Why defect size changes the repair options available

The question most patients arrive with is straightforward: the defect is too large for the usual options — so what comes next?

For focal, full-thickness cartilage injuries of less than roughly 2 cm², marrow-stimulation techniques such as microfracture and single-plug osteochondral transfer (OATS) are established choices. Once a defect exceeds approximately 2–4 cm², neither approach reliably covers the damage. ACI and its matrix-assisted successor MACI are designed specifically for this range, with published experience extending to defects of around 10 cm².

The most direct prospective evidence for that threshold sits in the SUMMIT trial, which enrolled patients with cartilage injuries of 3 cm² or greater and compared MACI against microfracture. At both 2 and 5 years, MACI produced meaningfully improved KOOS pain and function scores — the strongest single dataset supporting cell-based repair for larger defects.

Size alone, however, does not capture the full clinical picture. Articular cartilage is avascular; it cannot repair itself the way vascularised tissue can. Defects much above 1 cm tend to deteriorate progressively, eventually threatening the wider joint surface and raising the risk of osteoarthritis. Acting earlier, before that deterioration accelerates, matters.

Microfracture also carries a structural cost that extends beyond coverage area. The fibrocartilage it generates — predominantly type I collagen rather than the hyaline type II collagen of native cartilage — is mechanically inferior and tends to break down within 2–3 years. The procedure also disrupts the subchondral bone plate, which can narrow the options available for any subsequent repair attempt. For a large defect, those downstream consequences shift the calculation considerably.

The joint conditions ACI requires before planning begins

Size determines whether ACI is in scope; the condition of the surrounding joint determines whether it will work.

The graft does not survive in a mechanically hostile environment. Uncorrected varus or valgus malalignment channels load directly onto the repair site, and the evidence is clear that implanted chondrocytes cannot withstand that kind of concentrated stress. Where alignment is a factor, a corrective osteotomy — high tibial (HTO) or distal femoral (DFO) depending on which compartment is affected — may be planned as a concurrent or staged procedure before ACI proceeds. This is not a complication of the process; it is how careful pre-operative planning is supposed to work.

Ligament stability follows the same logic. An ACL-deficient or PCL-deficient knee produces abnormal shear forces throughout the joint; ACI into an unstable knee is likely to fail, so ligament reconstruction must either precede or accompany the cartilage repair. The same applies to meniscal status: the menisci act as load distributors, and a knee without adequate meniscal cover places disproportionate stress on the articular surface the graft is trying to restore.

Marginal cartilage quality is a subtler but equally important check. The tissue surrounding the defect provides the containment wall the graft integrates into; significantly degenerate or thinned margins are a relative contraindication.

Finally, diffuse osteoarthritis excludes ACI entirely. The procedure targets focal, symptomatic lesions — not widespread joint degeneration. Distinguishing between the two is the first filter in any assessment, and pre-operative MRI is the tool used to make that determination precisely. Advanced sequences including T2 mapping and dGEMRIC add a further layer of detail, characterising cartilage composition and surrounding tissue integrity before any staging decisions are confirmed.

How the two stages work — and how the procedure has evolved

Staging is built into ACI by design, and understanding why helps patients plan realistically for what lies ahead.

Stage 1 — the biopsy. A short arthroscopic procedure harvests a small sample of healthy cartilage from a low-load area of the knee, typically the medial intercondylar notch. The sample is small — a few grams — and the donor site is chosen to minimise any lasting impact on joint function.

The culture interval. The biopsy is sent to a licensed laboratory where the harvested chondrocytes are grown in controlled conditions over several weeks. This gap is the defining logistical feature of the entire two-stage model: patients need to factor it into work, travel, and rehabilitation planning before committing to the process.

Stage 2 — implantation, and how it has changed across three generations. First-generation ACI involves an open procedure in which a periosteal flap, taken from the shin, is sutured over the prepared defect to contain the expanded cells beneath it. This works, but periosteal hypertrophy — overgrowth of the flap tissue — became the procedure's most recognised complication. Second-generation ACI addressed that directly by replacing the periosteal patch with a bilayer collagen membrane, retaining the cell-containment principle while removing the need to harvest shin tissue.

