Liver failure is one of the most serious and deadly medical conditions, claiming thousands of lives each year as patients in the United States wait for a donor organ. An up to $25.8 million research project at the University of California San Diego, funded by the Advanced Research Projects Agency for Health (ARPA-H), aims to change that by developing a fully functional, patient-specific, 3D bioprinted liver.
Led by 3D bioprinting expert Shaochen Chen, a professor in the Aiiso Yufeng Li Family Department of Chemical and Nano Engineering at the UC San Diego Jacobs School of Engineering, the project brings together a multidisciplinary team of specialists across the UC San Diego campus in engineering, liver biology, liver imaging, liver surgery and artificial intelligence. The goal is to create “made-to-order” livers grown from a patient’s own cells. The approach could offer a safe, scalable alternative to transplantation that eliminates the need for donor organs and lifelong immunosuppressant drugs.
“When people think about 3D printing, they often imagine making gadgets like cellphone holders or toys, not human organs,” Chen said. “But the need for organ transplants is enormous, and 3D bioprinting is uniquely suited to address that challenge, as it allows us to personalize each organ to the patient. Our ultimate goal — the holy grail — is to help solve the organ shortage by printing real, living human organs that can restore health and quality of life.”
The goals of this project represent the culmination of more than two decades of 3D bioprinting innovation by Chen and his lab. Together, the team has developed a technology capable of rapidly fabricating high-resolution biological tissues with complex, multi-cellular structures in just seconds rather than hours.
Chen and his team have recently integrated artificial intelligence into the design and manufacturing process to help engineer sophisticated vascular networks. This, Chen explained, is one of the key challenges in scaling up from small tissue samples to full-sized, living organs.
Through this new initiative, the team will now apply these cumulative advances to tackle their most ambitious goal yet: bioprinting a life-sized, transplantable human liver.
If successful, Chen said, the project could provide an on-demand source of functional liver tissue for transplantation, potentially saving the lives of more than 12,000 patients in the United States each year who are currently on the transplant waiting list. The approach could also significantly reduce healthcare costs and improve long-term outcomes for patients with chronic liver disease.
“For decades, the transplant community has dreamed of a future where the fate of thousands of patients each year is no longer determined by the scarcity of donor organs,” said Gabriel Schnickel, professor of surgery at UC San Diego School of Medicine, chief of the Division of Transplantation and Hepatobiliary Surgery at UC San Diego Health, and co-investigator on the project. “This work has the potential to fundamentally change countless lives by moving that vision from aspiration to reality.”
Other UC San Diego co-investigators on the project include David Berry, Ahmed El Kaffas, Padmini Rangamani, Bernd Schnabl and Claude Sirlin at UC San Diego School of Medicine, and Rose Yu at UC San Diego Jacobs School of Engineering.
The researchers are collaborating with Allele Biotechnology, an industry partner with expertise in personalized stem cell generation technologies and methods to efficiently produce different types of cells needed to bioprint livers for transplantation. The San Diego company, founded by its CEO Jiwu Wang, also owns specialized facilities for cell manufacturing that meet regulatory standards. Together, the team plans to advance the process from laboratory-grade to clinical-grade production.
From innovation to real-world impact
Unlike conventional 3D printing methods, Chen’s technology uses digitally controlled light patterns to solidify cell-laden materials layer by layer — this allows researchers to precisely recreate the fine microarchitecture found in living tissues, including intricate networks of blood vessels.
Over the years, Chen’s team refined both the bioprinting process and the biomaterials — known as bioinks — needed to support living human cells. In 2016, they reached a major milestone by demonstrating that their bioprinting technology could create lifelike human liver tissue models. Although they were just a few millimeters in size, these printed tissues closely replicated the structures and functions of a real human liver. And because the liver tissues are derived from human induced pluripotent stem cells, they are patient-specific, which reduces the risk of immune rejection.
Building on this success, Chen and his team launched a startup company, Allegro 3D (now Cellink), to translate the technology beyond the laboratory. As they worked to commercialize the bioprinting platform, they progressively advanced the system from an experimental prototype to an industrial-scale printer capable of producing much larger, more complex structures.
“UC San Diego is uniquely positioned to lead this kind of work,” Chen said. “We have a top-ten engineering school and a world-class medical school right across campus. We have a highly collaborative culture, which makes it easy to bring engineers, clinicians and biologists together to tackle a problem of this scale.”
This project is supported by the Advanced Research Projects Agency for Health (ARPA-H) under Award Number D25AC00432-00, providing up to $25,771,771 for a 60-month period. The project is under ARPA-H’s Personalized Regenerative Immunocompetent Nanotechnology Tissue (PRINT) program, which is led by ARPA-H Program Manager Ryan Spitler. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Advanced Research Projects Agency for Health.
