Avascular fat grafts show lower volume retention but higher hypoxia, angiogenesis, adipocyte proliferation, and macrophage infiltration than vascularized adipocutaneous flaps in an in vivo pilot mouse study Fat grafting vs. flap transfer in mice

BACKGROUND: Over 137,000 breast reconstructions are performed annually by ASPS member surgeons in the US alone. Vascularized flap transfer and avascular fat grafting each account for over 33,000 annual autologous reconstructions, respectively. And although autologous approaches yield superior long-term functional and aesthetic outcomes, clinical and experimental observations of both techniques suggest considerable biologic differences with diverging effects on locoregional tumor control. However, parallel small animal models to compare their inherent proliferative, angiogenic, metabolic, and immunogenic influences in vivo are lacking. Therefore, we standardized existing flap transfer and fat grafting models in immunocompetent mice to reduce experimental bias, guarantee comparability, and lay the methodological foundation for an in vivo model of autologous breast reconstruction combinable with orthotopic mammary tumor implantations.

METHODS: Autologous groin flaps (n=25) and syngeneic fat grafts (n=39) were transferred in 8-week-old female BALB/c-mice. Viable adipocytes were tracked via Hoechst-Calcein-DiI-staining (n=2/group) and postoperative graft versus flap volumes were compared via longitudinal MRI (n=3/group) on days 1, 11, 21, and 31. Proliferation indices, microvessel densities, tissue hypoxia, and macrophage infiltrates (graded 0-3) were compared via Ki67-, CD31-, pimonidazole-, and H&E-staining on days 5, 10, 15, 20, and 30 (n=4/group/timepoint).

RESULTS: Viable adipocytes were present in both transferred tissue types. Fat graft volume retentions plateaued at 42.7±1.2% versus 81.8±4.0% of flaps on day 31 (p<0.001). Contrary to flaps, fat grafts initially contained more hypoxic cells (D5: 15.192±1.249 vs. 1.157±192, p<0.001), followed by higher proliferation (D15: 25.2±1.0% vs. 0.0±0.0%, p<0.001) and higher microvessel numbers per high-power field (D30: 307.0±13.2 vs. 178.0±10.6, p<0.001), accompanied by higher-graded macrophage infiltrates (3 vs. 2, p<0.01).

CONCLUSIONS: Vascularized flaps and avascular lipofilling were compared in experimental mice in vivo. This comparative pilot study suggests differences in recipient site volume retention, adipocyte proliferation, angiogenesis, hypoxia, and macrophage recruitment.