Microbes That Cause Cavities Can Form Superorganisms Able to ‘Crawl’ and Spread On Teeth

by Katherine Unger Baillie

Hyun (Michel) Koo

A cross-kingdom partnership between bacteria and fungi can result in the two joining to form a “superorganism” with unusual strength and resilience. It may sound like the stuff of science fiction, but these microbial groupings are very much part of the here and now.

Found in the saliva of toddlers with severe childhood tooth decay, these assemblages can effectively colonize teeth. They were stickier, more resistant to antimicrobials, and more difficult to remove from teeth than either the bacteria or the fungi alone, according to the research team, led by University of Pennsylvania School of Dental Medicine scientists.

What’s more, the assemblages unexpectedly sprout “limbs” that propel them to “walk” and “leap” to quickly spread on the tooth surface, despite each microbe on its own being non-motile, the team reported in the journal Proceedings of the National Academy of Sciences

“This started with a very simple, almost accidental discovery, while looking at saliva samples from toddlers who develop aggressive tooth decay,” says Hyun (Michel) Koo, a professor at Penn Dental Medicine and a co-corresponding author on the paper. “Looking under the microscope, we noticed the bacteria and fungi forming these assemblages and developing motions we never thought they would possess: a ‘walking-like’ and ‘leaping-like’ mobility. They have a lot of what we call ‘emergent functions’ that bring new benefits to this assemblage that they could not achieve on their own. It’s almost like a new organism—a superorganism—with new functions.”

Read the full story in Penn Today.

Hyun (Michel) Koo is a professor in the Department of Orthodontics and the divisions of Community Oral Health and Pediatric Dentistry in the School of Dental Medicine, co-founder of the Center for Innovation & Precision Dentistry (CiPD) at the University of Pennsylvania, and member of the Penn Bioengineering Graduate Group.

Applying Microrobotics in Endodontic Treatment and Diagnostics

by Beth Adams

Controlled and actuated by magnetic fields, these mircrorobots are capable of precisely targeting the apical region — the opening where blood vessels and nerve enter the tooth — in a root canal.

With its irregularities and anatomical complexities, the root canal system is one of the most clinically challenging spaces in the oral cavity. As a result, biofilm not fully cleared from the nooks and crannies of the canals remains a leading cause of treatment failure and persistent endodontic infections, and there are limited means to diagnose or assess the efficacy of disinfection. One day, clinicians may have a new tool to overcome these challenges in the form of microrobots.

In a proof-of-concept study, researchers from Penn Dental Medicine and its Center for Innovation & Precision Dentistry (CiPD), have shown that microrobots can access the difficult to reach surfaces of the root canal with controlled precision, treating and disrupting biofilms and even retrieving samples for diagnostics, enabling a more personalized treatment plan. The Penn team shared their findings on the use of two different microrobotic platforms for endodontic therapy in the August issue of the Journal of Dental Research; the work was selected for the issue’s cover.

“The technology could enable multimodal functionalities to achieve controlled, precision targeting of biofilms in hard-to-reach spaces, obtain microbiological samples, and perform targeted drug delivery, ” says Dr. Alaa Babeer, lead author of the study and a Penn Dental Medicine Doctor of Science in Dentistry (DScD) and endodontics graduate, who is now within the lab of Dr. Michel Koo, co-director of the CiPD .

In both platforms, the building blocks for the microrobots are iron oxide nanoparticles (NPs) that have both catalytic and magnetic activity and have been FDA approved for other uses. In the first platform, a magnetic field is used to concentrate the NPs in aggregated microswarms and magnetically control them to the apical area of the tooth to disrupt and retrieve biofilms through a catalytic reaction. The second platform uses 3D printing to create miniaturized helix-shaped robots embedded with iron oxide NPs. These helicoids are guided by magnetic fields to move within the root canal, transporting bioactives or drugs that can be released on site.

