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3-D Printing

Cell culture devices made with paper

3-D printed scaffolds have indefinite shelf lives and channels that mimic vasculature

by Celia Henry Arnaud
May 8, 2019 | A version of this story appeared in Volume 97, Issue 19

GIF showing 3-D printing of channels in a cellulose matrix and filling of channels after device is made.
Credit: Nano Lett.
Researchers add channels to paper-based cell culture devices by 3-D printing a paraffin wax ink in a bacterial cellulose hydrogel matrix. After the device dries, they inject dye solutions in the channels.

A new approach to making organ-on-chip devices combines the cost effectiveness of paper with the geometry control of 3-D printing (Nano Lett. 2019, DOI: 10.1021/acs.nanolett.9b00583).

A team led by Yu Shrike Zhang, a bioengineer at Harvard Medical School and Brigham and Women’s Hospital, demonstrated a way to make paper-based cell culture scaffolds with features mimicking tissue vasculature. They start with a bacterial cellulose hydrogel matrix and then 3-D print hydrophobic paraffin wax in arbitrary patterns within the matrix and let the material dry into a paper-like device. Melting and removing the paraffin leaves channels that can form the basis of tissue vasculature.

The resulting devices can then be kept on the shelf indefinitely. “Once you print a device, it’s going to last until you want to use it,” Zhang says. Organ chips printed with conventional materials such as gels have to be used right away, he says.

Zhang and his colleagues used the paper-based devices to make models of breast cancer tissue. They seeded endothelial cells in the channels to form vasculature for the tissue, added cells from a breast cancer cell line to the surrounding cellulose matrix, and then cultured the cells for up to 14 days. Zhang anticipates that such devices could be used for screening drugs on personalized tissue models.

Illustration showing a 3-D printer and a paper-based cell culture device.
Credit: Nano Lett.
Scientists made breast cancer model tissue by seeding endothelial cells in channels in a printed paper-based device to make the vasculature and seeding breast cancer cells in the surrounding matrix.

The 3-D printing gives researchers the flexibility of tailoring the channels to the tissue type. “Every tissue type has a different vascularization pattern,” Zhang says.

“The printing method could be a game changer for paper-based cultures in its ability to generate arbitrary shapes not achievable with cutting or wax patterning,” says Matthew R. Lockett, a chemist at the University of North Carolina at Chapel Hill, who makes cell culture devices from patterned filter paper. But Lockett points out that the proposed breast cancer model will require further characterization of the barrier function of both the blood vessel and epithelial mimics.

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