Core technologies using generative AI in smart manufacturing of dental crowns

 

 

IMAGE: PROJECT CO-INVESTIGATOR DR HAO DING AND THE DESIGN OF A TOOTH CROWN USING GENERATIVE AI. (SMALL PHOTO) TOOTH TAILORED BY GENERATIVE AI. view more 

CREDIT: THE UNIVERSITY OF HONG KONG

Leading researchers from the Faculty of Dentistry at the University of Hong Kong (HKU) have developed a novel smart manufacturing on dental crowns by using generative artificial intelligence (AI) that leverage dental manufacturing technology.

The team, led by Dr James Tsoi, Associate Professor in Dental Materials Science collaborated with colleagues from HKU Faculty of Engineering’s Department of Computer Science to take a leap forward for the next-generation AI-designed dental prosthesis production workflow.

The researchers developed a generative AI algorithm that uses a true three-dimensional (3D) deep learning approach, producing personalised dental crowns with high accuracy that mimic the morphology and match the materials required for the biomechanics of natural teeth. Biomechanical finite element analysis revealed that by using lithium silicate, the AI-designed crown can come very close to achieving the expected lifespan of natural teeth. In contrast, the two existing methods of designing dental crowns result in crowns that are either too large or too thin, and fall short of matching the same lifespan as natural teeth.

The results have been published in leading academic journal Dental Materials in an article titled ‘Morphology and mechanical performance of dental crown designed by 3D-DCGAN’.

Currently, the Computer-Aided Design and Manufacturing (CAD/CAM) digital workflow has significantly improved dentistry but still has its challenges. From the design to the manufacture of dental prostheses, the process is labour-intensive, time-consuming, and generates health and environmental hazards during the 3D printing and milling processes. The software uses a ‘tooth library’ that contains predefined crown templates to assist in generating prosthetic designs but further adjustments are still needed by the operator to meet individual conditions.

The smart manufacturing method developed by the research team can meet the challenge and help replace the conventional approach to designing personalised dental crowns.

“We used a 3D-DCGAN (3D-Deep Convolutional Generative Adversarial Network) approach to ‘teach’ the AI algorithm ‘good’ designs by feeding the algorithm with over 600 cases of natural and healthy dentition. The algorithm improves the quality of the design through internal competition between a generator and a discriminator,” said Dr Hao Ding, a co-investigator on the project.

“During the training process, natural teeth morphological features were learned by the algorithm, so that it can design dental crowns comparable to a natural tooth — both morphologically and functionally.” Dr Ding added.

The 3D-DCGAN AI-designed crowns were compared with natural teeth and with two other conventional CAD methods of crown design methods. The results revealed that the generative AI-designed crowns had the lowest 3D discrepancy, closest cusp angle (morphological feature), and similar occlusal contacts (functional feature) as compared to natural teeth.

“This demonstrates that 3D-DCGAN could be utilised to design personalised dental crowns with high accuracy that can not only mimic both the morphology and biomechanics of natural teeth, but also operate without any additional human fine-tuning, thus saving additional costs in the production process,” said principal investigator Dr James Tsoi.

“Many AI approaches design a ‘look alike’ product, but I believe this is the first project that functionalise data-driven AI into real dental application. We hope this smart manufacturing technology will be the stepping-stone for driving Industry 4.0 in dentistry, which is vital to meet the challenges of ageing society and lack of dental personnel in Hong Kong.” He added.

Dr Tsoi said the breakthrough marks an important step towards leveraging the dental industry in Great Bay Area, which sees an annual USD3.3B revenue for producing 25-30% dental prosthesis globally, and to align with the National 14th Five-year plan in developing new forms of industrialisation and informatisation viz. smart intelligent manufacturing.

Clinical trials for using this generative AI for dental crowns are underway. The team is also working on the applicability of this tool in other dental prostheses such as bridges and dentures.

The study was supported by the General Research Fund (GRF), the Innovation and Technology Fund Mainland-Hong Kong Joint Funding Scheme (ITF-MHKJFS), and the Health and Medical Research Fund (HMRF). Its preliminary results were presented by Dr Hao Ding at the 35th Annual Scientific Meeting of the International Association of Dental Research (IADR) Southeast Asia (SEA) and it was awarded the leading IADR-SEA Research Category Award (Dental Materials and Biomaterials Category) in 2021.