“This technology offers the potential to advance clinical care on a variety of levels,” says Dr. Koo, co-corresponding author of the study with Dr. Edward Steager, a senior research investigator in Penn’s School of Engineering and Applied Science. “One important aspect is the ability to have diagnostic as well as therapeutic applications. In the microswarm platform, we can not only remove the biofilm, but also retrieve it, enabling us identify what microorganisms caused the infection. In addition, the ability to conform to the narrow and difficult-to-reach spaces within the root canal allows for a more effective disinfection in comparison to the files and instrumentation techniques presently used.”

Continue reading at Penn Dental Medicine News

Michel Koo is a professor in the Department of Orthodontics and divisions of Community Oral Health and Pediatric Dentistry in Penn Dental Medicine and co-director of the Center for Innovation & Precision Dentistry. He is a member of the Penn Bioengineering Graduate Group.

Penn Dental Medicine, Penn Engineering Award First IDEA Prize to Advance Oral Health Care Innovation

Henry Daniell and Daeyeon Lee

by Beth Adams

Penn Dental Medicine and Penn Engineering, which teamed earlier this year to launch the Center for Innovation and Precision Dentistry (CiPD), recently awarded the Center’s first IDEA (Innovation in Dental Medicine and Engineering to Advance Oral Health) Prize. Dr. Henry Daniell, W.B. Miller Professor and Vice Chair in the Department of Basic & Translational Sciences at Penn Dental Medicine, and his collaborator, Dr. Daeyeon Lee, Professor of Chemical and Biomolecular Engineering at Penn Engineering, are the inaugural recipients, awarded the Prize for a project titled “Engineered Chewing Gum for Debulking Biofilm and Oral SARS-CoV-2.”

“The IDEA Prize was created to support Penn Dental and Penn Engineering collaboration, and this project exemplifies the transformative potential of this interface to develop new solutions to treat oral diseases,” says Dr. Michel Koo, Professor in the Department of Orthodontics and Divisions of Pediatric Dentistry and Community Oral Health at Penn Dental Medicine and Co-Director of the CiPD.

“The prize is an exciting opportunity to unite Drs. Lee and Daniell and their vision to bring together state-of-the-art functional materials and drug-delivery platforms,” adds Dr. Kathleen Stebe, CiPD Co-Director and Goodwin Professor of Engineering and Applied Science at Penn Engineering.

Open to faculty from Penn Dental Medicine and Penn Engineering, the IDEA Prize, to be awarded annually, supports collaborative teams investigating novel ideas using engineering approaches to kickstart competitive proposals for federal funding and/or private sector/industry for commercialization. Awardees are selected based on originality and novelty; the impact of the proposed innovation of oral/craniofacial health; and the team composition with complementary expertise. Indeed, the project of Drs. Daniell and Lee reflects all three.

The collaborative proposal combines Dr. Daniell’s novel plant-based drug development/delivery platform with Dr. Lee’s novel polymeric structures to create an affordable, long-lasting way to reduce dental biofilms (plaque) and oral SARS-CoV-2 transmission using a uniquely consumer-friendly delivery system — chewing gum.

“Oral diseases afflict 3.5 billion people worldwide, and many of these conditions are caused by microbes that accumulate on teeth, forming difficult to treat biofilms,” says Dr. Daniell. “In addition, saliva is a source of pathogenic microbes and aerosolized particles transmit disease, including COVID-19, so there is an urgent need to develop new methods to debulk pathogens in the saliva and decrease their aerosol transmission.”

Continue reading at Penn Dental Medicine News.

N.B. Henry Daniell and Daeyeon Lee are members of the Penn Bioengineering Graduate Group.

Penn Dental, Penn Engineering Unite to Form Center for Innovation & Precision Dentistry

by Beth Adams

With the shared vision to transform the future of oral health care, Penn Dental Medicine and Penn’s School of Engineering and Applied Sciences have united to form the Center for Innovation & Precision Dentistry (CiPD). The new Center marked its official launch on January 22 with a virtual program celebrating the goals and plans of this unique partnership. Along with the Deans from both schools, the event gathered partners from throughout the University of Pennsylvania and invited guests, including the National Institute of Dental and Craniofacial Research Director (NIDCR) Dr. Rena D’Souza and IADR Executive Director Chris Fox.

