Effects of intra-articular micro-fragmented adipose tissue alone or combined with hyaluronic acid or collagen on cartilage degeneration and oxidative stress in an experimental rabbit osteoarthritis model

Abstract

Background: Osteoarthritis is a prevalent, debilitating, progressive joint disease characterized by articular cartilage degradation, synovial inflammation, and subchondral bone remodeling. This study evaluated the local structural and systemic oxidative stress effects of intra-articular human-derived micro-fragmented adipose tissue (MFAT), administered alone or combined with hyaluronic acid (HA) or injectable collagen (COL), in an experimental rabbit osteoarthritis model. 

Methods: Twenty-four rabbits underwent bilateral arthroscopic anterior cruciate ligament transection. Twenty-one rabbits were allocated to MFAT, MFAT+HA, or MFAT+COL treatment groups and received intra-articular treatment in one knee at weeks 8 and 10, with the contralateral knee serving as an untreated internal control. An additional pilot cohort of three rabbits (six knees) underwent arthroscopic anterior cruciate ligament transection without treatment to characterize untreated disease progression. At week 12, outcomes included macroscopic cartilage scoring, Picrosirius Red (PSR) collagen birefringence, and serum oxidative stress profiling.

Results: Macroscopically, intra-articular interventions demonstrated a trend toward reduced cartilage degeneration relative to paired untreated knees, reaching statistical significance in the MFAT+HA and MFAT+COL groups (adjusted p = 0.047). Additionally, treated cohorts exhibited lower macroscopic degeneration scores compared to the untreated pilot control (p = 0.050), with no significant structural differences observed among the treatments themselves. Histologically, the MFAT+COL group showed an increase in PSR birefringence of thin, loosely-packed fibers compared to the paired control (p = 0.047). Systemically, all three MFAT-based therapies significantly decreased nitric oxide (NO) production relative to controls (p < 0.0001). While total antioxidant response (TAR) remained comparable across groups, total oxidative status (TOS), oxidative stress index (OSI) and the systemic lipid peroxidation marker were elevated primarily in the MFAT (p=0.024, p=0.023, 0.0085) and MFAT+HA (p=0.013, p=0.013, 0.0046) cohorts.

Conclusions: In this experimental rabbit model, intra-articular micro-fragmented adipose tissue attenuated macroscopic cartilage degeneration in the presence of uncorrected mechanical joint instability. Systemic oxidative stress findings were mixed: NO was reduced across all treated groups, while TOS, OSI, and the systemic lipid peroxidation marker were elevated in MFAT and MFAT+HA relative to control, precluding a conclusion of an overall favorable systemic oxidative stress effect. The addition of injectable collagen was associated with a shift in PSR birefringence patterns and should be regarded as hypothesis-generating rather than confirmatory of extracellular matrix remodeling given the semi-quantitative nature of this method, whereas hyaluronic acid provided no additional structural benefit under the present experimental conditions