No wonder many people fear the dentist. Replacing a tooth often requires invasive surgery to implant a titanium screw into the patient’s jaw, then wait several months for it to harden into an artificial root, and then attach a crown or cap to it.
However, research groups around the world are looking for ways to implant or grow real biological teeth in the human jaw.
That may be an option, but Ana Angelova Volponi, director of the postgraduate program in regenerative dentistry at King’s College London, has been experimenting with lab-grown teeth for nearly two decades and was part of the team that in 2013 grew a tooth from human and mouse cells.
This year, she led research that built on that work and made a breakthrough using a material used to hold growing teeth in the lab that better mimics the real environment in which biological teeth grow in the mouth. This is a key step in replacing mouse cells with human cells and encouraging them to form a tooth.
The idea of creating lab-grown teeth dates back to the 1980s, Volponi said, but the one she and her colleagues created a decade ago was the first to use adult human gingival cells, which make up gums and are obtained by easily scratching the inside of the mouth, and combine them with “progenitor” tooth cells taken from a mouse stem.
“It’s almost like a tripod,” she said of the elements that go into growing a tooth in the lab. “Two types of cells are engaged in tooth formation, some kind of conversation, and then we have an environment where that happens.
The environment, which scientists call “scaffolding,” is essential for a lab-grown tooth to form, and it’s the subject of Volponi’s latest research. in 2013 Volponi used a scaffold made from the protein collagen, but now uses a hydrogel, a type of polymer that contains a lot of water, explained Xuechen Zhang, a doctoral student at King’s College London and co-author of the study. “We first collect cells from mouse embryos, then we mix them and spin them down to get a pellet of small cells,” he said. “We then inject this cell deposit into the hydrogel and grow it for about eight days. Because the work was focused on the environment, no human cells are needed.”
After eight days, the hydrogel, which was developed in collaboration with Imperial College London, will form tooth-like structures. in 2013 in the study, these “tooth rudiments” were transferred to a mouse, where a tooth structure developed with developing roots and enamel.
Xuechen Zhang and ana Angelova Volponi in the lab at King’s College London. – Liqun Xu
Many challenges remain before a lab-grown tooth can be used in humans, but the new material helps tackle some pieces of that puzzle, Volponi said, by improving the “conversation” between the cells tasked with making the tooth.
Researchers still don’t know exactly how to replace embryonic mouse cells with adult human cells, but if that puzzle is solved, Volponi envisions two possible ways to integrate lab-grown teeth into everyday dentistry: “We either grow the tooth to a certain stage of development, and then we insert it into the (tooth socket) where the tooth was lost, and where the new tooth will grow in completely. structures such as bone and ligament. Or we first fully grow the tooth and then implant it surgically. It is too early to say which method will be more promising.
Advantages of real teeth
A real, biological replacement tooth grown from the patient’s own cells would have many advantages over a crown or implant. First, it would be accepted into the tissue without inflammation or rejection, but would also feel like a real tooth – unlike implants, which lack feel and elasticity because they simply fuse with bone.
According to Vitor CM Neves, a senior clinical lecturer at the School of Clinical Dentistry at the University of Sheffield in England, Volponi has long been a pioneer in whole tooth regeneration, inspiring many researchers around the world. “Her new study addresses a key factor in the production and potential industrialization of this technology, the use of matrices to regenerate a whole tooth,” said Neves, who was not involved in Volponi’s research.
He added that the findings highlight the importance of creating an environment that can support all dental engineering for clinical applications: “The more scientists contribute to the advancement of this field, the sooner humanity can reap its benefits.”
Other researchers working in the same field use different methods to grow teeth.
Katsu Takahashi and his colleagues at Osaka Medical Research Institute’s Kitano Hospital are developing an antibody-based treatment that aims to stimulate tooth growth in people with conditions such as anodontia, or congenitally missing teeth. The treatment has begun clinical trials in humans and could be ready by the end of the decade.
in 2024 At the end of last year, a team led by Pamela Yelick from the Tufts University School of Dental Medicine grew human-like teeth in pigs, created from human and pig cells. Pigs, unlike humans, regrow their teeth several times during their lifetime. The ultimate goal is to stimulate human jaw cells to grow new teeth without using pig cells.
At the University of Washington, a team led by Hannele Ruohola-Baker, professor of biochemistry and associate director of the university’s Institute for Stem Cell and Regenerative Medicine, has successfully grown dental pulp stem cells from human stem cells extracted from donated wisdom teeth: “We aim to unravel the molecular process of formation and restore the human creative project. “Although Volponi’s research creates tooth-like structures from existing tooth tissue, our platform creates the basic types of human tooth-forming cells (from scratch) and directs them along authentic developmental trajectories.
As for when the fruits of all this research will be available, Ruohola-Baker thinks we won’t have to wait that long. “While clinical translation will take time, momentum in the field is accelerating, which bodes well for a future where biological tooth repair or replacement will become a viable option within the next decade,” she said.
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