Engineering Functional Human Liver Tissues: From 3D-Bioprinted Bioartificial Organs to Dynamic Disease Models

The development of functional bioartificial liver tissues requires the integration of abundant and functional hepatocytes with biomaterials, tissue architecture, and vascular connectivity. In this presentation, I will describe our efforts to engineer functional liver tissues from expanded primary hepatocytes and to develop their applications in liver regeneration and disease modeling.

We first established a strategy to generate transplantable 3D-bioprinted liver tissues using in vitro–expanded primary hepatocytes and a liver-derived bioink with tailored mechanical and rheological properties. The resulting 3D-bioprinted liver acquired mature hepatic functions, including metabolic and detoxification activities, and restored liver function after heterotopic transplantation into mouse models of liver failure. Incorporation of artificial vascular conduits further enabled biomolecule transport and direct vascular anastomosis, providing a potential route toward vascularized bioartificial liver transplantation.

Building on this platform, we next developed a dynamic perfusable human vascularized liver module (DPHV-LM) incorporating expanded primary human hepatocytes, endothelial cells, and patient-derived acute myeloid leukemia cells. Dynamic perfusion enhanced hepatocyte maturation and metabolic function, while enabling real-time modeling of leukemic infiltration into liver tissue. The platform reproduced chemotherapy-induced hepatotoxicity and enabled identification of ammonium glycyrrhizinate as a hepatoprotective agent that reduced cytarabine-induced liver injury while suppressing leukemic infiltration without compromising antileukemic efficacy.

Together, these studies illustrate a continuum from cell expansion and tissue fabrication to vascular integration, organ transplantation, disease modeling, and therapeutic discovery. Our work aims to establish bioengineered liver tissues not only as potential therapeutic grafts, but also as physiologically relevant human platforms for studying liver disease and developing safer and more effective therapies.

Pengyu Huang is a Professor at Peking Union Medical College, Deputy Director (Presiding) of the Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Executive Vice President of the Tianjin Institutes of Health Science, Deputy Director of the State Key Laboratory of Advanced Medical Materials and Devices, Director of the Engineering Research Center of Pulmonary and Critical Care Medicine Technology and Devices, Ministry of Education, and Director of the Department of Biomedical Engineering at Peking Union Medical College. He also serves as an Executive Council Member of the Chinese Society of Biomedical Engineering, Vice Chair of the 3D Bioprinting Branch, Deputy Secretary-General of the Cell and Gene Therapy Branch of the Chinese Society for Cell Biology, and Vice Chair of the Tianjin Society for Cell Biology.

Dr. Huang's research focuses on the development and application of bioartificial organs based on primary adult cells. His work has established scalable in vitro expansion technologies for adult human cells from the liver, lung, skin, and other tissues; developed a biomaterial platform with precisely tunable physicochemical properties; and pioneered a series of advanced biomanufacturing technologies, including integrated bioprinting of vascularized liver tissue and rapid self-assembly of cells into coagulation-mimicking systems.

Using extensively expanded adult hepatocytes, his team has developed centimeter-scale, 3D-bioprinted liver tissues and demonstrated their transplantation in vivo for the treatment of liver failure in mice. A bioartificial liver life-support system based on transdifferentiated hepatocytes has advanced to Phase II clinical trials.

To date, Dr. Huang has published 23 papers as first or corresponding author in leading international journals, including Nature, Nature Neuroscience, Cell Stem Cell, Nature Communications, Science Advances, Cell Research, Gut, Advanced Science, Hepatology, Biomaterials, Cell Discovery, and Chemical Engineering Journal.

Dr. Huang has led a Key Research and Development Program project of the Ministry of Science and Technology of China, with total funding of RMB 17.966 million. His research achievements were selected among China's Top Ten Scientific and Technological Advances in 2011 and received the First Prize of the Shanghai Natural Science Award in 2018.