A new method – inspired by kid’s pop-up books – for making 3D artificial tissue

BUFFALO, N.Y. — University at Buffalo researchers have developed a new process for creating three-dimensional artificial tissue, an advancement that could improve experimental drug testing, the quality of artificial organs and more.

Described in Advanced Science, the method is based upon compressive buckling – the structural engineering principle that explains why figures project outward from the pages of children’s pop-up books.

“When you turn to a new page, you create force. This force pulls on the feet of the figure, which forces the folds to open and the figure to pop out,” says the study’s co-corresponding author Ruogang Zhao, PhD, associate professor of biomedical engineering. “With this study, we have shown the same principle can be applied to artificially engineered tissue.”

In a series of experiments, researchers used the compressive buckling method to fabricate a variety of three-dimensional polymeric structures. These include simple shapes, such as a box and a pyramid, as well as more complex demonstrations, such as a sound wave and an eight-legged design that resembles an octopus.

To showcase the method’s utility for tissue engineering, the team created an osteon-like structure. Osteon is the basic building unit of bone tissue and is characterized by osteocytes sparsely distributed in a mineral bone scaffold. Each osteocyte rests in a small cavity, known as lacunae, and different osteocytes are connected through canaliculi, which are small channels in the bone scaffold.

The results are important, Zhao says, because most tissue engineers rely on two-dimensional tissue fabrication methods to create very thin tissues that do not represent the volume of the human tissue. The planar nature of these tissue models limits their application in disease modeling and drug testing, he says.

The compressive buckling method can be used to rapidly transform a two-dimensional tissue to a three-dimensional tissue with substantial thickness, thus allowing researchers to create more realistic tissue and opening new possibilities in tissue engineering and regenerative medicine. It also has the potential to outperform other method of 3D tissue engineering, such as 3D bioprinting, in terms of the fabrication speed and spatial resolution, Zhao says.

The research was supported by UB’s Department of Biomedical Engineering, a program of the School of Engineering and Applied Sciences and the Jacobs School of Medicine and Biomedical Sciences at UB. Additional support came from the National Institutes of Health.

The study’s co-corresponding author is Zhaowei Chen, who earned a PhD in Zhao’s lab,did a postdoctoral study at Duke University and is now a postdoc at the Center for Excellence in Molecular Cell Science, Chinese Academy of Science. Additional authors include Nanditha Anandakrishnan, who earned a PhD in Zhao’s lab and is now a postdoctoral student at the Icahn School of Medicine at Mount Sinai, and Ying Xu, a PhD candidate in Zhao’s lab.