The short answer: what MACI candidacy looks like

Several criteria need to line up before MACI becomes the right option — and most patients who are good candidates share a recognisable profile.

At its core, MACI is designed for people who have a symptomatic, full-thickness cartilage defect in the knee — damage rated ICRS Grade III or IV, where the cartilage has worn away more than half its depth or reached the underlying bone, and the affected area measures more than 2 cm². Shallower or smaller lesions typically have better-matched alternatives.

The FDA-approved age window is 18 to 55; safety and efficacy above 55 have not been established. That said, biological fitness tends to matter more than the number itself — the procedure is best suited to active adults whose joints are otherwise in good condition.

'Good condition' has a precise meaning here. The knee must be structurally sound: no generalised or multi-compartmental osteoarthritis, stable ligaments, and correctly aligned limb mechanics. Where those conditions are not met, MACI's results are compromised.

Before MACI is considered at all, non-surgical management must have been tried and found insufficient — physiotherapy, weight management, injections, and analgesia are all expected to have been attempted first.

Finally, MACI is a two-stage procedure followed by a demanding, multi-month rehabilitation. Commitment to that recovery process is itself part of the candidacy assessment. The sections below examine each of these criteria in detail.

Lesion size and grade: why the numbers matter

Grade and size are the two axes clinicians use to decide whether MACI is technically appropriate — and they interact in ways that matter for anyone reading their own MRI report.

What the ICRS grade tells a surgeon

The ICRS scale runs from I (surface softening) to IV (cartilage worn entirely through to subchondral bone). Grade III marks the point where damage has breached more than half the cartilage depth; Grade IV means the bone beneath is exposed. MACI addresses only these two grades — the defect must extend deep enough that the body cannot reconstitute the tissue on its own, yet the damage must still be focal and bounded rather than spread across a compartment.

The size threshold — and why it is a range, not a hard line

Defects below roughly 2–4 cm² can generally be managed with simpler single-stage approaches. Microfracture — which drills into subchondral bone to recruit marrow cells — and osteochondral autograft transfer (mosaicplasty) are both established in this smaller range, carrying less procedural complexity and shorter recovery. The 2–4 cm² zone is deliberately framed as a range because clinicians weigh size alongside other factors — lesion location, patient biology, and prior treatments — rather than applying a single numerical cut-off.

MACI's clearest evidence advantage emerges at ≥3 cm². The SUMMIT phase 3 randomised controlled trial (N=144; mean lesion size 4.8 cm²) demonstrated statistically significant superiority over microfracture across KOOS pain, function, activities of daily living, symptoms, and quality of life at two years (P=0.001 for pain and function). The biological reason is meaningful: microfracture produces fibrocartilage — a weaker tissue type that published evidence suggests tends to deteriorate at roughly two to three years — whereas MACI generates hyaline-like repair tissue more closely resembling native joint cartilage, though long-term durability data beyond 15 years remain limited.

Real-world practice reflects this. Registry data from Foldager (2015), covering 2,690 patients across Europe, Australia, and Asia, found that 70% of those treated outside clinical trials had defects measuring between 3 and 10 cm² — considerably larger than trial cohorts. Mean defect size in that population was 5.64 cm², suggesting that in clinical practice, MACI is being selected where other techniques are expected to underperform.

Where in the knee the defect sits

Location within the knee is not simply a technical detail — it shapes both whether MACI applies and what else may need to happen at the same time.

Femoral condyle defects make up the large majority of real-world cases. In the SUMMIT phase 3 trial, 74% of lesions were sited on the medial femoral condyle, reflecting the joint surface most exposed to compressive load. MACI is, however, applied beyond the condyle. A prospective study following 82 patients for more than ten years confirmed sustained improvements in patient-reported outcomes for both patellar and trochlear MACI, with no statistically significant difference in results between the two patellofemoral locations.

Patellofemoral cases carry additional considerations. Abnormal patellar tracking concentrates load unevenly across the repair site, so alignment is assessed carefully and may need to be corrected concurrently — consistent with the structural prerequisites outlined in the section above.

Where damage involves multiple compartments or the opposing joint surface, the clinical picture moves away from focal repair and towards generalised osteoarthritis, which falls outside MACI's scope.

Joint health requirements: alignment, ligaments, and the mechanical environment

Cartilage repair does not occur in isolation — the knee must be mechanically competent for the implant to have a reasonable chance of surviving. Surgeons address three structural conditions before or alongside MACI, often as part of a combined procedure rather than a separate step.

