Effects of Intramuscular Human Fat Grafting on Muscle Structure and Function Using Nude Mice

Background: Intramuscular fat grafting is used for soft tissue augmentation, yet its effects on muscle structure and function remain unclear.

Objectives: The aim of this study was to evaluate structural and functional outcomes of intramuscular fat grafting using human lipoaspirate in a nude mouse model and assess its regenerative potential.

Methods: Fifty-nine female athymic mice received 100 µL injections of low-density fat (n = 20), high-density fat (n = 20), or saline (n = 19) into hind limb muscles. In vivo grip strength was measured weekly for 6 months. Ex vivo mechanical testing was performed at the study endpoint. Histology (hematoxylin and eosin, Masson's trichrome) assessed muscle architecture and fibrosis, whereas immunofluorescence with human-specific markers evaluated graft persistence and cellular contribution.

Results: No statistically significant differences in muscle strength were observed between groups. Peak in vivo hind limb grip strength ranged from 82 to 96 grams-force (gf), with saline-treated limbs generally demonstrating higher final values (78 gf) than high-density (61 gf) and low-density fat groups (50 gf). Ex vivo peak force measured 9.0 ± 1.8 N (saline), 8.0 ± 0.4 N (high-density), and 7.8 ± 0.5 N (low-density). At 6 months, most adipocytes were resorbed and replaced by collagen-rich extracellular matrix. Fibrosis was greater in high-density fat grafts (25.49 ± 3.28%) than saline (19.42 ± 4.05%) or low-density fat (19.61 ± 3.53%). Limited new muscle formation was observed, predominantly of mouse origin.

Conclusions: Intramuscular fat grafting resulted in transient graft survival followed by fibrosis and structural remodeling without functional improvement at 6 months, suggesting a primarily structural rather than regenerative role.