Pharmacology of the inner ear

We develop and examine strategies to deliver drugs to the auditory system in order to prevent hearing loss and improve the outcome of cochlear implants by protecting the auditory neurons and residual sensory cells as well as reducing fibrous tissue reactions. We are identifying relevant drug targets, kinetics and pharmacotherapies in addition to development and testing of suitable drug delivery systems. Our methodology covers the whole range from in vitro cell culture and explant studies via in vivo research onto clinical trial conduction.

Research

GROUP LEADER
PD Dr.
Verena Scheper
Department of Otorhinolaryngology
Nina Armbrecht
Ziwen Gao
PhD student
M. Sc.
Marleen Grzybowski
Martina Knabel
Finnja Köpke
Michaela Kreienmeyer
Technical assistance
Yanjing Luo
Kathrin Anja Malfeld
PhD student
Dr.
Farnaz Matin
Dr.
Jana Schwieger
Post-Doc
Chunjiang Wei

Publications

2021

Gao Z, Schwieger J, Matin-Mann F, Behrens P, Lenarz T, Scheper V. Dexamethasone for Inner Ear Therapy: Biocompatibility and Bio-Efficacy of Different Dexamethasone Formulations In Vitro Biomolecules, December 2021.

Gao Z, Matin-Mann F, Wei C, Lenarz T, Weber C, John S, Scheper V. 3D Printed Individualized Frontal Neo-Ostium Implant in Endoscopic Sinus Surgery - a Proof of Concept Study Current Directions in Biomedical Engineering, December 2021.

Abdoul T, Schwieger J, Lenarz T, Nogueira W, Scheper V. Investigation of auditory neuronal survival and outgrowth using a cochlear implant in an artificial cochlear model Current Directions in Biomedical Engineering, December 2021.

Peck CT, Schwieger J, Lenarz T, Scheper V. Stability and Biocompatibility Tests of Alginate as Cochlear Implant Coating Material Current Directions in Biomedical Engineering, December 2021.

Mau R, Jüttner G, Gao Z, Matin F, Alcacer Labrador D, Repp F, John S, Scheper V, Lenarz T, Seitz H. Micro injection molding of individualised implants using 3D printed molds manufactured via digital light processing Current Directions in Biomedical Engineering, December 2021.

Usevitch DE, Park A, Scheper V, Abbott JJ. Estimating the Pose of a Guinea-pig Cochlea Without Medical Imaging Otology & Neurotology, October 2021.

Angrisani N, Willumeit-Römer R, Windhagen H, Mavila Chathoth B, Scheper V, Wiese B, Helmholz H, Reifenrath J. Small-sized magnesium cylinders influence subchondral bone quality in osteoarthritic rabbits - an in vivo pilot study European Cells & Materials 42:179-195, September 2021.

Matin F, Gao Z, Bronzlik P, Lenarz T, Scheper V. A 3D printed patient specific artificial outer ear model for use in auricle reconstruction surgery: a clinical feasibility study Transactions on Additive Manufacturing Meets Medicine, Vol 3 No 1 (2021);

Mau R, Jüttner G, Gao Z, Matin F, Alcacer Labrador D, Repp F, John S, Scheper V, Lenarz T, Seitz H. Rapid tooling for micro injection molding of micro medical devices via digital light processing Transactions on Additive Manufacturing Meets Medicine, Vol 3 No 1 (2021).

Shityakov S, Hayashi K, Störk S, Scheper V, Lenarz T, Förster CY The Conspicuous Link between Ear, Brain and Heart-Could Neurotrophin Treatment of Age-Related Hearing Loss Help Prevent Alzheimer's Disease and Associated Amyloid Cardiomyopathy? Biomolecules, 2021; 11(6):900

Matin F, Gao Z, Repp F, John S, Lenarz T, Scheper V. Determination of the Round Window Niche Anatomy Using Cone Beam Computed Tomography Imaging as Preparatory Work for Individualized Drug-Releasing Implants Journal of Imaging, 2021 April 23.

Schurzig D, Fröhlich M, Raggl S, Scheper V, Lenarz T, Rau TS. Uncoiling the Human Cochlea-Physical Scala Tympani Models to Study Pharmacokinetics Inside the Inner Ear Life, 2021 April 21.

Malfeld K, Armbrecht N, Volk HA, Lenarz T, Scheper V. In Situ 3D-Imaging of the Inner Ear Synapses with a Cochlear Implant Life, 2021 April 01.

