In tissue engineering, rapid ingrowth of blood vessels into scaffolds is a major prerequisite for the survival of three-dimensional tissue constructs. In the present study, we investigated whether the vascularization of implanted poly-D,L-lactic-co-glycolic acid (PLGA) scaffolds may be accelerated by incorporation of Matrigel. For this purpose, we investigated in the aortic ring assay the proangiogenic properties of growth factor reduced Matrigel (GFRM) and growth factor containing Matrigel (GFCM), which were then incorporated into the pores of PLGA scaffolds. Subsequently, we analyzed vascularization, biocompatibility, and incorporation of these scaffolds during 14 days after implantation into dorsal skinfold chambers of balb/c mice by means of intravital microscopy, histology, and immunohistochemistry. Matrigel-free scaffolds served as controls. In the aortic ring assay, GFCM stimulated the development of a network of tubular vessel structures with a significantly increased sprout area and density when compared with GFRM. Accordingly, GFCM accelerated and improved in vivo the ingrowth of new blood vessels into scaffolds, resulting in the formation of a pericyte-coated vascular network with an increased functional capillary density in comparison to the GFRM and control group. Besides, analysis of leukocyte-endothelial cell interaction in host tissue venules located in close vicinity to the scaffolds showed no marked differences in numbers of rolling and adherent leukocytes between the observation groups, indicating that incorporation of Matrigel did not affect biocompatibility of PLGA scaffolds. These findings demonstrate that the combination of proangiogenic extracellular matrices with solid scaffold biomaterials may represent a novel approach to accelerate adequate vascularization of tissue engineering constructs.