{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T21:12:56Z","timestamp":1783977176912,"version":"3.55.0"},"reference-count":70,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"690","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,4,5]]},"abstract":"<jats:p>Implantable tubes, shunts, and other medical conduits are crucial for treating a wide range of conditions from ears and eyes to brain and liver but often impose serious risks of device infection, obstruction, migration, unreliable function, and tissue damage. Efforts to alleviate these complications remain at an impasse because of fundamentally conflicting design requirements: Millimeter-scale size is required to minimize invasiveness but exacerbates occlusion and malfunction. Here, we present a rational design strategy that reconciles these trade-offs in an implantable tube that is even smaller than the current standard of care. Using tympanostomy tubes (ear tubes) as an exemplary case, we developed an iterative screening algorithm and show how unique curved lumen geometries of the liquid-infused conduit can be designed to co-optimize drug delivery, effusion drainage, water resistance, and biocontamination\/ingrowth prevention in a single subcapillary\u2013length-scale device. Through extensive in vitro studies, we demonstrate that the engineered tubes enabled selective uni- and bidirectional fluid transport; nearly eliminated adhesion and growth of common pathogenic bacteria, blood, and cells; and prevented tissue ingrowth. The engineered tubes also enabled complete eardrum healing and hearing preservation and exhibited more efficient and rapid antibiotic delivery to the middle ear in healthy chinchillas compared with current tympanostomy tubes, without resulting in ototoxicity at up to 24 weeks. The design principle and optimization algorithm presented here may enable tubes to be customized for a wide range of patient needs.<\/jats:p>","DOI":"10.1126\/scitranslmed.add9779","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T17:58:24Z","timestamp":1680717504000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Design of medical tympanostomy conduits with selective fluid transport properties"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2892-1974","authenticated-orcid":true,"given":"Haritosh","family":"Patel","sequence":"first","affiliation":[{"name":"Harvard John A.\u00a0Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1599-5683","authenticated-orcid":true,"given":"Ida","family":"Pavlichenko","sequence":"additional","affiliation":[{"name":"Harvard John A.\u00a0Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Grinthal","sequence":"additional","affiliation":[{"name":"Harvard John A.\u00a0Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3154-795X","authenticated-orcid":true,"given":"Cathy T.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Harvard John A.\u00a0Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7131-5945","authenticated-orcid":true,"given":"Jack","family":"Alvarenga","sequence":"additional","affiliation":[{"name":"Harvard John A.\u00a0Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Kreder","sequence":"additional","affiliation":[{"name":"Harvard John A.\u00a0Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Harvard John A.\u00a0Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7325-1052","authenticated-orcid":true,"given":"Qin","family":"Ji","sequence":"additional","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2786-1751","authenticated-orcid":true,"given":"Christopher W.\u00a0F.","family":"Ling","sequence":"additional","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6282-9437","authenticated-orcid":true,"given":"Joseph","family":"Choy","sequence":"additional","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0101-977X","authenticated-orcid":true,"given":"Zihan","family":"Li","sequence":"additional","affiliation":[{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2535-5986","authenticated-orcid":true,"given":"Nicole L.","family":"Black","sequence":"additional","affiliation":[{"name":"Harvard John A.\u00a0Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2867-1450","authenticated-orcid":true,"given":"Paulo J.\u00a0M.","family":"Bispo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA 02114, USA."},{"name":"Harvard Medical School, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0280-2774","authenticated-orcid":true,"given":"Jennifer A.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Harvard John A.\u00a0Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott D.","family":"Kozin","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Harvard University, Boston, MA 02115, USA."},{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2343-8705","authenticated-orcid":true,"given":"Joanna","family":"Aizenberg","sequence":"additional","affiliation":[{"name":"Harvard John A.\u00a0Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA 02134, USA."},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA."},{"name":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0989-6264","authenticated-orcid":true,"given":"Aaron K.","family":"Remenschneider","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Harvard University, Boston, MA 02115, USA."},{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","first-page":"S1","article-title":"Clinical practice guideline: Tympanostomy tubes in children (update)","volume":"166","author":"Rosenfeld R. M.","year":"2022","unstructured":"R. M.\u00a0Rosenfeld, D. E.\u00a0Tunkel, S. R.\u00a0Schwartz, S.\u00a0Anne, C. E.\u00a0Bishop, D. C.\u00a0Chelius, J.\u00a0Hackell, L. L.\u00a0Hunter, K. L.\u00a0Keppel, A. H.\u00a0Kim, T. W.\u00a0Kim, J. M.\u00a0Levine, M. T.\u00a0Maksimoski, D. J.\u00a0Moore, D. A.\u00a0Preciado, N. P.\u00a0Raol, W. K.\u00a0Vaughan, E. A.\u00a0Walker, T. M.\u00a0Monjur, Clinical practice guideline: Tympanostomy tubes in children (update). Otolaryngol. Head Neck Surg. 166, S1\u2013S55 (2022).","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2011.10.026"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1291633"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1227\/NEU.0b013e318244695f"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.63"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2011.10.024"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1177\/0194599820917397"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.11.005"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/0194599813487302"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1067\/mhn.2001.113941"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoto.2014.1176"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1067\/mhn.2000.101954"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.HJ.0000575344.83197.6d"},{"key":"e_1_3_3_15_2","first-page":"S1","article-title":"Clinical practice guideline: Sudden hearing loss (update)","volume":"161","author":"Chandrasekhar S. S.","year":"2019","unstructured":"S. S.