Nonmuscle-Mediated Effects of Botulinum Toxin A on Fat Graft Survival in Nude Mice: Timing-Dependent Graft Outcomes.

Background: Enhancing fat graft survival is a key goal in adipose regenerative medicine. Although botulinum toxin type A (BoNTA) has shown potential benefits, its effects beyond muscle paralysis remain incompletely understood.

Objectives: The authors of this study aim to investigate the nonmuscle-mediated effects of BoNTA on fat graft survival and quality.

Methods: BALB/c-nu nude mice, with the subcutaneous skull area selected for fat transplantation because of its minimal muscular activity, were assigned to 3 groups (n = 5/group/time point): a control group receiving only fat graft and saline, and 2 experimental groups receiving BoNTA either simultaneously (BoNTA group) or 1 week (Pre-BoNTA group) before grafting. Graft volume was measured through liquid overflow at 1, 4, 8, and 12 weeks. Histological analysis and immunostaining were performed to assess adipose integrity, vascularization, inflammation, fibrosis, apoptosis, and proliferation.

Results: At Week 12, fat retention rates reached 33.67% in the Pre-BoNTA group and 35.16% in the BoNTA group, both significantly higher than the control (20.79%, P < .01). Histological analyses demonstrated superior outcomes in these treatment groups, characterized by improved vascularization, preserved adipocyte morphology, reduced inflammation and fibrosis, and favorable apoptotic and proliferative profiles. Notably, the BoNTA group showed greater preservation of adipocyte architecture, lower inflammatory cell presence, and stronger antiapoptotic effects than the Pre-BoNTA group, despite comparable volume retention.

Conclusions: BoNTA improves the survival rate and quality of fat grafts through nonmuscle-mediated effects. Additionally, the timing of BoNTA administration exerts a significant influence on graft outcomes.