Gärtner L, Klötzer K, Lenarz T, Scheper V. Correlation of Electrically Evoked Compound Action Potential Amplitude Growth Function Slope and Anamnestic Parameters in Cochlear Implant Patients-Identification of Predictors for the Neuronal Health Status Life, 2021 March 05.

2020

Gao Z, Matin F, Weber C, John S, Lenarz T, Scheper V. High Variability of Postsurgical Anatomy Supports the Need for Individualized Drug-Eluting Implants to Treat Chronic Rhinosinusitis Life (Basel), 2020 Dec 17.

Nagai M, Scheper V, Lenarz T, Förster CY. The insular cortex as a vestibular area in relation to autonomic function Clin Auton Res. 2020 Dec 1.

Knipper M, van Dijk P,Schulze H, Mazurek B, Krauss P, Scheper V, Warnecke A, Schlee W, Schwabe K, Singer W, Braun C, Delano PH, Fallgatter AJ, Ehlis A, Searchfield GD, Munk MHJ, Baguley DM, Rüttiger L. The Neural Bases of Tinnitus: Lessons from Deafness and Cochlear Implants J. Neurosci. Res., 2020 Sep 16.

Scheper V, Seidel-Effenberg I, Lenarz T, Stöver T, Paasche G. Consecutive Treatment with Brain-Derived Neurotrophic Factor and Electrical Stimulation Has a Protective Effect on Primary Auditory Neurons. Brain Sci.2020, August 15.

Scheper V, Schmidtheisler M, Lasch F, von der Leyen H, Koch A, Schwieger J, Büchner A, Lesinski-Schiedat A, Lenarz T. Randomized placebo-controlled clinical trial investigating the effect of antioxidants and a vasodilator on overall safety and residual hearing preservation in cochlear implant patients . Trials, 2020 July 15.

Schwieger J, Hamm A, Gepp M M, Schulz A, Hoffmann A, Lenarz T, Scheper V Alginate-encapsulated brain-derived neurotrophic factor-overexpressing mesenchymal stem cells are a promising drug delivery system for protection of auditory neurons . J Tissue Eng. 11, 2020 April 17.

2019

Förster CY, Scheper V, Lenarz T. Hearing loss and strial microvascular pathology-towards unravelling the functional contribution of the blood-labyrinth barrier. Otorhinolaryngol Head Neck Surg, 2019 Nov 25.

Yilmaz-Bayraktar S, Schwieger J, Scheper V, Lenarz T, Böer U, Kreienmeyer M, Torrente M, Doll T. Decellularized equine carotid artery layers as matrix for regenerated neurites of spiral ganglion neurons. Int. J. Art. Organs, 2019 August 22.

Scheper V, Schwieger J, Hamm A, Lenarz T, Hoffmann A. BDNF-overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro. J. Neurosci. Res., 2019 June 30.

Scheper V, Hoffmann A, Gepp M M, Schulz A, Hamm A, Pannier C, Hubka P, Lenarz T, Schwieger J. Stem Cell Based Drug Delivery for Protection of Auditory Neurons in a Guinea Pig Model of Cochlear Implantation. Front. Cell. Neurosci., 2019 May 14.

Hügl S, Scheper V, Gepp M M, Lenarz Th, Rau Th S, Schwieger J. Coating stability and insertion forces of an alginate-cell-based drug delivery implant system for the inner ear. J Mech Behav Biomed Mater. doi: 10.1016/j.jmbbm.2019.05.007. Epub 2019 May 4.

2017

Berger C, Kühne D, Scheper V, Kral A. Congenital deafness affects deep layers in primary and secondary auditory cortex. J Comp Neurol. 2017 Oct 1;525(14):3110-3125. doi: 10.1002/cne.24267. epub 2017 Jul 13.

Scheper V, Hessler R, Hütten M, Wilk M, Jolly C, Lenarz T, Paasche G. Local inner ear application of dexamethasone in cochlear implant models is safe for auditory neurons and increases the neuroprotective effect of chronic electrical stimulation.PLoS One. 2017 Aug 31;12(8):e0183820. doi: 10.1371/journal.pone.0183820. eCollection 2017.

Konerding WS, Janssen H, Hubka P, Tornøe J, Mistrik P, Wahlberg L, Lenarz T, Kral A, Scheper V. Encapsulated cell device approach for combined electrical stimulation and neurotrophic treatment of the deaf cochlea. Hear Res. 2017 Apr 25;350:110-121.

