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

doi:10.1016/j.bioactmat.2022.06.019

A breakthrough trial of an artificial liver without systemic heparinization in hyperbilirubinemia beagle models

Bioact Mater. 2022 Jul 6:20:651-662. doi: 10.1016/j.bioactmat.2022.06.019. eCollection 2023 Feb.

Authors

Yilin Wang^{1

2}, Shanshan Wang^{1

2}, Xueqin He³, Yupei Li³, Tao Xu^{1

2}, Lin Xu^{1

2}, Bo Yang^{1

2}, Xinnian Fan¹, Weifeng Zhao^{1

2}, Changsheng Zhao^{1

2}

Affiliations

¹ College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.
² Med-X Center for Materials, Sichuan University, Chengdu, 610041, China.
³ Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China.

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.

Keywords: Anticoagulant; Bilirubin; Kevlar; Microspheres; Wearable artificial liver.