Can Cartilage Repair Work in a Knee That Already Has Some Arthritis?

Overview

Agili-C is a single-stage, cell-free, off-the-shelf cartilage scaffold, and it holds an FDA indication no other cartilage implant has: use in a knee that already has mild-to-moderate arthritis. Dr. Raffo uses it for patients whose defect and arthritis grade fit that labeled window. The 2-year trial data is strong; longer-term data is still limited, and he says so plainly.

Who this is for

Agili-C's verbatim FDA indication is "the treatment of an International Cartilage Repair Society (ICRS) grade III or above knee-joint surface lesion(s), with a total treatable area of 1-7cm², without severe osteoarthritis (Kellgren-Lawrence grade 0-3)" (FDA PMA P210034). That single line is the reason this implant exists as a distinct option: it is the only FDA-approved cartilage-repair implant whose label permits use in a knee with radiographic osteoarthritis, up to and including KL grade 3. KL grade 4, meaning severe arthritis, is excluded (FDA PMA P210034). The pivotal trial further specified eligibility of age 21-75, up to 3 lesions, bony defect depth of 8 mm or less, BMI of 35 or less, and malalignment of no more than 8 degrees varus or valgus (FDA SSED P210034b). Agili-C is not appropriate for a knee with severe, bone-on-bone arthritis, nor for a lesion larger than the 7 cm² labeled ceiling.

How I approach it

The reason I bring up Agili-C at all is the KL 0-3 label. Most patients who come in with a cartilage defect and early arthritis on their X-ray have already been told, implicitly or explicitly, that cartilage restoration "isn't for them anymore" because some degenerative change is present. Agili-C is the one implant where that's not automatically true, and the trial data in that specific subgroup is what makes me comfortable using it there: in patients with mild-to-moderate OA at baseline, treatment failure was only 5.3% with Agili-C versus 27.8% with standard-of-care surgery in the same subgroup, and the FDA states superiority was confirmed across all subgroups studied (FDA SSED P210034b).

But I'm equally direct about the limits of what's known. The 251-patient pivotal trial has excellent 2-year results, and 5-year follow-up was planned in the original protocol — but as of this writing, the only published data past 2 years is a single-center case series of just 13 patients (de Caro et al. 2024). Thirteen patients is not a number I'd use to promise a decade of durability, and I don't. I tell patients the 2-year data is strong and the 5-to-10-year picture is, for now, genuinely unknown.

The operation

Agili-C is implanted in a single stage, without the biopsy-and-culture sequence that MACI requires. The defect is prepared to accept the implant, and the off-the-shelf aragonite scaffold — a bi-phasic design with a cartilage-facing layer of aragonite and hyaluronic acid — is sized and press-fit into place (Smith+Nephew Agili-C reimbursement guide). Because the scaffold is cell-free and resorbable, there is no separate cell-harvesting procedure or waiting period before implantation, unlike MACI's two-stage structure (FDA — MACI, for comparison).

Risks and honest tradeoffs

The pivotal trial showed a favorable safety profile relative to standard-of-care surgery: overall adverse event rate was 59.3% for Agili-C versus 77.4% for standard-of-care, severe adverse events were 10.2% versus 20.2%, and there were no unanticipated serious adverse device effects and no deaths in either arm (FDA SSED P210034b). Treatment failure in the full trial cohort was 7.2% at 24 months, and of the 12 Agili-C failures, 8 involved removal of the device itself (FDA SSED P210034b). The central honest tradeoff of this implant is durability uncertainty, not safety: the only published minimum 5-year outcomes come from a 13-patient case series, in which 2 patients failed between years 3 and 5 — one from an unrelated arthritic condition and one from a high-energy fall requiring revision to a focal arthroplasty at age 48 (de Caro et al. 2024). The larger 251-patient trial cohort has 60-month follow-up planned in its protocol, but those results are not yet published.

Recovery and rehabilitation

Agili-C's single-stage, cell-free design allows for a recovery protocol that does not carry the biopsy-to-implantation delay inherent to MACI.

• 0–6 weeks: Protected weight-bearing while the scaffold begins to integrate.
• 6–12 weeks: Progressive weight-bearing and range-of-motion advancement.
• 3–6 months: Return to low-impact activity for most patients, guided by individual healing.
• 24 months: The trial's primary endpoint window, where MRI showed 75% or greater defect fill in 88.5% of Agili-C patients versus 30.9% of standard-of-care patients (Altschuler et al. 2023).

1. 0–6 weeks

   Protected weight-bearing while the scaffold begins to integrate.

2. 6–12 weeks

   Progressive weight-bearing and range-of-motion advancement.

3. 3–6 months

   Return to low-impact activity for most patients, guided by individual healing.

4. 24 months

   The trial's primary endpoint window.

   where MRI showed 75% or greater defect fill in 88.5% of Agili-C patients versus 30.9% of standard-of-care patients (Altschuler et al. 2023).

Alternatives I considered

For a patient with a similar lesion size but no arthritis at all, I weigh MACI or OCA depending on bone involvement, since both have longer track records even though they lack Agili-C's OA-friendly label. For a patient whose arthritis is severe rather than mild-to-moderate — KL grade 4 — no cartilage implant, Agili-C included, is appropriate, and the more honest conversation at that point is about robotic total knee replacement.

Biologics used