MACI — Matrix-Induced Autologous Chondrocyte Implantation
Fellowship-trained cartilage restoration surgeons Christopher Raffo, MD and John Christoforetti, MD perform MACI for patients with symptomatic full-thickness cartilage defects who are candidates for biological joint preservation.
What is MACI — Matrix-Induced Autologous Chondrocyte Implantation?
MACI (Matrix-Induced Autologous Chondrocyte Implantation) is a two-stage FDA-approved procedure that uses a patient's own harvested and cultured cartilage cells, seeded onto a collagen scaffold, to repair full-thickness knee cartilage defects of 2–10 cm². It produces hyaline-like cartilage rather than the weaker fibrocartilage of microfracture, with 80–90% good-to-excellent outcomes at five years.
Why this approach — at MOS
MACI is what we reach for when a cartilage defect is too large for microfracture to hold up. The tissue microfracture produces is fibrocartilage (type I collagen, mechanically weaker than the cartilage it replaces), and for defects beyond roughly 2 cm² it reliably deteriorates. MACI regenerates hyaline-like tissue from the patient's own chondrocytes, and the randomized evidence shows that biological difference translating into better pain and function scores and fewer failures.
The two-stage structure is a feature, not a cost. The biopsy arthroscopy lets us characterize the lesion definitively before committing to a reconstruction, and the 3–5 week culture window is time we use to plan and stage concurrent work. Malalignment, ligamentous insufficiency, and meniscal deficiency are corrected at the time of implantation. An unstable or malaligned knee will destroy the graft, and we do not implant into one.
We are equally direct about what MACI asks of the patient: six to eight weeks of protected weight-bearing and a 12-to-18-month rehabilitation driven by cartilage biology rather than by how the knee feels. Return-to-sport clearance at MOS is criteria-based, not calendar-based, and rehabilitation runs through our in-house physical therapy team.
The SUMMIT randomized trial
The evidence behind the FDA approval is the SUMMIT trial (Saris et al., *American Journal of Sports Medicine*, 2014). This was a prospective, multicenter, randomized Phase 3 study of 144 patients (mean age 33.8, mean lesion size 4.8 cm²) comparing MACI with microfracture. At two years:
- Responder rate: 87.5% with MACI vs. 68.1% with microfracture
- Treatment failure: 12.5% vs. 31.9%
- Significantly greater improvement in KOOS pain and function, with superiority also seen in activities of daily living, quality of life, and symptoms
- The advantage was largest in lesions over 4 cm², in younger patients, and in trochlear lesions
Improvements seen at two years were maintained at the five-year extension.
Long-term durability
A systematic review of MACI outcomes at 10 years or more (Wang et al., AJSM, 2024) (168 patients, 188 defects) found durable improvement at 10 to 17 years, a 9.0% all-cause reoperation rate, and only 7.4% progression to knee replacement. In the longest ACI follow-up available, Peterson et al. (AJSM, 2010) reported that 92% of 224 patients at a mean of 12.8 years were satisfied and would have the procedure again.
A meta-analysis of six randomized trials (Dhillon et al., *Arthroscopy*, 2022) confirmed that third-generation ACI produces lower failure rates and greater improvement in patient-reported outcomes than microfracture.
What that means in practice
- Good-to-excellent outcomes in roughly 80–90% of appropriately selected patients at five years
- Best suited to defects larger than 2 cm² and to trochlear and patellofemoral lesions, where microfracture has historically underperformed
- Conversion to knee replacement at 10 or more years is approximately 7–9%, which is what makes MACI a genuine joint-preserving option in a young, active knee
Who is a candidate?
Indications
- A symptomatic, focal, full-thickness cartilage or osteochondral defect of the knee (ICRS Grade III or IV)
- Defect size of roughly 2–10 cm². Smaller lesions are usually better served by microfracture or OATS; very large lesions may need an osteochondral allograft or a staged approach
- Skeletally mature adults, typically under 55, for the best biological response
- A contained lesion with stable, well-defined borders
- Normal or correctable alignment — varus or valgus malalignment must be corrected, either at the same operation or in advance
- A stable ligamentous environment. ACL or PCL insufficiency must be reconstructed
- Adequate meniscal tissue — a meniscus-deficient knee needs concurrent or staged meniscal allograft transplantation
- Failure of, or unsuitability for, marrow-stimulation techniques such as microfracture
- Willingness and ability to complete a long, criteria-based rehabilitation
Contraindications
- Advanced osteoarthritis (Kellgren-Lawrence Grade 3–4). MACI is not indicated for diffuse arthritis or for bipolar "kissing" lesions on opposing surfaces
- Inflammatory arthritis (rheumatoid, psoriatic, gout) — per the FDA label
- BMI over 35: the added mechanical load compromises graft maturation
- Knee surgery within the past 6 months, excluding the MACI biopsy itself
- Known hypersensitivity to gentamicin, aminoglycosides, or products of porcine or bovine origin
- Uncorrected coagulation disorders
- Inability to comply with the post-operative rehabilitation protocol
- A prior failed ACI or MACI at the same site: a relative contraindication, considered case by case
How We Assess Candidacy
Evaluation at MOS includes standing long-leg X-rays to assess alignment, weight-bearing knee X-rays, and a dedicated cartilage MRI protocol (3T preferred, cartilage-sensitive sequences). Arthroscopy at the time of the Stage 1 biopsy allows the lesion to be characterized definitively before the reconstruction is planned.
