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In most cases, vascularization is the first requirement to achieve tissue regeneration. The delivery from implants of angiogenic factors, like VEGF, has been widely investigated for establishing a vascular network within the developing tissue. In this report, we investigated if encapsulation of VEGF in nanoparticles could enhance angiogenesis in vivo as compared to free VEGF when incorporated into two different types of 3D matrices: Matrigel™ hydrogels and PLGA scaffolds. Negatively charged nanoparticles encapsulating VEGF were obtained with a high efficiency by complex formation with dextran sulfate and coacervation by chitosan. After 2 weeks, encapsulation reduced VEGF release from hydrogels from 30% to 1% and increased VEGF release from scaffolds from 20% to 30% in comparison with free VEGF. VEGF encapsulation consistently improved angiogenesis in vivo with both type of 3D matrices: up to 7.5- to 3.5-times more endothelial and red blood cells were observed, respectively, into hydrogels and scaffolds. Hence, encapsulation in nanoparticles enhanced VEGF efficiency by protection and controlled release from 3D implants. Encapsulation and incorporation of VEGF into 3D implants that, in addition to sustaining cell infiltration and organization, will stimulate blood vessel are a promising approach for tissue regeneration engineering.VEGF encapsulation in dextran sulfate/chitosan nanoparticles increases angiogenesis within 3D implants.