choice: ACI/MACI**
- This size is ideal for ACI (over 2cm²)
- Two-stage procedure but produces hyaline-like cartilage
- Prior microfracture does not preclude ACI
- May need to address subchondral changes
**Alternative: OATS**
- Would require 3-4 plugs for 3cm² lesion
- At upper limit of donor capacity
- Single-stage advantage
**Alternative: OCA** (if available)
- Single-stage, no donor morbidity
- Good for failed prior surgery
- Limited availability may be issue
Given her age (32), athlete status, and lesion size, I would recommend MACI:
- Stage 1: Arthroscopic biopsy from non-weight-bearing area
- 4-6 weeks cell culture
- Stage 2: MACI implantation with scaffold
I would also confirm alignment is normal and address any malalignment with osteotomy if needed.
KEY POINTS TO SCORE
Recognize microfracture was likely suboptimal choice for 3cm²
Know salvage options (ACI, OATS, OCA)
Understand two-stage ACI process
Consider alignment in failed cartilage surgery
COMMON TRAPS
✗Suggesting repeat microfracture
✗Not recognizing original size was too large
✗Forgetting to check alignment
✗Not knowing ACI is two-stage
LIKELY FOLLOW-UPS
"What is the difference between ACI generations?"
"How does MACI work technically?"
"What if there was significant subchondral bone loss?"
VIVA SCENARIOChallenging
Scenario 2: ACI Technique (~3-4 min)
EXAMINER
"Describe the MACI implantation technique for a 4cm² trochlear lesion."
EXCEPTIONAL ANSWER
MACI for a trochlear lesion requires careful attention to technique:
**Pre-operative:**
- Confirm cell culture successful (12-48M cells on collagen scaffold)
- MACI scaffold arrives ready to implant
- Plan approach - trochlear lesions often need mini-arthrotomy
**Surgical Steps:**
**Exposure:**
Mini-arthrotomy through medial or lateral parapatellar approach, depending on lesion location. Evert patella or sublux to expose trochlea. May need to flex knee for access.
**Debridement:**
- Debride unstable cartilage to stable vertical shoulders
- Create well-contained defect
- Curette to remove calcified cartilage layer
- Preserve subchondral plate - do not violate excessively
- Dry the defect base
**Template and Sizing:**
- Create template using sterile foil
- Trace exact defect shape
- Cut MACI scaffold to match template precisely
**Implantation:**
- Apply fibrin glue to defect base
- Orient scaffold correctly - cell-seeded side DOWN (toward bone)
- Place scaffold into defect
- Apply additional fibrin glue around edges
- Ensure secure attachment
**Confirmation:**
- Cycle knee through ROM multiple times
- Confirm scaffold remains stable and does not delaminate
- Ensure edges are well-sealed
For trochlear lesions specifically, the contouring is challenging due to the sulcus geometry. May need multiple pieces of scaffold for complex shapes.
KEY POINTS TO SCORE
Know the step-by-step MACI technique
Emphasize scaffold orientation (cells down)
Fibrin glue fixation without sutures
Confirm stability with ROM testing
COMMON TRAPS
✗Incorrect scaffold orientation (cells up instead of down)
✗Violating subchondral bone excessively
✗Not confirming stability with knee motion
✗Forgetting to dry the defect before glue
LIKELY FOLLOW-UPS
"What if the scaffold delaminates when you flex the knee?"
"How does MACI differ from first-generation ACI?"
"What is the rehabilitation protocol?"
VIVA SCENARIOCritical
Scenario 3: Patient Selection (~2-3 min)
EXAMINER
"A 52-year-old man with a 2cm² medial femoral condyle lesion asks about ACI. His MRI also shows Grade 2 changes in the patellofemoral joint and mild medial joint space narrowing. Is he a candidate?"
EXCEPTIONAL ANSWER
This case requires careful consideration of several factors that may affect ACI candidacy.
**Concerning features:**
1. Age 52 - at upper limit for ACI (typically under 45-50)
2. PF changes (Grade 2) - suggests early generalized OA
3. Medial joint space narrowing - may indicate bipolar disease
4. 2cm² lesion - at lower threshold where simpler options exist
**My assessment:**
This patient may not be ideal for ACI for several reasons:
1. **Age**: At 52, healing potential is reduced, and longevity of repair is a concern. ACI is best for patients who need 10-20+ years of benefit.
2. **Generalized changes**: The PF changes and medial narrowing suggest this may be early OA rather than isolated focal cartilage damage. ACI works best for focal defects in otherwise healthy joints.
3. **Lesion size**: At 2cm², simpler options like microfracture or even debridement may be reasonable first-line treatments.
