Journal
ADVANCED HEALTHCARE MATERIALS
Volume 10, Issue 23, Pages -Publisher
WILEY
DOI: 10.1002/adhm.202101580
Keywords
acute liver failure; bioartificial livers; bioinspired; microcarriers; microfluidics; tissue engineering
Funding
- National Natural Science Foundation of China [81872359, 81670566]
- Jiangsu Province's Key Provincial Talents Program [ZDRCA2016066]
- Certificate of China Postdoctoral Science Foundation [2018M642222]
- Jiangsu Province Natural Science Foundation [BK20190114]
- Nanjing Medical Science and Technique Development Foundation [QRX17129]
- Nanjing health science and technology development project for Distinguished Young Scholars [JQX19002]
- Nanjing health Science and Technology Development project for Medical and Health Research [YKK19070]
- Nanjing Science and Technology project [201911039]
- Innovation and Entrepreneurship Education Incubation project of Nanjing University
- Aid project of Nanjing Drum Tower Hospital Health, Education & Research Foundation [NDYG2020047]
- Project of Modern Hospital Management and Development Institute, Nanjing University
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The novel biomimetic bioartificial liver system, inspired by the natural microstructure of hepatic lobules, integrates human induced pluripotent stem cell-derived hepatocytes-laden microparticles and semipermeable microtubes into a microfluidic platform, resulting in functional cell aggregates and effective substances exchange. A 3D liver chip with multiple parallel BBALS units demonstrates its potential in filtering the plasma of ALF rabbits, showing advantages in increasing survival, generating serum proteins, and decreasing inflammation. These properties highlight the broad prospects of BBALS in treating related diseases and enhancing traditional clinical methods.
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.
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