Creating Blueprints for Optimized Eustachian Tubes and Other Implantable Fluid-Transporting Devices — ScienceDaily

As a treatment, a doctor may surgically insert an ear tube, known as a “tympanostomy tube” (TT), into the eardrum to create an opening between the ear canal and the middle ear. Ideally, these ducts would ventilate the middle ear, provide a pathway for fluids to drain, and allow drops of antibiotics to reach infection-causing bacteria. These tiny hollow cylindrical devices are not fully functional. Bacteria can lay biofilms on which local tissue can grow. This will block the lumen of the TT and push it out. Also, antibiotic ear drops applied to the ear canal may not reach the site of infection. These complications pose risks, resulting in the need for frequent replacement surgeries and incurring significant financial costs to the healthcare system.

Importantly, the issues affecting TT are other fluid transport “implantables” such as catheters, shunts, and various small tubes used in the brain, liver, eyes, and other organs that are hampered by high-pressure barriers. The “medical conduit” (IMC) is also plagued. Prevents fluid from flowing through the conduit. A fundamental challenge facing biomedical engineers in search of superior devices is rooted in the conflict that reducing the size and invasiveness of IMC devices comes at the cost of increased risk of blockage and malfunction.

Currently undergoing a complete design overhaul in interdisciplinary research collaborations at Harvard University’s Wyss Institute of Biotechnology, Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), and Massachusetts Eye and Year (MEE) in Boston is taking place. By creating a broadly applicable strategy to solve this challenge, we provide the best solution for IMC. Their approach enables his IMC at the millimeter scale for predictable and effective unidirectional and bidirectional fluid transport that withstands a variety of contaminations. Example of TT manufactured from liquid injection material (ITT stands for “infused tympanostomy tube” and is a difficult-to-adjust tube that provides rapid drug delivery to the middle ear and drainage of fluid from the middle ear and resistance to water crossing from the outside to the middle ear. We jointly optimized the features. By introducing a new curved lumen shape of the tubing, it prevents adhesion of bacteria and cells to the tubing.Findings are published in our recent cover article Science Translational Medicine.

“As a clinical otologist, I routinely treat pediatric and adult patients with recurrent ear infections and routinely place myringotomy tubes. Pediatric surgery has remained relatively unchanged over the past 50 years,” said co-lead author Aaron Remenschneider, MD, MPH. ITTs show reduced cell adhesion and improved selective fluid transport, but how ITT results in reduced tympanic scarring and preservation of hearing compared to standard-of-care control TT. ITT may also be an effective tool for delivering various drugs to the middle ear. Remenschneider is a lecturer at the Harvard Medical School (HMS) and at MEE works closely with co-authors, MEE otologist colleagues, and her HMS Assistant Professor. Elliott Kozin, MD, who also researches therapeutic approaches to ear disorders at MEE.

Materials Scientists and Clinical Scientists Listen Together

Prior to this collaboration, co-lead author Dr. Joanna Aizenberg, Associate Professor at the Wyss Institute and Amy Smith Berylson Professor of Materials Science at SEAS, developed a bio-inspired material with entirely new functionality. These include SLIPS (short for “Slippery Liquid-Infused Porous Surfaces”) that expose a thin layer of oily liquid to prevent biofouling by a variety of organisms while allowing specific interactions with other liquids. It was Aizenberg’s group applied SLIPS technology to a variety of industrial and environmental “biofouling” problems, looking for unmet needs in the medical field that their materials could help address, Remenschneider, Kozin, and consulted other doctors. The complete design overhaul of TT and others of her IMC was the goal of a long-term collaboration driven by Aizenberg’s group and her Remenschneider and Kozin, including other researchers and clinicians. The cross-organizational project was recognized as her Wyss Institute Validation Project providing additional financial, technical and translational support during its progress.

Original author Haritosh Patel, an engineering graduate student in the Eisenberg Lab, and Dr. Ida Pavlichenko, a former Weiss Technology Development Fellow, began initial development. IA TT prototype using materials with liquid-infused surfaces and the 3D printing expertise of co-author Jennifer Lewis, Sd.D. at SEAS. “As a mother of a child who had repeated ear infections and experienced their pain and harmful consequences, I immediately felt empathy for the clinical problem and spearheaded a project that could solve it,” Pavlichenko said. “We immediately started investigating geometry as a possible solution to solving the fundamental design challenges of IMC. Amazing! Unfortunately, only cylindrical TTs with straight internal lumen channels existed. IChannels in TT may allow small-scale discrimination of different fluids. ”

while sticking to IWith TTs as their first application, the team developed a much more widely applicable modeling-enabled design process that can be applied to IMCs with a variety of tasks and locations in the body. Based on the physical parameters of the liquid, material, and size, hydrodynamics-based prediction of specific geometries of millimeter-sized IMCs fabricated on liquid-infused surfaces and different liquid directions passing through them Control transportation. “In addition to validating the predicted transport of rationally designed and manufactured fluids, ITT prototype in vitro These strains were isolated directly from patients with chronic middle ear infections by co-author Dr. Paulo Bispo. .D., another of his MEE collaborators on the project, and an assistant professor at HMS.

closer to the human ear

to investigate their performance ITT compared to conventional TT live To create a model relevant to the human ear, collaborators tested the approach on chinchilla ears. Chinchillas are the gold standard for studying middle ear diseases and therapeutic approaches. Chinchillas have eardrums about the size of humans and hearing over a similar frequency range, and Remenschneider and Kozin used them routinely in his MEE research lab. “Check all required boxes, IWhen TT was implanted into the chinchilla’s eardrum, it blocked out the surrounding water, prevented infection from accumulating, reduced scarring, and remained clear for aeration and pressure equalization,” Patel said. Compared to conventional TT, the dose of antibiotic ear drops into the middle ear is particularly irritating. According to Remenschneider, ITTs open the door to rethinking the management of middle and inner ear conditions such as hearing loss. ”

“Based on our excellent safety and efficacy results, ITT may next be tested in clinical trials in human patients. But what also excites us is the extension of our patented design approach to other important IMCs. For example, brain, eye and bile duct shunts. This technology and manufacturing process also enables the creation of personalized devices that are optimized for specific patient characteristics and needs,” he said. IIn the future, we will reverse engineer the material and geometric properties of TT and other IMCs to adapt them to different formulations and improve the drug discovery process for efficient local delivery of therapeutics and treatment of various diseases. can be part ”

“This is a great example of what happens when innovative materials scientists, engineers and clinicians work together to come up with new approaches that meet the needs of specific patients. Judah Folkman Professor of Vascular Biology HMS and Boston Children’s Hospital, and Hansjörg Wyss Professor of Biomedical Engineering at SEAS.

Other authors of this study are Alison Grinthal, Cathy Chan, Jack Alvarenga, Michael Kleder, James Weaver, Ching Ji, Christopher Lin, Joseph Choi, Zeehan Lee, and Nicole Black. . This research was funded by the Wyeth Institute for Biotechnology at Harvard University, the National Science Foundation (under Award # DMR-2011754), and the National Institutes of Health (under Award # R43DC019318 and K08DC018575).