Abstract

The immunogenicity of heterogeneous pericardium is a major factor causing the failure of commercial biological valves. Both decellularization and glutaraldehyde crosslinking can reduce the immunogenicity of pericardium, but it is difficult to completely remove it. Getting gene knockout pigs is considered a highly efficient method to obtain low-immunogenic biological tissues, including the pericardium. Our results showed that repeated cycles of decellularization could obviously reduce the residual DNA in tissues for pigs without gene knockout, but at the same time they could also break down the components of pericardia, resulting in a decline in mechanical properties. We compared the mechanical and biological properties of the glutaraldehyde crosslinked pericardia of GGTA1 knockout pig, GGTA1/CMAH knockout pig, GGTA1/β4GalNT2 knockout pig and wild type (WT) pig. The mechanical properties of the pericardia of GGTA1 knockout pig and GGTA1/CMAH knockout pig were similar to those of control pig (WT), and the experimental results of subdermal implantation in rats showed significantly reduced immune rejection and calcification. Pulsatile flow and fatigue in vitro tests showed that the fabricated artificial aortic valve met the hydrodynamic requirements after 2×10^8 accelerated fatigue cycles. Gene knockout pigs have great potential in the application of artificial biological valve products.

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