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Clinical and dGEMRIC Evaluation of Microfragmented Adipose Tissue Versus Hyaluronic Acid in Inflammatory Phenotype of Knee Osteoarthritis: A Randomized Controlled Trial

ORCID
0000-0001-5361-6499
Affiliation
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia;(Ž.J.);(E.R.);(D.H.);(P.B.);(I.B.);(V.M.);(J.M.);(E.S.P.);
Molnar, Vilim;
ORCID
0000-0002-0475-0197
Affiliation
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia;(Ž.J.);(E.R.);(D.H.);(P.B.);(I.B.);(V.M.);(J.M.);(E.S.P.);
Jeleč, Željko;
Affiliation
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia;(Ž.J.);(E.R.);(D.H.);(P.B.);(I.B.);(V.M.);(J.M.);(E.S.P.);
Rod, Eduard;
ORCID
0000-0003-0883-2525
Affiliation
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia;(Ž.J.);(E.R.);(D.H.);(P.B.);(I.B.);(V.M.);(J.M.);(E.S.P.);
Hudetz, Damir;
ORCID
0000-0001-8022-4095
Affiliation
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia;(Ž.J.);(E.R.);(D.H.);(P.B.);(I.B.);(V.M.);(J.M.);(E.S.P.);
Brlek, Petar;
ORCID
0000-0003-0607-2462
Affiliation
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia;(Ž.J.);(E.R.);(D.H.);(P.B.);(I.B.);(V.M.);(J.M.);(E.S.P.);
Borić, Igor;
ORCID
0000-0003-4536-285X
Affiliation
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia;(Ž.J.);(E.R.);(D.H.);(P.B.);(I.B.);(V.M.);(J.M.);(E.S.P.);
Matišić, Vid;
Affiliation
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia;(Ž.J.);(E.R.);(D.H.);(P.B.);(I.B.);(V.M.);(J.M.);(E.S.P.);
Mešić, Jana;
ORCID
0000-0002-2978-7121
Affiliation
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia;(Ž.J.);(E.R.);(D.H.);(P.B.);(I.B.);(V.M.);(J.M.);(E.S.P.);
Pavelić, Eduard Stjepan;
Affiliation
Department of Traumatology, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia;(D.V.);(D.B.);(D.G.W.)
Vidović, Dinko;
ORCID
0000-0003-2908-2508
Affiliation
Department of Traumatology, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia;(D.V.);(D.B.);(D.G.W.)
Blažević, Dejan;
Affiliation
School of Medicine, University of Split, 21000 Split, Croatia;(F.Č.);(S.S.)
Čukelj, Fabijan;
ORCID
0000-0003-0070-5206
Affiliation
School of Medicine, University of Split, 21000 Split, Croatia;(F.Č.);(S.S.)
Sabalić, Srećko;
Affiliation
Clinic for Surgery, Department of General and Sports Traumatology, University Hospital Merkur, 10000 Zagreb, Croatia;(J.Š.);
Štivičić, Josip;
ORCID
0009-0003-5040-1945
Affiliation
Clinic for Surgery, Department of General and Sports Traumatology, University Hospital Merkur, 10000 Zagreb, Croatia;(J.Š.);
Dujmović, Tomislav;
Affiliation
School of Medicine, University of Zagreb, 10000 Zagreb, Croatia;
Starešinić, Mario;
ORCID
0000-0002-5293-6981
Affiliation
Department of Orthopaedics and Traumatology, University Hospital Dubrava, 10000 Zagreb, Croatia;
Čemerin, Martin;
ORCID
0000-0003-4671-7499
Affiliation
Department of Traumatology, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia;(D.V.);(D.B.);(D.G.W.)
Weinberger, David Glavaš;
Affiliation
Health Centre Zagreb County, 10310 Ivanić Grad, Croatia;
Molnar, Iva;
ORCID
0000-0002-6867-826X
Affiliation
Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia
Smolić, Martina;
ORCID
0000-0001-5565-080X
Affiliation
St. Catherine Specialty Hospital, 10000 Zagreb, Croatia;(Ž.J.);(E.R.);(D.H.);(P.B.);(I.B.);(V.M.);(J.M.);(E.S.P.);
Primorac, Dragan

Background : Knee osteoarthritis (OA) is a leading cause of disability, with limited therapies that modify both symptoms and structural degeneration. Autologous microfragmented adipose tissue (MFAT) has emerged as a promising regenerative option, especially in phenotypically distinct OA subgroups. This randomized controlled trial evaluated the clinical and structural efficacy of intra-articular MFAT versus hyaluronic acid (HA) in patients with early to moderate inflammatory phenotype knee OA. Methods : Fifty-three patients were randomized in a 2:1 ratio to receive either MFAT (n = 35) or HA (n = 18). Patients were followed-up for six months post-injection and evaluated using patient-reported outcome measures (KOOS, WOMAC, VAS) and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). A responder analysis defined structural response as ≥10% increase in dGEMRIC in ≥3 of 7 predefined cartilage regions. Results : Both MFAT and HA led to statistically significant improvements in clinical scores and cartilage glycosaminoglycan content. MFAT showed greater mean improvements across most clinical and dGEMRIC measures, although without reaching statistical significance, except for KOOS Symptoms (MFAT: +25.0 vs. HA: +12.7, p = 0.008). Responder-level analysis revealed that all patients who demonstrated structural response also experienced clinically meaningful pain improvement (KOOS Pain ≥ 10), while no patient showed structural benefit without parallel symptomatic relief. Conclusions : MFAT led to greater improvement in symptoms related to joint stiffness, swelling, and crepitus compared to HA, reflecting its potential benefit in targeting the inflammatory features of knee OA. Importantly, HA also led to significant clinical and structural improvements, supporting its continued role as a standard-of-care comparator in knee OA management. Furthermore, the correlation between dGEMRIC and clinical response suggests its utility as a predictive biomarker of treatment success.

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Editor:
Belluzzi, Elisa
Published in:
Biomedicines  
Vol. 13, No. 9 (19.09.2025)
Volume:
13
No.:
9
Date Issued:
19.09.2025
DOI:
10.3390/biomedicines13092301
Language:
English
Type of Resource:
Text
Keywords:
adipose tissue; hyaluronic acid; injections; intra-articular; knee joint; mesenchymal stem cells; osteoarthritis
DDC:
610 Medizin und Gesundheit

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