Infiltration level of macrophages and its impact on fat graft retention in mouse free fat grafting model

BACKGROUND: Autologous fat grafting faces the clinical challenge of unstable absorption rates, and the regulatory mechanisms of macrophages need to be elucidated. OBJECTIVES: It aimed to investigate the infiltration levels and phenotypic dynamics of macrophages and explore their impact on graft retention rate (RR). METHODS: A total of 180 C57BL/6J mice were randomly divided into experimental (AG, fat grafting), sham (BG, no grafting), and intervention (CG, macrophage depletion followed by grafting) groups. Graft RR was assessed, and macrophage status was analyzed by flow cytometry and immunofluorescence postoperatively. Levels of inflammatory, pro-fibrotic, and angiogenic factors were also detected. RESULTS: Macrophage infiltration in the AG peaked at week 2 (21.3 ± 1.5%) and then shifted from M1 to M2 phenotype. The graft RR in the AG was visibly higher as against the CG (p < 0.05). M2 macrophages were strongly positively correlated with RR (based on the aggregated data of all time points, r = 0.821, p < 0.0001), while pro-inflammatory factors suggested negative correlation. The AG had visibly elevated levels of angiogenic factors, which were strongly positively correlated with RR (p < 0.05). CONCLUSION: Macrophages (especially the M2 subtype) play a key role in fat graft survival by modulating inflammatory responses and promoting angiogenesis. Targeting macrophage polarization may be a novel strategy to improve fat grafting outcomes.