MSGID: 1:317/3 642e4aec   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Creating a blueprint for optimized ear tubes and other implantable   
   fluid-transporting devices    
      
     Date:   
         April 5, 2023   
     Source:   
         Wyss Institute for Biologically Inspired Engineering at Harvard   
     Summary:   
         A new study provides a complete design overhaul for IMCs by creating   
         a broadly applicable strategy that solves key challenges in the   
         design of ear tubes and other 'implantable medical conduits.' The   
         approach enables IMCs with predictable and effective uni- and   
         bi-directional fluid transport at the millimeter scale that resist   
         various contaminations.   
      
      
         Facebook Twitter Pinterest LinkedIN Email   
   FULL STORY   
   ==========================================================================   
   Infections of the middle ear, the air-filled space behind the eardrum   
   that contains the tiny vibrating bones of hearing, annually affect   
   more than 700 million people worldwide. Children are especially prone   
   to ear infections, with 40% of them developing recurrent or chronic   
   infections that can lead to complications like impaired hearing,   
   speech and language delays, perforations in their eardrums, and even   
   life-threatening meningitis.   
      
      
   ==========================================================================   
   As a treatment, doctors may surgically insert ear tubes knowns as   
   "tympanostomy tubes" (TTs) into the eardrum to create an opening between   
   the ear canal and middle ear. Ideally, these conduits ventilate the middle   
   ear, provide a route for fluid to drain out, and allow antibiotic drops   
   to reach the infection- causing bacteria. But in reality, these small   
   hollow cylindrical devices made of plastic or metal function far from   
   perfectly. Bacteria can lay down biofilms and local tissue can grow on   
   their surfaces, which blocks TTs' lumen and causes them to extrude. Also,   
   antibiotic ear drops applied in the ear canal may not reach the site of   
   infection anymore. These complications pose risks and result in the need   
   for frequent replacement surgeries, producing sizeable economic costs   
   to the health care system.   
      
   Importantly, problems affecting TTs also plague other fluid-transporting   
   "implantable medical conduits" (IMCs), such as catheters, shunts, and   
   various small tubes with use in the brain, liver, eyes, and other organs   
   where a high- pressure barrier prevents fluids from flowing through the   
   conduit. In the quest for superior devices, the fundamental challenge   
   faced by biomedical engineers is rooted in the conflict that reducing   
   IMC devices' size and invasiveness comes at the price of increasing   
   their risk of becoming blocked and malfunctioning.   
      
   Now, a multi-disciplinary research collaboration at the Wyss Institute for   
   Biologically Inspired Engineering at Harvard University, Harvard John A.   
      
   Paulson School of Engineering and Applied Sciences (SEAS), and   
   Massachusetts Eye and Ear (MEE) in Boston provides a complete design   
   overhaul for IMCs by creating a broadly applicable strategy that solves   
   this challenge. Their approach enables IMCs with predictable and effective   
   uni- and bi-directional fluid transport at the millimeter scale that   
   resist various contaminations.   
      
   With the example of TTs fabricated from a liquid-infused material   
   (iTTs, short for "infused tympanostomy tubes"), they co-optimized   
   difficult-to-reconcile functions, including fast drug delivery into   
   and drainage of fluids out of the middle ear, resistance against water   
   crossing from the outside into the middle ear, as well as the prevention   
   of bacterial and cell adhesion to tubes, by introducing a novel curved   
   lumen geometry of the tube. The findings are published in the recent   
   cover article of Science Translational Medicine.   
      
   "As a clinical otologist, I treat pediatric and adult patients with   
   recurrent ear infections on a daily basis and I routinely place   
   tympanostomy tubes, which in children is the most common surgical   
   procedure performed in the United States. Yet, TT medical device   
   technology has remained relatively unchanged for the past 50 years,"   
   said co-senior author Aaron Remenschneider, M.D., M.P.H.   
      
