Why some cartilage defects need a two-stage approach

When a surgeon mentions ACI or MACI, the natural question is: why does this need two operations rather than one? The answer comes down to defect size.

For focal cartilage damage covering roughly 2 cm² or less, single-stage procedures — microfracture or osteochondral autograft transfer (OATS/mosaicplasty) — can be performed in a single operating session and often produce adequate results. Beyond that threshold, however, these techniques cannot generate enough repair tissue to reliably fill a larger lesion or sustain durable function over time.

Both ACI and MACI address this by introducing a laboratory phase between the two operations. In Stage 1, a small arthroscopic biopsy harvests a sample of the patient's own healthy chondrocytes. Those cells are then cultured and multiplied in a specialist laboratory over several weeks. Only with that expanded cell population available does Stage 2 — the implantation — become viable. Without it, there are simply not enough cells to achieve meaningful regeneration across a large defect.

The clinical case for this additional commitment is anchored by the SUMMIT trial, which found that for defects of 3 cm² or more, MACI produced significantly better KOOS pain and function scores than microfracture at both two and five years. The two-stage pathway takes longer and requires greater commitment from the patient — but for larger lesions, the evidence suggests the outcome justifies that trade-off.

Stage 1 and Stage 2: what both procedures share

Both procedures begin with an arthroscopic biopsy in which the surgeon removes a small sample of healthy cartilage from a low-load area of the knee — typically the intercondylar notch or the periphery of a femoral condyle, where harvesting causes minimal functional disruption. Stage 1 is generally the shorter and less demanding of the two surgical episodes; patients mobilise relatively quickly and can return to light daily activity well before Stage 2 is scheduled.

That sample is then transferred to a specialist laboratory, where chondrocytes are isolated, purified, and expanded in culture. The manufacturing interval typically runs to several weeks or longer, varying by laboratory protocol and surgical scheduling — patients should expect to wait before a Stage 2 date is confirmed. This shared dependency on laboratory cell expansion is what separates both ACI and MACI from same-session procedures: the expanded cell population is what makes large-defect repair viable, but the process cannot be shortened. Both are indicated for focal, isolated articular cartilage damage in otherwise structurally sound adult knees. Where they diverge is in how those cultured cells are delivered and fixed at Stage 2.

First-generation ACI: the periosteal patch and its drawbacks

Original ACI — the first generation — works by injecting cultured chondrocytes as a liquid cell suspension directly into the prepared defect site. To keep those cells in place, the surgeon harvests a small patch of periosteal tissue from the patient's tibia through a separate incision, sutures it over the defect like a lid, and injects the suspension underneath. The periosteal flap acts as a biological seal, holding the cells against the cartilage surface while they integrate and mature.

The main technical problem with this approach is the periosteal tissue itself. Harvesting and suturing it adds operative time and demands precise technique; more significantly, periosteal overgrowth — hypertrophy — was the most frequently reported complication of first-generation ACI, sometimes requiring a further arthroscopic procedure to trim the excess tissue. Keeping liquid cells securely in position under a sutured membrane also carries an inherent risk of leakage, particularly during the immediate post-operative period before any biological adhesion has occurred.

Second-generation ACI — known as CACI — replaced the periosteal flap with a biodegradable collagen membrane, which largely eliminated hypertrophy. Suture fixation was retained, however, and with it the associated risks of microtrauma to the surrounding tissue and cell leakage at the membrane margins.

Despite this technical complexity, ACI's long-term clinical record is substantial. Published data report success rates of approximately 92% for isolated articular cartilage lesions and around 85% for multiple lesions within the same knee — figures that establish ACI as a durable intervention. The later evolution into MACI was driven by a desire to simplify delivery and reduce surgical risk, not by any fundamental failure of the cell-based principle itself.

How MACI changed the delivery

The critical difference MACI introduces happens before the patient returns to theatre. During the manufacturing stage, the laboratory seeds the expanded chondrocytes directly and uniformly onto a resorbable Type I/III porcine collagen membrane — so by the time the membrane reaches the operating table, the cells are already embedded within it, distributed evenly across its surface.

