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Bio-Gel Designed to Transform into Precursor Tooth Material

Dental visit

(butler.VA.gov)

5 March 2014. Life science and engineering researchers at Harvard University developed a sponge-like gel material that when seeded with embryonic cells in lab tests shrinks and hardens into a predecessor of human tooth tissue. The team led by Donald Ingber, director of Harvard’s Wyss Institute for Biologically Inspired Engineering, published its findings online last month in the journal Advanced Materials (paid subscription required).

Ingber’s team, including colleagues from Boston Children’s Hospital, aimed to emulate a process used by human embryos to develop specialized tissue such as teeth and bone, where growth factor proteins combine with chemicals that activate genes and mechanical forces to differentiate stem cells into those specialized cells. Earlier research at the Wyss Institute and Boston Children’s Hospital examined the process and found loose, unorganized embryonic cells known as mesenchyme exchange signals with a covering layer of epithelial cells that cause the mesenchyme to compress into a small, tight formation.

The earlier research reported that in the lab, this tight collection of cells forms at the spot in the anatomy for the new tissue, activates genes, and develops into functioning tissue or organs. And those lab tests isolated tissues from the jaws of mouse embryos that differentiated into whole teeth, including enamel and dentin.

The new research, led by engineering Ph.D. candidate Basma Hashmi, sought to emulate the process, but with a bio-compatible material that could transform into artificial teeth when implanted in the body. With chemistry colleagues, the researchers started with a gel-forming polymer called poly-isopropylacrylamide or PNIPAAm that is biocompatible and used to deliver drugs into the body.

PNIPAAm is thermo-sensitive, and responds to heat by immediately contracting, but in its original state shrinks at too low a temperature to be useful. The researchers needed the gel to begin contracting precisely at body temperature, 37 degrees Celsius (98.6 F). Hashmi — the publication’s first author — and her chemistry colleagues spent a year modifying PNIPAAm to the point where, cells stuck to it and the material began contracting at 37 C.

In initial lab tests, the researchers seeded PNIPAAm gel with mesenchymal cells, and when warmed to 37 C, shrunk to form tight packs. The cells inside the tight packs stayed alive and activated three genes that form tooth tissue.

The researchers then, as a proof of concept, implanted the seeded PNIPAAm gel into mice beneath the kidney, an area that is well supplied with blood. The results show the implanted gel contracted inside the body, activated tooth-forming genes, and began forming calcium and minerals in preparation for making teeth. “They were in full-throttle tooth-development mode,” says Hashmi in a university statement.

In the next stage, the researchers plan to combine mesenchymal cells with epithelial cells in the polymer gel, which they expect to develop into fully functional teeth.

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