**My recommendation:**
I would counsel this patient that ACI may not be the best option. I would consider:
1. **Conservative management** optimization
2. **Debridement +/- microfracture** as first-line
3. If he fails these, consider **unloader brace** or **HTO** if varus
4. Eventually may need **UKA or TKA**
ACI should be reserved for younger patients with truly focal defects in otherwise healthy joints where long-term biological repair is the goal.
KEY POINTS TO SCORE
Recognize concerning features for ACI
Age 52 is at upper limit
Generalized changes suggest OA not focal defect
Simpler options may be more appropriate
COMMON TRAPS
✗Recommending ACI for borderline candidate
✗Ignoring the generalized OA changes
✗Not considering simpler alternatives first
✗Not discussing realistic expectations
LIKELY FOLLOW-UPS
"What if he was 35 with the same findings?"
"What is the upper age limit for ACI?"
"How do you counsel about expectations?"
MCQ Practice Points
Stage Question
Q: How many surgical stages are required for ACI? A: Two stages - Stage 1 is cartilage biopsy for cell harvest. Cells are cultured for 4-6 weeks. Stage 2 is implantation of expanded cells. This is a key disadvantage compared to single-stage OATS.
Cell Expansion Question
Q: How many cells are implanted during ACI? A: 12-48 million cells - The initial biopsy (200-300mg) contains approximately 200,000-300,000 chondrocytes. Cell culture expands this to 12-48 million cells for implantation.
MACI Definition Question
Q: What does MACI stand for? A: Matrix-induced Autologous Chondrocyte Implantation - MACI is third-generation ACI where cells are seeded on a collagen scaffold, eliminating the need for periosteal harvest or watertight membrane suturing.
Hypertrophy Question
Q: Which generation of ACI had the highest rate of graft hypertrophy? A: First-generation (periosteal ACI) - Hypertrophy rates of 20-30% were seen with periosteal flaps. This was significantly reduced with collagen membranes (second-gen) and MACI (third-gen).
Long-term Results Question
Q: What is the longest reported follow-up for ACI outcomes? A: 20 years (Peterson series) - The original Brittberg/Peterson series reported 84% good/excellent results at 20 years, demonstrating exceptional durability of the technique.
Lesion Size Question
Q: What lesion size is typically considered ideal for ACI? A: Over 2cm² - ACI is typically reserved for lesions over 2cm² where microfracture outcomes are suboptimal and OATS donor capacity may be limiting. It is especially valuable for lesions over 4cm².
Australian Context and Medicolegal Considerations
Australian Practice
- MACI available through specialized centers
- Requires TGA-approved cell culture facilities
- PBS does not cover cell therapy costs
- Significant out-of-pocket expense for patients
- Some private insurers may provide partial coverage
Documentation Standards
- Document two-stage consent thoroughly
- Record cell culture laboratory and tracking
- Document scaffold orientation at implantation
- Record all associated procedures (osteotomy)
- Consent must cover extended rehabilitation timeline
Medicolegal Considerations
Key documentation requirements:
- Two-stage consent with clear explanation of process
- Document cell culture tracking and viability confirmation
- Record surgical technique details (scaffold orientation, fixation)
- Consent must include: extended rehabilitation (12-18 months), two surgeries, cost implications, realistic sport expectations
- If failure occurs, documentation of proper indication and technique is protective
AUTOLOGOUS CHONDROCYTE IMPLANTATION (ACI)
High-Yield Exam Summary
Definition
- •Two-stage cell-based cartilage repair
- •Patient's own chondrocytes expanded in culture
- •Hyaline-like cartilage formation
- •MACI = cells on collagen scaffold (current standard)
Generations
- •First-gen: Periosteal flap (hypertrophy 20-30%)
- •Second-gen: Collagen membrane
- •Third-gen: MACI scaffold (current standard)
Key Numbers
- •Over 2cm² = typical lesion indication
- •4-6 weeks = cell culture duration
- •12-48 million = cells implanted
- •84-90% = good results at 10 years
- •12-18 months = full cartilage maturation
Two-Stage Process
- •Stage 1: Biopsy (200-300mg cartilage)
- •Culture: 4-6 weeks expansion
- •Stage 2: MACI scaffold implantation
- •Fibrin glue fixation (no sutures)
Advantages
- •Hyaline-like cartilage (Type II collagen)
- •Durable 10-20 year results
- •Minimal donor morbidity (small biopsy only)
- •Can treat large/multiple lesions
- •MACI simpler than periosteal technique
Disadvantages
- •Two-stage procedure
- •High cost (cell culture)
- •Extended rehabilitation (12-18 months)
- •Requires intact subchondral bone
- •Not for diffuse OA