\u00a0Chandrasekhar, B. S.\u00a0Tsai Do, S. R.\u00a0Schwartz, L. J.\u00a0Bontempo, E. A.\u00a0Faucett, S. A.\u00a0Finestone, D. B.\u00a0Hollingsworth, D. M.\u00a0Kelley, S. T.\u00a0Kmucha, G.\u00a0Moonis, G. L.\u00a0Poling, J. K.\u00a0Roberts, R. J.\u00a0Stachler, D. M.\u00a0Zeitler, M. D.\u00a0Corrigan, L. C.\u00a0Nnacheta, L.\u00a0Satterfield, Clinical practice guideline: Sudden hearing loss (update). Otolaryngol. Head Neck Surg. 161, S1\u2013S45 (2019).","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14253"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1088\/0960-1317\/16\/5\/R01"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1039\/b926918e"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1039\/c2jm15022k"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/0145561320924910"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1109\/18.256500"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5876(88)90049-3"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1177\/0145561320929885"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1177\/014556130708611s08"},{"key":"e_1_3_3_25_2","first-page":"907","article-title":"Inhibition of biofilm formation on ventilation tubes by surface modification","volume":"26","author":"Song J.-J.","year":"2012","unstructured":"J.-J.\u00a0Song, I.\u00a0Noh, S.-W.\u00a0Chae, Inhibition of biofilm formation on ventilation tubes by surface modification. In Vivo 26, 907\u2013911 (2012).","journal-title":"In Vivo"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.2001.01338.x"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstl.1805.0005"},{"key":"e_1_3_3_28_2","unstructured":"P.\u00a0S.\u00a0de Laplace Trait\u00e9 De M\u00e9canique C\u00e9leste: Suppl\u00e9ment au dixi\u00e8me livre du trait\u00e9 de m\u00e9chanique c\u00e9leste sur l\u2019action capillaire (Duprat 1806)."},{"key":"e_1_3_3_29_2","first-page":"031053","article-title":"Film dynamics and lubricant depletion by droplets moving on lubricated surfaces","volume":"8","author":"Kreder M. J.","year":"2018","unstructured":"M. J.\u00a0Kreder, D.\u00a0Daniel, A.\u00a0Tetreault, Z.\u00a0Cao, B.\u00a0Lemaire, J.\u00a0V.\u00a0I.\u00a0Timonen, J.\u00a0Aizenberg, Film dynamics and lubricant depletion by droplets moving on lubricated surfaces. Phys. Rev. X 8, 031053 (2018).","journal-title":"Phys. Rev. X"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10447"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b04129"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nphys4177"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2015.3"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5SM01809A"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1017\/jfm.2016.517"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201802724"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3020"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.09.028"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1177\/1535370216640942"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201973109"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aai8977"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep26109"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1177\/0145561320914437"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2003.08.043"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1086\/509332"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0150949"},{"key":"e_1_3_3_47_2","first-page":"6","article-title":"Role of TGF-\u03b21-mediated epithelial-mesenchymal transition in the pathogenesis of tympanosclerosis","volume":"21","author":"Qiu J.","year":"2021","unstructured":"J.\u00a0Qiu, Y.\u00a0Wang, W.\u00a0Guo, L.\u00a0Xu, Y.\u00a0Mou, L.\u00a0Cui, F.\u00a0Han, Y.\u00a0Sun, Role of TGF-\u03b21-mediated epithelial-mesenchymal transition in the pathogenesis of tympanosclerosis. Exp. Ther. Med. 21, 6 (2021).","journal-title":"Exp. Ther. Med."},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1177\/014556130708611s11"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1177\/0885328218802103"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1097\/MLG.0b013e3181671b02"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5BM00140D"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.04.021"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.06.009"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066725"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.10.002"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034609"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2016.03.009"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/pen.25618"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep38059"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1177\/014107688307600106"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2018.06.022"},{"key":"e_1_3_3_62_2","doi-asserted-by":"crossref","unstructured":"R. Mauri Transport Phenomena in Multiphase Flows (Springer 2015).","DOI":"10.1007\/978-3-319-15793-1"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1039\/df9480300011"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1021\/ie50480a028"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-018-0060-6"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1021\/am503150y"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2014.05.025"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000001331"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2012.09.003"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2010.06.906"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1002\/lary.27239"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.add9779","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T17:55:17Z","timestamp":1705427717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.add9779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,5]]},"references-count":70,"journal-issue":{"issue":"690","published-print":{"date-parts":[[2023,4,5]]}},"alternative-id":["10.1126\/scitranslmed.add9779"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.add9779","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,5]]},"assertion":[{"value":"2022-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadd9779"}}