In just two years since CiPD was founded, the outcomes of this newly conceived research partnership have proven its value: microrobots that clean teeth for people with limited mobility, a completely new understanding of bacterial physics in tooth decay, enzymes from plant chloroplasts that degrade plaque, promising futures for lipid nanoparticles in oral cancer treatment and new techniques and materials to restore nerves in facial reconstructive surgery.
In addition, CiPD is training the next generation of dentists, scientists and engineers through an NIH/NIDCR-sponsored postdoctoral training program as well as fellowships from industry.
The two urge “the academic community to adopt a coordinated approach uniting dental medicine and engineering to support research, training and entrepreneurship to address unmet needs and spur oral health care innovations.”
Collaborating researchers from the University of Pennsylvania School of Dental Medicine and the Adams School of Dentistry and Gillings School of Global Public Health at the University of North Carolina have discovered that a bacterial species called Selenomonas sputigena can have a major role in causing tooth decay.
Scientists have long considered another bacterial species, the plaque-forming, acid-making Streptococcus mutans, as the principal cause of tooth decay—also known as dental caries. However, in the study, published in Nature Communications, the Penn Dental Medicine and UNC researchers showed that S. sputigena, previously associated only with gum disease, can work as a key partner of S. mutans, greatly enhancing its cavity-making power.
“This was an unexpected finding that gives us new insights into the development of caries, highlights potential future targets for cavity prevention, and reveals novel mechanisms of bacterial biofilm formation that may be relevant in other clinical contexts,” says study co-senior author Hyun (Michel) Koo, a professor in the Department of Orthodontics and Divisions of Pediatrics and Community Oral Health and co-director of the Center for Innovation & Precision Dentistry at Penn Dental Medicine.
The other two co-senior authors of the study were Kimon Divaris, professor at UNC’s Adams School of Dentistry, and Di Wu, associate professor at the Adams School and at the UNC Gillings School of Global Public Health.
“This was a perfect example of collaborative science that couldn’t have been done without the complementary expertise of many groups and individual investigators and trainees,” Divaris says.
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.
Infections caused by fungi, such as Candida albicans, pose a significant global health risk due to their resistance to existing treatments, so much so that the World Health Organization has highlighted this as a priority issue.
Although nanomaterials show promise as antifungal agents, current iterations lack the potency and specificity needed for quick and targeted treatment, leading to prolonged treatment times and potential off-target effects and drug resistance.
“Candida forms tenacious biofilm infections that are particularly hard to treat,” Koo says. “Current antifungal therapies lack the potency and specificity required to quickly and effectively eliminate these pathogens, so this collaboration draws from our clinical knowledge and combines Ed’s team and their robotic expertise to offer a new approach.”
The team of researchers is a part of Penn Dental’s Center for Innovation & Precision Dentistry, an initiative that leverages engineering and computational approaches to uncover new knowledge for disease mitigation and advance oral and craniofacial health care innovation.
For this paper, published in Advanced Materials, the researchers capitalized on recent advancements in catalytic nanoparticles, known as nanozymes, and they built miniature robotic systems that could accurately target and quickly destroy fungal cells. They achieved this by using electromagnetic fields to control the shape and movements of these nanozyme microrobots with great precision.
“The methods we use to control the nanoparticles in this study are magnetic, which allows us to direct them to the exact infection location,” Steager says. “We use iron oxide nanoparticles, which have another important property, namely that they’re catalytic.”
Other authors include Min Jun Oh, Alaa Babeer, Yuan Liu, Zhi Ren, Zhenting Xiang, Yilan Miao, and Chider Chen of Penn Dental; and David P. Cormode and Seokyoung Yoon of the Perelman School of Medicine. Cormode also holds a secondary appointment in Bioengineering.
This research was supported in part by the National Institute for Dental and Craniofacial Research (R01 DE025848, R56 DE029985, R90DE031532 and; the Basic Science Research Program through the National Research Foundation of Korea of the Ministry of Education (NRF-2021R1A6A3A03044553).
