{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T11:43:09Z","timestamp":1792755789389,"version":"4.5.0"},"reference-count":107,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Hearing loss is the most common neurosensory disorder, and with the constant increase in etiological factors, combined with early detection protocols, numbers will continue to rise. Cochlear implantation has become the gold standard for patients with severe hearing loss, and interest has shifted from implantation principles to the preservation of residual hearing following the procedure itself. As the audiological criteria for cochlear implant eligibility have expanded to include patients with good residual hearing, more attention is focused on complementary development of otoprotective agents, electrode design, and surgical approaches. The focus of this review is current aspects of preserving residual hearing through a summary of recent trends regarding surgical and pharmacological fundamentals. Subsequently, the assessment of new pharmacological options, novel bioactive molecules (neurotrophins, growth factors, etc.), nanoparticles, stem cells, and gene therapy are discussed.<\/jats:p>","DOI":"10.3390\/medicina58060747","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T05:25:42Z","timestamp":1653974742000},"page":"747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Current Concepts and Future Trends in Increasing the Benefits of Cochlear Implantation: A Narrative Review"],"prefix":"10.3390","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2230-3435","authenticated-orcid":false,"given":"Cristina Maria","family":"Blebea","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400347 Cluj Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo Peter","family":"Ujvary","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400347 Cluj Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8415-555X","authenticated-orcid":false,"given":"Violeta","family":"Necula","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400347 Cluj Napoca, Romania"},{"name":"County Clinical Emergency Hospital Cluj, 400347 Cluj Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4334-0967","authenticated-orcid":false,"given":"Maximilian George","family":"Dindelegan","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400347 Cluj Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8581-0982","authenticated-orcid":false,"given":"Maria","family":"Perde-Schrepler","sequence":"additional","affiliation":[{"name":"Institute of Oncology \u201cProf.Dr. Ion Chiricuta\u201d, 400015 Cluj Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirela Cristina","family":"Stamate","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400347 Cluj Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Cosgarea","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400347 Cluj Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma Aurelia","family":"Maniu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400347 Cluj Napoca, Romania"},{"name":"County Clinical Emergency Hospital Cluj, 400347 Cluj Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1002\/ar.22580","article-title":"The Cochlear Implant: Historical Aspects and Future Prospects","volume":"295","author":"Eshraghi","year":"2012","journal-title":"Anat. Rec."},{"key":"ref_2","first-page":"356","article-title":"Intracochlear Placement of Cochlear Implant Electrodes in Soft Surgery Technique","volume":"41","author":"Lehnhardt","year":"1993","journal-title":"HNO"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1177\/1084713809336422","article-title":"Soft Cochlear Implantation: Rationale for the Surgical Approach","volume":"13","author":"Friedland","year":"2009","journal-title":"Trends Amplif."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1055\/s-0035-1558871","article-title":"Non-Mastoidectomy Cochlear Implant Approaches: A Literature Review","volume":"20","author":"Elaassar","year":"2016","journal-title":"Int. Arch. Otorhinolaryngol."