   "Given our findings, I do see hope on the horizon for patients with   
   chronic ear infections. Not only do our iTTs demonstrate a reduction   
   in cell adhesion and improved selective fluid transport, but we showed   
   how iTTs result in decreased scarring of the eardrum and preserved   
   hearing when compared to standard-of-care control TTs. iTTs could also   
   become an effective tool for delivering a range of drugs to the middle   
   ear." Remenschneider is a lecturer at Harvard Medical School (HMS), and   
   at MEE collaborates closely with co-author, MEE otologist- colleague,   
   and HMS Assistant Professor Elliott Kozin, M.D., who also investigates   
   therapeutic approaches to ear disorders at MEE.   
      
   Material and clinical scientists listen closely -- together Preceding   
   this collaboration, co-senior author Joanna Aizenberg, Ph.D., who is an   
   Associate Faculty member of the Wyss Institute and the Amy Smith Berylson   
   Professor of Material Sciences at SEAS, has pioneered bio-inspired   
   materials with entirely new functionalities. These included SLIPS   
   (short for "Slippery Liquid-Infused Porous Surfaces"), which expose a   
   thin layer of oil-based liquid to prevent biofouling by various organisms   
   while enabling specific interactions with other fluids. Aizenberg's group   
   had applied SLIPS technology to different industrial and environmental   
   "biofouling" problems and, in search of unmet needs in the medical   
   field that their materials could help address, they consulted with   
   Remenschneider, Kozin and other physicians. A complete design overhaul   
   of TTs and other IMCs became the goal of a long-standing collaboration   
   driven by Aizenberg's group, and Remenschneider and Kozin, which also   
   included other researchers and clinicians. During its advancement,   
   the cross- institutional project was recognized as a Validation Project   
   at the Wyss Institute, which provided additional financial, technical,   
   and translational support.   
      
   First-authors Haritosh Patel, a graduate engineering student in the   
   Aizenberg lab, and Ida Pavlichenko, Ph.D., a former Wyss Technology   
   Development Fellow began to develop the first iTT prototypes, 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   
   experienced recurrent ear infections and some of their pain and harmful   
   consequences, I could immediately relate to the clinical problem, and   
   felt strongly compelled to spearhead a project with the potential to   
   solve it," said Pavlichenko. "We soon began to investigate geometry as   
   a possible solution for solving IMCs' fundamental design challenge.   
      
   Surprisingly, only cylindrical TTs with straight internal lumen channels   
   existed. We hypothesized that introducing specific curvatures into iTTs'   
   channels could allow them to discriminate between different fluids at   
   a small scale."  While focusing on iTTs as a first application, the   
   team developed a much more broadly applicable modeling-enabled design   
   process that can be applied to IMCs with different tasks and locations   
   in the body. Based on the physical parameters of liquids, materials, and   
   size, it starts with the fluid dynamics- based prediction of specific   
   geometries for millimeter-sized IMCs fabricated with liquid-infused   
   surfaces to control the directional transport of different liquids through   
   them. "Besides validating the predicted transport of fluids through   
   rationally designed and fabricated iTT prototypes in in vitromodels of   
   the middle ear, we also demonstrated their resistance against adhesion   
   by the five most common bacterial strains causing ear infection in   
   children," said Patel. The strains were directly isolated from patients   
   with chronic middle ear infections by co-author Paulo Bispo, Ph.D.,   
   another MEE collaborator on the project and an Assistant Professor at HMS.   
      
