Locally Increased Level of Inorganic Phosphate Induced Nodules or Calcification After Bolus Fat Grafting

Background: Nodules or calcifications have been a common complication after breast augmentation with fat grafting, especially in cases with partial bolus fat grafting. There are some clinical preventive measures, but mechanisms related to this complication have not been elucidated yet. Inorganic phosphate (PI), being a product of fat metabolism, is a well-known stimulus of other kinds of pathological calcification such as vascular calcification. We aimed to determine whether PI had a similar effect on formation of nodules after fat grafting.

Methods: Nodules or calcification after fat grafting models using nude mice were created by bolus fat injection. Levels of PI of necrotic liquid located in the central zone and mineralization deposition of graft were examined 1 week, 2 weeks, 1 month, 2 months and 7 months after bolus fat injection. External high phosphate solution was injected 3 times a week to the fat grafts for 2 months, and mineral deposition was examined. In addition, adipose-derived stem cells (ADSCs) were treated with high phosphate osteogenic differentiation medium in various concentrations and times. ADSCs were also treated with osteogenic differentiation in addition to tetramisole which could reduce the level of PI. Mineral depositions of the cells were examined. The central necrotic liquid was extracted from patients who found palpable nodules after breast augmentation with fat grafting. The level of PI of this necrotic liquid and normal lipoaspirates from patients who received normal liposuction for body contouring was compared.

Results: The in vivo study indicated that the local PI concentration of the necrotic zone increased significantly 2 months after large volume bolus fat injection. Calcification was not formed after 2 months, but was formed after 7 months, indicating that the effect of PI on calcification was time-dependent. In addition, with the effect of external injection of high phosphate solution into the fat graft, calcification was formed after 2 months, indicating the effect of PI on calcification was dose-dependent. The in vitro study also indicated PI could induce calcification of ADSC in a time- and dose-dependent manner. The study in humans indicated that the level of PI in the necrotic zone of nodules after fat grafting was higher than that in normal lipoaspirates.

Conclusions: This study indicated that the level of PI in the central necrotic zone was elevated after bolus fat injection, which could provide an environment to induce calcification of surrounding tissue.

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