Degeneration, regeneration, and cicatrization after fat grafting: dynamic total tissue remodeling during the first 3 months.

BACKGROUND: Fat grafting is promising, but clinical outcomes are not always predictable. The mechanisms of tissue revascularization/regeneration, and tissue necrosis and subsequent absorption/fibrosis of the graft, are poorly understood.
METHODS: An autologous inguinal fat pad was transplanted under the scalp of mice, and detailed cellular events during the first 3 months were investigated with immunohistochemistry.
RESULTS: Except for the most superficial surviving zone, death of all adipocytes was confirmed at 1 week. Perilipin-positive small new adipocytes appeared at 1 week and peaked in number at 4 weeks in the regenerating zone (the second zone). In the most central necrotizing zone, adipogenesis did not occur and many inflammatory cells were observed after 2 weeks. CD34+/Ki67+ proliferating adipose stem/progenitor cells were seen at 1 to 4 weeks, but the majority of proliferating cells were MAC2+ monocytes/macrophages. Although CD206+ M1 macrophages surrounded oil droplets for phagocytosis, CD206+ M2 macrophages appeared in areas where adipocyte replacement failed and formed multiple layers for cicatrization of oil drop spaces. Adipogenesis was complete by 12 weeks, but stabilization of nonregenerated areas was still ongoing at that time. Lipid droplets derived from dead adipocytes were absorbed slowly and thus aided adipose remodeling by maintaining the space until adipocyte regeneration.
CONCLUSIONS: Dynamic remodeling after fat grafting was confirmed. Adipocyte fate differed, depending on the microenvironment: intact survival, replacement with a new adipocyte, or replacement with cicatrization/oil cyst. This detailed understanding will help refine surgical grafting procedures and postoperative evaluation.