Startup’s Prototype Gel Regrows Enamel and Halts Decay

02 Dec 2016
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This is a scanning electron microscope image of newly grown enamel using amelogenin-chitosan hydrogel. This is a scanning electron microscope image of newly grown enamel using amelogenin-chitosan hydrogel. Photo by Herman Ostrow School of Dentistry of USC.

Tooth decay remains a key challenge for general practitioners. Drilling and filling doesn’t have to be the only answer, though. A startup company called Auxomel formed at the University of Southern California (USC) Herman Ostrow School of Dentistry is developing a peptide-gel prototype to regrow superficial human tooth enamel and slow decay. 

The university recently recognized Auxomel with an award for innovation at the USC Stevens Student Innovator Showcase, an annual competition that gives the school’s entrepreneurs an opportunity to present their ideas to the business community. Auxomel also won the Venture Validation award sponsored by the Lloyd Greif Center for Entrepreneurial Studies at the USC Marshall School of Business.

The fledgling company will use the $10,000 Stevens Student Innovator and the $2,500 Venture Validation prizes to fund the clinical translation and commercialization of its prototype. Kaushik Mukherjee, a graduate researcher with the Ostrow School of Dentistry’s Center for Craniofacial Molecular Biology and a member of the Auxomel team, shared his insights about the startup’s work with Dentistry Today

Q: Mature enamel doesn’t regrow. Why is this an issue in terms of oral health?

A: The failure of tooth enamel to regenerate after exposure to a microbial attack in the mouth predisposes it to an irreversible state of tissue destruction. Dental diseases have an economic impact amounting to billions of dollars annually, particularly affecting young children. In the United States alone, 92% of adults aged 20 to 64 years have had dental decay in their permanent teeth. Hence, designing innovative approaches aimed at repairing superficial enamel defects is imperative to advancing dental material science and curbing the progression of dental caries, or tooth decay.

Q: What can you tell us about your peptide-gel prototype, and how does it solve this problem? 

A: We have developed a peptide-gel prototype that mimics natural enamel-forming proteins (amelogenin) to repair superficial enamel defects. When applied on dental lesions, it entraps calcium and phosphorous mineral ions from natural saliva to form a highly oriented enamel-like mineralized layer that restores up to 80% of the hardness of healthy enamel. These peptides can infiltrate the pores created by the acidic dissolution of enamel by microbes and recover the lost minerals. The major value propositions for our prototype are that it’s a pain-free, non-invasive, speedier, preventive strategy that restores diseased tooth structure and confers significant mechanical strength to the repaired tissue. Currently, other preventive strategies such as fluorides, which have been routinely used for decades, have proven ineffective in treating patients at high carious risk.

Q: What previous work led you to this hypothesis? 

A: Our study is based on the fact that amelogenin, the most predominant protein in the enamel matrix, plays a vital role in regulating the orientation and elongated growth of enamel crystals. The initial project was spearheaded by professor Janet Moradian-Oldak, MSc, PhD, and postdoctoral research associate Qichao Ruan, PhD, at USC, who developed a novel amelogenin-chitosan hydrogel to treat artificially induced tooth decay in sectioned human molars.

I started working closely with Dr. Oldak in 2014 towards making this methodology clinically viable. Inspired by the functional role of native amelogenin in orchestrating enamel mineralization and based on a critical understanding of its active domains, we designed 2 smaller amelogenin-inspired peptides. The objective was to evaluate the mineralization efficacy of the smaller synthetic peptides while drawing comparison to their full-length natural counterparts.

Q: Could you tell us about some of the experiments or trials you performed in developing your gel? 

A: The first step was developing the amelogenin-chitosan hydrogel. Once we had this material, we started to optimize the treatment protocol by testing different parameters such as the protein concentration and gel viscosity. We first investigated how well the hydrogel stimulated the growth of synthetic enamel on a section of a tooth outside of the body, in artificial saliva under different conditions, to evaluate the structure, attachment, and mechanical properties of the newly grown mineral. From there, we designed smaller amelogenin-inspired peptides for clinical translation. One key step was the addition of matrix metalloproteinase-20 (MMP-20) proteolytic enzyme that degrades the amelogenin protein, creating spaces to enable the volumetric expansion of enamel-like crystals. This eventually forms a highly mineralized layer composed of hydroxyapatite crystals, the principal ingredient of tooth enamel.

Q: What led you to make the jump from research to startup? 

A: The lack of a robust treatment strategy to combat the silent epidemic of dental caries motivated us to develop a gel-based prototype and assess its commercial readiness for the global market. Based on valuable input from financial advisers and dental specialists, we created a business model canvas that gave us a positive indication of the potential impact of our innovation globally. Hence, we would like to keep the window of opportunity open and consider a potential startup.

Q: What is the next step for Auxomel? 

A: Right now, our next step is to complete efficacy tests to compare our product with what is commercially available in the market. It will also be very important to conduct cytotoxicity tests to demonstrate the biocompatibility of the peptide-based gel in the oral environment. We are also pursuing regulatory requirements for US Food and Drug Administration approval, which is a necessary step towards the design of our clinical trials.

Using this gel application, we would like to target initial signs of dental caries (white spot lesions), dentin hypersensitivity, and root caries. We are currently investigating the application of peptides in deeper lesions extending to the dentin and cementum. Compared to enamel, dentin poses a greater challenge in guiding mineralization due to a more complex organic matrix that delays the kinetics and growth of residual crystals.

Q: Finally, how do you anticipate dentists using the gel in their treatment? 

A: The gel could be loaded on a customized tray for overnight application at home. Alternatively, we have also considered a method of directly applying the peptides to a defect during a dental office visit. Clinical trials will give us a clearer picture as to which of the 2 strategies would work best.

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