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

Abstract

Intramuscular fat grafting is used for soft tissue augmentation, yet its effects on muscle structure and function remain unclear. To evaluate structural and functional outcomes of intramuscular fat grafting using human lipoaspirate in a nude mouse model and assess its regenerative potential. 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 study endpoint. Histology (H&E, Masson's trichrome) assessed muscle architecture and fibrosis, while immunofluorescence with human-specific markers evaluated graft persistence and cellular contribution. No statistically significant differences in muscle strength were observed between groups. Peak in vivo hind limb grip strength ranged from 82-96 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. 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.