{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:19:36Z","timestamp":1789996776742,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T00:00:00Z","timestamp":1737158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"BMBF RESPONSE FKZ","doi-asserted-by":"publisher","award":["03ZZ0933H"],"award-info":[{"award-number":["03ZZ0933H"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"BMBF RESPONSE FKZ","doi-asserted-by":"publisher","award":["03ZZ0933A"],"award-info":[{"award-number":["03ZZ0933A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"BMBF RESPONSE FKZ","doi-asserted-by":"publisher","award":["03ZZ0933G"],"award-info":[{"award-number":["03ZZ0933G"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>Cochlear implants are well established devices for treating severe hearing loss. However, due to the trauma caused by the insertion of the electrode and the subsequent formation of connective tissue, their clinical effectiveness varies. The aim of the current study was to achieve a long-term reduction in connective tissue growth and impedance by combining surface patterns on the electrode array with a poly-L-lactide coating containing 20% diclofenac. Three groups of six guinea pigs each (control, structure, structure with diclofenac in the coating) were implanted for four weeks. The hearing thresholds were measured before implantation and after 28 days, and impedances were monitored over time. After histological preparation, connective tissue growth and spiral ganglion neuron (SGN) survival were quantified. The hearing thresholds and impedances increased over time in all groups, showing no significant differences. The treatment groups showed increased damage in the cochlea, which appeared to be caused by the elevated parts of the microstructures. This seems to be amplified by the trauma model used in the current study. The impedances correlated with connective tissue growth near the electrode contacts. In addition, SGN survival was negatively correlated with the presence of connective tissue, both of which highlight the importance of successfully reducing connective tissue formation after cochlear implantation.<\/jats:p>","DOI":"10.3390\/jfb16010033","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T09:11:13Z","timestamp":1737364273000},"page":"33","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of Microstructured and Anti-Inflammatory-Coated Cochlear Implant Electrodes on Fibrous Tissue Growth and Neuronal Survival"],"prefix":"10.3390","volume":"16","author":[{"given":"Lennart","family":"Fibranz","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Behrends","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9891-5174","authenticated-orcid":false,"given":"Katharina","family":"Wulf","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering, Rostock University Medical Center, 18119 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Raggl","sequence":"additional","affiliation":[{"name":"MED-EL Medical Electronics, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"K\u00f6tter","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Eickner","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering, Rostock University Medical Center, 18119 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soeren","family":"Schilp","sequence":"additional","affiliation":[{"name":"MED-EL Medical Electronics, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9307-5989","authenticated-orcid":false,"given":"Thomas","family":"Lenarz","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, 30625 Hannover, Germany"},{"name":"Hearing4all Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit","family":"Paasche","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Lower Saxony Center for Biomedical Engineering, Implant Research and Development (NIFE), Hannover Medical School, 30625 Hannover, Germany"},{"name":"Hearing4all Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s10162-020-00761-4","article-title":"Relationships between Intrascalar Tissue, Neuron Survival, and Cochlear Implant Function","volume":"21","author":"Swiderski","year":"2020","journal-title":"JARO"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1097\/MAO.0000000000001686","article-title":"Preservation of Cells of the Organ of Corti and Innervating Dendritic Processes Following Cochlear Implantation in the Human: An Immunohistochemical Study","volume":"39","author":"Kamakura","year":"2018","journal-title":"Otol. Neurotol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-5955(96)00193-1","article-title":"Chronic Electrical Stimulation of the Auditory Nerve at High Stimulus Rates: A Physiological and Histopathological Study","volume":"105","author":"Xu","year":"1997","journal-title":"Hear. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wilk, M., Hessler, R., Mugridge, K., Jolly, C., Fehr, M., Lenarz, T., and Scheper, V. (2016). Impedance Changes and Fibrous Tissue Growth after Cochlear Implantation Are Correlated and Can Be Reduced Using a Dexamethasone Eluting Electrode. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147552"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.heares.2013.01.012","article-title":"Relations between Cochlear Histopathology and Hearing Loss in Experimental Cochlear Implantation","volume":"298","author":"Monksfield","year":"2013","journal-title":"Hear. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1159\/000103208","article-title":"Quantitative Evaluation of New Bone and Fibrous Tissue in the Cochlea Following Cochlear Implantation in the Human","volume":"12","author":"Somdas","year":"2007","journal-title":"Audiol. Neurotol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.otohns.2009.03.031","article-title":"Histopathologic Assessment of Fibrosis and New Bone Formation in Implanted Human Temporal Bones Using 3D Reconstruction","volume":"141","author":"Fayad","year":"2009","journal-title":"Otolaryngol.\u2014Head Neck Surg."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hrn\u010di\u0159\u00edk, F., Nagy, L., Grimes, H.L., Iftikhar, H., Muzaffar, J., and Bance, M. (2024). Impact of Insertion Speed, Depth, and Robotic Assistance on Cochlear Implant Insertion Forces and Intracochlear Pressure: A Scoping Review. Sensors, 24.","DOI":"10.3390\/s24113307"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1080\/00016480410018179","article-title":"Cochlear Implantation via the Round Window Membrane Minimizes Trauma to Cochlear Structures: A Histologically Controlled Insertion Study","volume":"124","author":"Adunka","year":"2004","journal-title":"Acta Oto-Laryngol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1682\/JRRD.2007.08.0119","article-title":"Considerations for the Design of Future Cochlear Implant Electrode Arrays: Electrode Array Stiffness, Size and Depth of Insertion","volume":"45","author":"Rebscher","year":"2008","journal-title":"J. Rehabil. Res. Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1179\/1754762811Y.0000000024","article-title":"Dexamethasone Eluting Cochlear Implant: Histological Study in Animal Model","volume":"14","author":"Farhadi","year":"2013","journal-title":"Cochlear Implant. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19160216241288819","DOI":"10.1177\/19160216241288819","article-title":"A Single Intratympanic Triamcinolone Acetonide Administration Elicits Long-Term Reduction in Impedances Following Cochlear Implantation","volume":"53","author":"Nieratschker","year":"2024","journal-title":"J. Otolaryngol.\u2014Head Neck Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1179\/1754762813Y.0000000054","article-title":"Development of a Safe Dexamethasone-Eluting Electrode Array for Cochlear Implantation","volume":"15","author":"Stathopoulos","year":"2014","journal-title":"Cochlear Implant. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107924","DOI":"10.1016\/j.heares.2020.107924","article-title":"Comparison of Electrode Impedance Measures between a Dexamethasone-Eluting and Standard CochlearTM Contour Advance\u00ae Electrode in Adult Cochlear Implant Recipients","volume":"390","author":"Briggs","year":"2020","journal-title":"Hear. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jsps.2015.01.002","article-title":"Antiproliferative Effects of Aspirin and Diclofenac against the Growth of Cancer and Fibroblast Cells: In Vitro Comparative Study","volume":"23","author":"Hameed","year":"2015","journal-title":"Saudi Pharm. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1177\/193229681100500111","article-title":"\u201cSmart Tattoo\u201d Glucose Biosensors and Effect of Coencapsulated Anti-Inflammatory Agents","volume":"5","author":"Srivastava","year":"2011","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wulf, K., Goblet, M., Raggl, S., Teske, M., Eickner, T., Lenarz, T., Grabow, N., and Paasche, G. (2022). PLLA Coating of Active Implants for Dual Drug Release. Molecules, 27.","DOI":"10.3390\/molecules27041417"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Behrends, W., Wulf, K., Raggl, S., Fr\u00f6hlich, M., Eickner, T., Dohr, D., Esser, K.