title: Functional Outcomes of Heparin-Binding Epidermal Growth Factor-Like Growth Factor for Regeneration of Chronic Tympanic Membrane Perforations in Mice.
abstract: We aim to demonstrate that regeneration of chronic tympanic perforations with heparin-binding epidermal growth factor-like growth factor (HB-EGF) delivered by an injectable hydrogel restored hearing to levels similar to that of nonperforated tympanic membranes. Chronic tympanic membrane perforation is currently managed as an outpatient surgery with tympanoplasty. Due to the costs of this procedure in the developed world and a lack of accessibility and resources in developing countries, there is a great need for a new treatment that does not require surgery. In this study, we show in a mouse model through measurement of auditory brainstem response and distortion product otoacoustic emissions that tympanic perforations lead to hearing loss and this can be predominantly recovered with HB-EGF treatment (5 μg/mL). Our animal model suggests a return to function between 2 and 6 months after treatment. Auditory brainstem response thresholds had returned to the control levels at 2 months, but the distortion product otoacoustic emissions returned between 2 and 6 months. We also show how the vibration characteristics of the regenerated tympanic membrane, as measured by laser Doppler vibrometry, can be similar to that of an unperforated tympanic membrane. Using the best available methods for preclinical evaluation in animal models, it is likely that HB-EGF-like growth factor treatment leads to regeneration of chronic tympanic membrane perforations and restoration of the tympanic membrane to normal function, suggesting a potential route for nonsurgical treatment.
authors.affiliation: 1 Department of Otolaryngology, Head and Neck Surgery, Stanford University , Stanford, California.|2 Ear Sciences Centre, The University of Western Australia , Nedlands, Australia .|3 Ear Science Institute Australia , Subiaco, Australia .
authors.forename: Peter Luke
authors.initials: PL
authors.lastname: Santa Maria
authors.affiliation: 4 Department of Mechanical Engineering, Stanford University , Stanford, California.
authors.forename: Peter
authors.initials: P
authors.lastname: Gottlieb
authors.affiliation: 1 Department of Otolaryngology, Head and Neck Surgery, Stanford University , Stanford, California.|2 Ear Sciences Centre, The University of Western Australia , Nedlands, Australia .|3 Ear Science Institute Australia , Subiaco, Australia .
authors.forename: Chloe
authors.initials: C
authors.lastname: Santa Maria
authors.affiliation: 5 Department of Orthopedic Surgery, Stanford University , Stanford, California.
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Kim
authors.affiliation: 1 Department of Otolaryngology, Head and Neck Surgery, Stanford University , Stanford, California.|4 Department of Mechanical Engineering, Stanford University , Stanford, California.
authors.forename: Sunil
authors.initials: S
authors.lastname: Puria
authors.affiliation: 5 Department of Orthopedic Surgery, Stanford University , Stanford, California.|6 Department of Materials Science and Engineering, Stanford University , Stanford, California.|7 Department of Bioengineering, Stanford University , Stanford, California.
authors.forename: Yunzhi Peter
authors.initials: YP
authors.lastname: Yang
mesh_terms: D000818:Animals; D002908:Chronic Disease; D066257:Heparin-binding EGF-like Growth Factor / Q000494:pharmacology*; D051379:Mice; D012038:Regeneration / Q000187:drug effects*; D014432:Tympanic Membrane / Q000502:physiology*; D018058:Tympanic Membrane Perforation / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D066257:Heparin-binding EGF-like Growth Factor
keywords: HB-EGF; chronic perforation; tympanic membrane; tympanic regeneration