While scientists have successfully printed small patches of human tissue, scaling those tissues into full-sized organs has remained elusive. In natural organisms, every cell must be within roughly 100 to 200 micrometers—about the thickness of two human hairs—of a blood vessel to receive oxygen and nutrients. Without this intricate, life-giving network, cells starve and die.
To address this grand challenge, a multi-institutional team of engineers and bioscientists has launched a four-year project to create functional, microscopic blood vessels in lab-grown organs. The project is being led by Yanliang Zhang, the Advanced Materials and Manufacturing Collegiate Professor at the University of Notre Dame, in collaboration with co-investigator professor Y. Shrike Zhang of Brigham and Women’s Hospital and Harvard Medical School, with the support of a $2.6 million award from the National Institutes of Health.
“Bioprinting holds the potential to produce personalized organs that could save countless lives,” said Yanliang Zhang. “However, it has been a long-standing challenge to print the complex, hierarchical vascular networks required for these organs to survive and function.”
The team proposes to develop a next-generation technology known as Hybrid Multi-material and Multi-scale Autonomous Printing (HM²AP). The process combines two highly complementary and coordinated printing approaches. One extrusion print head deposits a biocompatible hydrogel that forms the bulk of the tissue, while a second uses a focused aerosol jet to draw temporary, or “sacrificial,” patterns as small as 10 micrometers that form a hollow, branching network of channels once removed upon dissolution. These channels are then seeded with living blood vessel cells, creating a functional vascular system within the printed tissue.
The system avoids a common limitation of conventional bioprinters: clogging. Because it relies on an air-focused spray rather than a fine nozzle, it can produce extremely small features with greater reliability. In addition, integrated cameras and sensors enable machine learning algorithms to monitor the printing process and automatically optimize the print process and correct errors in real time.
The four-year project will focus initially on the liver, an organ with exceptionally dense vascular networks. The research will proceed through several stages, beginning with laboratory-grown “mini-liver” systems to test whether human cells thrive within the printed structures. In the final phase, the team will test the tissue in animal models, looking for successful integration with the host’s circulatory system.
If successful, the technology could extend far beyond liver tissue. By enabling the creation of complex vascular networks, the system may provide a foundation for printing a wide range of organs, including but not limited to kidneys and hearts.
“The success of this project will build a strong foundation for regenerative medicine,” Yanliang Zhang said. “We are not just building a better printer; we are shaping the future of transplantation.”
—Karla Cruise, Notre Dame Engineering