The article in Dental Materials titled ‘Morphology and mechanical performance of dental crown designed by 3D-DCGAN’  published in Dental Materials, can be accessed through this link. 

Novel antibiotic-delivery system to target aggressive gum infections in adolescents

 

IMAGE: ANGELA BROWN, AN ASSOCIATE PROFESSOR OF CHEMICAL AND BIOMOLECULAR ENGINEERING IN LEHIGH UNIVERSITY’S P.C. ROSSIN COLLEGE OF ENGINEERING AND APPLIED SCIENCE, RECEIVED AN EXPLORATORY/DEVELOPMENT RESEARCH GRANT AWARD (R21) FROM THE NIH TO DEVELOP A NONSURGICAL DRUG DELIVERY SYSTEM THAT WILL ENABLE THE CONTROLLED DELIVERY OF ANTIBIOTICS TO TREAT AGGRESSIVE PERIODONTITIS IN ADOLESCENTS. view more 

CREDIT: LEHIGH UNIVERSITY

Aggressive periodontitis is a severe type of gum infection that causes the destruction of ligament and bone and can lead to tooth loss in otherwise healthy individuals. Traditional treatment typically involves deep cleaning and antibiotics. 

Lehigh University researcher Angela Brown and her team were recently awarded a grant from the National Institutes of Health (NIH) to pursue a novel treatment alternative. 

Brown, an associate professor of chemical and biomolecular engineering in Lehigh’s P.C. Rossin College of Engineering and Applied Science, received an Exploratory/Development Research Grant Award (R21) to develop a nonsurgical drug delivery system that will enable the controlled delivery of antibiotics to treat aggressive periodontitis in adolescents. According to the NIH, R21 grants are meant to encourage research in high risk/high reward areas that could lead to significant breakthroughs or yield novel techniques, methods, and applications that will benefit biomedical, behavioral, or clinical research. 

“The way these infections are typically treated is by scaling and planing, which essentially means scraping off the bacteria, and then prescribing oral antibiotics,” says Brown. “And while that tends to work, sometimes the bacteria come back, and then you have to start the course of antibiotics all over again. The more frequently you take antibiotics, the greater the chances the bacteria will become resistant to them.” 

Antibiotic resistance is indeed a growing problem. According to the Centers for Disease Control and Prevention, more than 2.8 million antimicrobial-resistant infections occur every year in the U.S., and more than 35,000 people die as a result.

In previous work, Brown and her team have shown that antibiotics can be encapsulated in liposomes—tiny, round vesicles that contain one or more membranes and can be used as a delivery mechanism. They’ve also shown that the toxin released by the periodontitis-causing bacteria, called leukotoxin, triggers the release of the antibiotics.

“Leukotoxin fights the body’s immune response by binding with cholesterol in the membrane of white blood cells, disrupting the membrane and killing the cells,” she says. “So we’re creating a liposome that has cholesterol, and we’re hoping that all or most of the toxin will bind onto the liposome instead of the host cells,” says Brown. “When the toxin binds to the liposome, it should cause a release of the antibiotics, killing the disease-causing bacteria.”

This grant will support the cell culture work her lab will perform to determine if the approach can protect the host cells from the toxin while simultaneously killing the bacterial cells. They will do this using a "co-culture" model, in which human immune cells and bacterial cells are grown together. 

The ultimate goal, she says, is to provide an alternative method of delivering antibiotics to treat aggressive periodontitis. 

“We’d also like to continue showing the advantages of using controlled delivery strategies for antibiotics,” she says. “And because this toxin we’re working with is closely related to those that cause diseases like whooping cough and cholera and E. coli infections, this approach could be useful against a range of bacteria.”

Brown has been working with leukotoxins since she was a postdoctoral student. At that time, she was focusing on how the toxin interacted with the cell membrane. Her research team found that when they encapsulated fluorescent dye inside a cell, the toxin caused the release of the dye.

“Because I’m an engineer, I had this thought, Okay, now that we know the toxin has that effect, how can we use that?” she says. “It was just a vague idea back then, but I was thinking about how cool it would be if we could encapsulate antibiotics inside cells.”

Years later, the vague idea became real. One of her master’s students, Ziang Li—now a PhD student co-advised by both Brown and Professor Steve McIntosh, who chairs Lehigh’s chemical and biomolecular engineering department—wanted to research drug delivery mechanisms.

“At the time, it wasn’t something our lab was doing, but I said to him, ‘I have this crazy idea, do you want to try it?’”