Ligament stability comes first. If the ACL is torn or incompetent, the joint shifts abnormally under load, concentrating force on the repair site in a way that increases the risk of graft failure. An ACL reconstruction can be carried out at the same time as MACI, but the instability cannot be left untreated.

Limb alignment is equally important. When the mechanical axis of the leg passes unevenly through the knee, abnormal load concentrates on whichever compartment bears the most weight — and if that compartment contains the repair, the implant is under chronic stress. Correcting malalignment, through procedures such as a high tibial osteotomy (HTO) or distal femoral osteotomy (DFO), is addressed before or concurrently with cartilage work.

Meniscal integrity supports even load distribution across the joint surface. Significant meniscal deficiency is a complicating factor that alters the force environment around a repair.

A 2026 clinical framework formalises this thinking as a 'mechanics-first' hierarchy — placing alignment, meniscal integrity, and ligament stability upstream of technique selection, with the condition of the opposing cartilage surface also assessed before committing to a repair plan. This framework is hypothesis-level and awaits prospective validation, but it provides a useful organising principle: the mechanical environment may influence long-term durability as much as which restorative technique is chosen.

Who is excluded from MACI

Knowing what rules a patient out is often as clarifying as knowing what qualifies them — and for each exclusion, there is a clinical reason, not an arbitrary rule.

• Generalised or multi-compartment osteoarthritis. MACI is designed for isolated focal damage. When cartilage loss is diffuse, there is no clear repair boundary, and the joint-wide inflammatory and mechanical environment undermines cell-based regeneration. Patients in this category are more likely to be assessed for joint preservation procedures or, where degeneration is advanced, joint replacement.
• Active inflammatory arthritis. Conditions such as rheumatoid arthritis create a systemic inflammatory environment in the joint that interferes with the repair process; chondrocyte survival and matrix integration are both compromised.
• Prior joint infection in the affected knee. A history of septic arthritis raises the risk of reactivation and impairs the biological environment needed for new cartilage tissue to form.
• Allergy to porcine-derived products or aminoglycoside antibiotics. The MACI scaffold is made from porcine type I/III collagen, and gentamicin — an aminoglycoside — is used during manufacture. Either sensitivity contraindicates the product at the material level.
• Previous cartilage surgery on the affected knee (NHS). Under NICE TA477 (2017), any prior cartilage procedure on the same knee disqualifies a patient from NHS-funded MACI. This criterion does not necessarily apply in private settings, where individual assessment applies.
• Age above 55. The FDA-defined approval window runs to 55, but this boundary reflects the limits of clinical trial data rather than a fixed biological cut-off. Evidence above 55 is limited, and older patients who present with otherwise suitable joint profiles would need individual specialist assessment rather than automatic exclusion.
• Inability to complete the rehabilitation programme. The post-operative protocol is lengthy — return to sport typically takes the better part of a year — and requires consistent physiotherapy access and graded weight-bearing. This is a question of capacity and circumstance rather than motivation; a patient whose access to rehabilitation is genuinely limited may not achieve the conditions in which the implant can mature successfully.

The pathway to MACI: what comes before and what to expect next

Once surgical restoration is on the table, the pathway branches before reaching MACI.

For defects sitting at the lower end of the size range — roughly 2–4 cm² — single-stage options such as OATS or AMIC (matrix-augmented microfracture) are typically considered first, carrying less procedural complexity and completed in a single operating list. MACI tends to follow when those approaches have not provided durable relief, or when defect size and patient profile make them unsuitable from the outset.

One nuance worth raising with a treating surgeon before committing to MACI: at two years, some comparative data between MACI and single-stage alternatives such as AMIC suggests no statistically significant difference in outcomes, particularly for smaller defects. For larger lesions the picture is clearer — the SUMMIT phase 3 RCT, in which mean defect size was 4.8 cm², demonstrated statistically significant superiority over microfracture across pain, function, and quality of life. But defect size and prior surgical history remain the key variables to work through with a specialist.

The two-stage process

MACT involves two separate procedures with several weeks in between. In the first stage, the surgeon takes a small arthroscopic biopsy of healthy cartilage from a low-load area of the knee; those chondrocytes are sent to a laboratory, cultured, and seeded onto a porcine collagen membrane — a process taking roughly four to six weeks. The second stage implants that loaded scaffold into the prepared defect site.

Rehabilitation

Recovery is demanding and structured. Physiotherapy begins immediately and continues for several months; return to sport typically takes the better part of a year or longer. The loading schedule is graded because the implant matures progressively — consistent access to rehabilitation is a practical prerequisite, not an optional addition.