},{"key":"ref_5","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"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/MAO.0b013e31802e29f2","article-title":"Vibration-Induced Hearing Loss: Mechanical and Physiological Aspects","volume":"28","author":"Sutinen","year":"2007","journal-title":"Otol. Neurotol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1177\/0194599811409516","article-title":"Effect of Aspiration of Perilymph during Stapes Surgery on the Endocochlear Potential of Guinea Pig","volume":"145","author":"Ikeda","year":"2011","journal-title":"Otolaryng. Head Neck Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/S0194-5998(97)70176-1","article-title":"Cochlear Implant Soft Surgery: Fact or Fantasy?","volume":"117","author":"Cohen","year":"1997","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_9","first-page":"45","article-title":"Initial investigation of the efficacy and biosafety of sodium hyaluronate (Healon) as an aid to electrode array insertion","volume":"166","author":"Donnelly","year":"1995","journal-title":"Ann. Otol. Rhinol. Laryngol. Suppl."},{"key":"ref_10","first-page":"64","article-title":"Effects of Glycerin, Hyaluronic Acid, and Hydroxypropyl Methylcellulose on the Spiral Ganglion of the Guinea Pig Cochlea","volume":"166","author":"Roland","year":"1995","journal-title":"Ann. Otol. Rhinol. Laryngol. Suppl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4279","DOI":"10.1007\/s00405-020-06554-y","article-title":"Comparison of Hearing Outcomes in Stapedotomy with Fat and Hyaluronic Acid Gel as a Sealing Material: A Prospective Double-Blind Randomized Clinical Trial","volume":"278","author":"Faramarzi","year":"2021","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1097\/MAO.0b013e31825f24de","article-title":"Friction Force Measurement during Cochlear Implant Insertion: Application to a Force-Controlled Insertion Tool Design","volume":"33","author":"Miroir","year":"2012","journal-title":"Otol. Neurotol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1001\/archotol.127.5.534","article-title":"Evaluation of Esterified Hyaluronic Acid as Middle Ear\u2013Packing Material","volume":"127","author":"Li","year":"2001","journal-title":"Arch. Otolaryngol. Neck Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1258\/0022215021910816","article-title":"Intracochlear Insertion of Electrodes Using Hyaluronic Acid in Cochlear Implant Surgery","volume":"116","author":"Laszig","year":"2002","journal-title":"J. Laryngol. Otol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1097\/MAO.0000000000002083","article-title":"Hearing Preservation in Cochlear Implant Surgery: A Meta-Analysis","volume":"40","author":"Snels","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"E326","DOI":"10.1097\/MAO.0000000000002127","article-title":"Individual Hearing Preservation Cochlear Implantation Using the Concept of Partial Insertion","volume":"40","author":"Lenarz","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1097\/01.mlg.0000173169.45262.ae","article-title":"Mild Hypothermia Protects Auditory Function during Cochlear Implant Surgery","volume":"115","author":"Balkany","year":"2005","journal-title":"Laryngoscope"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.heares.2016.05.015","article-title":"A Cool Approach to Reducing Electrode-Induced Trauma: Localized Therapeutic Hypothermia Conserves Residual Hearing in Cochlear Implantation","volume":"339","author":"Tamames","year":"2016","journal-title":"Hear. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1097\/AUD.0000000000000529","article-title":"Theoretical Evaluation and Experimental Validation of Localized Therapeutic Hypothermia Application to Preserve Residual Hearing following Cochlear Implantation","volume":"39","author":"Tamames","year":"2018","journal-title":"Ear Hear."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1097\/MAO.0000000000002373","article-title":"Anatomical Correlates and Surgical Considerations for Localized Therapeutic Hypothermia Application in Cochlear Implantation Surgery","volume":"40","author":"Perez","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"620691","DOI":"10.3389\/fneur.2020.620691","article-title":"Measurement of the Intracochlear Hypothermia Distribution Utilizing Tympanic Cavity Hypothermic Rinsing Technique in a Cochlea Hypothermia Model","volume":"11","author":"Bader","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_22","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 Otolaryngol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1055\/s-0036-1585094","article-title":"Methods of Hearing Preservation during Cochlear Implantation","volume":"21","author":"Khater","year":"2017","journal-title":"Int. Arch. Otorhinolaryngol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1097\/MAO.0b013e318288643e","article-title":"Hearing Preservation Surgery: Cochleostomy or Round Window Approach? A Systematic Review","volume":"34","author":"Havenith","year":"2013","journal-title":"Otol. Neurotol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e256","DOI":"10.1097\/MAO.0000000000000561","article-title":"Hearing