New sponge-like gel steers tooth formation

Scientists have developed a new shrinking sponge-like gel which squeezes unspecialised cells inside it to turn them into cells that begin to form teeth.
The bioinspired gel material could one day help repair or replace damaged organs, such as teeth and bone, and possibly other organs as well, scientists said.
"Tissue engineers have long raised the idea of using synthetic materials to mimic the inductive power of the embryo," said Don Ingber, Founding Director of the Wyss Institute for Biologically Inspired Engineering at Harvard University and Judah Folkman Professor of Vascular Biology at Harvard Medical School.
"We're excited about this work because it shows that it really is possible," said Ingber, who is also Professor of Bioengineering at Harvard School of Engineering and Applied Sciences (SEAS) and senior author of the study published in the journal Advanced Materials.

Ingber and colleagues investigated a process called mesenchymal condensation that embryos use to begin forming a variety of organs, including teeth, cartilage and bone.
In mesenchymal condensation, two adjacent tissue layers - loosely packed connective-tissue cells called mesenchyme and sheet-like tissue called an epithelium that covers it - exchange biochemical signals.

This exchange causes the mesenchymal cells to squeeze themselves tightly into a small knot directly below where the new organ will form.
Examining tissues isolated from jaws of embryonic mice, researchers showed that when compressed mesenchymal cells turn on genes that stimulate them to generate whole teeth composed of mineralised tissues, including dentin and enamel.

Inspired by this embryonic induction mechanism, Ingber and Basma Hashmi, a PhD candidate at SEAS who is the lead author of the current paper, set out to develop a way to engineer artificial teeth by creating a tissue-friendly material that accomplishes the same goal.
Specifically, they wanted a porous sponge-like gel that could be impregnated with mesenchymal cells, then, when implanted into the body, induced to shrink in 3D to physically compact the cells inside it.
Researchers chemically modified a special gel-forming polymer called PNIPAAm that scientists have used to deliver drugs to the body's tissues. PNIPAAm gels have an unusual property: they contract abruptly when they warm.

Researchers then developed a polymer that forms a tissue-friendly gel with two key properties: cells stick to it, and it compresses when warmed to body temperature.
In an experiment, Hashmi loaded mesenchymal cells into the gel and implanted it beneath the mouse kidney capsule.
The implanted cells not only expressed tooth-development genes - they laid down calcium and minerals, just as mesenchymal cells do in the body as they begin to form teeth.
"They were in full-throttle tooth-development mode," Hashmi said.