Tag Archives: teeth

Mesenchymal condensation (a process embryos use to begin forming a variety of organs, including teeth, cartilage, bone, muscle, tendon, and kidney) for complex 3D tissue engineering

It seems that there are three strategies for creating complex 3D tissues and until now scientists have used only two of the three. From a March 5, 2014 news item on ScienceDaily,

A bit of pressure from a new shrinking, sponge-like gel is all it takes to turn transplanted unspecialized cells into cells that lay down minerals and 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 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, …, 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.”

The March 5, 2014 Wyss Institute news release, which originated the news item, delves into the nature of the research,

Embryonic tissues have the power to drive cells and tissues to specialize and form organs. To do that, they employ biomolecules called growth factors to stimulate growth; gene-activating chemicals that cause the cells to specialize, and mechanical forces that modulate cell responses to these other factors.

But so far tissue engineers who want to build organs in the laboratory have employed only two of the three strategies — growth factors and gene-activating chemicals. Perhaps as a result, they have not yet succeeded in producing complex three-dimensional tissues.

A few years ago, Ingber and Tadanori Mammoto, M.D., Ph.D., Instructor in Surgery at Boston Children’s Hospital and Harvard Medical School, investigated a process called mesenchymal condensation that embryos use to begin forming a variety of organs, including teeth, cartilage, bone, muscle, tendon, and kidney.

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.

Here’s a video from the Wyss Institute illustrating the squeezing process,

When the temperature rises to just below body temperature, this biocompatible gel shrinks dramatically within minutes, bringing tooth-precursor cells (green) closer together. Credit: Basma Hashmi

Getting back to the research (from the news release),

By examining tissues isolated from the jaws of embryonic mice, Mammoto and Ingber showed that when the compressed mesenchymal cells turn on genes that stimulate them to generate whole teeth composed of mineralized tissues, including dentin and enamel.

Inspired by this embryonic induction mechanism, 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 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.

To develop such a material, Ingber and Hashmi teamed up with researchers led by Joanna Aizenberg, Ph.D., a Wyss Institute Core Faculty member who leads the Institute’s Adaptive Materials Technologies platform. Aizenberg is the Amy Smith Berylson Professor of Materials Science at SEAS and Professor of Chemistry and Chemical Biology at Harvard University.

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.

But they do this at a lukewarm temperature, whereas the researchers wanted them to shrink specifically at 37°C — body temperature — so that they’d squeeze their contents as soon as they were injected into the body. Hashmi worked with Lauren Zarzar, Ph.D., a former SEAS graduate student who’s now a postdoctoral associate at Massachusetts Institute of Technology, for more than a year, modifying PNIPAAm and testing the resulting materials. Ultimately, they developed a polymer that forms a tissue-friendly gel with two key properties: cells stick to it, and it compresses abruptly when warmed to body temperature.

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, 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 three 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.

The researchers have future plans (from the news release),

In the embryo, mesenchymal cells can’t build teeth alone — they need to be combined with cells that form the epithelium. In the future, the scientists plan to test whether the shrinking gel can stimulate both tissues to generate an entire functional tooth.

Here’s a link to and a citation for the paper about the successful attempt to stimulate mesenchymal cells into the beginnings of tooth formation,

Developmentally-Inspired Shrink-Wrap Polymers for Mechanical Induction of Tissue Differentiation by Basma Hashmi, Lauren D. Zarzar, Tadanori Mammoto, Akiko Mammoto, Amanda Jiang, Joanna Aizenberg, and Donald E. Ingber. Advanced Materials Article first published online: 18 FEB 2014 DOI: 10.1002/adma.201304995

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

This paper is behind a paywall.

Growing a tooth—as an adult

These days it seems that teeth are the most erogenous zone of all. Actors on screens of all types flash pearly whites that are increasingly blinding while the rest of us are enjoined to buy teeth whiteners in toothpastes, mouthwashes, whitening strips, and/or find dental professionals to assist us in our quest for the brightest and whitest teeth. It would all be so much easier if we could just grow new teeth and discard the old ones.

Coincidentally or not, it seems researchers at King’s College London have also been thinking about how we might grow new teeth. Ben Schiller in a Mar. 14, 2013 article for Fast Company highlights the work,

Researchers from the U.K. have successfully bioengineered teeth from gum tissue and cells taken from mice. By combining and transplanting two groups of cells, they were able to grow full teeth, complete with roots, dentine, and enamel.

This King’s College London Mar. 11, 2013 news release provides more details,

New research published in the Journal of Dental Research describes an advance in efforts to develop a method to replace missing teeth with new bioengineered teeth generated from a person’s own gum cells. …

Current implant-based methods of whole tooth replacement fail to reproduce a natural root structure and as a consequence of the friction from eating and other jaw movement, loss of jaw bone can occur around the implant.

Research towards achieving the aim of producing bioengineered teeth (bioteeth) has largely focused on the generation of immature teeth (teeth primordia) that mimic those in the embryo that can be transplanted as small cell ‘pellets’ into the adult jaw to develop into functional teeth. Remarkably, despite the very different environments, embryonic teeth primordia can develop normally in the adult mouth and thus if suitable cells can be identified that can be combined in such a way to produce an immature tooth, there is a realistic prospect bioteeth can become a clinical reality. Subsequent studies have largely focussed on the use of embryonic cells and although it is clear that embryonic tooth primordia cells can readily form immature teeth following dissociation into single cell populations and subsequent recombination, such cell sources are impractical to use in a general therapy.