Schmitt HA, Pich A, Schröder A, Scheper V, Lilli G, Reuter G, Lenarz T. Proteome Analysis of Human Perilymph Using an Intraoperative Sampling Method. J Proteome Res. 2017 Apr 13. doi: 10.1021/acs.jproteome.6b00986.

2016

Scheper V, Leifholz M, von der Leyen H, Keller M, Denkena U, Koch A, Karch A, Miller J, Lenarz T. ACEMg-mediated hearing preservation in cochlear implant patients receiving different electrode lengths (PROHEARING): study protocol for a randomized controlled trial. Trials. 2016 Aug 8;17:394. doi: 10.1186/s13063-016-1526-7

Schwieger J, Esser KH, Lenarz T, Scheper V. Establishment of a long-term spiral ganglion neuron culture with reduced glial cell number: Effects of AraC on cell composition and neurons. J Neurosci Methods. 2016 Aug 1;268:106-16. doi: 10.1016/j.jneumeth.2016.05.001. Epub 2016 May 3.

Wilk M, Hessler R, Mugridge K, Jolly C, Fehr M, Lenarz T, Scheper V. Impedance Changes and Fibrous Tissue Growth after Cochlear Implantation Are Correlated and Can Be Reduced Using a Dexamethasone Eluting Electrode. PLoS One. 2016 Feb 3;11(2):e0147552. doi: 10.1371/journal.pone.0147552.

2015

Schwieger J, Warnecke A, Lenarz T, Esser KH, Scheper V. Neuronal Survival, Morphology and Outgrowth of Spiral Ganglion Neurons Using a Defined Growth Factor Combination. PLoS One. 2015 Aug 11;10(8):e0133680. doi: 10.1371/journal.pone.0133680.

Lenarz T, Scheper V. Preserving Residual Hearing in Cochlear Implant Patients. in Free Radicals in ENT Pathology. Eds: Miller J, LePrell CG, Rybak L, Springer 2015, ISBN 978-3-319-13473-4.

Linke I, Fadeeva E, Scheper V, Esser KH, Koch J, Chichkov B, Lenarz T, Paasche G. Nanostructuring of cochlear implant electrode contacts induces delayed impedance increase in vivo. Phys. Status Solidi A. 2015 Feb. 3;6; 1210-1215.

2014

Miller F, Burghard A, Salcher R, Scheper V, Leibold W, Lenarz T, Paasche G. Treatment of middle ear ventilation disorders: sheep as animal model for stenting the human eustachian tube - a cadaver study. PLoS One. 2014 Nov 24;9(11):e113906. doi: 10.1371/journal.pone.0113906. eCollection 2014.

Hütten M, Dhanasingh A, Hessler R, Stöver T, Esser KH, Möller M, Lenarz T, Jolly C, Groll J, Scheper V. In vitro and in vivo evaluation of a hydrogel reservoir as a continuous drug delivery system for inner ear treatment. PLoS One. 2014 Aug 8;9(8):e104564. doi: 10.1371/journal.pone.0104564. eCollection 2014.

Kranz K, Warnecke A, Lenarz T, Durisin M, Scheper V. Phosphodiesterase type 4 inhibitor rolipram improves survival of spiral ganglion neurons in vitro. PLoS One. 2014 Mar 18;9(3):e92157. doi: 10.1371/journal.pone.0092157. eCollection 2014.

Ceschi P, Bohl A, Sternberg K, Neumeister A, Senz V, Schmitz KP, Kietzmann M, Scheper V, Lenarz T, Stöver T, Paasche G. Biodegradable polymeric coatings on cochlear implant surfaces and their influence on spiral ganglion cell survival. J Biomed Mater Res B Appl Biomater. 2014 Aug;102(6):1255-67. doi: 10.1002/jbm.b.33110. epub 2014 Jan 17.

2013

Rode T, Hartmann T, Hubka P, Scheper V, Lenarz M, Lenarz T, Kral A, Lim HH. Neural representation in the auditory midbrain of the envelope of vocalizations based on a peripheral ear model. Front Neural Circuits. 2013 Oct 21;7:166. doi: 10.3389/fncir.2013.00166. eCollection 2013.

Wrzeszcz A, Reuter G, Nolte I, Lenarz T, Scheper V. Spiral ganglion neuron quantification in the guinea pig cochlea using confocal laser scanning microscopy compared to embedding methods. Hear Res. 2013 Dec;306:145-55. doi:10.1016/j.heares.2013.08.002. Epub 2013 Aug 20.

