Efficacy and safety of microfragmented adipose tissue versus platelet-rich plasma, hyaluronic acid and saline for knee osteoarthritis.

PURPOSE: To compare the efficacy and safety of intra-articular microfragmented adipose tissue (MFAT) injection with platelet-rich plasma (PRP), hyaluronic acid (HA), and saline injection for knee osteoarthritis treatment. METHODS: PubMed, Embase, the Cochrane Library and Web of Science were searched for randomized controlled trials (RCTs) published before April 15, 2026. Patients were assessed for efficacy (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and visual analog scale (VAS), International Knee Documentation Committee (IKDC), and Tegner scores and safety (treatment-related adverse events (AEs)) outcomes. RESULTS: Eleven RCTs were identified. At the 6-month and 12-month follow-ups, compared with the control interventions (PRP, HA and saline), intra-articular MFAT injection significantly improved efficacy outcomes (VAS and KOOS symptom). At the 24-month follow-up, intra-articular MFAT injection was significantly more advantageous than control interventions for reducing pain (VAS score) and improving WOMAC scores. Subgroup analysis results of only RCTs directly comparing MFAT with PRP or HA injection were consistent with the primary analysis results: MFAT was significantly superior to PRP and HA in terms of patient-reported outcomes at the 6- and 12-month follow-ups. Heterogeneity was markedly reduced in this subgroup analysis. Regarding safety, compared with control interventions, IA MFAT was associated with no statistically significant difference in AE incidence. The overall methodological quality of the included studies was relatively high. CONCLUSION: At both 6- and 12-month follow-ups, intra-articular MFAT significantly improved core symptom endpoints (VAS, KOOS symptom, WOMAC (6- and 24-month)) versus controls (PRP, HA, or saline), whereas distal functional endpoints (IKDC, KOOS-ADL, KOOS-Sport) showed no significant differences. However, all pooled effect sizes remained below MCID thresholds, indicating that current 12-month evidence does not support definitive clinical meaningfulness. Treatment-related AEs were comparable to controls, supporting favorable short-term safety. These hypothesis-generating findings underscore the urgent need for large-scale RCTs with follow-up exceeding 24 months and prespecified subgroup analyses to determine sustained efficacy, disease modification, and late-onset safety.