Preservation Surgery for Cochlear Implantation: A Meta-Analysis","volume":"35","author":"Gluth","year":"2014","journal-title":"Otol. Neurotol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1186\/s13063-021-05878-2","article-title":"Evaluating Cochlear Insertion Trauma and Hearing Preservation after Cochlear Implantation (CIPRES): A Study Protocol for a Randomized Single-Blind Controlled Trial","volume":"22","author":"Jwair","year":"2021","journal-title":"Trials"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e825","DOI":"10.1097\/MAO.0000000000003165","article-title":"Robotics for Cochlear Implantation Surgery: Challenges and Opportunities","volume":"42","author":"Panara","year":"2021","journal-title":"Otol. Neurotol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1097\/MAO.0b013e318219f6ac","article-title":"Impact of the Insertion Speed of Cochlear Implant Electrodes on the Insertion Forces","volume":"32","author":"Kontorinis","year":"2011","journal-title":"Otol. Neurotol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1177\/0194599818792232","article-title":"An Optimized Robot-Based Technique for Cochlear Implantation to Reduce Array Insertion Trauma","volume":"159","author":"Torres","year":"2018","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_30","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_31","first-page":"11","article-title":"Cochlear and Brainstem Implants","volume":"64","author":"Roland","year":"2006","journal-title":"Adv. Otorhinolaryngol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1159\/000513509","article-title":"The Use of a Robot to Insert an Electrode Array of Cochlear Implants in the Cochlea: A Feasibility Study and Preliminary Results","volume":"26","author":"Barriat","year":"2021","journal-title":"Audiol. Neurootol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"695728","DOI":"10.3389\/fsurg.2021.695728","article-title":"Robot-Assisted Electrode Array Insertion Becomes Available in Pediatric Cochlear Implant Recipients: First Report and an Intra-Individual Study","volume":"8","author":"Jia","year":"2021","journal-title":"Front. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e438","DOI":"10.1097\/MAO.0000000000003002","article-title":"Robot-Assisted Cochlear Implant Electrode Array Insertion in Adults: A Comparative Study with Manual Insertion","volume":"42","author":"Daoudi","year":"2021","journal-title":"Otol. Neurotol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"729736","DOI":"10.3389\/fsurg.2021.729736","article-title":"Restoration of High Frequency Auditory Perception after Robot-Assisted or Manual Cochlear Implantation in Profoundly Deaf Adults Improves Speech Recognition","volume":"8","author":"Torres","year":"2021","journal-title":"Front. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"359","DOI":"10.4103\/tcmj.tcmj_181_20","article-title":"Residual Hearing Preservation for Cochlear Implantation Surgery","volume":"33","author":"Lin","year":"2021","journal-title":"Tzu-Chi Med. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1159\/000073516","article-title":"Cortisol Levels in the Human Perilymph after Intravenous Administration of Prednisolone","volume":"8","author":"Niedermeyer","year":"2003","journal-title":"Audiol. Neurootol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.heares.2015.06.010","article-title":"The Role of Extended Preoperative Steroids in Hearing Preservation Cochlear Implantation","volume":"327","author":"Kuthubutheen","year":"2015","journal-title":"Hear. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.heares.2009.05.010","article-title":"Factors Influencing the Efficacy of Round Window Dexamethasone Protection of Residual Hearing Post-Cochlear Implant Surgery","volume":"255","author":"Chang","year":"2009","journal-title":"Hear. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lyu, A.R., Kim, D.H., Lee, S.H., Shin, D.S., Shin, S.A., and Park, Y.H. (2018). Effects of Dexamethasone on Intracochlear Inflammation and Residual Hearing after Cochleostomy: A Comparison of Administration Routes. