Complex Tissues Square Pegs and Round Holes Provide Inspiration for Rapid Template Tissue Engineering

The image above illustrates mathematical modeling of the migration of mesenchymal stem cells (encapsulated in cylinders) in response to signals released by endothelial cells (encapsulated in rectangles). The color intensity corresponds to concentration, and the arrows represent directions of cell motion. —Illustration by George Eng

As tissue engineering is becoming more practical and gaining acceptance in clinical use, new techniques that can improve and automate the creation of entire volumes of artificial tissue would be most welcome.

Complex Tissues 2 Square Pegs and Round Holes Provide Inspiration for Rapid Template Tissue Engineering

Shapes in their congruent wells after sorting.

A team of scientists from Columbia University have reported in Proceedings of the National Academy of Sciences the development of a new method of bringing together mesenchymal stem cells and endotheleal cells using variously shaped hydrogel capsules. The different shapes allow the creation of a special template to which the pieces will naturally fit, creating a predefined network of cells that can grow into real tissue.

Each shape can dock only into its matching well—the rectangular blocks dock only into the exact same rectangular wells, cylindrical blocks into cylindrical wells, and so on, in a lock-and-key manner. After up to ten short cycles of shaking, the template becomes filled with shapes to form a precisely defined pattern. This docking technique thus allows rapid assembly of a large number of subunits to create new tissues.

“We used a LEGO-like lock-and-key docking system to spatially localize different cell populations with high specificity and precision,” Eng explains. “And, since each shape is docking independent of each other, large tissues can be organized simultaneously, instead of having to create a sequential, brick-by-brick type of organization. With this method, we can design and create better tissues for potential organ replacement.”

Next steps in the application of this new technique include fabrication of different types of functional tissues, such as well-organized cardiac muscle, a tissue whose function critically depends on its architecture and cell alignment, incorporating blood vessel networks along with organized cardiac cells. The method will also be extended to the design of pathological microenvironments of interest, such as tumor models.

Study in Proceedings of the National Academy of SciencesAssembly of complex cell microenvironments using geometrically docked hydrogel shapes

Columbia Engineering press statement: Designing Interlocking Building Blocks to Create Complex Tissues…