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.”
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.
The inaugural class of the CiPD NIDCR T90/R90 Postdoctoral Training Program Fellows with Dean Mark Wolff (center); Dr. Michel Koo, Founding Director of CiPD (far right); and CiPD Co-Director Dr. Kathleen Stebe of Penn’s School of Engineering and Applied Science (far left).
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.
In a proof-of-concept study, researchers from the School of Dental Medicine and School of Engineering and Applied Science shows that a hands-free system could effectively automate the treatment and removal of tooth-decay-causing bacteria and dental plaque. (Illustration: Melissa Pappas)
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.
A Philadelphia life sciences company spun out of Penn is emerging from stealth mode with nearly $10 million from a seed funding round. Vittoria Biotherapeutics’ mission is to overcome limitations of CAR T cell therapy by using unique cell engineering and gene editing technologies to create new therapies that address unmet clinical needs. The technology the company is attempting to commercialize was developed by Marco Ruella, M.D., Assistant Professor of Medicine in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group, who is the company’s scientific founder.
The dynamics governing mechanointelligence vary greatly along time- and length-scales, so detailed models of individual cells and their components are necessary to connect the effects of their physical environments to the downstream effects those forces have on biological processes.
The National Science Foundation’s Science and Technology Center (STC) program is its flagship funding mechanism for organizing interdisciplinary research on cutting-edge topics. Penn’s Center for Engineering MechanoBiology (CEMB) is one of the 18 active STCs, bringing together dozens of researchers from Penn Engineering and the Perelman School of Medicine, as well as others spread across campus and at partner institutions around the world.
With its NSF funding now renewed for another five years, the Center is entering into a new phase of its mission, centered on the nascent concept of “mechanointelligence.”
Mechanobiology is the study of the physical forces that govern the behavior of cells and their communication with their neighbors. Mechanointelligence adds another layer of complexity, attempting to understand the forces that allow cells to sense, remember and adapt to their environments.
Ultimately, harnessing these forces would allow researchers to help multicellular organisms — plants, animals and humans — better adapt to their environments as well.
“Mechanointelligence is a key element of a cell’s ability to survive and reproduce,” says CEMB Director and Eduardo D. Glandt President’s Distinguished Professor Vivek Shenoy. “Just like with complex organisms, a cell’s ‘fitness’ depends on its environment, and adapting means rewiring how its genes are expressed.”
Vivek Shenoy is Eduardo D. Glandt President’s Distinguished Professor in Materials Science and Engineering, Bioengineering and Mechanical Engineering and Applied Mechanics.
César de la Fuente, Presidential Assistant Professor in Psychiatry, Bioengineering, Microbiology, and in Chemical and Biomolecular Engineering has been honored with a 2022 Young Investigator Award by the Royal Spanish Society of Chemistry (RSEQ) for his pioneering research efforts to combine the power of machines and biology to help prevent, detect, and treat infectious diseases.
Congratulations to the two Bioengineering students to receive 2022 National Science Foundation Graduate Research Fellowship Program (NSF GRFP) fellowships. The prestigious NSF GRFP program recognizes and supports outstanding graduate students in NSF-supported fields. The eighteen Penn 2022 honorees were selected from a highly-competitive pool of over 12,000 applications nationwide. Further information about the program can be found on the NSF website.
Gianna Therese Busch, PhD student, Bioengineering
Gianna is a member of the systems biology lab of Arjun Raj, Professor in Bioengineering and Genetics. Her research focuses on single-cell differences in cancer metabolism and drug resistance.
Shawn Kang, BSE/MSE, Bioengineering (’22)
Shawn conducted research in the BIOLines Lab of Dan Huh, Associate Professor in Bioengineering, where he worked to develop more physiologically relevant models of human health and disease by combining organs-on-a-chip and organoid technology.
The following Bioengineering students also received Honorable Mentions: Michael Steven DiStefano, PhD student Rohan Dipak Patel, PhD student Abraham Joseph Waldman, PhD student
William Danon and Luka Yancopoulos, winners of the 2022 President’s Innovation Prize, will offer a software solution to make the health care supply chain more efficient.
by Brandon Baker
William Danon and Luka Yancopoulos pose in front of College Hall in April 2022. They are co-founders of Grapevine and the winners of the 2022 President’s Innovation Prize.
William Danon and Luka Yancopoulos are best friends. They’re also business partners.
The duo, who received this year’s President’s Innovation Prize (PIP) for Grapevine, met during sophomore year, connected through Yancopoulos’ roommate. As time went on, they did everything together: cooked meals, played basketball, and read and discussed fantasy novels.
“We spent a lot of time together,” Danon says.
It was only natural, then, that when the time came to start an actual venture, they’d do it together.
“They’re like brothers, in a very good way,” says mentor David Meaney of the School of Engineering and Applied Science, who describes their working dynamic as “complementary.” “I think that will serve them well. Most of what we do in faculty is collaborative, and I see elements of that in their partnership. I give them credit for stepping out and doing something unusual and keeping at it.”
