What this combination treatment offers patients with advanced knee OA

For many patients with bone-on-bone knee arthritis, the conversation with a surgeon tends to end at total knee replacement — but a growing number of people in their fifties, sixties, and beyond are asking whether there is anything worth trying before that step. A 2025 prospective controlled trial published by Weninger and colleagues at Avancell Medical in Vienna suggests one combination may be worth serious consideration: an intra-articular injection of autologous blood-derived mesenchymal stem cell (MSC) concentrate given alongside a ChondroFiller® Liquid injection — an acellular collagen scaffold that gels inside the joint within minutes.

The trial enrolled 25 patients, all with Kellgren-Lawrence Grade IV knee osteoarthritis — the most advanced stage, characterised by near-complete cartilage loss — and found that patients who received the combination achieved measurably greater improvements in pain and function at two months than those who received the MSC concentrate alone. Both treatments were delivered by injection; no surgery or general anaesthetic was involved.

This is early, pilot-level evidence from a small, non-randomised study with a short follow-up. The combination does not reverse end-stage joint damage. What the trial does offer is the first direct, controlled comparison between these two approaches in this specific patient group — and an honest account of what that comparison can and cannot yet tell us.

How ChondroFiller injection and MSC concentrate work together

Two distinct biologics are injected in this protocol, each addressing a different limitation of cartilage repair in the osteoarthritic knee.

ChondroFiller® Liquid is a CE-marked Class III acellular type I collagen hydrogel manufactured by Meidrix Biomedicals. Delivered by ultrasound-guided outpatient injection, it gels within approximately three to five minutes of entering the joint, conforming to the contours of the damaged area and forming a porous three-dimensional matrix. It contains no cells of its own. Instead, its proposed role is matrix-induced chondrogenesis: the scaffold is designed to attract the patient's own progenitor cells from surrounding tissue and subchondral bone, providing a physical environment that may support their migration, retention, and differentiation toward cartilage tissue. Because no prior cell harvesting or biopsy is required, the entire treatment takes place in a single outpatient visit.

The MSC concentrate used in the Weninger 2025 trial was derived from autologous blood — no donor tissue, no second procedure. It delivers a high density of mesenchymal stem cells directly into the joint space, where systematic review evidence suggests these cells can contribute to cartilage repair and clinical improvement.

The proposed biological logic of combining them is straightforward: MSCs introduced without a supportive structure may disperse or fail to establish effectively within a severely degraded joint. ChondroFiller's porous matrix may give those cells a stable three-dimensional environment to colonise and remain active within — addressing a gap that neither component alone resolves. Long-term structural confirmation of this synergy is still lacking, but the early molecular signal from Weninger 2025, including reduced MMP-13 expression in the combination arm, is consistent with the hypothesis.

What the Weninger 2025 trial found at two months

The primary results were measured using the KOOS — a validated five-domain patient questionnaire covering pain, symptoms, activities of daily living (ADL), sport and recreation, and quality of life — assessed at the two-month mark.

Both groups improved significantly from their pre-treatment scores across all five subscales (p<0.01). The thirteen patients who received MSC concentrate combined with ChondroFiller injection consistently outscored the twelve who received MSC concentrate alone on every KOOS domain, indicating the scaffold added a measurable functional benefit beyond what the cell concentrate achieved on its own.

MRI in the combination group showed significant reductions in bone marrow oedema, joint effusion, and synovitis — tissue-level changes that extend beyond subjective symptom relief and point toward a degree of structural settling within the treated joint. Separately, MMP-13 — an enzyme that breaks down collagen within the cartilage matrix and serves as a molecular marker of active degradation — fell more sharply in the combination arm than in the MSC-alone group. A greater reduction in MMP-13 suggests the protocol may attenuate cartilage breakdown at a biochemical level, although the two-month window is too short to confirm durable cartilage regeneration.

No serious adverse events were recorded in either group. The safety signal matters in context: patients with Kellgren-Lawrence Grade IV disease face a realistic pathway to total knee replacement, so any combination approach that raised procedural risk would require a substantially larger clinical benefit to justify consideration. In this pilot cohort, no such trade-off was apparent.

Which patients this evidence applies to

The Weninger trial enrolled a tightly defined group: adults aged 50 to 99 years with Kellgren-Lawrence Grade IV knee osteoarthritis affecting at least two compartments of the joint. KL Grade IV represents the most advanced stage of radiological degeneration — near-complete or complete loss of cartilage, bone-on-bone contact visible on X-ray, and a joint that conventional orthopaedic pathways would typically refer for total knee replacement. This was not a mildly symptomatic cohort; these were patients already at the conventional surgical threshold.