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195230"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Skarzynska, M.B., Kolodziejak, A., Gos, E., and Skarzynski, P.H. (2021). The Clinical Effects of Steroids Therapy in the Preserving Residual Hearing after Cochlear Implantation with the OTICON Neuro Zti EVO. J. Clin. Med., 10.","DOI":"10.3390\/jcm10132868"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"468515","DOI":"10.1155\/2014\/468515","article-title":"Hearing Preservation in Cochlear Implant Surgery","volume":"2014","author":"Miranda","year":"2014","journal-title":"Int. J. Otolaryngol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00106-016-0285-9","article-title":"Intracochlear Drug Delivery in Combination with Cochlear Implants: Current Aspects","volume":"65","author":"Plontke","year":"2017","journal-title":"HNO"},{"key":"ref_44","first-page":"564","article-title":"Intratympanic Injection of Dexamethasone: Time Course of Inner Ear Distribution and Conversion to Its Active Form","volume":"27","author":"Hargunani","year":"2006","journal-title":"Otol. Neurotol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10162-013-0372-5","article-title":"Effects of Brain-Derived Neurotrophic Factor (BDNF) and Electrical Stimulation on Survival and Function of Cochlear Spiral Ganglion Neurons in Deafened, Developing Cats","volume":"14","author":"Leake","year":"2013","journal-title":"JARO J. Assoc. Res. Otolaryngol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.heares.2007.02.010","article-title":"Cochlear Implants and Ex Vivo BDNF Gene Therapy Protect Spiral Ganglion Neurons","volume":"228","author":"Rejali","year":"2007","journal-title":"Hear. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.heares.2012.04.007","article-title":"Stable Release of BDNF from the Fibroblast Cell Line NIH3T3 Grown on Silicone Elastomers Enhances Survival of Spiral Ganglion Cells in Vitro and in Vivo","volume":"289","author":"Warnecke","year":"2012","journal-title":"Hear. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biomaterials.2016.12.020","article-title":"Guided Growth of Auditory Neurons: Bioactive Particles towards Gapless Neural\u2014Electrode Interface","volume":"122","author":"Li","year":"2017","journal-title":"Biomaterials"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s10162-017-0633-9","article-title":"Neurotrophin Gene Therapy in Deafened Ears with Cochlear Implants: Long-Term Effects on Nerve Survival and Functional Measures","volume":"18","author":"Pfingst","year":"2017","journal-title":"JARO J. Assoc. Res. Otolaryngol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.mcn.2013.03.003","article-title":"Insulin-like Growth Factor 1 Inhibits Hair Cell Apoptosis and Promotes the Cell Cycle of Supporting Cells by Activating Different Downstream Cascades after Pharmacological Hair Cell Injury in Neonatal Mice","volume":"56","author":"Hayashi","year":"2013","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.heares.2015.04.009","article-title":"Insulin-like Growth Factor 1: A Novel Treatment for the Protection or Regeneration of Cochlear Hair Cells","volume":"330 Pt A","author":"Yamahara","year":"2015","journal-title":"Hear. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3389\/fnagi.2017.00411","article-title":"The Role of Insulin-Like Growth Factor 1 in the Progression of Age-Related Hearing Loss","volume":"9","author":"Lassaletta","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"571155","DOI":"10.3389\/fncel.2020.571155","article-title":"Insulin-Like Growth Factor 1 on the Maintenance of Ribbon Synapses in Mouse Cochlear Explant Cultures","volume":"14","author":"Gao","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Nakagawa, T., Sakamoto, T., Hiraumi, H., Kikkawa, Y.S., Yamamoto, N., Hamaguchi, K., Ono, K., Yamamoto, M., Tabata, Y., and Teramukai, S. (2010). Topical Insulin-like Growth Factor 1 Treatment Using Gelatin Hydrogels for Glucocorticoid-Resistant Sudden Sensorineural Hearing Loss: A Prospective Clinical Trial. BMC Med., 8.","DOI":"10.1186\/1741-7015-8-76"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"207","DOI":"10.5152\/iao.2021.8549","article-title":"Effects of Insulin-Like Growth Factor (IGF-1) in Patients with Sensorineural Hearing Loss","volume":"17","author":"Dave","year":"2021","journal-title":"J. Int. Adv. Otol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1186\/s12967-014-0280-4","article-title":"Growth Factor-Eluting Cochlear Implant Electrode: Impact on Residual Auditory Function, Insertional Trauma, and Fibrosis","volume":"12","author":"Kikkawa","year":"2014","journal-title":"J. Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1017\/S0022215117000135","article-title":"The Effect of Local Application of Insulin-like Growth Factor for Prevention of Inner-Ear Damage Caused by Electrode Trauma","volume":"131","author":"Gur","year":"2017","journal-title":"J. Laryngol. Otol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1183\/09031936.06.00012106","article-title":"C-Jun N-Terminal Kinase-Dependent Mechanisms in Respiratory Disease","volume":"28","author":"Bennett","year":"2006","journal-title":"Eur. Respir. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/ar.a.20305","article-title":"Cochlear Implantation Trauma and Noise-Induced Hearing Loss: Apoptosis and Therapeutic Strategies","volume":"288A","author":"Eshraghi","year":"2006","journal-title":"Anat. Rec. Part A Discov. Mol. Cell. Evol. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8596","DOI":"10.1523\/JNEUROSCI.23-24-08596.2003","article-title":"A Peptide Inhibitor of C-Jun N-Terminal Kinase Protects against Both Aminoglycoside and Acoustic Trauma-Induced Auditory Hair Cell Death and Hearing Loss","volume":"23","author":"Wang","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1097\/MAO.0000000000002229","article-title":"Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness\u2014A Double-Blind, Randomized, Placebo-Controlled Phase 3 Study","volume":"40","author":"Staecker","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1097\/00129492-200606000-00012","article-title":"D-JNKI-1 Treatment Prevents the Progression of Hearing Loss in a Model of Cochlear Implantation Trauma","volume":"27","author":"Eshraghi","year":"2006","journal-title":"Otol. Neurotol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.heares.2006.09.008","article-title":"Blocking C-Jun-N-Terminal Kinase Signaling Can Prevent Hearing Loss Induced by Both Electrode Insertion Trauma and Neomycin Ototoxicity","volume":"226","author":"Eshraghi","year":"2007","journal-title":"Hear. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1179\/146701010X12671177544104","article-title":"Inhibition of the JNK Signal Cascade Conserves Hearing against Electrode Insertion Trauma-Induced Loss","volume":"11","author":"Eshraghi","year":"2010","journal-title":"Cochlear Implant. Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1002\/lary.23902","article-title":"Molecular Mechanisms Involved in Cochlear Implantation Trauma and the Protection of Hearing and Auditory Sensory Cells by Inhibition of C-Jun-N-Terminal Kinase Signaling","volume":"123","author":"Eshraghi","year":"2013","journal-title":"Laryngoscope"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Sekulic-Jablanovic, M., Petkovic, V., Wright, M.B., Kucharava, K., Huerzeler, N., Levano, S., Brand, Y., Leitmeyer, K., Glutz, A., and Bausch, A. (2017). Effects of Peroxisome Proliferator Activated Receptors (PPAR)-\u03b3 and -\u03b1 Agonists on Cochlear Protection from Oxidative Stress. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188596"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"566148","DOI":"10.3389\/fncel.2020.566148","article-title":"Pioglitazone Ameliorates Gentamicin Ototoxicity by Affecting the TLR and STAT Pathways in the Early Postnatal Organ of Corti","volume":"14","author":"Wright","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.3389\/fphar.2018.01103","article-title":"Pioglitazone Represents an Effective Therapeutic Target in Preventing Oxidative\/Inflammatory Cochlear Damage Induced by Noise Exposure","volume":"9","author":"Paciello","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Paciello, F., Pisani, A., Rolesi, R., Escarrat, V., Galli, J., Paludetti, G., Grassi, C., Troiani, D., and Fetoni, A.R. (2021). Noise-Induced Cochlear Damage Involves PPAR Down-Regulation through the Interplay between Oxidative Stress and Inflammation. Antioxidants, 10.","DOI":"10.3390\/antiox10081188"},{"key":"ref_70","unstructured":"(2022, March 17). Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL. ClinicalTrials.gov Identifier NCT03331627. Updated 25 March 2020, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03331627."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"960","DOI":"10.3892\/ijmm.2017.2916","article-title":"Fenofibrate Exerts Protective Effects against Gentamicin-Induced Toxicity in Cochlear Hair Cells by Activating Antioxidant Enzymes","volume":"39","author":"Park","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1152\/jn.00417.2020","article-title":"Metformin Alleviates Cisplatin-Induced Ototoxicity by Autophagy Induction Possibly via the AMPK\/FOXO3a Pathway","volume":"125","author":"Liang","year":"2021","journal-title":"J. Neurophysiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"102328","DOI":"10.1016\/j.amjoto.2019.102328","article-title":"Therapeutic Effects of Metformin for Noise Induced Hearing Loss","volume":"41","author":"Gedik","year":"2020","journal-title":"Am. J. Otolaryngol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1159\/000438918","article-title":"Metformin Protects Auditory Hair Cells from Gentamicin-Induced Toxicity in Vitro","volume":"20","author":"Glutz","year":"2015","journal-title":"Audiol. Neurotol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.heares.2006.10.008","article-title":"NAC for Noise: From the Bench Top to the Clinic","volume":"226","author":"Kopke","year":"2007","journal-title":"Hear. