The short answer: what MACI candidacy requires

MACI suits a specific type of knee problem: a painful, discrete hole in the cartilage that goes all the way through to — or into — the bone beneath. Three requirements define the core of candidacy, and all three need to be present.

First, the defect must be symptomatic. An incidental finding on an MRI scan — cartilage damage that causes no pain and no loss of function — does not meet the FDA indication. The damage must be actively affecting the patient's life.

Second, it must be full-thickness. MACI is indicated for ICRS Grade 3 or Grade 4 lesions: defects extending more than halfway through the cartilage depth, or penetrating the subchondral bone entirely. Partial-thickness surface damage falls outside the approved indication.

Third, the defect must be focal and contained — a discrete lesion with intact cartilage around its borders, not widespread degeneration across the joint. Where damage is diffuse or the knee is broadly arthritic, MACI is not the appropriate pathway; those presentations call for a different clinical conversation.

Finally, MACI is a two-stage procedure: an initial arthroscopic biopsy to harvest cartilage cells, followed weeks later by open implantation of the cultured cells on a collagen scaffold. Candidates need to be willing — and physically able — to commit to both stages and the rehabilitation that follows.

How age affects candidacy

Age shapes candidacy more than almost any other variable outside the defect itself. Cartilage cells in younger joints tend to be more biologically active, healing capacity is greater, and — perhaps most practically — a successful repair has more years of active life to justify the procedural commitment. Clinical guidance across specialist practice consistently identifies patients under 40 as the strongest candidates, with up to 45 considered in selected cases.

Registry data bears this out: in cell-based cartilage repair programmes, the typical patient is around 37 years old, with a mean defect size of approximately 3.4 cm². That figure reflects real-world selection, not an arbitrary rule.

The FDA label itself sets no upper age limit — MACI is indicated in adults, full stop. The under-40 and up-to-45 thresholds come from clinical experience and specialist consensus, which means they function as starting points rather than absolute exclusions. A consultant considering a 43-year-old with an isolated condylar defect, excellent surrounding cartilage, and an active lifestyle is looking at a genuinely different picture from a 36-year-old with early diffuse degeneration and poor tissue quality. Biological age — the health of the joint, the quality of the remaining cartilage, and what the patient actually demands of their knee — carries more weight than the number on the birth certificate.

The practical upshot: if you are in your late thirties or early forties and otherwise fit the candidacy profile, age alone is unlikely to close the door. A consultant assessment is what determines whether the biology supports it.

Defect size: the clearest decision threshold

Defect area is where the evidence speaks most clearly. The SUMMIT randomised controlled trial — the landmark head-to-head study comparing MACI with microfracture — demonstrated that for cartilage injuries of 3 cm² or greater, MACI delivered significantly better KOOS pain and function scores at both two and five years. Three square centimetres is roughly a circle 1.5 cm across: not a large injury in everyday terms, but one that consistently responds better to cell-based repair than to marrow-stimulation techniques.

Below this threshold — broadly in the 2–4 cm² range — microfracture and mosaicplasty (osteochondral autograft transfer) remain clinically acceptable alternatives. It is worth noting that microfracture carries well-documented long-term limitations: the fibrocartilage it generates tends to degrade at two to three years, and the procedure can damage the subchondral bone plate in ways that complicate any future repair. Even where it is technically reasonable in the short term, those downstream considerations form part of any honest discussion about smaller defects.

At the other end of the spectrum, very extensive damage — affecting multiple compartments or the joint as a whole — moves patients out of MACI territory. Defects of that scale are more likely to require a fresh osteochondral allograft (OCA) or, where joint-wide degeneration is established, a conversation about joint replacement.

MACI's evidence base is strongest in roughly the 2–10 cm² range. Even within that window, size works alongside depth, lesion morphology, and the presence of symptoms — it is one dimension of a multivariable clinical picture, not a single qualifying number.

