A breakthrough trial of an artificial liver without systemic heparinization in hyperbilirubinemia beagle models
Yilin Wang, Shanshan Wang, Xueqin He, Yupei Li, Tao Xu, Lin Xu, Bo Yang, Xinnian Fan, Weifeng Zhao, Changsheng Zhao
Abstract
The development of wearable artificial livers was restricted to device miniaturization and bleeding risk with water-soluble anticoagulants. Herein, a double-deck column filled with solid anticoagulant microspheres and Kevlar porous microspheres (KPMs, bilirubin adsorbents) was connected with the principle machine of wearable artificial liver (approximately 9 kg) to treat hyperbilirubinemia beagles for the first time. With the initial normal dose of heparin, the double-deck column could afford 3 h hemoperfusion in whole blood without thrombus formation. The removal efficiency of the double-deck column for total bilirubin (TBIL) was 31.4%. Interestingly, the excessive amounts of hepatocyte metabolites were also decreased by approximately 25%. The "anticoagulant + column" realized safe and effective whole blood hemoperfusion without the plasma separation system and heparin pump; however, the proposed principle machine of wearable artificial liver and "anticoagulant + column" cannot completely replace the bio-liver now. The intelligence of the device and the versatility of the adsorbent need to be improved; moreover, advanced experimental techniques need to be developed to validate the survival rates in animals. Overall, this study is a meaningful trial for the development of wearable artificial livers in the future.