With significant support from a Lehigh Faculty Innovation Grant, Li was able to collect the preliminary data that ultimately led to the NIH funding.

“Looking at different delivery strategies for antibiotics represents a new direction for my lab,” she says. “This is our first externally funded project to do this work, and it validates the idea that this approach has a lot of potential to solve problems with both disease and with antibiotic resistance.”    

Research reported in this story is supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health under award number R21DE032153.

Related Links

• Faculty Profile: Angela Brown
• NIH RePORTER (R21DE032153): "Controlled antibiotic delivery vehicle for treatment of aggressive periodontitis"

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Gum disease may lie at the root of some arthritis flare-ups

 NEWS RELEASE 17-APR-2023

Peer-Reviewed Publication

ROCKEFELLER UNIVERSITY

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IMAGE: BLOOD VESSELS IN THE SOFT TISSUE BETWEEN JOINTS, DURING A RHEUMATOID ARTHRITIS FLARE-UP. view more 

CREDIT: LABORATORY OF MOLECULAR NEURO-ONCOLOGY AT THE ROCKEFELLER UNIVERSITY

It’s a well-documented medical mystery: Patients with gum disease are less likely to respond to rheumatoid arthritis treatments. But new research may help explain this link between gum disease and an otherwise disparate condition. The findings, published in Science Translational Medicine, suggests that breaches in damaged gums allow bacteria in the mouth to seep into the bloodstream, activating an immune response that ultimately pivots to target the body’s own proteins and causes arthritis flare-ups.

“If oral bacteria are getting in and repeatedly triggering immune responses relevant to rheumatoid arthritis, that could make it harder to treat,” says Dana Orange, a professor of clinical investigation in the laboratory of Robert B. Darnell at The Rockefeller University. “When doctors encounter arthritis patients who do not respond to treatment, it would be worth it to make sure they aren’t missing an underlying gum disease, which is quite treatable.”

The Darnell lab had been following a small group of arthritis patients over the course of several years, collecting weekly blood samples and looking for changes in gene expression to help explain why painful flare-ups occur, when they noticed a surprising trend. Two of their patients, who had moderate to severe periodontal disease, had repeated episodes of oral bacteria in their bloodstreams, even when they weren’t having dental work.

Orange knew that rheumatoid arthritis patients generally have autoantibodies in their bloodstream (rheumatoid arthritis is an auto-immune disease, wherein antibodies attack the body’s own proteins and peptides). In many cases, autoantibodies take specific aim at proteins bearing the signs of citrullination, a process by which one amino acid in the protein is converted into a different one.

Upon further examination, the team discovered that the oral bacteria they detected in the blood are also citrullinated in the mouth, much like the proteins targeted by autoantibodies in arthritis. They then demonstrated that the same autoantibodies that take potshots at the body’s citrullinated proteins activate in response to citrullinated bacteria.

The results may explain why arthritis treatments do not work as well in patients with gum disease. If the gums are continuously releasing immune triggers into the bloodstream, treating arthritis without first solving the periodontal problem is like trying to haul water out of a ship without first plugging up its leaks.

“Gum disease is quite curable; rheumatoid arthritis can be much more difficult to treat,” Orange says. “Our results indicate that periodontal disease leads to leaky gums that allow oral bacteria to enter the blood repeatedly. This level of oral bacteria in blood doesn’t cause obvious symptoms, so the patients were not aware this was happening, but they do trigger inflammatory and auto-antibody responses that are highly relevant to rheumatoid arthritis.”

These findings also demonstrate the importance of conducting long-term research to better understand chronic diseases. The present study would not have been possible without a unique initiative, pioneered by Orange and Darnell several years ago, that empowers arthritis patients to collect their own blood samples at home with a finger-prick kit and mail weekly samples to Rockefeller. The lab now has several years of data to help track what happens in the blood right before an arthritis flare.

“Without having weekly blood samples for at least a year, we wouldn’t have been able to find out what was happening before the patients had symptoms of their flares,” Orange says. “Our study revealed a plausible mechanism to explain why rheumatoid arthritis patients with periodontal disease do not respond well to treatment—something very hard to capture without long-term monitoring.”

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JOURNAL

Science Translational Medicine

DOI

10.1126/scitranslmed.abq8476 

ARTICLE TITLE

Oral mucosal breaks trigger anti-citrullinated bacterial and human protein antibody responses in rheumatoid arthritis