The procedure
What Is MACI?
Articular cartilage has virtually no capacity to repair itself. Full-thickness defects (from acute injury, repetitive loading, or osteochondritis dissecans) cause pain, swelling, and mechanical symptoms, and untreated lesions can progress to early osteoarthritis.
MACI (autologous cultured chondrocytes on a porcine collagen membrane) is a third-generation autologous chondrocyte implantation technique. It was approved by the FDA on December 13, 2016, is manufactured by Vericel Corporation, and remains the only FDA-approved cellularized scaffold product for this indication in the United States.
How MACI Compares to Other Cartilage Procedures
- Microfracture produces fibrocartilage (type I collagen) and suits defects under 2 cm². It is mechanically inferior and deteriorates over time in larger lesions.
- OATS / mosaicplasty transplants plugs of the patient's own hyaline cartilage for defects of 1–4 cm², at the cost of a donor site and limited ability to fill irregular defects.
- Osteochondral allograft uses donor hyaline cartilage and bone for defects of 2 cm² and up, and depends on graft availability.
- MACI produces hyaline-like cartilage (type II collagen) for defects of 2–10 cm². Its costs are two operations and a long rehabilitation.
The defining feature of MACI, and of ACI technology generally, is the hyaline-like repair tissue rich in type II collagen, the collagen of native articular cartilage. Microfracture, by contrast, recruits marrow-derived cells that lay down mostly type I collagen, which is weaker under repeated joint loading. Randomized trials and systematic reviews confirm that this biological difference produces measurably better outcomes, particularly for defects larger than 2 cm².
The Scaffold
The MACI implant is the patient's own chondrocytes seeded evenly onto a porcine type I/III collagen membrane. The three-dimensional scaffold distributes cells uniformly across the defect, can be cut to match an irregular defect shape, and is fixed with fibrin glue. This eliminates the sutures required by earlier periosteal-patch ACI, which carried a real risk of graft hypertrophy and delamination.
The Two-Stage Procedure
MACI is performed in two operations separated by roughly 3–5 weeks of cell culture.
Stage 1 — Cartilage Biopsy (Arthroscopic)
Performed at an ambulatory surgery center under general or spinal anesthesia, taking approximately 30–45 minutes.
A diagnostic arthroscopy is performed first, confirming the diagnosis and characterizing the defect (size, borders, depth, bone involvement) and assessing the menisci, ligaments, and opposing surfaces to plan Stage 2.
200–300 mg of healthy cartilage is then harvested from a low-load region of the knee (typically the margins of the trochlear notch or the intercondylar notch wall), where removing cartilage has minimal functional consequence.
The biopsy is shipped overnight to Vericel's facility, where the chondrocytes are isolated and expanded in culture over roughly 3–5 weeks and seeded onto the collagen membrane. Each patient-specific implant undergoes quality release testing before it is returned to the surgical center.
Most patients have minimal restrictions after Stage 1 and resume normal activity within one to two weeks. That interval is used for pre-operative rehabilitation, education, and planning of any concurrent procedures.
Stage 2 — MACI Implantation
Performed under general or spinal anesthesia, taking roughly one to two hours depending on defect complexity and any concurrent procedures.
Stage 2 requires a mini-open or open arthrotomy rather than arthroscopy. The scaffold has to be handled directly. The approach depends on where the lesion is: a medial or lateral parapatellar mini-arthrotomy for femoral condyle lesions, a medial parapatellar arthrotomy for trochlear and patellofemoral lesions, and a compartmental exposure for the uncommon tibial lesion.
Step 1: Defect preparation. Unstable and calcified cartilage is debrided back to stable, perpendicular borders. Removing the calcified layer is essential for integration, while the subchondral bone plate is preserved. If bone involvement is deeper than roughly 6–8 mm, bone grafting is performed concurrently or in a prior staged procedure.
Step 2: Template and sizing. A foil template is shaped to the exact geometry of the debrided defect and used to cut the scaffold to a precise fit.