-H., Lenarz, T., Scheper, V., and Paasche, G. (2023). Dual Drug Delivery in Cochlear Implants: In Vivo Study of Dexamethasone Combined with Diclofenac or Immunophilin Inhibitor MM284 in Guinea Pigs. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030726"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.1179\/146701011X13001035753254","article-title":"Local Drug Delivery to Conserve Hearing: Mechanisms of Action of Eluted Dexamethasone within the Cochlea","volume":"12","author":"Eshraghi","year":"2011","journal-title":"Cochlear Implant. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1080\/00016489.2023.2241877","article-title":"Cochlear Implant Surgery Facilitates Intracochlear Distribution of Perioperative Systemic Steroids","volume":"143","author":"Creber","year":"2023","journal-title":"Acta Oto-Laryngol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1517\/17425247.2011.588207","article-title":"Intracochlear Drug Delivery Systems","volume":"8","author":"Borenstein","year":"2011","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1159\/000322504","article-title":"Distribution of Dexamethasone and Preservation of Inner Ear Function Following Intratympanic Delivery of a Gel-Based Formulation","volume":"16","author":"Salt","year":"2011","journal-title":"Audiol. Neurotol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.2147\/DDDT.S318117","article-title":"Hearing Protection Outcomes of Analog Electrode Arrays Coated with Different Drug-Eluting Polymer Films Implanted into Guinea Pig Cochleae","volume":"15","author":"Huang","year":"2021","journal-title":"DDDT"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1007\/s10856-012-4698-z","article-title":"Development of a Specially Tailored Local Drug Delivery System for the Prevention of Fibrosis after Insertion of Cochlear Implants into the Inner Ear","volume":"23","author":"Bohl","year":"2012","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1002\/jbm.b.33110","article-title":"Biodegradable Polymeric Coatings on Cochlear Implant Surfaces and Their Influence on Spiral Ganglion Cell Survival","volume":"102","author":"Ceschi","year":"2014","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dohr, D., Wulf, K., Grabow, N., Mlynski, R., and Schraven, S.P. (2022). A PLLA Coating Does Not Affect the Insertion Pressure or Frictional Behavior of a CI Electrode Array at Higher Insertion Speeds. Materials, 15.","DOI":"10.1055\/s-0042-1746741"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1093\/eurheartj\/ehs086","article-title":"Biodegradable Polymer Drug-Eluting Stents Reduce the Risk of Stent Thrombosis at 4 Years in Patients Undergoing Percutaneous Coronary Intervention: A Pooled Analysis of Individual Patient Data from the ISAR-TEST 3, ISAR-TEST 4, and LEADERS Randomized Trials","volume":"33","author":"Stefanini","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/cm.970310207","article-title":"Role of the Cytoskeleton in the Reaction of Fibroblasts to Multiple Grooved Substrata","volume":"31","author":"Curtis","year":"1995","journal-title":"Cell Motil. Cytoskelet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.1016\/j.bpj.2008.11.074","article-title":"Cell-Shape Regulation of Smooth Muscle Cell Proliferation","volume":"96","author":"Thakar","year":"2009","journal-title":"Biophys. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1097-4636(199821)43:1<1::AID-JBM1>3.0.CO;2-T","article-title":"Influence of Silicone (PDMS) Surface Texture on Human Skin Fibroblast Proliferation as Determined by Cell Cycle Analysis","volume":"43","author":"Whitesides","year":"1998","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0378-5955(01)00320-3","article-title":"Chronic Electrical Stimulation of the Auditory Nerve Using High Surface Area (HiQ) Platinum Electrodes","volume":"159","author":"Tykocinski","year":"2001","journal-title":"Hear. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1177\/019459988709600408","article-title":"Electrical stimulation of the guinea pig cochlea","volume":"96","author":"Maslan","year":"1987","journal-title":"Otolaryngol.\u2014Head Neck Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.heares.2008.05.009","article-title":"Three-Dimensional Imaging of the Intact Mouse Cochlea by Fluorescent Laser Scanning Confocal Microscopy","volume":"243","author":"MacDonald","year":"2008","journal-title":"Hear. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.heares.2013.08.002","article-title":"Spiral Ganglion Neuron Quantification in the Guinea Pig Cochlea Using Confocal Laser Scanning Microscopy Compared to Embedding Methods","volume":"306","author":"Wrzeszcz","year":"2013","journal-title":"Hear. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.heares.2016.02.003","article-title":"Electrode Array-Eluted Dexamethasone Protects against Electrode Insertion Trauma Induced Hearing and Hair Cell Losses, Damage to Neural Elements, Increases in Impedance and Fibrosis: A Dose Response Study","volume":"337","author":"Bas","year":"2016","journal-title":"Hear. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e168","DOI":"10.1097\/AUD.0000000000000394","article-title":"Three-Dimensional Force Profile During Cochlear Implantation Depends on Individual Geometry and Insertion Trauma","volume":"38","author":"Avci","year":"2017","journal-title":"Ear Hear."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1097\/MAO.0000000000002608","article-title":"Evaluation of Insertion Forces and Cochlea Trauma Following Robotics-Assisted Cochlear Implant Electrode Array Insertion","volume":"41","author":"Kaufmann","year":"2020","journal-title":"Otol. Neurotol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.3762\/bjnano.5.122","article-title":"Dry Friction of Microstructured Polymer Surfaces Inspired by Snake Skin","volume":"5","author":"Baum","year":"2014","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Tomanik, M., Kobielarz, M., Filipiak, J., Szymonowicz, M., Rusak, A., Mroczkowska, K., Anto\u0144czak, A., and Pezowicz, C. (2020). Laser Texturing as a Way of Influencing the Micromechanical and Biological Properties of the Poly(L-Lactide) Surface. Materials, 13.","DOI":"10.3390\/ma13173786"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1097\/00005537-200309000-00003","article-title":"Surgery of the Inner Ear With Hearing Preservation: Serial Histological Changes","volume":"113","author":"Smouha","year":"2003","journal-title":"Laryngoscope"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Simoni, E., Gentilin, E., Candito, M., Borile, G., Romanato, F., Chicca, M., Nordio, S., Aspidistria, M., Martini, A., and Cazzador, D. (2020). Immune Response After Cochlear Implantation. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00341"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1097\/01.mlg.0000242073.02488.f4","article-title":"Impact of Intrascalar Blood on Hearing","volume":"117","author":"Radeloff","year":"2007","journal-title":"Laryngoscope"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1097\/MAO.0000000000001454","article-title":"Foreign Body Response to Silicone in Cochlear Implant Electrodes in the Human","volume":"38","author":"Burgess","year":"2017","journal-title":"Otol. Neurotol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.smim.2007.11.004","article-title":"Foreign Body Reaction to Biomaterials","volume":"20","author":"Anderson","year":"2008","journal-title":"Semin. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/jbm.a.36006","article-title":"Multinucleated Giant Cells in the Implant Bed of Bone Substitutes Are Foreign Body Giant Cells\u2014New Insights into the Material-mediated Healing Process","volume":"105","author":"Barbeck","year":"2017","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12557","DOI":"10.1021\/la302868q","article-title":"Photocured Biodegradable Polymer Substrates of Varying Stiffness and Microgroove Dimensions for Promoting Nerve Cell Guidance and Differentiation","volume":"28","author":"Cai","year":"2012","journal-title":"Langmuir"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1097\/MLG.0b013e31802f4169","article-title":"Noise Exposure of the Inner Ear During Drilling a Cochleostomy for Cochlear Implantation","volume":"117","author":"Pau","year":"2007","journal-title":"Laryngoscope"}],"container-title":["Journal of Functional Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4983\/16\/1\/33\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:31:30Z","timestamp":1759919490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4983\/16\/1\/33"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,18]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["jfb16010033"],"URL":"https:\/\/doi.org\/10.3390\/jfb16010033","relation":{},"ISSN":["2079-4983"],"issn-type":[{"value":"2079-4983","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,18]]}}}