Conceived and brought to fruition by co-directors Dr. Michel Koo of Penn Dental Medicine and Dr. Kathleen Stebe of Penn Engineering, the CiPD is bridging the two schools through cutting-edge research and technologies to accelerate the development of new solutions and devices to address unmet needs in oral health, particularly in the areas of dental caries, periodontal disease, and head and neck cancer. The CiPD will also place a high priority on programs to train the next generation of leaders in oral health care innovation.

“We have a tremendous global health challenge. Oral diseases and craniofacial disorders affect 3.5 billion people, disproportionately affecting the poor and the medically and physically compromised,” says Dr. Koo, Professor in the Department of Orthodontics and Divisions of Community Oral Health and Pediatric Dentistry, in describing their motivation to form the Center. “There is an urgent need to find better ways to diagnose, prevent, and treat these conditions, particularly in ways that are affordable and accessible for the most susceptible populations. That is our driving force for putting this Center together.”

“We have united our schools around this mission,” adds Dr. Stebe, Richer & Elizabeth Goodwin Professor in the Department of Chemical and Biomolecular Engineering. “We have formed a community of scholars to develop and harness new engineering paradigms, to generate new knowledge, and to seek new approaches that are more effective, precise, and affordable to address oral health. More importantly, we will train a new community of scholars to impact this space.”

Born through Interdisciplinary Research

A serendipitous connection born through Penn’s interdisciplinary research environment itself brought Drs. Koo and Stebe together more than five years ago, an introduction that would eventually lead to creating the CiPD.

Dr. Tagbo Niepa, now assistant professor at the University of Pittsburgh, came to Penn Engineering in 2014 as part of Penn’s Postdoctoral Fellowship for Academic Diversity, an initiative from the office of the Vice Provost for Research. His studies on the microbiome led him to reach out to Dr. Stebe and Dr. Daeyeon Lee (also at Penn Engineering), and to connect them to Dr. Koo, initiating collaboration between their labs.

“Tagbo embodies what we are trying to do with the CiPD,” recalls Dr. Stebe. “He had initiative, he identified new tools and important context, and he did good science that may help us understand how to interrupt the disease process and identify new underlying mechanisms that can inspire new therapies.” Dr. Niepa worked on applying microfluidics and engineering to study the oral microbiome and better understand how the interactions between fungi and bacteria could impact dental caries.

“Upon meeting Michel, we became excited about the possibilities of bringing talent from the two schools together,” notes Dr. Stebe. A 2018 workshop organized by Drs. Koo and Stebe and funded by Penn’s Vice Provost of Research explored the potential for expanding cross-school research. “We invited researchers from dental medicine and engineering as well as relevant people from the arts and sciences to see if we could find a way to collaborate to advance oral and craniofacial health,” says Dr. Koo. “That was the catalyst for the Center; after the workshop, we put together a task force which would become the core members of the CiPD.”

In addition to Drs. Koo and Stebe, the CiPD Executive Committee includes Associate Directors Dr. Henry Daniell, Vice-Chair and W.D. Miller Professor, Department of Basic & Translational Sciences, Penn Dental Medicine, and Dr. Anh Le, Chair and Norman Vine Endowed Professor of Oral Rehabilitation, Department of Oral and Maxillofacial Surgery / Pharmacology, Penn Dental Medicine; as well as Dr. Andrew Tsourkas, Professor, Department of Bioengineering, Co-Director, Center for Targeted Therapeutics & Translational Nanomedicine (CT3N) and Chemical and Nanoparticle Synthesis Core, Penn Engineering; and Dr. Jason Moore, Edward Rose Professor of Informatics, Director of the Penn Institute for Biomedical Informatics. The core members of CiPD include 26 faculty from across both Penn Dental Medicine and Penn Engineering, and also from the Schools of Medicine and Arts & Sciences.

Read the full story in Penn Today.