   Moving closer to the human ear To investigate the performance of their   
   iTTs in comparison with conventional TTs in an in vivo model with   
   relevance to the human ear, the collaborators tested their approach   
   on the ears of chinchillas, the gold-standard for studying middle   
   ear diseases and treatment approaches. Chinchillas have a tympanic   
   membrane about the same size of that of humans and a similar frequency   
   range of hearing, and Remenschneider and Kozin had routinely used them   
   in their MEE research lab. "Checking off all essential boxes, iTTs,   
   when implanted into chinchillas' eardrum, kept out environmental water,   
   prevented infectious buildup, reduced scarring, and remained clear for   
   aeration and pressure equalization," said Patel. Pavlichenko added,   
   "Importantly, they preserved hearing and enabled more easy and reliable   
   dosing of antibiotic ear drops to the middle ear compared to conventional   
   TTs, which is particularly exciting."  According to Remenschneider,   
   "reliable dosing of medications to the middle ear through iTTs opens the   
   door to rethinking our management of middle and even inner ear conditions,   
   like hearing loss."  "Based on our excellent safety and efficacy results,   
   iTTs could next be tested in a clinical trial in human patients. But   
   what equally excites us is to extend our patented design approach to   
   other important IMCs, for example, as shunts for the brain, eye, and   
   bile duct. The technology and fabrication process would even enable   
   the creation of personalized devices optimized for specific patients'   
   characteristics and needs," said Aizenberg. "We envision that iTTs'   
   and other IMCs' material and geometrical properties in the future could   
   be reverse-engineered to adapt them to different drug formulations   
   and make them a part of the drug discovery process for an efficient   
   topical delivery of therapeutics and treatment of various diseases."   
   "This is wonderful example of what can happen when you have innovative   
   materials scientists, engineers, and clinicians working together hand   
   in hand to devise a new approach to meet specific patients' needs,"   
   said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the   
   Judah Folkman Professor of Vascular Biology at HMS and Boston Children's   
   Hospital, and the Hansjo"rg Wyss Professor of Bioinspired Engineering   
   at SEAS.   
      
   Other authors on the study are Alison Grinthal, Cathy Zhang, Jack   
   Alvarenga, Michael Kreder, James Weaver, Qin Ji, Christopher Ling, Joseph   
   Choy, Zihan Li, and Nicole Black. The study has been funded by the Wyss   
   Institute for Biologically Inspired Engineering at Harvard University,   
   National Science Foundation (under award# DMR-2011754), and National   
   Institutes of Health (under award# R43DC019318 and K08DC018575).   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Hearing_Loss # Disability # Diseases_and_Conditions #   
                   Today's_Healthcare   
             o Matter_&_Energy   
                   # Nature_of_Water # Civil_Engineering # Materials_Science   
                   # Engineering_and_Construction   
       * RELATED_TERMS   
             o Architecture o Circuit_design o Construction o Middle_ear o   
             Automobile_safety o Engineering o Scale_model o Fluid_mechanics   
      
   ==========================================================================   
   Story Source: Materials provided   
   by Wyss_Institute_for_Biologically_Inspired_Engineering_at   
   Harvard. Original written by Benjamin Boettner. Note: Content may be   
   edited for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Haritosh Patel, Ida Pavlichenko, Alison Grinthal, Cathy T. Zhang,   
      Jack   
         Alvarenga, Michael J. Kreder, James C. Weaver, Qin Ji, Christopher   
         W. F.   
      
         Ling, Joseph Choy, Zihan Li, Nicole L. Black, Paulo J. M. Bispo,   
         Jennifer A. Lewis, Elliott D. Kozin, Joanna Aizenberg, Aaron   
         K. Remenschneider.   
      
         Design of medical tympanostomy conduits with selective fluid   
         transport properties. Science Translational Medicine, 2023; 15   
         (690) DOI: 10.1126/ scitranslmed.add9779   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/04/230405161310.htm   
      
   --- up 1 year, 5 weeks, 2 days, 10 hours, 50 minutes   
    * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)   
   SEEN-BY: 15/0 106/201 114/705 123/120 153/7715 226/30 227/114 229/110   
   SEEN-BY: 229/111 112 113 307 317 400 426 428 470 664 700 292/854 298/25   
   SEEN-BY: 305/3 317/3 320/219 396/45   
   PATH: 317/3 229/426