Professor Sharpe [Paul Sharpe, an expert in craniofacial development and stem cell biology at King’s College London’s Dental Institute] said: ‘What is required is the identification of adult sources of human epithelial and mesenchymal cells that can be obtained in sufficient numbers to make biotooth formation a viable alternative to dental implants.’

In this new work, the researchers isolated adult human gum (gingival) tissue from patients at the Dental Institute at King’s College London, grew more of it in the lab, and then combined it with the cells of mice that form teeth (mesenchyme cells). By transplanting this combination of cells into mice the researchers were able to grow hybrid human/mouse teeth containing dentine and enamel, as well as viable roots.

Professor Sharpe concluded: ‘Epithelial cells derived from adult human gum tissue are capable of responding to tooth inducing signals from embryonic tooth mesenchyme in an appropriate way to contribute to tooth crown and root formation and give rise to relevant differentiated cell types, following in vitro culture. These easily accessible epithelial cells are thus a realistic source for consideration in human biotooth formation. The next major challenge is to identify a way to culture adult human mesenchymal cells to be tooth-inducing, as at the moment we can only make embryonic mesenchymal cells do this.’

If I read this rightly, researchers are several years away from actually growing a new tooth in an adult human mouth but this work suggests they might be on the right research track.

A ‘wandering meatloaf’ with teeth inspires nanomaterials for solar cells and Li-ion batteries

The ‘wandering meatloaf’ is a species of marine snail (or chiton) that has extraordinary teeth according to the Jan. 16, 2013 news item on ScienceDaily,

An assistant professor [David Kisailus] at the University of California, Riverside’s Bourns College of Engineering is using the teeth of a marine snail found off the coast of California to create less costly and more efficient nanoscale materials to improve solar cells and lithium-ion batteries.

The paper is focused on the gumboot chiton, the largest type of chiton, which can be up to a foot-long. They are found along the shores of the Pacific Ocean from central California to Alaska. They have a leathery upper skin, which is usually reddish-brown and occasionally orange, leading some to give it the nickname “wandering meatloaf.”

Over time, chitons have evolved to eat algae growing on and within rocks using a specialized rasping organ called a radula, a conveyer belt-like structure in the mouth that contains 70 to 80 parallel rows of teeth. During the feeding process, the first few rows of the teeth are used to grind rock to get to the algae. They become worn, but new teeth are continuously produced and enter the “wear zone” at the same rate as teeth are shed.

The University of California Riverside Jan. 15, 2013 news release by Sean Nealon, which originated the news item, describes the chiton’s teeth and the specifics of Kisailus’ inspiration (Note: A link has been removed),

Over time, chitons have evolved to eat algae growing on and within rocks using a specialized rasping organ called a radula, a conveyer belt-like structure in the mouth that contains 70 to 80 parallel rows of teeth. During the feeding process, the first few rows of the teeth are used to grind rock to get to the algae. They become worn, but new teeth are continuously produced and enter the “wear zone” at the same rate as teeth are shed.

Kisailus, who uses nature as inspiration to design next generation engineering products and materials, started studying chitons five years ago because he was interested in abrasion and impact-resistant materials. He has previously determined that the chiton teeth contain the hardest biomineral known on Earth, magnetite, which is the key mineral that not only makes the tooth hard, but also magnetic.

Kisailus is using the lessons learned from this biomineralization pathway as inspiration in his lab to guide the growth of minerals used in solar cells and lithium-ion [li-ion] batteries. By controlling the crystal size, shape and orientation of engineering nanomaterials, he believes he can build materials that will allow the solar cells and lithium-ion batteries to operate more efficiently. In other words, the solar cells will be able to capture a greater percentage of sunlight and convert it to electricity more efficiently and the lithium-ion batteries could need significantly less time to recharge.

Using the chiton teeth model has another advantage: engineering nanocrystals can be grown at significantly lower temperatures, which means significantly lower production costs.

While Kisailus is focused on solar cells and lithium-ion batteries, the same techniques could be used to develop everything from materials for car and airplane frames to abrasion resistant clothing. In addition, understanding the formation and properties of the chiton teeth could help to create better design parameters for better oil drills and dental drill bits.

Here’s a representation of the teeth from the University of California Riverside,

A series of images that show the teeth of the gumboot chiton (aka, snail, aka, wandering meatloaf)

A series of images that show the teeth of the gumboot chiton (aka, snail, aka, wandering meatloaf)

You can find other images and media materials in the ScienceDaily news item or the University of California Riverside news release. This citation and link for the research paper is from the ScienceDaily news item,

Qianqian Wang, Michiko Nemoto, Dongsheng Li, James C. Weaver, Brian Weden, John Stegemeier, Krassimir N. Bozhilov, Leslie R. Wood, Garrett W. Milliron, Christopher S. Kim, Elaine DiMasi, David Kisailus. Phase Transformations and Structural Developments in the Radular Teeth ofCryptochiton Stelleri. Advanced Functional Materials, 2013; DOI: 10.1002/adfm.201202894

This article is behind a paywall.