PC222. Engineered Vascular Grafts Using Three-Dimensional Printed Guides and the Ring Stacking Method

Abstract

Results: The endogenous thrombin potential (ETP) was significantly higher for Rip3 +/+ vs Rip3 À/À PPP (Fig 1). With the addition of recombinant RIP3 (rRIP3), ETP was enhanced in Rip3 À/À PPP. Furthermore, the addition of rRIP3 to Rip3 +/+ PPP was able to enhance its ETP. Using the RIP3 inhibitor GSK 0 843, the ETP of Rip3 +/+ PPP was significantly reduced compared with untreated plasma (Fig 1). There was no change in ETP when RIP3 inhibitors were used on Rip3 À/À PPP (Fig 1). Human PPP was also subjected to treatment with RIP3 inhibitor GSK 0 843. Untreated human PPP had significantly higher ETP than treated human PPP. In addition, we used our novel RIP3 inhibitor, code name C9, and found that it lowered human ETP at much lower concentrations. The in vivo effect of RIP3 on coagulation was evaluated by use of the IVC ligation models. The thrombus weight of Rip3 +/+ mice (n ¼ 6) was larger compared with Rip3 À/À mice (n ¼ 4; P < .01; Fig 2). Rip3 +/+ mice treated with C9 (n ¼ 6) vs dimethyl sulfoxide (n ¼ 5) showed a significant reduction in thrombus weight (P < .01; Fig 2).Conclusions: RIP3 appears to have a functional role in thrombus formation. The thrombin generation assays using PPP suggest that RIP3 has a functional role in coagulation outside of the cell, a novel finding. In addition, the IVC ligation models suggest that the absence and inhibition of RIP3 are capable of reducing thrombus formation in vivo. Rip3 À/À mice do not have a bleeding phenotype, suggesting that targeting RIP3 for its anticoagulative properties may be safer than current pharmaceutical treatments today.