Effect of N-Acetylcysteine on Autologous Fat Graft Survival

Adipose Tissue Atrophy, Deformity of Reconstructed Breast, Graft Loss

acetylcysteine, three-dimensional reconstruction, autologous fat grafting

A single-centre triple-blind study looking at the addition of NAC to tumescent solution for liposuction and fat grafting in healthy patient volunteers already undergoing bilateral breast reduction. Three-dimensional reconstructions and volumetric analysis will be performed based on CT scans at 0, 1 and 3 months and then histological analysis will be performed after fat graft explantation at 3 months to determine fat graft vascularity and quality.

Autologous fat grafting is an increasingly popular technique for soft tissue reconstruction; however, the surgical technique is limited by inconsistent graft take, undercorrection, and requirement for repeat procedures. The authors previously examined whether a widely available, clinically safe anti-oxidant, N-acetylcysteine (NAC), could improve adipose-derived stem cell survival and subsequent graft take when added to tumescent solution at the time of fat harvest in mice. The addition of NAC to tumescent fluid during fat harvest in mice protects ADSCs against oxidative stress, increases their survival and proliferation, and inhibits their early differentiation into mature adipocytes in vitro. In an in vivo model, NAC treatment at the time of harvest improved survival and quality of autologous fat grafts. These observations provide proof-of-principle for the use of NAC in the clinical setting to optimize fat graft yields. Hypothesis: The addition of NAC to the tumescent solution used in fat grafting will improve fat graft survival in humans to potentially decrease the amount of re-operations and undercorrection that occurs. Plan: The study will be conducted as a single-centre, randomized, triple-blind placebo-controlled trial to be performed at the QEII Health Sciences Centre, Halifax, Nova Scotia. Subjects will be chosen as healthy female patients already presenting to the operating room for elective breast reduction surgery. These patients will be enrolled and booked for surgery as they present to clinic and will not be expedited in receiving their elective surgery if enrolled in the study. Each subject will serve as her own control. The hypothesis will be tested by performing lipoaspiration of the thigh/hip region of healthy patients after the addition of tumescent solution with or without NAC. Approximately 10 millilitres of the fat graft will be injected into each pre-tibial area depending on the randomization allocation, as described by Kolle et al. (1) The volume of fat graft will be measured at 0, 1 and 3 months using computed tomographic (CT) scans according to institutional standards. The CT images will be exported into Materialise Interactive Medical Image Control System (MIMICS) and volumetric three-dimensional reconstructions will be made to measure the size and volume of the grafts at each of the time points. The grafts will then be explanted at 3 months and weighed. The histologic appearance, graded on the amount of inflammation, cysts/vacuoles, integrity and vascularity with CD31 staining will be assessed. The results will be compared using two-tailed t-tests. Statistical significance will be set at p\<0.05.

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