Both procedures are two-stage — so what actually differs?

The most common misconception about these two procedures is that one requires two operations and the other requires only one. In fact, both ACI and MACI follow an identical two-stage structure: an initial arthroscopic biopsy removes 200–300 mg of healthy cartilage from a non-weight-bearing zone of the knee, and the harvested cells are then expanded in a laboratory over three to six weeks before a second open operation delivers them back into the damaged area. The number of surgical episodes is the same — what differs is everything that happens at that second stage.

In first-generation ACI, the laboratory-expanded chondrocytes are injected as a liquid suspension beneath a periosteal patch — a membrane harvested from the upper tibia (shin) and sutured over the defect. This technique is technically demanding, creates a separate donor-site wound at the periosteal harvest site, and carries a risk of uneven pooling of cells within the defect.

MACI removes both problems by pre-seeding those same expanded chondrocytes directly and uniformly onto a porcine collagen Type I/III membrane (Chondro-Gide) before the patient enters theatre. At the implantation stage, the membrane is shaped to fit the defect and secured with fibrin glue — no periosteal harvest, no sutures, and a more consistent distribution of cells across the repair site.

This distinction in delivery method carries genuine clinical weight, but it should not be mistaken for a difference in procedural complexity at the top level. For most patients being assessed today, the practical question is not ACI versus MACI — first-generation ACI has been largely phased out in favour of the membrane-based approach. The real decision is whether MACI is the right pathway at all.

How MACI improved on the original technique

The periosteal patch was the defining weakness of first-generation ACI — and not only because of the donor-site wound it created at the upper tibia. The patch itself carried a recognised risk of periosteal hypertrophy: unwanted tissue overgrowth beneath the sutured membrane that could cause mechanical catching or pain, and in some cases required a further arthroscopic procedure to trim. Liquid cell suspension also pooled unpredictably beneath the patch rather than spreading evenly, making outcomes partly dependent on surgical precision and technique.

Second-generation ACI (ACI-C) tackled hypertrophy and donor morbidity together by replacing the periosteal patch with a pre-formed porcine collagen type I/III membrane, sutured directly over the defect. The tibial harvest was no longer needed, removing a meaningful source of post-operative discomfort. The sutures remained, however — a technically demanding step that risked wrinkling the membrane under uneven tension, which could in turn disrupt the cell layer it was meant to protect.

MACI — the third generation — removed the suturing requirement by making the collagen membrane the delivery vehicle rather than just a cover. Chondrocytes are pre-seeded onto Chondro-Gide in the laboratory before the patient enters theatre; the construct is then trimmed precisely to the defect shape and held in position with fibrin glue alone. The membrane's structural rigidity also gives MACI a practical advantage with uncontained defects — lesions lacking a surrounding cartilage rim to anchor a softer patch — which were more challenging to manage with earlier techniques.

Each of these changes is primarily technical and procedural. The cartilage-forming cells remain the patient's own expanded chondrocytes at every generation, and the underlying biology is the same. MACI is now frequently described as the gold standard for focal cartilage repair (Schneider et al., 2025), a label that reflects its refined delivery and accumulated evidence base rather than a categorically superior cellular result.

Which patients are candidates for ACI or MACI

Suitability for either procedure rests on the same set of criteria — ACI and MACI share essentially identical eligibility requirements, so the assessment process is the same whichever path the surgeon ultimately recommends.

The defining requirement is a focal, full-thickness cartilage defect — ICRS Grade 3 or 4 — typically on the femoral condyle or the patellofemoral surface. 'Focal' matters here: cell-based repair is designed for discrete, localised damage rather than the widespread joint thinning seen in osteoarthritis. Patients with multi-compartment disease or diffuse OA are generally not suitable candidates.

Defect size is the most practical filter. Both procedures are generally applied to lesions in the 2–20 cm² range. Below approximately 2 cm², marrow-stimulation techniques such as microfracture, or an osteochondral autograft (mosaicplasty), may achieve adequate results without the added complexity and recovery burden of a cell-based approach. Above roughly 3 cm², the evidence becomes clearer: the SUMMIT Phase 3 RCT demonstrated that MACI outperformed microfracture on KOOS pain and function scores at both two and five years for defects at or above this threshold — making 3 cm² a useful practical marker rather than a rigid rule.