How Grapevine came to be
Grapevine is a software solution and professional networking platform that connects small-to-medium-size players in the health care supply chain. It’s a sort of two-pronged solution: It helps institutions like hospital systems connect disjointed operations like procurement and inventory management internally, but also serves as a glue between these institutions and purveyors of medical equipment.
“William and Luka are impact-driven entrepreneurs whose collaborative synergies will take them far,” says Penn Interim President Wendell Pritchett. “The software provided by Grapevine is poised to reinvent how the health care industry buys and sells medical supplies and services and, truly, could not come at a timelier moment.”
The company is the evolution of a project they began at the onset of the COVID-19 pandemic, called Pandemic Relief Supply, which delivered $20 million of health care supplies to frontline workers.
“My mom was a nurse practitioner at New York Presbyterian Hospital, the largest hospital in the United States, and she was coming home with horror stories,” recalls Yancopoulos. “In surgery or the ER, a surgeon had to put on a garbage bag because they didn’t have a gown. And they gave her one mask to use for the rest of the month, and I’m seeing on the news, ‘Don’t wear a mask for more than three days.’”
This is where Yancopoulos and Danon first developed an interest in the health care supply chain. Using a database Penn allows students access to that maps the import of any good in the country, they did keyword matching to identify instreams of different goods and handed off findings to New York Presbyterian procurement staff. When McKesson, the largest provider of health care products and services in the U.S., took notice of what they were doing and reached out, they realized they were onto something. In response to their success, they started a company called Pandemic Relief Supply to distribute reliable medical supplies, including items like medical-grade masks and gloves, to frontline workers in the healthcare space.
As time passed, that project evolved into something larger: Grapevine.
A mock-up screenshot of a business profile on the Grapevine professional networking platform. (Image: William Danon)
In short, Grapevine’s software creates a professional networking platform to resolve miscommunications between suppliers and buyers, as well as adds a layer of transparency between interactants. Suppliers on the platform display real-time data about their inventory and shipping process, with timestamps; this prohibits companies from cherry-picking data or making false claims and creates a more health-care-supply-specific space for companies to interact than, say, LinkedIn.
“Primarily, the first step is we want people to use it internally, and streamline operations, and then through that centralized operational data, you can push that externally and that’s where [Grapevine] becomes a connector,” explains Danon. “Because when you’re choosing to connect with someone, the reason you can do so way more efficiently or quickly, is that data is actual operational data.”
To accomplish this level of transparency, the beginnings of Grapevine involved lots of legwork. Last year, the duo moved to Los Angeles to take stock of what suppliers existed where, and how reliable they were. They realized that many suppliers existed around Los Angeles because of port access; many medical supplies are imported from Asia. Their time in LA made the problem feel even more tangible, they agree.
“We were able to see people were doing outdated processes—manual processes—because there’s no other option,” Danon says. “So, we said, ‘Let’s get out there and do some work to be digital and technologically innovative.”
N.B.: Yancopolous’s senior design team created “Harvest” for their capstone project in Bioengineering, building on the existing Grapevine software package. Read Harvest’s abstract and view their final presentation on the BE Labs website.
Congratulations to recent Penn Bioengineering graduate Jason Andrechak on winning a Graduate Leadership Awards for 2022. Each year a select number of students across the university are recognized for their service and lasting contributions to graduate student life at Penn. Andrechak, one of only ten recipients in 2022, won a Dr. Andy Binns Award for Outstanding Service to Graduate and Professional Student Life. This award is presented to “graduate or professional students, upon their graduation from Penn, who have significantly impacted graduate and professional student life through service involvement in student life initiatives or organizations.” Andrechak won this award for his “service and leadership in advocating for equity and accessibility during the transition to virtual operations and following a period of leadership transition within the Graduate and Professional Student Assembly (GAPSA). ”
Andrechak completed his Ph.D. in Bioengineering in 2022, where he studied macrophage immunotherapy in solid tumors in the lab of Dennis E. Discher, Robert D. Bent Professor in Chemical and Biomolecular Engineering, Bioengineering, and Mechanical Engineering and Applied Mechanics. He was named a National Science Foundation Graduate Research Fellow in 2018. He has actively led the Graduate Association of Bioengineers (GABE) as Community Service & Outreach chair from 2017-2019 and as co-President from 2019-2022. He also served as the Director of Equity & Access for the Graduate & Professional Student Assembly (GAPSA) from 2020-2021, in addition to several other service and advisory roles at the department, school, and university levels.
Learn more about the Penn Graduate Leadership Awards and read the full list of recipients on the Grad Center at Penn website.
After a year of hybrid learning, Penn Bioengineering (BE) seniors were excited to return to the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace for Senior Design (BE 495 & 496), a two-semester course in which students work in teams to conceive, design and pitch their capstone projects in bioengineering. This year’s projects include tools for monitoring health, software to improve communication for the healthcare and supply chain industries, and devices to improve patient care for women and underrepresented minorities.
Team 11 (ReiniSpec) From L to R: Ifeoluwa Popoola, Alexa Rybicki, JeongInn Park (TA), Caitlin Frazee, Michelle White, Caroline Kavanagh (on laptop).
The three winning teams went on to compete in the annual interdepartmental Senior Design Competition sponsored by the Penn Engineering Alumni Society. BE took home two of the four interdepartmental awards: Team Modulo Prosthetics won the “Technology and Innovation Prize,” recognizing the project which best represents the highest and best use of technology and innovation to leverage engineering principles; and Team ReiniSpec won the “Leadership Prize,” which recognizes the team which most professionally and persuasively presents their group project to incorporate a full analysis of their project scope, advantages, and challenges, and addresses the commercialization and future potential of their research.
All BE teams were also required to submit their projects to local and national competitions, and were met with resounding success. “The creativity and accomplishment of this Senior Design class is really unparalleled,” said David Meaney, Solomon R. Pollack Professor in Bioengineering, Senior Associate Dean of Penn Engineering, and instructor for Senior Design. “The number of accolades received by these students, as well as the interest in transforming their ideas into real products for patients, reached a new level that makes us extremely proud.”
Keep reading for a full list of this year’s projects and awards.
Team 1 – MEViD
MEViD (Multichannel Electrochemical Viral Diagnostic) is a modular, low cost device that leverages electrochemistry to rapidly diagnose viral diseases from saliva samples.
Team members: Yuzheng (George) Feng, Daphne Kontogiorgos-Heintz, Carisa Shah, Pranshu Suri, & Rachel Zoneraich
MOD EZ-IO is a low-cost, novel intraosseous drill that uses force and RPM readings to alert the user via an LED when they have breached cortical bone and entered cancellous bone, guiding proper IO placement.
Team members: Gregory Glova, Kaiser Okyan, Patrick Paglia, Rohan Vemu, & Tshepo Yane
Harvest by Grapevine is a user-centric software solution that merges social network communication and supply chain logistics to connect hospitals and suppliers under one unified platform.
Winner of the 2022 President’s Innovation Prize (team member Lukas Yancopoulos and partner William Kohler Danon [SAS 2022] for “Grapevine,” the larger software package of which “Harvest” was a part)
CliniCall helps streamline and centralize communication channels, offering a real-time monitoring device that enables on-site/attending physicians to communicate with on-call physicians through a livestream of patients and data.
Team members: Neepa Gupta, Santoshi Kandula, Sue Yun Lee, & Ronil Synghal
Team 5 – PneuSonus
PneuSonus is a low-cost, user-friendly wearable strap that aids in detecting pediatric pneumonia by using frequency analysis of sound waves transmitted through the lungs to identify specific properties related to fluid presence, a valid indicator specific to pneumonia.
Team members: Iman Hossain, Kelly Lopez, Sophia Mark, Simi Serfati, & Nicole Wojnowski
Team 6 – Chrysalis
Chrysalis is a smart swaddle system comprising an electric swaddle and accompanying iOS application that comforts neonatal abstinence syndrome infants via stochastic resonance and maternal heartbeat vibrational patterns to reduce opioid withdrawal symptoms without pharmacological intervention or constant nurse oversight as well as streamlines the Eat, Sleep, Console documentation process for nurses.
Team members: Julia Dunn, Rachel Gu, Julia Lasater, & Carolyn Zhang
EquitOx is a revolutionized fingertip pulse oximeter designed for EMS that addresses racial inequality in medicine through the use of one-off tongue-calibrated SpO2 measurements.
Team members: Ronak Bhagia, Estelle Burkhardt, Juliette Hooper, Caroline Smith, & Kevin Zhao
Modulo Prosthetic is an adjustable, low-cost, thumb prosthetic with integrated haptic feedback that attaches to the metacarpophalangeal (MCP) joint of partial hand amputees and assists in activities of daily living (ADLs).
Team members: Alisha Agarwal, Michelle Kwon, Gary Lin, Ian Ong, & Zachary Spalding
COR-ASSIST by Cygno Technologies is a low-cost intra-aortic balloon enhancement that directly supports heart function by increasing cardiac output to 2.8L/min, at a much lower cost and bleeding risk than the current Impella cardiac assist device.
Team members: Francesca Cimino, Allen Gan, Shawn Kang, Kristina Khaw, & William Zhang
Pedalytics Footwear is a rechargeable sandal that continuously monitors foot health and prevents diabetic foot ulcer formation by novelly tracking three key metrics indicative of ulceration, temperature, oxygen saturation, and pressure, and sending alerts to patients via the Pedalytics app when metric abnormalities are detected.
Team members: Samantha Brosler, Constantine Constantinidis, Quincy Hendricks, Ananyaa Kumar, & María José Suárez
ReiniSpec is a redesigned speculum to improve the gynecological exam experience, increasing patient comfort with a silicone shell and using motorized arm adjustments to make it easily adjustable for each patient, while also incorporating a camera, lights, and machine learning to aid in better diagnosis by gynecologists.
Team members: Caitlin Frazee, Caroline Kavanagh, Ifeoluwa Popoola, Alexa Rybicki, & Michelle White
Shawn Kang, BSE/MSE, Bioengineering (’22)
After a year of hybrid learning, Penn Bioengineering (BE) seniors were excited to return to the 