Syntheses and characterization of anti-thrombotic and anti-oxidative Gastrodin-modified polyurethane for vascular tissue engineering

ABSTRACT: Vascular grafts must avoid negative inflammatory responses and thrombogenesis to prohibit fibrotic deposition immediately upon implantation and promote the regeneration of small diameter blood vessels (<6 mm inner diameter). Here, polyurethane (PU) elastomers incorporating anti-coagulative and anti-inflammatory Gastrodin were fabricated. The films had inter-connected pores with porosities equal to or greater than 86% and pore sizes ranging from 250 to 400 ?m. Incorporation of Gastrodin into PU films resulted in desirable mechanical properties, hydrophilicity, swelling ratios and degradation rates without collapse. The released Gastrodin maintained bioactivity over 21 days as assessed by its anti-oxidative capability. The Gastrodin/PU had better anti-coagulation response (less observable BSA, fibrinogen and platelet adhesion/activation and suppressed clotting in whole blood). Red blood cell compatibility, measured by hemolysis, was greatly improved with 2Gastrodin/PU compared to other Gastrodin/PU groups. Notably, Gastrodin/PU upregulated anti-oxidant factors Nrf2 and HO-1 expression in H2O2 treated HUVECs, correlated with decreasing pro-inflammatory cytokines TNF-? and IL-1? in RAW 264.7 cells. Upon implantation in a subcutaneous pocket, PU was encapsulated by an obvious fibrous capsule, concurrent with a large amount of inflammatory cell infiltration, while Gastrodin/PU induced a thinner fibrous capsule, especially 2Gastrodin/PU. Further, enhanced adhesion and proliferation of HUVECs seeded onto films in vitro demonstrated that 2Gastrodin/PU could help cell recruitment, as evidenced by rapid host cell infiltration and substantial blood vessel formation in vivo. These results indicate that 2Gastrodin/PU has the potential to facilitate blood vessel regeneration, thus providing new insight into the development of clinically effective vascular grafts. Graphical abstract Gastrodin-modified polyurethane exhibited both anti-coagulation and anti-inflammatory properties,further led to angiogenesis, serving as a promising blood-contacting anti-thrombotic material.Image 1 Highlights • Gastrodin-modified PU films had desirable pore structure and mechanical properties.• Gastrodin/PU exhibited better anti-coagulation and anti-inflammatory response.• 2Gastrodin/PU effectively drove adhesion and proliferation of HUVECs in vitro.• 2Gastrodin/PU facilitated neo-vessels formation in vivo subcutaneous implantation.• Gastrodin/PU is a potential candidate blood-contacting anti-thrombotic material.

SUBMITTER: Zheng M 

PROVIDER: S-EPMC7486448 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature