Koo shared findings from one of his recent studies conducted in collaboration with Penn Engineering, which showed that a shapeshifting robotic microswarm can brush and floss teeth.
“Routine oral care is cumbersome and can pose challenges for many people, especially those who have a hard time cleaning their teeth” says Koo. “You have to brush your teeth, then floss your teeth, then rinse your mouth; it’s a manual, multistep process. The big innovation here is that the robotics system can do all three in a single, hands-free, automated way.”
The building blocks of these microrobots are iron oxide nanoparticles that have both catalytic and magnetic activity. Using a magnetic field, researchers could direct their motion and configuration to form either bristlelike structures that sweep away dental plaque from the broad surfaces of teeth, or elongated strings that can slip between teeth like a length of floss.
“Nanoparticles can be shaped and controlled with magnetic fields in surprising ways,” says Edward Steager, a senior research investigator at Penn Engineering and co-corresponding author. “We form bristles that can extend, sweep, and even transfer back and forth across a space, much like flossing. The way it works is similar to how a robotic arm might reach out and clean a surface. The system can be programmed to do the nanoparticle assembly and motion control automatically.”
“Padilla came to the CiPD training program earlier this year with a Ph.D. in Chemistry from the University of Wisconsin-Madison. He is currently a postdoctoral fellow in the lab of Dr. Michael J. Mitchell of Penn’s Department of Bioengineering, where his research focuses on developing new materials to enhance the efficacy and safety of biological therapeutics. While passionate about research, he also has a strong interest in developing mentoring relationships and in teaching. At Wisconsin, Marshall earned a certificate in research, teaching, and learning, in which he conducted a research project on developing positive metacognitive practices in introductory organic chemistry. Additionally, he taught a course on mentoring in a research setting, and is passionate about promoting diversity and inclusiveness in biomedical sciences.”
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 PennsylvaniaSchool 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.”
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.
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.”
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.
Fibrosis is the thickening of various tissues caused by the deposition of fibrillar extracellular matrix (ECM) in tissues and organs as part of the body’s wound healing response to various forms of damage. When accompanied by chronic inflammation, fibrosis can go into overdrive and produce excess scar tissue that can no longer be degraded. This process causes many diseases in multiple organs, including lung fibrosis induced by smoking or asbestos, liver fibrosis induced by alcohol abuse, and heart fibrosis often following heart attacks. Fibrosis can also occur in the bone marrow, the spongy tissue inside some bones that houses blood-producing hematopoietic stem cells (HSCs) and can lead to scarring and the disruption of normal functions.
Chronic blood cancers known as “myeloproliferative neoplasms” (MPNs) are one example, in which patients can develop fibrotic bone marrow, or myelofibrosis, that disrupts the normal production of blood cells. Monocytes, a type of white blood cell belonging to the group of myeloid cells, are overproduced from HSCs in neoplasms and contribute to the inflammation in the bone marrow environment, or niche. However, how the fibrotic bone marrow niche itself impacts the function of monocytes and inflammation in the bone marrow was unknown.
Now, a collaborative team from Penn, Harvard, the Dana-Farber Cancer Institute (DFCI), and Brigham and Women’s Hospital has created a programmable hydrogel-based in vitro model mimicking healthy and fibrotic human bone marrow. Combining this system with mouse in vivo models of myelofibrosis, the researchers demonstrated that monocytes decide whether to enter a pro-inflammatory state and go on to differentiate into inflammatory dendritic cells based on specific mechanical properties of the bone marrow niche with its densely packed ECM molecules. Importantly, the team found a drug that could tone down these pathological mechanical effects on monocytes, reducing their numbers as well as the numbers of inflammatory myeloid cells in mice with myelofibrosis. The findings are published in Nature Materials.
“We found that stiff and more elastic slow-relaxing artificial ECMs induced immature monocytes to differentiate into monocytes with a pro-inflammatory program strongly resembling that of monocytes in myelofibrosis patients, and the monocytes to differentiate further into inflammatory dendritic cells,” says co-first author Kyle Vining, who recently joined Penn’s School of Dental Medicine and School of Engineering and Applied Science as an assistant professor of preventive and restorative sciences. “More viscous fast-relaxing artificial ECMs suppressed this myelofibrosis-like effect on monocytes. This opened up the possibility of a mechanical checkpoint that could be disrupted in myelofibrotic bone marrow and also may be at play in other fibrotic diseases.”
Vining worked on the study as a postdoctoral fellow at Harvard in the lab of David Mooney. “Our study shows that the differentiation state of monocytes, which are key players in the immune system, is highly regulated by mechanical changes in the ECM they encounter,” says Mooney, who co-led the study with DFCI researcher Kai Wucherpfennig. “Specifically, the ECM’s viscoelasticity has been a historically under-appreciated aspect of its mechanical properties that we find correlates strongly between our in vitro and the in vivo models and human disease. It turns out that myelofibrosis is a mechano-related disease that could be treated by interfering with the mechanical signaling in bone marrow cells.”
With one of its key missions to develop a new generation of scientists at the interface of dental medicine and engineering, the Center for Innovation & Precision Dentistry (CiPD) has selected its inaugural class of fellows for its new postdoctoral training program.
The CiPD was awarded a $2.5 million T90/R90 grant from the National Institute of Dental and Craniofacial Research (NIDCR) last summer to establish the program, recently naming this first cohort of fellows that includes Justin Burrell, Marshall Padilla, Zhi Ren, and Dennis Sourvanos.
“We’re hoping this program will promote cross-pollination and create a culture between these two fields to help dentists develop innovative strategies with engineers,” says Penn Dental Medicine’s Michel Koo, Co-Director of CiPD, who launched the Center in 2021 with Co-Director Kathleen Stebe, Richer & Elizabeth Goodwin Professor in Penn Engineering’s Department of Chemical and Biomolecular Engineering. “Dentists can learn from engineering principles and tools, and engineers can understand more about the needs of the dental and craniofacial fields. We’re providing a platform for them to work together to address unmet clinical needs and develop careers in that interface.”
The NIDCR T90/R90 Postdoctoral Training Program aims to specifically focus on the oral microbiome, host immunity, and tissue regeneration, each of which ties into different aspects of oral health, from tooth decay and periodontal disease to the needs of head and neck cancer patients. To advance these areas, emerging approaches, from advanced materials, robotics, and artificial intelligence to tissue engineering, chloroplast- and nanoparticle-based technologies, will be leveraged.
As part of the two-year training, each postdoc will receive co-mentorship from faculty from each school in conjunction with a career development committee of clinicians, basic scientists, as well as engineers. These mentorships will be focused on research outcomes and readying participants to submit grants and compete for positions in academia or industry.
The inaugural class of fellows includes Justin Burrell, a postdoctoral student in the lab of D. Kacy Cullen, Associate Professor of Neurosurgery; Marshall Padilla, a postdoc in the lab of Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering; and Zhi Ren, a postdoc in the lab of Michael Koo; and Dennis Sourvanos, an Advanced Graduate Dental Education resident at Penn Dental Medicine whose research has been co-directed by Timothy C. Zhu, Professor of Radiation Oncology in the Perelman School of Medicine. Cullen, Mitchell, Koo and Zhu are all members of the Penn Bioengineering Graduate Group.
A shapeshifting robotic microswarm may one day act as a toothbrush, rinse, and dental floss in one.
The technology, developed by a multidisciplinary team at the University of Pennsylvania, is poised to offer a new and automated way to perform the mundane but critical daily tasks of brushing and flossing. It’s a system that could be particularly valuable for those who lack the manual dexterity to clean their teeth effectively themselves.
The building blocks of these microrobots are iron oxide nanoparticles that have both catalytic and magnetic activity. Using a magnetic field, researchers could direct their motion and configuration to form either bristlelike structures that sweep away dental plaque from the broad surfaces of teeth, or elongated strings that can slip between teeth like a length of floss. In both instances, a catalytic reaction drives the nanoparticles to produce antimicrobials that kill harmful oral bacteria on site.
Experiments using this system on mock and real human teeth showed that the robotic assemblies can conform to a variety of shapes to nearly eliminate the sticky biofilms that lead to cavities and gum disease. The Penn team shared their findings establishing a proof-of-concept for the robotic system in the journal ACS Nano.
“Routine oral care is cumbersome and can pose challenges for many people, especially those who have hard time cleaning their teeth” says Hyun (Michel) Koo, a professor in the Department of Orthodontics and divisions of Community Oral Health and Pediatric Dentistry in Penn’s School of Dental Medicine and co-corresponding author on the study. “You have to brush your teeth, then floss your teeth, then rinse your mouth; it’s a manual, multistep process. The big innovation here is that the robotics system can do all three in a single, hands-free, automated way.”
Hyun (Michel) Koo is a professor in the Department of Orthodontics and divisions of Community Oral Health and Pediatric Dentistry in the School of Dental Medicine, co-director of the Center for Innovation & Precision Dentistry, and member of the Penn Bioengineering Graduate Group at the University of Pennsylvania.
