Construction of small-diameter vascular grafts by electrospun zwitterionic diselenide-containing poly(ester urethane)urea with enhanced endothelialization.

Abstract

Cardiovascular diseases are the leading threat to human health. However, as an essential tool of vascular transplantation, small-diameter vascular grafts are still needed to intensify in rapid endothelialization and enhanced elasticity for vascular reconstruction. Herein, a series of zwitterionic diselenide-containing poly(ester urethane)ureas (zSePEUUs) are synthesized through modulation of the molar ratios of sulfobetaine-diol (SB-diol) and poly(ε-caprolactone)-diol (PCL-diol) (SB-diol/PCL-diol=1/0∼0/1) as diol components, along with selenocystamine and 1,4-butanediamine (7:3) as chain extenders. At the equal amount of SB-diol and PCL-diol, the synthesized zSePEUU polymer with enhanced hydrophilicity and suitable mechanical properties is subsequently utilized for preparation of electrospun tubular scaffolds. In vitro assays demonstrate that the zSePEUU electrospun membranes can inhibit protein adsorption and facilitate cell proliferation. Due to the in situ catalysis of diselenide, it is supposed that vasoregulatory nitric oxide (NO) can be generated to promote endothelialization. Then, the zSePEUU electrospun tubular scaffold remains vascular patency with formation of endothelial coverage and collagen deposition during in vivo implantation in a rat abdominal aorta interposition model for 4 weeks in comparison with the PCL control. Therefore, zwitterionic diselenide-containing zSePEUU with controllable NO generation provides a synergistic strategy for vascular regeneration. STATEMENT OF SIGNIFICANCE: Transplantation of vascular grafts is one of the effective approaches for treating cardiovascular diseases, however, this remains a challenge with the small-diameter vascular grafts. Herein, electrospun fibrous scaffolds made from elastic zwitterionic diselenide-containing poly(ester urethane)urea (zSePEUU) are reported, displaying increased hydrophilicity and compliance. By using equal amounts of sulfobetaine-diol and poly(ε-caprolactone)-diol, the zSePEUU electrospun scaffold exhibits optimal mechanical properties and nitric oxide-generating ability. Evaluation in a rat abdominal aorta interposition model suggests that the zSePEUU electrospun scaffold can achieve a high level of endothelial coverage and vascular regeneration. This finding provides a feasible method to address the issue of rapid endothelialization for long-term patency in vascular regeneration.