Tissue engineering is dedicated to the repair, restoration, or improvement of the functions of degenerated human tissues. However, the widespread clinical application of tissue engineering products has been hindered due to various issues, among which the most serious is the lack of vascularization. In this study, we describe a simple method for the fabrication of a plasma gel that mimics the in vivo three-dimensional vascularization environment. Endothelial progenitor cells (EPCs) were used to form microvascular structures in plasma gel, with an expression of spred-1 protein that was negatively correlated with vascularization. The process of angiogenesis of EPC was found that associated with the VEGF/MAPK pathway, KLF-2 protein, and miR-126 in a time-dependent manner. We than encapsulated spred-1 siRNA transfected EPCs in 3D simulated plasma gel as a functional dressing and transplanted the functional dressing onto diabetic NU mice wound model. After 14 days, the wound was healed well without scar or infection. Our findings indicate that three-dimensional engineered tissue containing EPC grafts is capable of rapid microvascularization for use in the acceleration of wound healing.