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. Proangiogenic factors were assessed with tissue qRT-PCR. Finally, we traced the grafted human tissue with immunofluorescence. Results: SW-gel-treated flaps have the smallest necrotic zones (22.05% 0.0438) compared with the saline controls (53.78% 0.1412) or SW-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 gm) among three groups (F = 10.83, p = 0.0102) while saline-treated flap distal appeared fibrotic. SVF-gel-treated flaps also had similar to 43% more CD31 (+) capillaries (p = 0.0152) with similar to 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 (alpha-smooth muscle actin, alpha-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. (C) 2017 Elsevier Inc. All rights reserved.