Ischemic flap survival improvement by composition-selective fat grafting with novel adipose tissue derived product - stromal vascular fraction gel

摘要

Abstract Background Flap necrosis due to insufficient blood supply is a common postoperative complication in random pattern flaps. Stem cell therapies have emerged as promising biologics for tissue ischemia. A novel fat derived product, stromal vascular fraction gel (SVF-gel), can be prepared with lipoaspirate through simple mechanical processing, removing only the lipid content. SVF-gel enriches adipose-derived stem cells and potentially beneficial for flap necrosis. Methods Nude mice ischemic flaps were treated with human SVF-gel, stromal vascular fraction (SVF) cell suspension or saline (n?=?10). They were injected to the flap recipient beds, and necrosis and vascularization was assessed on postoperative day 14. We harvested the necrosis-free distal to evaluated skin healthiness and neovasculogenesis by Masson's trichrome stain and immunofluorescence, etc. Pro-angiogenic factors were assessed with tissue qRT-PCR. Finally, we traced the grafted human tissue with immunofluorescence. Results SVF-gel-treated flaps have the smallest necrotic zones (22.05%?±?0.0438) compared with the saline controls (53.78%?±?0.1412) or SVF-treated ones (35.54%?±?0.0850, p ?=?0.039). Numerous functional musculocutaneous perforators were developed around SVF-gel grafts. The SVF-gel-treated skin had the best fat restoration (231.3?±?48.1?μm) among three groups (F?=?10.83, p ?=?0.0102) while saline-treated flap distal appeared fibrotic. SVF-gel-treated flaps also had ～43% more CD31? + ?capillaries ( p ?=?0.0152) with ～3 folds more gene expression of angiogenic cytokines of VEGF and bFGF ( p ?=?0.0310 and 0.0303, respectively) than saline-treated controls. Furthermore, we found hSVF-gel cells (hGolgi+) had directly engrafted as vessel component (α-smooth muscle actin, α-SMA+) to the flap. Conclusion Adipose cellular matrix enhanced flap neovascularization partly by direct incorporation, improved flap survival and fat restoration. The composition-selective fat grafting with SVF-gel demonstrated efficacy comparable with stem cell therapy and is especially valuable for clinical translation. Highlights ? SVF-gel is a minimal manipulated fat product accommodating SVF cells. ? SVF-gel improves ischemic skin flap survival with comparable efficacy as cell therapy. ? Pro-angiogenic effect's partly from direct SVF-gel incorporation.