Two mechanical pre-conditions also need to be confirmed before proceeding. Any significant malalignment or ligament instability in the affected knee should be addressed first, because implanting cartilage cells into a mechanically compromised joint undermines the repair. A consultant assessment will establish whether osteotomy or ligament reconstruction is needed as a prior or concurrent procedure.

Age and lifestyle context also shape the decision. Both ACI and MACI tend to be most appropriate in younger, active patients — particularly those who want to return to sport — for whom preserving native cartilage has the greatest long-term value.

What the evidence says about outcomes

Published series give ACI a success rate of approximately 92% for isolated articular cartilage lesions, falling to around 85% where multiple lesions in the same knee are treated simultaneously. MACI, assessed at ten-year follow-up, shows sustained improvements in pain and function with low reoperation rates — durable results that have supported its gradual replacement of first-generation ACI in most centres. A 2024 comparative analysis by Manjunath and colleagues found that both procedures deliver good short-term clinical improvement in pain and activity levels over pre-operative baseline, without a demonstrable biological difference between them in that timeframe.

What the evidence does not yet establish is whether MACI produces better cartilage outcomes than first-generation ACI. The SUMMIT Phase 3 RCT compared MACI against microfracture — a different question entirely — and its findings speak to where cell-based repair earns its added complexity over marrow stimulation, not to whether one cell-based technique regenerates cartilage more effectively than the other. Direct head-to-head trial data between ACI and MACI remains limited; most comparative evidence is observational. The gains MACI offers are primarily technical — simpler fixation, no periosteal harvest, more uniform cell distribution — and these reduce procedural burden for both surgeon and patient without appearing to translate into a categorically superior biological result.

Recovery expectations are shared across both procedures. Light sporting activity is typically possible at around six months; full return to sport generally falls in the nine-to-twelve-month range.

The genuinely single-stage option and when it applies

For patients who specifically want to avoid a second operation, a genuinely single-stage cell-based option exists: STACi. Rather than culturing chondrocytes in a laboratory between two theatre visits, STACi harvests cartilage, enzymatically digests it in the operating theatre, and combines the released chondrocytes with bone-marrow–derived mesenchymal stem cells from the same surgical field — all within a single anaesthetic. There is no culture interval, no waiting weeks, and no second procedure.

The scaffold architecture also differs from MACI. Where MACI uses a flat collagen sheet, STACi seeds cells onto a three-dimensional volumetric scaffold designed to support cell growth through the depth of the defect as well as across its surface — an arrangement claimed to more closely mirror native cartilage structure. That same three-dimensional format makes STACi applicable across more joints than MACI, including the hip, shoulder, and ankle.

The meaningful caveat is evidence maturity. STACi is not yet in routine use across most UK markets, and its published evidence base is substantially thinner than the decade-plus of MACI outcome data. For most patients with a suitable focal defect, MACI remains the better-evidenced choice.

STACi is most worth raising with a specialist when avoiding two anaesthetics is a genuine priority — for instance, patients with anaesthetic risk factors, those who cannot accommodate two separate recovery periods, or those whose defect is too large or complex for standard MACI and who want to understand what lies beyond it.

Finding the right specialist for cell-based cartilage repair

Cell-based cartilage repair is carried out by a relatively small number of knee surgeons in the UK. Not every orthopaedic surgeon who operates on knees will have the case volume or procedural familiarity to assess which procedure generation is appropriate, manage uncontained defects, or plan a combined repair and alignment correction where one is needed. For a patient weighing ACI, MACI, or a single-stage variant, the surgeon's specific experience with cell-based techniques is as consequential as the choice of procedure itself.

A specialist consultation will typically involve MRI review, an assessment of defect grade, alignment, and ligament stability, and a discussion of activity goals — the full clinical picture that determines whether cell-based repair is appropriate and, if so, which approach fits. Some complex presentations benefit from multidisciplinary input before a final plan is agreed.

Surgeons with specific experience in cell-based cartilage repair are spread across the UK but are not present at every centre. Search MSK lists knee cartilage specialists by region and treatment offered — a practical way to identify who in your area performs this work.