Edward Steager is a senior research investigator in Penn’s School of Engineering and Applied Science.
Koo and Steager’s coauthors on the paper are Penn Dental Medicine’s Min Jun Oh, Alaa Babeer, Yuan Liu, and Zhi Ren and Penn Engineering’s Jingyu Wu, David A. Issadore, Kathleen J. Stebe, and Daeyeon Lee.
This work was supported in part by the National Institute for Dental and Craniofacial Research (grants DE025848 and DE029985), Procter & Gamble, and the Postdoctoral Research Program of Sungkyunkwan University.
In a new publication in the journal npjRegenerative Medicine, a team of Penn researchers from the School of Dental Medicine and the Perelman School of Medicine “coaxed human gingiva-derived mesenchymal stem cells (GMSCs) to grow Schwann-like cells, the pro-regenerative cells of the peripheral nervous system that make myelin and neural growth factors,” addressing the need for regrowing functional nerves involving commercially-available scaffolds to guide nerve growth. The study was led by Anh Le, Chair and Norman Vine Endowed Professor of Oral Rehabilitation in the Department of Oral and Maxillofacial Surgery/Pharmacology at the University of Pennsylvania School of Dental Medicine, and was co-authored by D. Kacy Cullen, Associate Professor in Neurosurgery at the Perelman School of Medicine at Penn and the Philadelphia Veterans Affairs Medical Center and member of the Bioengineering Graduate Group:
“To get host Schwann cells all throughout a bioscaffold, you’re basically approximating natural nerve repair,” Cullen says. Indeed, when Le and Cullen’s groups collaborated to implant these grafts into rodents with a facial nerve injury and then tested the results, they saw evidence of a functional repair. The animals had less facial droop than those that received an “empty” graft and nerve conduction was restored. The implanted stem cells also survived in the animals for months following the transplant.
“The animals that received nerve conduits laden with the infused cells had a performance that matched the group that received an autograft for their repair,” he says. “When you’re able to match the performance of the gold-standard procedure without a second surgery to acquire the autograft, that is definitely a technology to pursue further.”
Read the full story and view the full list of collaborators in Penn Today.
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.”
Researchers from Penn and CHOP detail the mechanism by which HIV infection blocks the maturation process of brain cells that produce myelin, a fatty substance that insulates neurons.
It’s long been known that people living with HIV experience a loss of white matter in their brains. As opposed to gray matter, which is composed of the cell bodies of neurons, white matter is made up of a fatty substance called myelin that coats neurons, offering protection and helping them transmit signals quickly and efficiently. A reduction in white matter is associated with motor and cognitive impairment.
In a new study using both human and rodent cells, the team has hammered out a detailed mechanism, revealing how HIV prevents the myelin-making brain cells called oligodendrocytes from maturing, thus putting a wrench in white matter production. When the researchers applied a compound blocking this process, the cells were once again able to mature.
“Even when people with HIV have their disease well-controlled by antiretrovirals, they still have the virus present in their bodies, so this study came out of our interest in understanding how HIV infection itself affects white matter,” says Kelly Jordan-Sciutto, a professor in Penn’s School of Dental Medicine and co-senior author on the study. “By understanding those mechanisms, we can take the next step to protect people with HIV infection from these impacts.”
“When people think about the brain, they think of neurons, but they often don’t think about white matter, as important as it is,” says Judith Grinspan, a research scientist at CHOP and the study’s other co-senior author. “But it’s clear that myelination is playing key roles in various stages of life: in infancy, in adolescence, and likely during learning in adulthood too. The more we find out about this biology, the more we can do to prevent white matter loss and the harms that can cause.”
Jordan-Sciutto and Grinspan have been collaborating for several years to elucidate how ART and HIV affect the brain, and specifically oligodendrocytes, a focus of Grinspan’s research. Their previous work on antiretrovirals had shown that commonly used drugs disrupted the function of oligodendrocytes, reducing myelin formation.
In the current study, they aimed to isolate the effect of HIV on this process. Led by Lindsay Roth, who recently earned her doctoral degree within the Biomedical Graduate Studies group at Penn and completed a postdoctoral fellowship working with Jordan-Sciutto and Grinspan, the investigation began by looking at human macrophages, one of the major cell types that HIV infects.
Kelly Jordan-Sciutto is vice chair and professor in the University of Pennsylvania School of Dental Medicine’s Department of Basic & Translational Sciences and is director of Biomedical Graduate Studies. She is a member of the Penn Bioengineering Graduate Group.