Enhancing Autologous Fat Graft Retention: The Impact of Inactive Vitamin D3 on Immune Modulation and Extracellular Matrix Remodeling in a Swine Model

Abstract

Abstract Autologous fat grafting (AFG) is a widely utilized surgical technique, but graft survival rates remain inconsistent and unpredictable. The aim of this study was to evaluate the efficacy of oral vitamin D3 (VD3) on long-term AFG retention in a porcine model and examine its mechanisms. Inguinally harvested adipose tissue from 3 female Yucatán pigs was autologously grafted into 16 dorsal sites (5 cc per graft). Pig 1 received no treatment; Pig 2 received oral VD3 (100 K IU) thrice weekly postoperatively; Pig 3 received oral VD3 (100 K IU) thrice weekly for 2 weeks preoperatively and continuously postoperatively. Pigs were sacrificed at 3 months. Grafts were extracted and evaluated for histological, volumetric, and molecular changes. Hematoxylin and eosin, Sirius red, immunohistochemistry (IHC), and quantitative polymerase chain reaction tests were performed. VD3 improved AFG volume retention at 3 months (P = .01). VD3 enhanced adipocyte viability and vascular migration into the graft core, measured by perilipin+ (P = .003) and CD31+ (P = .003) IHC, respectively. VD3-treated grafts showed a decrease in pro-inflammatory cytokine tumor necrosis factor-α expression compared with the control (P = .0005) and an increase in pro-regenerative M2 macrophages (P = .002). VD3 increased graft extracellular matrix (ECM) composition (P = .03) and Collagen III (P = .001). No significant differences were observed in fibrosis markers (transforming growth factor beta and Collagen I) or adiposity biomarkers (adipocyte count and adiponectin). In this pilot study, oral VD3 significantly increased fat graft retention, likely through modulation of inflammation, enhanced ECM remodeling, and improved vascular migration into the graft core. These findings support the potential of VD3 to improve AFG outcomes in large animal models. Level of Evidence: 5 (Therapeutic) For image description, please refer to the figure legend and surrounding text.