Electrospun tubular conduit (4mm inner diameter) based on blends of polydioxanone (PDS II1) and proteins such as gelatin and elastin having a spatially designed trilayer structure was prepared for arterial scaffolds. SEM analysis of scaffolds showed random nanofibrous morphology and well-interconnected pore network. Due to protein blending, the fiber diameter was reduced from 800-950nm range to 300-500nm range. Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) results confirmed the blended composition and crystallinity of fibers. Pure PDS scaffold under hydrated state exhibited a tensile strength of 5.61 ± 0.42 MPa and a modulus of 17.11 ± 1.13 MPa with a failure strain of 216.7 ± 13%. The blending of PDS with elastin and gelatin has decreased the tensile properties. A trilayer tubular scaffold was fabricated by sequential electrospinning of blends of elastin/gelatin, PDS/elastin/gelatin, and PDS/gelatin (EG/PEG/PG) to mimic the complex matrix structure of native arteries. Under hydrated state, the trilayer conduit exhibited tensile properties (tensile strength of 1.77 ± 0.2 MPa and elastic modulus of 5.74 ± 3 MPa with a failure strain of 75.08 ± 10%) comparable to those of native arteries. In vitro degradation studies for up to 30 days showed about 40% mass loss and increase in crystallinity due to the removal of proteins and "cleavage-induced crystallization" of PDS. © 2009 Wiley Periodicals, Inc.