“Delayed Post-conditioning with External Volume Expansion (EVE) Improves Survival of Adipose Tissue Grafts in a Murine Model”

Background: External volume expansion (EVE) improves the survival of adipose tissue grafts by pre-operatively conditioning ('pre-conditioning') tissues that will receive the graft. EVE's mechanisms of action (induction of angiogenesis and of adipogenesis) could improve graft survival also when applied post-operatively (post-conditioning). We tested this hypothesis and optimized the parameters of post-operative application of EVE in a murine model. Methods: Fifty-six 8-week-old athymic (nu/nu) mice received dorsal subcutaneous grafts of human lipoaspirate (0.3 ml each) bilaterally before undergoing EVE (left dorsum) or no treatment (right dorsum, controls). EVE was started either on the same day of (Immediate group), two days after (Early group), or one week after surgery (Delayed group). At follow-up, grafts were analyzed for tissue survival, remodeling, adipogenesis, and angiogenesis using histology. Volume retention was assessed by MRI. We subsequently assessed the effects of the Delayed application of EVE adopting a foam-shaped interface (F-EVE) to deliver the treatment. Results: At 28 days follow-up delayed post-conditioning with EVE significantly improved the survival of grafts (+18%) compared to controls (viable graft thickness ratio: 58 ±15% vs 49 ±13%) and increased the density of blood vessels within the graft (+63%: blood vessels/ 10x magnification field: 44 ±12 vs 27 ±11). Other groups did not lead to significant changes. Adoption of F-EVE similarly improved outcomes while further reducing fibrosis within the grafts. Conclusions: Post-operative delayed application of EVE modestly improves the survival of adipose tissue grafts by inducing adipogenesis and angiogenesis. Use of a foam-shaped interface decreases the fibrosis induced in the grafts. # co-first authors Acknowledgments, conflict of interest and role of funding sources disclosure statement: Dr. Orgill receives research funding through grants from Acelity L.P. to Brigham and Women's Hospital and is a consultant for Acelity L.P. All other authors declare no actual or potential conflict of interests: in addition, they disclose no commercial or financial associations, personal or other relationships with other people or organizations that could inappropriately influence the reported manuscript or create a conflict of interest with the information presented. This study was funded by a research grant from Acelity L.P. Inc. to Brigham and Women's Hospital and a research grant by the Gillian Reny Stepping Strong Foundation to Brigham and Women's Hospital. Authorship: All authors had full access to the data and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors have seen and agreed to the submitted version of the manuscript and bear responsibility for it. Ethics: The study was carried out under high ethical standards. All the studies have been approved, when required, by the appropriate ethics committee and have been performed in accordance and in conformity to the World Medical Association Declaration of Helsinki (June 1964) and subsequent amendments. Meetings at which the paper has been presented: None. Corresponding authors: Dennis P. Orgill (* corresponding author), Tissue Engineering and Wound Healing Laboratory, Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital - Harvard Medical School, 75 Francis St., Boston MA 02115 (USA). T: 617-732-5456F: 617-730-2855E:dorgill@partners.org ©2018American Society of Plastic Surgeons

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