3D-printed liver tissue: ImPLANT project combines bioprinting and immunoengineering

Liver diseases are among the most common causes of organ-related deaths worldwide. Around two million people die each year from the consequences of liver failure, while organ transplants are severely limited due to a lack of donors. Against this backdrop, a U.S.-based research consortium is pursuing a new approach in which 3D printing plays a central role. As part of the ImPLANT project, implantable liver tissues are to be developed that are available independently of donor organs.

The initiative is being funded by the Advanced Research Projects Agency for Health under the PRINT program with up to 25 million U.S. dollars over five years. Participating institutions include the Wyss Institute at Harvard University, the Massachusetts Institute of Technology, and Columbia University. The project is led by Christopher Chen, who describes the combination of additive manufacturing, synthetic biology, and stem cell technology as crucial for producing functional liver tissue.

“I am thrilled to be working with this mission-driven dream team of pioneers to carve a new path toward the clinic, made possible by the timely confluence of foundational advances in regenerative medicine and tissue manufacturing. We all recognize the moonshot nature of the program and are thankful that ARPA-H is making it possible,” said Chen, the ImPLANT project’s Principal Investigator (PI) at the Wyss Institute. He is also the William Fairfield Warren Distinguished Professor at Boston University, Founding Director of the Biological Design Center at Boston University, a Paul G. Allen Distinguished Investigator. Chen was recently elected to the National Academy of Medicine.

Technically, ImPLANT is based on induced pluripotent stem cells that are differentiated into different liver cell types using genetic circuits. These cells are then immunologically modified to prevent rejection reactions. For the actual tissue fabrication, 3D bioprinting methods are used to generate vascularized structures. The vascular networks are necessary to maintain metabolic processes such as detoxification, protein synthesis, and glucose metabolism.

The cell–biomaterial constructs are printed in specialized bioreactors that simultaneously serve for maturation and quality control.

“The Wyss Institute is extremely excited to be part of ARPA-H’s PRINT program, and proud of Chris Chen’s leadership role in the ImPLANT project. The sheer visionary power of the project and impressive scientific expertise provided by this exceptional team have great potential for positively transforming the lives of patients whose livers fail by making science fiction a reality,” said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard John A. Paulson School of Engineering and Applied Sciences.

In the long term, the approach could further strengthen the role of 3D printing in regenerative medicine. Instead of complete organs, the initial focus is on modular, printed tissues designed to complement existing therapies and alleviate transplant bottlenecks.