Electospuin tubular conduit (4mm inner diameter) based on blends of polydioxanone (PDS II (R)) 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 wll-interconnected pore network. Due to protein blending, the fiber diameter was reduced from 800-950 nm range to 300-500 nm range. Fourier transofrm 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 +/- 1.3%. 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 +/- 0.2 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. Biotechnol. Bioeng. 2009;104: 1025-1033. (C) 2009 Wiley Periodicals, Inc.