MACI, the third-generation form, takes a different approach: the expanded cells are seeded directly onto a collagen scaffold sheet in the laboratory before Stage 2, then fixed into the prepared defect using fibrin glue. This eliminates the periosteum harvest entirely and simplifies fixation at the implantation site.

Each generation, in other words, solved a specific problem its predecessor created. Single-stage platforms such as STACi go further still — aiming to collapse both stages into one and remove the weeks-long laboratory wait — but that remains an emerging pathway rather than the established standard.

What to expect between biopsy and implantation

Planning around the culture interval is, for many patients, the most practically disruptive aspect of the whole commitment.

During the weeks between Stage 1 and Stage 2, the knee itself is not immobilised. Most patients remain mobile, attend outpatient physiotherapy, and manage daily life with reasonable comfort. The wait is logistical — laboratory-side — rather than clinical.

Stage 2 and its recovery are where the time commitment becomes substantial. Return to unrestricted activity after ACI or MACI is measured in many months rather than weeks — often the better part of a year — reflecting the period required for implanted cells to integrate and mature into load-bearing tissue. That is considerably longer than the rehabilitation following single-stage procedures, and patients with rigid work schedules, caring responsibilities, or fixed professional commitments need to understand the full timeline at assessment, before a surgical date is booked.

For those who cannot accommodate two operations and a prolonged inter-stage wait, Taylor and Lee described a single-stage ACI approach in 2019 that addresses precisely this scheduling burden. The evidence base for that approach remains limited and it has not become standard practice, but its existence is worth raising in the candidacy discussion for patients to whom timing is a decisive factor.

Ten-year outcomes: tissue quality and durability

The biological reason ACI holds up over a decade comes down to what the repair tissue actually is.

Marrow-stimulation techniques, including microfracture, fill the defect with fibrocartilage — a repair tissue composed predominantly of type I collagen. It is mechanically weaker and less wear-resistant than native articular cartilage, and in published series its structural quality tends to decline visibly by two to three years. ACI, by contrast, generates hyaline-like repair tissue rich in type II collagen — the same structural protein that gives healthy articular cartilage its load-bearing resilience. That biochemical difference is the principal explanation for why the long-term outcome curves between the two approaches diverge: the ACI repair tissue continues to function where fibrocartilage degrades.

The clinical landmark for long-term evidence is Minas, Von Keudell, Bryant, and Gomoll (Clin Orthop Relat Res, 2014), a John Insall Award study reporting minimum 10-year outcomes after ACI. Its headline findings — durable clinical benefit and considerable delay of partial or total knee replacement — are consistent with what the tissue biology would predict. Specific survival rates, functional scores, and revision data from that series are not reproduced here, but the broad conclusion that ACI can protect the joint well beyond the five-year window is the best-evidenced long-duration statement the literature currently supports.

Two intermediate studies provide the evidence arc that leads to the 10-year data. Behrens et al. (Knee, 2006) reported five-year outcomes for matrix-associated ACI, and Ebert et al. combined clinical and MRI-based assessment at the same follow-up point — both consistent with durable fill and maintained function. Comparative randomised data extending to 10 years for MACI versus first-generation ACI is sparse, and that gap in the evidence base is worth acknowledging honestly.

The realistic long-term frame for younger patients with large defects is joint replacement delay, not permanent avoidance. For many, that delay is clinically meaningful — protecting a decade or more of active life before reconstruction becomes necessary.

Getting assessed for ACI

Deciding whether ACI or MACI is the right approach requires weighing defect geometry, tissue quality, surrounding cartilage health, joint mechanics, imaging findings, and individual patient circumstances together. It is an integrative clinical judgement rather than a simple threshold decision — the same lesion area in two patients may lead to different recommendations depending on alignment history, prior surgery, and what the MRI reveals about marginal tissue.

Assessment typically includes a structured clinical review, careful scrutiny of imaging (including advanced MRI sequences such as T2 mapping where the clinical picture warrants it), and formal evaluation of limb alignment and ligamentous stability. Where any of those factors are borderline, they generally need to be addressed before — or in concert with — any cartilage reconstruction plan.

Professor Paul Y. F. Lee at the London Cartilage Clinic on Harley Street leads candidacy assessment and surgical planning for patients who may be suitable for staged ACI or MACI. Patients wishing to explore whether either procedure is appropriate for their situation can request a consultation at londoncartilage.com.

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