Why the shape and depth of the defect matters

The depth threshold — full-thickness, ICRS Grade 3 or Grade 4 — is only part of what makes a defect surgically appropriate. Shape matters just as much, and for a specific mechanical reason: the collagen scaffold carrying the cultured cells needs an intact cartilage rim around the defect to anchor against. Without that surrounding wall of healthy tissue, there is nothing to hold the implant in place or support ingrowth from the edges.

This is why diffuse lesions — damage that spreads across large areas of the joint surface without a clear boundary — fall outside what MACI can address. The same logic applies to kissing lesions, where both opposing cartilage surfaces are damaged. Cell-based repair works on one surface at a time; where both sides of the joint are compromised, the conditions for reliable scaffold integration are not in place.

Bone involvement, by contrast, is not automatically disqualifying, and patients sometimes assume it is. The FDA label explicitly covers defects with or without involvement of the underlying bone, and where bone loss is significant, bone grafting can be incorporated to restore the foundation before the cell layer is applied.

The practical question at assessment is whether imaging and, where needed, arthroscopic evaluation reveal a discrete, well-bordered lesion — the structural geography that makes surgical repair feasible.

Other clinical factors assessed before MACI

Even when a defect meets the size, depth, and morphology criteria, a consultant will look beyond the lesion itself before recommending MACI. Several mechanical and surgical factors shape whether a graft is likely to survive long term — and whether any additional procedures are needed first.

Alignment. If the knee is significantly bowed or knock-kneed, load concentrates on the damaged compartment rather than distributing evenly. Implanting cells into that environment without addressing the mechanics is unlikely to produce a durable result. In these cases, a corrective osteotomy — high tibial or distal femoral — may be planned alongside or prior to MACI to shift loading away from the repair site. Objective biomechanical assessment, including gait analysis, informs this planning.

Ligament stability. An unstable joint — most commonly from unresolved ACL laxity — generates abnormal shear forces across the cartilage surface. Addressing ligament insufficiency before or at the same time as cartilage repair is generally considered a prerequisite for protecting the graft.

Body weight. Higher joint loading affects the likelihood of durable scaffold integration. BMI forms part of the clinical picture, though it is weighed against the individual's overall health profile rather than applied as a fixed cut-off.

Prior marrow-stimulation procedures. Previous microfracture can alter the subchondral bone plate in ways that complicate subsequent cell-based repair. This history is factored into pre-operative planning, though it does not automatically exclude a patient.

None of these factors are formally codified as hard contraindications in published guidance — they represent the clinical judgement a consultant applies to each individual case.

When a different approach is the better fit

Three branches of the decision tree determine when a different procedure is the better fit.

When the lesion is smaller. Below roughly 2–3 cm², the evidence advantage MACI holds over less invasive options narrows considerably. OATS or mosaicplasty — a single-stage autograft — is a well-established alternative at this scale. For very small focal defects well below the MACI threshold, a ChondroFiller injection — an ultrasound-guided outpatient procedure using an injectable collagen scaffold — offers a minimally invasive route without the commitment of a two-stage operation.

When the damage is more extensive. Very large or post-traumatic defects push beyond what a cell-based scaffold can reliably cover, and fresh osteochondral allograft (OCA) transplantation is the more appropriate surgical option in that range. Widespread degenerative change throughout the joint moves the conversation into joint preservation or replacement; no cartilage restoration technique can reliably regenerate a broadly arthritic knee.

For patients in the UK. MACI as a branded product has not been available in the UK since its EU marketing authorisation was suspended in 2014 — it is currently a US-only, knee-only treatment. Patients who would otherwise fit the MACI profile, including some with larger or more complex defects that would previously have been turned away, are typically assessed for STACi: a single-stage scaffold-based procedure built on the same core candidacy principles and applicable across joints beyond the knee.

The clearest synthesis of the preceding sections is this: MACI — or STACi in the UK — suits a patient who is younger, carries a focal full-thickness lesion of roughly 3 cm² or more, and presents with a mechanically sound, non-arthritic knee. Where any of those features diverge materially, a different pathway is generally more appropriate, and identifying which one depends on weighing imaging, symptoms, and mechanical factors together rather than on any single criterion. Consultations at MSK Doctors are available without referral at mskdoctors.com.