Team:HZAU-China/Description
Description
Background and inspiration
Dental enamel, the outermost layer of teeth, is the hardest and most mineralized tissue in vertebrates. Enamel is mainly composed of highly ordered and specially arranged hydroxyapatite which gives enamel its hard character [1]. Although enamel is very hard, there are many factors that can cause it to be damaged in our daily life, such as physical knock, acid erosion, and bacterial infection [2]. And our body itself can't repair the missing enamel [3]. Many dental diseases begin with enamel damage, such as dental caries, teeth sensitive, and fractured teeth.
These facts make us think: "Is there a way to repair our enamel and prevent teeth diseases?" The structure of enamel is dense and ordered, so normal repair fillers can’t reproduce the structure of natural enamel, and the properties of fillers are not as good as original enamel. However, hydroxyapatite biomineralization mediated by polypeptide LRAP self-assembly can produce an enamel repair layer with a natural structure and various properties similar to the original enamel [4-7].
Bacteria will secrete acidic substances to erode enamel when they are colonized on the surface of teeth, but LRAP is powerless for bacterial enamel damage. Therefore, in order to solve the problem of bacterial infection, we need to start from its source and find a method to sterilize bacteria. Streptococcus mutans is an early colony in teeth and one of the most harmful bacteria in the oral cavity [8]. In addition to secreting acidic substances, S. mutans can also produce biofilm for more harmful bacteria to colonize, and will cause dental caries. If we can treat S. mutans in the early stage of its colonization, we can limit the bacterial infection to a safe level. In order to repair the enamel damage caused by physical knock, acid erosion, and bacterial infection, we intend to use the power of synthetic biology to modify the bacterial cell to have the function of secreting LRAP on the enamel and treat S. mutans infection. These functions is switchable based on the user's situation of teeth. Collectively, we’ve designed an automatic and personalized enamel repair scheme.
Our project
The name of our project is "Tooth Fairy". Like a real guardian fairy, she will focus on the health of our teeth in real time and make corresponding responses through "Detection and Report" modules. In addition, she can switch between two modules, "Sterilization" which treats S. mutans infection, "Repair" which repairs enamel. Considering the safety problem, we also add a "Suicide" module to Tooth Fairy. These modules are briefly described in the following paragraphs.
Detection and Report
This module will act as a switch to help Tooth Fairy choose whether to repair the enamel or eliminate S. mutans. The module is based on a two-component system of S. mutans quorum sensing, ComDE. This two-component system perceives CSP (competence-stimulating peptide) produced by S. mutans and transmits the signal to downstream circuits [9]. If there are S. mutans around users’ teeth, Tooth Fairy can sense CSP and report different colors according to the concentration of S. mutans in oral environments, which can indicate the conditions of users’ teeth.
If there are no S. mutans around the teeth, our teeth will be in a "safe" state, and the Tooth Fairy will not give users a report. The direct relationship between high concentrations of S. mutans and increased rates of dental caries has been widely acknowledged [10]. And the enamel damage caused by dental caries is serious and difficult to be repaired by biological methods. Therefore, we take a high concentration of S. mutans as the basis for judging the condition of teeth. If the concentration of S. mutans is lower than this concentration, we think that the situation is "solvable", and Tooth Fairy will report "solvable" color to remind the users to pay attention to the oral condition and activate the "Sterilization" module. If the concentration of S. mutans is higher than this concentration, we think it is "dangerous", and Tooth Fairy will report "dangerous" color to remind the users to go to hospital to treat their caries.
Sterilization
When the bacterial infection of S. mutans is sensed by Tooth Fairy, the "Sterilization" module will be started together with the "Report" module. This module secretes the protein ClyR which is specific to S. mutans [11], which will destroy the biofilm formed by S. mutans on the teeth surface and kill S. mutans.
Repair
This module is the initial status of the Tooth Fairy. When the user does not have S. mutans in the teeth, the repair module automatically starts to repair enamel by secreting LRAP.
Suicide
We also added a suicide function to avoid the risk of the engineered bacteria entering the mouth, gastrointestinal tract, or leaking into the environment. If Tooth Fairy goes out the braces, the "suicide" module will start.
Actual implementation
"Teeth braces"
When we put the project into implementation, we will create special braces where Tooth Fairy inhabited. Users can wear the braces to make their enamel restored.
"Box"
Since Tooth Fairy produces fluorescent protein as a signal to the users, we need to active it with exciting light. In order to prevent the influence of ambient light at different time and places on the excitation of the fluorescent protein, we designed a hardware "Box" with exciting lamp.
"App"
Different people have different subjective judgments on colors. In order to prevent users from misjudging their own teeth conditions, we will provide a simple "App" for users, which can recognize subtle differences between colors and give feedbacks to users.
References
[1] Carneiro K M M, Zhai H, Zhu L, et al. Amyloid-like ribbons of amelogenins in enamel mineralization[J]. Scientific reports, 2016, 6(1): 1-11.
[2] Tanzer J M, Livingston J, Thompson A M. The microbiology of primary dental caries in humans[J]. Journal of dental education, 2001, 65(10): 1028-1037.
[3] Pandya M, Diekwisch T G H. Enamel biomimetics—fiction or future of dentistry[J]. International journal of oral science, 2019, 11(1): 1-9.
[4] Kwak S Y, Litman A, Margolis H C, et al. Biomimetic enamel regeneration mediated by leucine-rich amelogenin peptide[J]. Journal of dental research, 2017, 96(5): 524-530.
[5] Le Norcy E, Kwak S Y, Wiedemann-Bidlack F B, et al. Leucine-rich amelogenin peptides regulate mineralization in vitro[J]. Journal of dental research, 2011, 90(9): 1091-1097.
[6] Mukherjee K, Ruan Q, Moradian-Oldak J. Peptide-Mediated Biomimetic Regrowth of Human Enamel In Situ[M]//Odontogenesis. Humana Press, New York, NY, 2019: 129-138.
[7] Shafiei F, Hossein B G, Farajollahi M M, et al. Leucine‐rich amelogenin peptide (LRAP) as a surface primer for biomimetic remineralization of superficial enamel defects: an in vitro study[J]. Scanning, 2015, 37(3): 179-185.
[8] Vinogradov A M, Winston M T, Rupp C J, et al. Rheology of biofilms formed from the dental plaque pathogen Streptococcus mutans[J]. Biofilms, 2004, 1(1): 49-56.
[9] Federle M J, Morrison D A. One if by land, two if by sea: signalling to the ranks with CSP and XIP[J]. Molecular microbiology, 2012, 86(2): 241-245.
[10] Giacaman R A, Araneda E, Padilla C. Association between biofilm-forming isolates of mutans streptococci and caries experience in adults[J]. archives of oral biology, 2010, 55(8): 550-554.
[11] Xu J, Yang H, Bi Y, et al. Activity of the chimeric lysin ClyR against common Gram-positive oral microbes and its anticaries efficacy in rat models[J]. Viruses, 2018, 10(7): 380.