Hütten M, Ehrhart F, Zimmermann H, Reich U, Esser KH, Lenarz T, Scheper V. UHV-alginate as matrix for neurotrophic factor producing cells--a novel biomaterial for cochlear implant optimization to preserve inner ear neurons from degeneration. Otol Neurotol. 2013 Aug;34(6):1127-33. doi: 10.1097/MAO.0b013e3182804949. Erratum in: Otol Neurotol. 2013 Dec;34(9):1751.

Before 2013
Meyer H, Stöver T, Fouchet F, Bastiat G, Saulnier P, Bäumer W, Lenarz T, Scheper V. Lipidic nanocapsule drug delivery: neuronal protection for cochlear implant optimization. Int J Nanomedicine. 2012;7:2449-64. doi: 10.2147/IJN.S29712. Epub 2012 May 15.

Kontorinis G, Scheper V, Wissel K, Stöver T, Lenarz T, Paasche G. In vitro modifications of the scala tympani environment and the cochlear implant array surface. Laryngoscope. 2012 Sep;122(9):2057-63. doi: 10.1002/lary.23408. epub 2012 May 30.

Calixto R, Lenarz M, Neuheiser A, Scheper V, Lenarz T, Lim HH. Coactivation of different neurons within an isofrequency lamina of the inferior colliculus elicits enhanced auditory cortical activation. J Neurophysiol. 2012 Aug;108(4):1199-210. doi: 10.1152/jn.00111.2012. epub 2012 May 23.

Warnecke A, Sasse S, Wenzel GI, Hoffmann A, Gross G, Paasche G, Scheper V, Reich U, Esser KH, Lenarz T, Stöver T, Wissel K. 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. Hear Res. 2012 Jul;289(1-2):86-97. doi: 10.1016/j.heares.2012.04.007. Epub 2012 Apr 28.

Warnecke A, Scheper V, Buhr I, Wenzel GI, Wissel K, Paasche G, Berkingali N, Jørgensen JR, Lenarz T, Stöver T. Artemin improves survival of spiral ganglion neurons in vivo and in vitro. Neuroreport. 2010 May 12;21(7):517-21. doi:10.1097/WNR.0b013e328339045b.

Scheper V, Wolf M, Scholl M, Kadlecova Z, Perrier T, Klok HA, Saulnier P, Lenarz T, Stöver T. Potential novel drug carriers for inner ear treatment: hyperbranched polylysine and lipid nanocapsules. Nanomedicine (Lond). 2009 Aug;4(6):623-35. doi: 10.2217/nnm.09.41.

Scheper V, Paasche G, Miller JM, Warnecke A, Berkingali N, Lenarz T, Stöver T. Effects of delayed treatment with combined GDNF and continuous electrical stimulation on spiral ganglion cell survival in deafened guinea pigs. J Neurosci Res. 2009 May 1;87(6):1389-99. doi: 10.1002/jnr.21964.

Stöver T, Scheper V, Diensthuber M, Lenarz T, Wefstaedt P. In vitro neurite outgrowth induced by BDNF and GDNF in combination with dexamethasone on cultured spiral ganglion cells. Laryngorhinootology. 2007 May;86(5):352-7. epub 2006 Dec 12. in German.

Wefstaedt P, Scheper V, Rieger H, Lenarz T, Stöver T. Neurotrophic factors of the GDNF family and their receptors are detectable in spiral ganglion cells of normal hearing as well as of deafened rats. Laryngorhinootology. 2006 Nov;85(11):802-8. epub 2006 Apr 10. in German.

Wefstaedt P, Scheper V, Lenarz T, Stöver T. Brain-derived neurotrophic factor/glial cell line-derived neurotrophic factor survival effects on auditory neurons are not limited by dexamethasone. Neuroreport. 2005 Dec 19;16(18):2011-4.

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Keywords
Hearing preservation, cochlear implant optimization, electrode-nerve interface, drug delivery, pharmacotherapy, hydrogel, neuritogenesis, neuroprotection, translational research, fibrosis, 3D printing.
Contact

Verena Scheper

+ 49 (0)511 532 4369

scheper.verena(at)mh-hannover.de

Hanover Medical School
Ear, Nose and Throat Clinic

NIFE
Stadtfelddamm 34
30625 Hanover

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