NIBIB-funded engineers at the University at Buffalo have perfected the use of stereolithography for 3D printing organ models containing living cells. The new technique is capable of printing the models between 10 and 50 times faster than the industry standard (in minutes instead of hours), an important step in the quest to create 3D printed replacement organs.
Conventional 3D printing involves meticulously adding material to the 3D model with a small needle that produces fine detail but is extremely slow: it takes six or seven hours to print a model of a human part, such as a hand, for example. The long process causes stress and cellular injuries that inhibit the ability to seed tissues with living, functional cells.
The method developed by the SUNY Buffalo group, led by Rougang Zhao, PhD, associate professor of biomedical engineering at the Jacobs School of Medicine and Biomedical Sciences, takes a different approach that minimizes damage to living cells. This rapid, cell-friendly technique is an important step toward creating printed tissues with large numbers of living cells.
Instead of a needle moving across a surface slowly building up the details of the 3D model, Zhao and his team members have developed a system that allows a small 10-centimeter model of a human hand to rise, quite dramatically, out of a vat of liquid in a matter of minutes, rather than hours (see video). The stereolithographic method uses light projected at the bottom of the tank that penetrates upward through a mixture of hydrogel and living cells. The light polymerizes the hydrogel/cell mixture at precise positions on the model, building entire layers of the model continuously, rather than one minute spot at a time.
“This is a significant step toward printing biologically active 3D tissues,” explained David Rampulla, Ph.D., director of the NIBIB program in Synthetic Biological Systems. “This new technique combines a highly cell-friendly hydrogel mixture with the rapid printing process, which prevents cells from being suspended in a cell-damaging environment for a prolonged period. The combination has allowed the team to introduce live cells into their 3D printed tissues and the vast majority of the cells remain alive and functional.”
Looking to move from small organ models to full-size replacement organs in the future, the engineering team successfully used the new method to print tissues containing internal branching networks that mimic blood vessels. “Keeping cells deep within a full-sized printed organ alive is one of the many challenges in creating functional replacement organs,” Zhao explained. “We found that our method worked well in terms of creating branching, vessel-like networks to facilitate nutrient delivery to cells embedded throughout the printed tissue.”
Going a step further, the team introduced live endothelial cells into the branching channels of their 3D printed tissues. The endothelial cells adhered to the walls of the artificial vasculature and expanded to form an endothelial lining similar to that found in real blood vessels.
The research team is now working to increase the size of printed tissues while maintaining structural integrity and cell viability. The work is a significant step toward the lofty but potentially achievable goal of many bioengineers: printing replacement organs, a biomedical breakthrough that could save countless lives lost due to widespread shortages of donor organs such as kidneys and livers.
This study was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under award number R01EB019411. The authors also acknowledge financial support from the College of Engineering and the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo. The work was published in Advanced Healthcare Materials.1
This Science Highlight describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is critical to promoting new and better ways to prevent, diagnose, and treat diseases. Science is an unpredictable and incremental process: each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without knowledge of fundamental basic research.
