Bioinspired Artificial Liver System with hiPSC‐Derived Hepatocytes for Acute Liver Failure Treatment

• Published in: Advanced healthcare materials 2021-12, Vol.10 (23), p.e2101580-n/a
• Main Authors: Wang, Jinglin, Ren, Haozhen, Liu, Yuxiao, Sun, Lingyu, Zhang, Zhuohao, Zhao, Yuanjin, Shi, Xiaolei
• Format: Article
• Language: English
• Subjects: acute liver failure; Animals; Artificial organs; bioartificial livers; bioinspired; Biomimetics; Cell viability; Hepatocytes; Humans; Induced Pluripotent Stem Cells; Liver; Liver failure; Liver Failure, Acute - therapy; Liver transplantation; Liver, Artificial; microcarriers; Microfluidics; Microparticles; Pluripotency; Rabbits; Regeneration; Serum proteins; Stem cells; Tissue engineering; Transplantation
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202101580

Bioartificial liver (BAL) system has become a promising alternative to traditional liver transplantation in rescuing acute liver failure (ALF) patients. Herein, inspired by natural microstructure of hepatic lobules, a novel biomimetic bioartificial liver system (BBALS) is developed by integrating human induced pluripotent stem cell‐derived hepatocytes (hiPSC‐Heps) ‐laden microparticles and semipermeable microtubes into a microfluidic platform. As the working units are hepatic lobules‐like semipermeable microtubes surrounding with serum‐free suspension differentiated hiPSC‐Heps microcarriers, the BBALS is endowed with functional cell aggregates and effective circulation system. Thus, the BBALS possesses high cell viability, favorable function regeneration, and effective substances exchange. Based on these features, a 3D liver chip with multiple parallel BBALS units is created for filtering the plasma of ALF rabbits, which validates the research significance and application potential of the proposed BBALS. Moreover, the novel integrated BBALS is applied to treat ALF rabbits and shows great advantages in increasing survival, generating serum proteins, and decreasing inflammation. These properties point to the broad prospects of BBALS in treating related diseases and improving traditional clinical methods. A new BBALS consists of hiPSC‐Heps‐laden GelMA microparticles and semipermeable microtubes. GelMA microparticles are served as excellent carriers for the hiPSC‐Heps for better liver functions in vitro. The cell‐laden microparticles are integrated with the semipermeable microtubes to enable efficient nutrient transport and toxins elimination. 3D liver chip and BBALS are demonstrated outstanding hepatic‐special functions in vitro and in vivo.