For several years, engineered tissues and organs have been cultured with varying degrees of success in laboratories.
Bioprinting the letter “C” using a stem cell only “bioink” into an alginate microbead supporting medium. (Video credit: Oju Jeon and Eben Alsberg, University of Illinois at Chicago)
Most of them have employed a scaffolding method in which cells are grown on biodegradable supportive structures that offer the fundamental architecture of the organ or tissue needed.
However, scaffolds can be challenging; they must degrade and disappear eventually, but the timing at which decomposition coincides with the maturation of the organ is complicated. And at times, degradation by-products can be harmful. Furthermore, scaffolds can interfere with the development of cell-to-cell connections, which are vital to the formation of functional tissues.
A group of scientists headed by Eben Alsberg, the Richard and Loan Hill Professor of Bioengineering and Orthopaedics at the University of Illinois at Chicago, has designed a process that allows 3D printing of biological tissues without scaffolds using “ink” solely composed of stem cells. They have published the study outcomes in the journal Materials Horizons.
Our cell only printing platform allows for the 3D printing of cells without a classical scaffold support using a temporary hydrogel bead bath in which printing takes place.
Eben Alsberg, Professor of Bioengineering and Orthopaedics, University of Illinois, Chicago
The micron-scale hydrogel beads permit the nozzle of the 3D printer to pass through it and place cells with less resistance to that nozzle movement or the discharge of the cells. The gel beads support the cells as they are printed, hold them in place, and maintain their shape.
After printing the cells into the hydrogel bead matrix, it is subjected to UV light exposure, which cross-links the beads together, as a result freezing them in place. This allows the printed cells to link with each other, mature, and develop within a stable structure.
The media that cleanses the cells flows through the cross-linked gel beads easily and can be replaced when required to supply fresh nutrients and discard waste products produced by the cells. The hydrogel beads can be detached through gentle agitation, or by controlling their decomposition, leaving the intact tissue behind.
“The hydrogel bead bath has unique properties which allow for both printings of the cell-only bioink in complex architectures, and subsequent temporary stabilization of these cell-only structures to allow for cell-cell junctions to form,” stated Alsberg. “Using chemistry, we can then regulate when the beads go away.”
The cells used by Alsberg’s group are stem cells that can differentiate into a broad range of other cell types. They 3D printed a cartilage ear and a rodent-sized “femur” in the hydrogel bead bath by using the stem cells. The cells printed by them could develop stable, cell-to-cell connections through specialized proteins.
“For the first time, cell-only constructs can be printed in intricate forms that are made up of different cell types without a hydrogel carrier or traditional scaffold that can then be stabilized for a period of a day to weeks. We’ve demonstrated that individual cells and cell aggregates can be organized and assembled using this platform strategy to form larger functional tissues, which may be valuable for tissue engineering, drug screening and as models to study developmental biology,” Alsberg stated.
The co-authors on the paper are Oju Jeon, Yu Bin Lee, Sang Jin Lee, and Derrick Wells from the bioengineering department at the University of Illinois at Chicago and Hyoen Jeong of Case Western Reserve University.
This research was supported by National Institutes of Health grants R01 AR063194, R01 AR066193, and R01 EB023907.