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"420","DOI":"10.3109\/00016489.2015.1134809","article-title":"A Novel Combination of Drug Therapy to Protect Residual Hearing Post Cochlear Implant Surgery","volume":"136","author":"Eshraghi","year":"2016","journal-title":"Acta Oto-Laryngol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1080\/00016489.2018.1440086","article-title":"L-N-Acetylcysteine Protects Outer Hair Cells against TNF\u03b1 Initiated Ototoxicity in Vitro","volume":"138","author":"Tillinger","year":"2018","journal-title":"Acta Otolaryngol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Eshraghi, A.A., Shahal, D., Davies, C., Mittal, J., Shah, V., Bulut, E., Garnham, C., Sinha, P., Mishra, D., and Marwede, H. (2020). Evaluating the Efficacy of L-N-Acetylcysteine and Dexamethasone in Combination to Provide Otoprotection for Electrode Insertion Trauma. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030716"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.heares.2009.08.010","article-title":"Permanent and Transient Effects of Locally Delivered N-Acetyl Cysteine in a Guinea Pig Model of Cochlear Implantation","volume":"259","author":"Eastwood","year":"2010","journal-title":"Hear. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"120757","DOI":"10.1016\/j.ijpharm.2021.120757","article-title":"Transtympanic Injection of a Liposomal Gel Loaded with N-Acetyl-L-Cysteine: A Relevant Strategy to Prevent Damage Induced by Cochlear Implantation in Guinea Pigs?","volume":"604","author":"Jaudoin","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1002\/ar.22574","article-title":"Conservation of Hearing and Protection of Hair Cells in Cochlear Implant Patients\u2019 with Residual Hearing","volume":"295","author":"Bas","year":"2012","journal-title":"Anat. Rec. Adv. Integr. Anat. Evol. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Bai, X., Wang, M., Niu, X., Yu, H., Yue, J., and Sun, Y. (2021). Effect of N-Acetyl-Cysteine Treatment on Sensorineural Hearing Loss: A Meta-Analysis. World J. Otorhinolaryngol. Head Neck Surg., in press.","DOI":"10.1016\/j.wjorl.2021.01.005"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3389\/fnmol.2020.00113","article-title":"Evaluating the Efficacy of Taurodeoxycholic Acid in Providing Otoprotection Using an in Vitro Model of Electrode Insertion Trauma","volume":"13","author":"Shah","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.jconrel.2011.12.032","article-title":"Predictability of Drug Release from Cochlear Implants","volume":"159","author":"Krenzlin","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"107825","DOI":"10.1016\/j.heares.2019.107825","article-title":"Long-Term Effects and Potential Limits of Intratympanic Dexamethasone-Loaded Hydrogels Combined with Dexamethasone-Eluting Cochlear Electrodes in a Low-Insertion Trauma Guinea Pig Model","volume":"384","author":"Ahmadi","year":"2019","journal-title":"Hear. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.3389\/fneur.2019.01377","article-title":"Long-Term in Vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs","volume":"10","author":"Liebau","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_87","first-page":"100088","article-title":"Dexamethasone-Loaded Cochlear Implants: How to Provide a Desired \u201cBurst Release\u201d","volume":"3","author":"Qnouch","year":"2021","journal-title":"Int. J. Pharm. X"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"492","DOI":"10.3389\/fncel.2019.00492","article-title":"Otoprotection to Implanted Cochlea Exposed to Noise Trauma with Dexamethasone Eluting Electrode","volume":"13","author":"Eshraghi","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_89","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_90","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1179\/1754762813Y.0000000053","article-title":"Dexamethasone Eluting Electrodes for Cochlear Implantation: Effect on Residual Hearing","volume":"16","author":"Douchement","year":"2015","journal-title":"Cochlear Implant. Int."