The practical implication is that the combination protocol's results speak most directly to people in that same position: significant multi-compartment disease, KL Grade IV confirmed on imaging, and an age profile that spans the typical replacement demographic. Patients who are already listed for or seriously weighing up total knee replacement represent the clearest parallel to the trial population.

The Grade III gap

KL Grade III patients — those with substantial but not complete cartilage loss — were not included in the Weninger study. Applying the trial's findings to Grade III disease is an inference rather than a direct extrapolation, and that distinction is worth being honest about. The broader ChondroFiller injection evidence base does encompass Grade III to IV focal cartilage defects, with published data suggesting 70 to 85% of treated patients achieve meaningful symptom relief at three to five years — but that figure comes from the wider scaffold literature, not from the Weninger combination study specifically. Grade III patients are not excluded from consideration for ChondroFiller injection; they simply cannot rely on this particular trial as direct evidence.

Confirming where any individual patient sits on that spectrum requires an accurate assessment of cartilage thickness, defect extent, and compartment involvement — detail that weight-bearing X-ray and MRI together can provide. A structured imaging review is the appropriate starting point before any discussion of suitability for this type of protocol.

How far this evidence goes— and where it stops

Promising early signals — the MMP-13 reduction and MRI structural changes described in the previous section — carry more weight when the study architecture behind them is strong enough to support firm conclusions. The Weninger 2025 trial generates those signals, but its design places them in hypothesis-generating territory rather than confirmatory evidence.

The trial is a prospective controlled study, not a randomised controlled trial. Treatment allocation followed individual clinical decisions rather than random assignment, which means the two groups may have differed in characteristics that influenced outcomes independently of the protocol itself. Without randomisation, the combination arm's consistent superiority across every KOOS domain is a coherent signal — but it cannot be attributed to the treatment alone with full confidence.

At 25 patients, this is pilot-scale work. A cohort of that size is useful for identifying signals worth investigating at larger scale; it is not sufficient to establish how reliably the protocol performs across the broader population of people with Kellgren-Lawrence Grade IV disease.

The two-month follow-up is the sharpest constraint of all. Knee osteoarthritis progresses over years, and the questions that matter most to patients — whether MMP-13 reduction persists, whether bone marrow oedema stays lower, whether functional gains are maintained at one or two years — remain unanswered for this combination protocol specifically. The Simeonov 2024 series, which followed 17 patients treated with ChondroFiller alone through 12 months, reported continued improvement on Lysholm and IKDC scores; but that is a different patient group and a different protocol, not a direct extension of the Weninger findings.

For someone already at the point of a total knee replacement recommendation, the honest position is this: the Weninger study offers encouraging early signals across clinical, imaging, and molecular endpoints, with no safety concerns identified. Whether those gains hold at one and two years is the question that the next generation of trials needs to answer — and the honest answer to that question matters when deciding how much weight to give this protocol in a real treatment decision today.

Getting assessed for ChondroFiller injection in Lincolnshire

Suitability for this combination protocol cannot be determined from a trial summary alone. The Weninger 2025 eligibility criteria — Kellgren-Lawrence Grade IV, multi-compartment involvement, adults aged 50 to 99 — provide a useful starting frame, but they do not account for factors that a clinical assessment must weigh: the pattern and extent of any focal defect, overall biomechanical alignment, the degree of bone marrow oedema, and whether the joint's structure is appropriate for an injectable scaffold approach rather than surgical joint preservation or replacement.

The foundation of any assessment is a detailed MRI reviewed with cartilage segmentation, which allows a clinician to quantify residual cartilage thickness and map which compartments are affected. That structural picture, combined with evaluation of pain pattern, range of motion, and functional demands, is what informs whether this type of protocol is reasonable to consider — or whether alignment correction, a different restorative pathway, or total knee replacement is the more appropriate recommendation. Determining candidacy requires that clinical process; the trial criteria alone are not a substitute for it.

This treatment is privately funded. It is not available on the NHS and is not routinely covered by major health insurers such as Bupa or AXA.

Lincolnshire Knee is part of the MSK Doctors group and accepts patients without a GP referral. Book an assessment at lincolnshireknee.co.uk.