Active Vitamin D3 (Calcitriol) Increases Adipose Graft Retention in a Xenograft Model

Abstract

Background Autologous fat grafting, while broadly indicated, is limited by unsatisfactory retention and often requires multiple procedures to achieve durable outcomes. Graft survival is strongly influenced by magnitude and duration of post-engraftment ischemia. Calcitriol is a pleiotropic, safe, nutrient with cell-specific influence on viability and metabolic flux. Objectives Evaluate the efficacy of activated vitamin D3 (calcitriol) to improve grafting outcomes and examine its mechanisms. Methods Lipoaspirate was collected for ex vivo culture (7 unique donors), in vitro bioenergetic analysis (6 unique donors), and in vivo transplantation (5 unique donors). Ex vivo samples were incubated for up to 2-weeks prior to extraction of the stromal vascular fraction (SVF) for viability or flow cytometry. SVF was collected for Seahorse analysis of metabolic activity. Human endothelial cell-lines were utilized for analyses of endothelial function. In vivo, samples were implanted into athymic mice with calcitriol-treatment either a) once locally or b) thrice weekly via intraperitoneal injection. Grafts were assessed photographically, volumetrically, and histologically at 1, 4, and 12-weeks. H&E, Sirius Red, perilipin, Hif1α, and CD31 were performed. Results Calcitriol-treated lipoaspirate demonstrated dose-dependent increases in SVF viability and metabolic reserve during hypoxic-stress. Calcitriol-treatment enhanced endothelial mobility ex vivo and endothelial function in vitro. In vivo, calcitriol enhanced adipocyte viability, reduced fibrosis, and improved vascularity. Continuous calcitriol was sufficient to improve graft retention at 12-weeks (p < 0.05). Conclusions Calcitriol increased fat graft retention in a xenograft model through. Calcitriol has potential to be a simple, economical means of increasing fat graft retention and long-term outcomes.

Experimental study: effects of folic acid, vitamin C, and vitamin E on fat graft survival

“…As the field of plastic and reconstructive surgery continues its evolution, 11-13 the integration of vitamin supplementation introduces an exciting avenue to enhance the reliability and durability of fat grafting procedures. 14 This, in turn, serves to benefit both the aesthetic and reconstructive aspects of patient care.…”