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"740576","DOI":"10.3389\/fcell.2021.740576","article-title":"Long-Term Release of Dexamethasone with a Polycaprolactone-Coated Electrode Alleviates Fibrosis in Cochlear Implantation","volume":"9","author":"Chen","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_92","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":"Drug Des. Devel. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7794384","DOI":"10.1155\/2022\/7794384","article-title":"Recent Advances and Future Research Directions for Hearing Loss Treatment Based on Nanoparticles","volume":"2022","author":"Dindelegan","year":"2022","journal-title":"J. Nanomater."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3098230","DOI":"10.1155\/2017\/3098230","article-title":"Nanomedicine for Inner Ear Diseases: A Review of Recent in Vivo Studies","volume":"2017","author":"Kim","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4244","DOI":"10.1002\/smll.201401767","article-title":"Mesoporous Silica Supraparticles for Sustained Inner-Ear Drug Delivery","volume":"10","author":"Wang","year":"2014","journal-title":"Small"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Wise, A.K., Tan, J., Wang, Y., Caruso, F., and Shepherd, R.K. (2016). Improved Auditory Nerve Survival with Nanoengineered Supraparticles for Neurotrophin Delivery into the Deafened Cochlea. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0164867"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1002\/adma.201200634","article-title":"Nanoporous Peptide Particles for Encapsulating and Releasing Neurotrophic Factors in an Animal Model of Neurodegeneration","volume":"24","author":"Tan","year":"2012","journal-title":"Adv. Mater."},{"key":"ref_98","first-page":"2449","article-title":"Lipidic Nanocapsule Drug Delivery: Neuronal Protection for Cochlear Implant Optimization","volume":"7","author":"Meyer","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kanzaki, S., Toyoda, M., Umezawa, A., and Ogawa, K. (2020). Application of Mesenchymal Stem Cell Therapy and Inner Ear Regeneration for Hearing Loss: A Review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165764"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3389\/fncel.2019.00177","article-title":"Stem Cell Based Drug Delivery for Protection of Auditory Neurons in a Guinea Pig Model of Cochlear Implantation","volume":"13","author":"Scheper","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13287-016-0408-y","article-title":"Biohybrid Cochlear Implants in Human Neurosensory Restoration","volume":"7","author":"Roemer","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_102","unstructured":"Shearer, A.E., Hildebrand, M.S., and Smith, R.J. (2022, May 30). Hereditary Hearing Loss and Deafness Overview, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1434\/."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3389\/fncel.2019.00323","article-title":"Gene Therapy for Human Sensorineural Hearing Loss","volume":"13","author":"Ren","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s10162-017-0634-8","article-title":"Emerging Gene Therapies for Genetic Hearing Loss","volume":"18","author":"Ahmed","year":"2017","journal-title":"JARO J. Assoc. Res. Otolaryngol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"233ra54","DOI":"10.1126\/scitranslmed.3008177","article-title":"Close-Field Electroporation Gene Delivery Using the Cochlear Implant Electrode Array Enhances the Bionic Ear","volume":"6","author":"Pinyon","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Atkinson, P.J., Wise, A.K., Flynn, B.O., Nayagam, B.A., Hume, C.R., O\u2019Leary, S.J., Shepherd, R.K., and Richardson, R.T. (2012). Neurotrophin Gene Therapy for Sustained Neural Preservation after Deafness. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052338"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/srep00838","article-title":"BDNF Gene Therapy Induces Auditory Nerve Survival and Fiber Sprouting in Deaf Pou4f3 Mutant Mice","volume":"2","author":"Fukui","year":"2012","journal-title":"Sci. Rep."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/6\/747\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:22:22Z","timestamp":1760138542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/6\/747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,31]]},"references-count":107,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["medicina58060747"],"URL":"https:\/\/doi.org\/10.3390\/medicina58060747","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,31]]}}}