Cardiovascular disease (CVD) remains the leading cause of death worldwide, with smalldiameter vascular grafts (SDVGs, less than 6 mm) presenting significant clinical challenges due to high failure rates from thrombosis, intimal hyperplasia, and compliance mismatch. Vascular tissue engineering (VTE) seeks to address these limitations by developing biocompatible, mechanically robust scaffolds that closely mimic native blood vessels. In this study, we focused on the fabrication and characterization of coelectrospun nanofibers composed of varying weight ratios of polyethylene terephthalate (PET) and polyurethane (PU). The structural analysis using field emission scanning electron microscopy (FE-SEM) revealed that all scaffolds exhibited uniformly distributed, bead-free, and randomly oriented fibers, except for the PET/PU (50:50) and (75:25) scaffolds, which presented a few beads. PET/PU nanofibrous scaffolds exhibited significantly smaller fiber diameters compared to pure scaffolds. Porosity percentage varied from 63.00 ± 0.46% for pure PU to 82.00 ± 2.1% for PET/PU (90:10), aligning well with the optimal range for cell proliferation. Fourier transform infrared spectroscopy (FTIR) confirmed the successful co-electrospinning of PET and PU, as evidenced by characteristic peaks consistently present across all composite scaffolds. Mechanical properties of PET/PU (75:25) and (25:75) as optimal composites achieve tensile strengths of 5.4 ± 0.69 and 4.73 ± 0.31 MPa and Young’s moduli of 44.4 ± 1.08 and 49.07 ± 1.59 MPa, closely approximating native vascular tissue properties. Burst pressure demonstrated that composite scaffolds containing more than 50% PET exceeded the clinically relevant threshold of 2000 mmHg. Compliance values were modulated by the PU content, with increasing PU proportions enhancing compliance, ranging from 5.04 ± 0.78% in PET/PU (90:10) to 8.84 ± 0.1% in PET/PU (10:90), thereby illustrating the tunable mechanical response attainable through polymer composite engineering. Biocompatibility assays confirmed significant NIH/3T3 cell viability increases on all scaffolds, notably a 3.8 time rise on PET/PU (25:75) nanofibrous composites by day 7, with preserved healthy cell morphology. In vivo assessments via rat and sheep carotid artery implantation demonstrated moderate, controlled inflammatory responses, effective tissue integration, and high long-term patency without thrombosis or hyperplasia up to 8 months, verified by histopathology and Doppler ultrasound. These results validate that coelectrospun PET/PU scaffolds, particularly at (75:25) and (25:75) ratios, exhibit a favorable combination of structural, mechanical, and biological properties suitable for SDVG applications.

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