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Tooth bioengineering: challenges and opportunities
Despite the advances made in dental treatment, tooth loss remains one of the most significant problems. Caries and periodontitis are thought to be the main reasons of tooth loss. Complete loss of teeth in particular is widespread among the elder people. Globally, about 30% of people aged between 65–74 years do not have teeth due to inflammatory periodontal diseases and pathology of hard dental tissues.
Therefore, it is not surprising that the state of the oral cavity in the population around the world is a serious problem, which offers opportunities both for studying and for finding new ways of treatment.
The main disadvantage of our teeth is that they grow only from two groups of buds formed during the period of prenatal development. Temporary crowns appear from the first group, while permanent ones from the second. After the loss a permanent tooth can be replaced only with “artificial crown”, which cannot fully perform natural functions, and what is more, the procedure cannot fit everyone.
In order to compensate for the functions of a lost tooth, dental prothese and implants are used now. But these are “artificial” substitutes: they lack blood vessels, nerve endings, receptors. Also one of the most important aspects is the absence of a periodontal ligament in the implant, which is still considered to be the gold standard of treatment in the absence of teeth.
All these shortcomings prompted scientists to the idea of growing human teeth. After a large amount of research and experimentation, it became possible to grow a tooth.
Growing teeth is a bioengineering technology with the ultimate goal to create or re-create new teeth in a person or an animal.
Let us briefly review the history of the development of tissue engineering in dentistry. The first developments on this project were launched in England in 2002. For their experiment, a group of scientists used six-month-old piglets and rats . Based on previous studies, the experiment was continued by scientists from the University of Science in Tokyo in 2007. Takashi Tsuji and his colleagues were able to grow new teeth and successfully implant them in young mice. The newly grown organs fully fulfilled their functions. They had formed dental tissues, however, they lacked a root part. The best result was achieved by the same group in 2009. For their research Tokyo scientists used another technology, which was different from the one used previously. To form a tooth germ, they took the mouse cells, which are responsible for the development and growth of the teeth, and stimulated their growth in the collagen medium. After that the tooth germs were replaced to the place of the removed crowns. In their place, normal teeth grew with a full-fledged crown and root part. During their growing, a neurovascular bundle was formed in the pulp, which is responsible for further feeding the dental tissue.
Genes.
For the identification of the gene responsible for the growth of teeth, scientists of the University of Zurich undertook. They found that the Jagged2 gene and a part of the chromosome called Notch are responsible for these processes. It was found that in the absence of the activity of this gene, Notch begins to work with pronounced errors.
The rudiments of stem cells.
Professor Mitsiadis, after a detailed study of the dependence of gene activity and the development of primordia, revealed that the genes responsible for their formation are actively involved in the production of dental tissue stem cells. These cells are the only ones that have the ability to repair damaged cells of the body, replacing them by their division. To form a crown, the stem cell is placed in an empty alveolar well and left alone. Over time, a new germ is formed there, and then a tooth. At the same time, the growth process is accompanied by the same feelings as in childhood. The shape of the crown and root do not differ from real teeth.
The only nuance of this method is that with age, the number of stem cells is hopelessly reduced. If under the age of 25 years you can find one such cell per 100 thousand, then for 50 years one cell accounts for 500 thousand. In addition, the process of collecting material for cell isolation is very painful. Therefore, at the moment, scientists are more engaged in developing methods that would allow the material to be taken more efficiently and less painfully.
2 main methods of growing teeth have been developed:
1) Internal.
This method involves growing directly in the oral cavity of a person. The internal method was developed by a Ukrainian scientist and consists in the introduction of stem cells into empty alveolar wells.
2) External.
The external method involves the formation of a tooth outside the oral cavity and then its further introduction into the well of the alveolar bone for engraftment. For this it is offered to use two methods of cultivation:
2.1) In organic culture. For this purpose, cells of the primitive type are used: mesenchymal and epithelial. The combination of these cells is placed in the collagen scaffold to form the bud. Then the bud is transferred to an organic culture and after 2 weeks a tooth with enamel, dentin, blood vessels and pulp is obtained.
2.2) In a special test tube. In this case exactly the same cells and the principle of the formation of the germ are used, but in the future the germ is placed not in organic matter, but in a capsule. In order to ensure the growth of the crown, the capsule is inserted into the liver of the mouse. The timing of the formation of the tooth in this case has no difference from the first method.
Disadvantages.
Despite the success of all recent research, these studies still have not received active developments. This is primarily due to the side effects that may accompany this procedure. When a tooth is replanted or grown, it is impossible to control the growth rate of each of its elements. In a normal process, the neurovascular bundle should develop at the same pace as dentin. Otherwise, you can get the pathological crown initially, which can affect both the health of the oral cavity, and any system of the body. There is also a problem with the body's immune response to the cells being injected. Perceiving them as foreign bodies, the immunity will reject them in every possible way.
However, inspired by a positive result, Tokyo scientists took up further study of this area. And there is no doubt that in the near future bioengineering of teeth will become an integral part of standard protocols for the treatment of dental lesions. The scale and pace of research has allowed scientists to assume that, closer to 2030, the method of growing a person’s teeth will become widespread and gradually supplant prosthetics and implantation. And it is important to remember that methods developed in accordance with the requirements and tasks of tooth bioengineering will be able to spur the development of new approaches in the regeneration of other tissues and organs and thus contribute to the progress not only in dentistry, but also in the field of regenerative medicine in general.
