Background:Survival and regeneration mechanisms of large (>250 mL) fat grafts remain incompletely understood. In fat grafts from volunteers with megavolume fat transfer breast augmentation, neovascularization and inflammatory cell infiltration decreased within 7 days according to histologic analysis. The authors further investigated this phenomenon using a nude mouse model. Methods:To simulate clinical contexts, chambers containing 1 mL of human fat were implanted into nude mice. Chambers allowed selective transfer of tissue fluid from recipient nude mice into chambers, but not capillaries or macrophages. Seven days later, fat was removed from the chamber and reimplanted into a new nude mouse in the open-chambered fat group (OCFG) (n = 45). Adipose samples from volunteers and explanted grafts from OCFG were subjected to histologic analyses. Graft weight, vascularization, and immune response were also compared between the OCFG and conventional direct fat grafting (control group [CG]). Results:Percentage tissue integrity, percentage fibrosis, adipocyte viability, and neovascularization did not significantly differ between volunteer samples and OCFG grafts at day 7. On day 90, OCFG retention rate was decreased relative to the CG, and the fibrosis area was larger in the OCFG than in the CG. However, the macrophage and capillary counts were lower in the OCFG group relative to the CG at days 7 and 14 after transplantation. Conclusions:The present study provides histologic analyses of megavolume fat grafts sampled from clinical breast augmentation tissues and a xenograft nude mouse model. However, these preliminary results in a small clinical cohort should be further assessed in large allogeneic animal models. Clinical Relevance Statement:The results of this study will help surgeons understand the early regeneration of transplanted fat after large volume fat grafting for breast augmentation.