Step 3: Scaffold placement. The scaffold is placed cell-side down into the defect and its orientation confirmed.
Step 4: Fibrin glue fixation. The scaffold is secured with fibrin glue around and beneath its perimeter. No sutures are used.
Step 5: Seal check. Saline is injected to confirm the scaffold neither migrates nor lifts under pressure.
Concurrent Procedures
A real strength of MACI is that corrective procedures can be done in the same setting: tibial or femoral osteotomy for malalignment, ACL reconstruction, meniscal repair or allograft transplantation. Correcting the biomechanics at the time of implantation reduces the total number of operations and gives the graft the mechanical environment it needs to mature.
Recovery timeline
Weeks 1–6 (Protection)
Continuous passive motion, non-weight-bearing or toe-touch weight-bearing on crutches, and range-of-motion exercises. CPM nourishes the graft, which has no blood supply of its own, through diffusion of synovial fluid.
Weeks 6–12 (Early Loading)
Progressive weight-bearing, weaning off crutches, and low-load closed-chain strengthening. Non-weight-bearing runs 6–8 weeks for femoral condyle defects; patellofemoral lesions follow a modified protocol.
Months 3–6 (Active Rehabilitation)
Full weight-bearing walking, cycling, swimming, and progressive neuromuscular training. No impact activity in this phase.
Months 6–12 (Sport-Specific Training)
Low-impact sport-specific drills, with straight-line jogging typically introduced around 4–6 months and progressed as strength and symptoms allow.
Months 12–18 (Return to Sport)
Full return to sport, contingent on criteria-based clearance (including quadriceps symmetry of at least 90%, proprioception, and functional movement quality) rather than on elapsed time.
MACI rehabilitation is driven by biology, not by pain. Chondrocytes on the scaffold follow a predictable sequence: proliferation and matrix synthesis through the first six weeks, remodeling and integration over months 2 to 12, and final maturation of hyaline-like tissue from 12 to 24 months. Loading the graft before it is ready disrupts that sequence, which is why the protected phase is not negotiable.
Physical therapy is central to the outcome. MOS provides in-house physical therapy with therapists experienced in cartilage restoration protocols, and clearance to advance is criteria-based. Patients progress when the knee meets the milestone, regardless of the date on the calendar.
The timeline is longer than most orthopedic procedures because newly implanted cells need 12 to 18 months or more to mature into mechanically competent tissue. Patients who commit to the rehabilitation consistently do better in the long run.
Frequently Asked Questions
How do I know if I'm a candidate for MACI?
How is MACI different from microfracture?
Will I need two surgeries?
How long until I can return to sport?
How long does MACI last? Is this a permanent fix?
Meet the surgeons

Christopher S. Raffo, MD
Orthopedic Surgery · Sports Medicine · Knee & Shoulder Arthroscopy · Joint Replacement
Meet Dr. Raffo →
John J. Christoforetti, MD
Orthopedic Surgery · Sports Medicine · Hip, Knee & Shoulder Arthroscopy · Shoulder Replacement
Meet Dr. Christoforetti →Related conditions
References
- Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. New England Journal of Medicine. 1994;331(14):889–895. doi:10.1056/NEJM199410063311401. PMID: 8078550.
- Saris D, Price A, Widuchowski W, et al; SUMMIT study group. Matrix-applied characterized autologous cultured chondrocytes versus microfracture: two-year follow-up of a prospective randomized trial. American Journal of Sports Medicine. 2014;42(6):1384–1394. doi:10.1177/0363546514528093. PMID: 24714783.
- Peterson L, Vasiliadis HS, Brittberg M, Lindahl A. Autologous chondrocyte implantation: a long-term follow-up. American Journal of Sports Medicine. 2010;38(6):1117–1124. doi:10.1177/0363546509357915. PMID: 20181804.
- Wang AS, Nagelli CV, Lamba A, Saris DBF, Krych AJ, Hevesi M. Minimum 10-year outcomes of matrix-induced autologous chondrocyte implantation in the knee: a systematic review. American Journal of Sports Medicine. 2024;52(9):2407–2414. doi:10.1177/03635465231205309. PMID: 38312085.
- Dhillon J, Decilveo AP, Kraeutler MJ, Belk JW, McCulloch PC, Scillia AJ. Third-generation autologous chondrocyte implantation is superior to microfracture for focal chondral defects of the knee joint: systematic review and meta-analysis. Arthroscopy. 2022;38(8):2579–2586. doi:10.1016/j.arthro.2022.02.011. PMID: 35283221.
- U.S. Food and Drug Administration. MACI (autologous cultured chondrocytes on porcine collagen membrane). Product Information. BLA STN 125603, Vericel Corporation. Original approval December 13, 2016.
