Affiliation:
1. Department of Rheumatology and Immunology Nanjing Drum Tower Hospital School of Biological Science and Medical Engineering Southeast University Nanjing 210096 China
2. Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine Vision and Brain Health) Wenzhou Institute University of Chinese Academy of Sciences Wenzhou Zhejiang 325001 China
3. Pharmaceutical Sciences Laboratory Åbo Akademi University Turku 20520 Finland
4. Turku Bioscience Centre University of Turku and Åbo Akademi University Turku 20520 Finland
Abstract
AbstractBioartificial livers have showcased significant value in the treatment of acute liver failure (ALF). Current efforts are directed toward overcoming challenges in the development of microcarriers, with a specific emphasis on integrating higher‐density liver cells to enhance detoxification capabilities. Here, inspired by the radial filtration model in hepatic lobules, ion‐specific silk fibroin microcarriers are proposed with biomimetic niches for cultivating functional liver cells at high density. These biomimetic microcarriers are generated by capillary microfluidic device with controllable adjustments of ion type or concentration within the aqueous phase. When cultivating human induced pluripotent stem cell ‐differentiated mature liver cells on these recrystallized microcarriers, notably enhanced cell proliferation activity, as well as increased metabolic and secretory functionality is observed. Based on these features, the microcarrier‐integrated bioreactor can effectively reduce hepatic transaminase levels and significantly improve urea, albumin production, and survival rate in rabbit ALF models is demonstrated. Thus, it is believed that the biomimetic microcarriers and their derived bioreactor may hold potential for clinical applications in managing ALF and other liver diseases.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Nanjing Medical Science and Technique Development Foundation