At Stage 2, the surgeon trims this cell-laden membrane to match the exact contours of the defect and fixes it in position using fibrin glue. No sutures pierce the tissue margins, which removes two of the persistent limitations of earlier generations: the microtrauma associated with suture placement, and the risk of cell leakage that came with holding a liquid suspension beneath a sutured cover. The procedure is mechanically simpler and less time-intensive in theatre than first-generation ACI.

MACI's anatomical range is also broader. The technique can address defects at the medial femoral condyle, lateral femoral condyle, patella, and trochlea, and it accommodates uncontained lesions — situations where the defect margin lacks a complete surrounding wall of cartilage — which sutured approaches handled less reliably.

On comparative outcomes, a 2024 study by Manjunath et al. (PubMed 38739659) found that patients treated with MACI achieved greater reductions in pain scores than those treated with conventional ACI. Direct head-to-head randomised trial data between the two generations remains limited, however: the strongest superiority evidence for MACI in the published literature comes from its comparison with microfracture rather than with ACI itself. The Manjunath finding is clinically meaningful but is best read with that context in mind.

Outcomes, durability, and realistic expectations

Published satisfaction data for both procedures consistently sit in the 85–90% range, with durable long-term results across follow-up periods extending beyond a decade in some series. More meaningfully for patients weighing operative against non-operative routes: both ACI and MACI are genuinely disease-modifying. By establishing viable hyaline-like cartilage tissue, they slow joint degeneration and may delay or avoid the need for partial or total knee replacement — an outcome that purely symptomatic treatments cannot reliably achieve.

The important caveat concerns specificity of indication. Neither procedure addresses diffuse cartilage loss from osteoarthritis; both are reserved for focal, isolated defects in a joint that is otherwise structurally sound. Where damage is widespread, a different clinical pathway is required.

On comparative outcomes between the two techniques, direct head-to-head randomised trial data in matched populations remains limited. The strongest published evidence — including the SUMMIT trial, which demonstrated meaningful gains in KOOS pain and function scores at two and five years — positions both against microfracture rather than against each other. That context matters when interpreting any apparent superiority claim.

Access to MACI also varies between NHS and private pathways in ways that are clinically relevant for UK patients; a full comparison of commissioning routes and associated costs falls outside the scope of this article and is best discussed with a specialist directly. In practice, the decision between ACI and MACI turns less on a single outcomes hierarchy and more on the defect's size, location, and containment, alongside the operating surgeon's experience with each technique.

Recovery, candidacy, and getting assessed

Recovery after either procedure follows a broadly predictable course. Crutch-assisted mobility is expected within the first week; graduated weight-bearing begins at weeks 2–3, increasing incrementally under physiotherapy supervision. Full articular cartilage maturation — the point at which the tissue is genuinely load-tolerant — takes between 9 and 18 months. Return to sport or demanding physical activity is planned around that horizon, not the early mobility milestones.

Candidacy rests on the same core criteria for both: adults with focal, isolated articular cartilage damage in a structurally sound joint. The choice between ACI and MACI is not a simple protocol decision; it turns on defect size, precise location, containment, prior procedures, and the operating team's experience with each technique. Neither recommendation can be reached without a specialist evaluation.

What that evaluation establishes is a clear pathway: whether cell-based restoration is appropriate at all, which technique best matches the defect's geometry, and whether any alignment issue warrants attention alongside it. The process typically involves MRI, clinical examination, and a structured discussion of activity level and goals — producing a treatment recommendation grounded in the specific lesion rather than a generic options list. Professor Paul Y. F. Lee assesses these cases at the London Cartilage Clinic, and patients wishing to begin that process can book through londoncartilage.com.

1. [1] Autologous chondrocyte implantation — Wikipedia. https://en.wikipedia.org/?curid=19074150 https://en.wikipedia.org/?curid=19074150