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 from the Wyss Institute for Biologically Inspired Engineering at Harvard University, Harvard School of Engineering and Applied Sciences (SEAS), and Boston Children's Hospital report recently in Advanced Materials.
"Tissue engineers have long raised the idea of using synthetic materials to mimic the inductive power of the embryo," said Don Ingber, M.D., Ph.D., Founding Director of the Wyss Institute, Judah Folkman Professor of Vascular Biology at Harvard Medical School, Professor of Bioengineering at SEAS, and senior author of the study. "We're excited about this work because it shows that it really is possible."
Ingber and Basma Hashmi, a Ph.D. 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 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.
They 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.
As an initial test, Hashmi implanted mesenchymal cells in the gel and warmed it in the lab. Sure enough, when the temperature reached 37°C (temperature of the human body), the gel shrank within 15 minutes, causing the cells inside the gel to round up, shrink, and pack tightly together.
"The reason that's cool is that the cells are alive," Hashmi said. "Usually when this happens, cells are dead or dying."
Not only were they alive-they activated 3 genes that drive tooth formation.
To see if the shrinking gel also worked its magic in the body, Hashmi worked with Mammoto to load mesenchymal cells into the gel, then implant the gel beneath the mouse kidney capsule-a tissue that is well supplied with blood and often used for transplantation experiments.
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.
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