Pro-angiogenic small-diameter tissue-engineered vascular grafts (TEVGs) fabricated from 2-deoxy-D-ribose (2dDR)-incorporated electrospun polycaprolactone (PCL) fibers

Cardiovascular diseases remain the leading cause of global mortality and frequently require surgical interventions such as bypass grafting. Although autologous vessels are considered the gold standard, their limited availability and donor site morbidity necessitate effective synthetic alternatives. However, small-diameter synthetic grafts often fail due to insufficient endothelialization, leading to rapid protein adsorption, thrombosis, intimal hyperplasia, and graft occlusion. This study aimed to develop a pro-angiogenic small-diameter tissue-engineered vascular graft based on electrospun polycaprolactone (PCL) functionalized with 2-deoxy-D-ribose (2dDR), a cost-effective and biologically safe pro-angiogenic molecule. Tubular grafts were fabricated by electrospinning a 15% (w/w) PCL solution prepared in a DCM:DMF (90:10 w/w) solvent mixture, followed by incorporation of 2dDR (66.7 mg g^-1polymer) into the spinning solution. Electrospinning parameters were systematically optimized to obtain uniform bead-free nanofibers. The resulting scaffolds were characterized in terms of fiber morphology, wettability, mechanical properties, release behavior, and<i>in vitro</i>endothelial cell response. Optimized conditions produced fibers with an average diameter of 0.77 ± 0.41 μm. Although incorporation of 2dDR did not change the mean fiber diameter (0.74 ± 0.37 μm), it markedly enhanced scaffold hydrophilicity, reducing the water contact angle from 111.82 ± 5.43° to complete spreading within 30 s. Mechanical testing demonstrated that 2dDR incorporation significantly increased tensile strength and suture retention by approximately 2-fold and 1.4-fold, respectively, without significantly altering elastic modulus or elongation at break. 2dDR release from PCL fibers was observed over 21 d, with concentrations remaining within the pro-angiogenic range of 1-2.5 mM.<i>In vitro</i>cytocompatibility assays demonstrated cell viability above 90%, and alamarBlue analysis indicated increased metabolic activity on 2dDR-loaded scaffolds, particularly on days 4 and 7, while scanning electron microscope observations showed endothelial cell coverage on the luminal surface by day 7 in both scaffold groups. Overall, this proof-of-concept study demonstrates the<i>in vitro</i>feasibility of 2dDR-functionalized electrospun PCL grafts for promoting rapid endothelialization in small-diameter vascular graft applications. Future studies will focus on dynamic conditioning and<i>in vivo</i>validation to further assess translational potential.