Abstract
Background/Objectives: Knee osteoarthritis (OA) is a major cause of pain and functional disability worldwide, leading to a growing interest in more durable and less invasive therapies. Micro-fragmented adipose tissue (MFAT) injections have emerged as a promising frontier in regenerative therapies using mesenchymal stem cells (MSCs). This study assessed the safety and effectiveness of MFAT injections for symptomatic knee OA while investigating the duration of treatment effects. Methods: This longitudinal study screened patients with symptomatic Kellgren-Lawrence (KL) grade II-IV knee OA who received single-dose MFAT injections. Outcomes were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales at baseline, 3, 6, and 12 months. A linear mixed effects model was performed to explore how age, BMI, sex, and OA severity influence outcomes. Results: Among 39 evaluable patients, mean baseline KOOS was 46.5 (SD 18.1). KOOS scores improved significantly across all subscales, peaking at six months and remaining higher than baseline at 12 months. Improvements exceeded clinically meaningful thresholds, including KL grades IV. Female patients reported significantly worse overall outcomes than male patients (p < 0.05). Minor self-limiting synovitis was reported in 18% of cases, and no severe adverse events were observed. Conclusions: MFAT infiltration may represent a safe, minimally invasive option to improve symptoms and delay surgery in patients with knee OA, including those with advanced disease. These findings highlight the potential role of MFAT as part of the treatment algorithm for knee OA, although strategies to sustain long-term benefits and confirmatory trials are needed.