Members of the inaugural cohort of fellows in the Center for Innovation and Precision Dentistry (CiPD)’s NIDCR T90/R90 Postdoctoral Training Program have been recognized for their research activities with fellows receiving awards from the American Association for Dental, Oral, and Craniofacial Research (AADOCR), the Society for Biomaterials, and the Osteology Foundation. All four of the honored postdocs are affiliated with Penn Bioengineering.
Zhi Ren won first place in the Fives-Taylor Award at the AADOCR Mini Symposium for Young Investigators. A postdoctoral fellow in the labs of Dr. Hyun (Michel) Koo at Penn Dental Medicine (and member of the Penn Bioengineering Graduate Group) and Dr. Kathleen Stebe of Penn Engineering, Dr. Ren’s research focuses on understanding how bacterial and fungal pathogens interact in the oral cavity to form a sticky plaque biofilm on teeth, which gives rise to severe childhood tooth decay that affects millions of children worldwide. In his award-winning study, titled “Interkingdom Assemblages in Saliva Display Group-Level Migratory Surface Mobility”, Dr. Ren discovered that bacteria and fungi naturally present in the saliva of toddlers with severe decay can form superorganisms able to move and rapidly spread on tooth surfaces.
Justin Burrell won second place in the AADOCR Hatton Competition postdoctoral category for his research. Dr. Burrell has been working with Dr. Anh Le in Penn Dental Medicine’s Department of Oral Surgery/Pharmacology and Dr. D. Kacy Cullen of Penn Medicine and Penn Bioengineering. Together, their interdisciplinary team of clinician-scientists, biologists, and neuroengineers have been developing novel therapies to expedite facial nerve regeneration and increase meaningful functional recovery.
Marshall Padilla earned third place at the Society for Biomaterials Postdoctoral Recognition Award Competition for a project titled, “Branched lipid architecture improves lipid-nanoparticle-based mRNA delivery to the liver via enhanced endosomal escape”. Padilla was also a finalist in the AADOCR Hatton Award Competition, presenting on a separate project titled, “Lipid Nanoparticle Optimization for mRNA-based Oral Cancer Therapy”. Both projects employ lipid nanoparticles, the same delivery vehicles used in the mRNA COVID-19 vaccine technology. A postdoctoral fellow in the lab of Dr. Michael J. Mitchell of Penn’s Department of Bioengineering, Dr. Padilla’s research focuses on developing new ways to enhance the efficacy and safety of lipid nanoparticle technology and its applications in dentistry and biomedicine. He has been working in collaboration with Dr. Shuying (Sheri) Yang and Dr. Anh Le in Penn Dental Medicine.
Dennis Sourvanos (GD’23, DScD’23) was the recipient of the Trainee Travel Grant award through the Osteology Foundation (Lucerne Switzerland). Dr. Sourvanos will be presenting his research related to medical dosimetry and tissue regeneration at the International Osteology Symposium in Barcelona, Spain (April 27th – 29th 2023). He also presented at the 2023 AADOCR/CADR Annual Meeting for his project titled, “Validating Head-and-Neck Human-Tissue Optical Properties for Photobiomodulation and Photodynamic Therapies.” Dr. Sourvanos has been working with Dr. Joseph Fiorellini in Penn Dental Medicine’s Department of Periodontics and Dr. Timothy Zhu in the Hospital of the University of Pennsylvania’s Department of Radiation Oncology and the Smilow Center for Translational Research (and member of the Penn Bioengineering Graduate Group).
“Through their collaborative research, they are aiming to develop next-generation treatments for dental caries (tooth-decay) using lipid nanoparticles, the same delivery vehicles employed in the mRNA COVID-19 vaccine technology.
‘This project shows the type of innovative ideas and collaborations that we are kickstarting through the IDEA prize,’ says Dr. Michel Koo, co-director of the CiPD and Professor at Penn Dental Medicine. ‘This is a great example of synergistic interaction at the interface of engineering and oral health’ adds Dr. Kate Stebe, co-director of the CiPD and Professor at Penn Engineering.”