Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model

Otol Neurotol. 2015 Aug;36(7):1279-83. doi: 10.1097/MAO.0000000000000795.


Hypothesis: That heparin binding epidermal growth factor-like growth factor (HB-EGF) heals chronic tympanic membrane (TM) perforations at higher rates than fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) in an animal model.

Background: A nonsurgical treatment for chronic TM perforation would benefit those unable to access surgery or those unable to have surgery, as well as reducing the cost of tympanoplasty. Growth factor (GF) treatments have been reported in the literature with variable success with the lack of a suitable animal providing a major obstacle.

Methods: The GFs were tested in a validated mouse model of chronic TM perforation. A bioabsorbable hydrogel polymer was used to deliver the GF at a steady concentration as it dissolved over 4 weeks. A control (polymer only, n = 18) was compared to polymer loaded with HB-EGF (5 μg/ml, n = 18), FGF2 (100 μg/ml, n = 19), and EGF (250 μg/ml, n = 19). Perforations were inspected at 4 weeks.

Results: The healing rates, as defined as 100% perforation closure, were control (5/18, 27.8%), HB-EGF (15/18, 83.3%), FGF2 (6/19, 31.6%), and EGF (3/19, 15.8%). There were no differences between FGF2 (p = 0.80) and EGF (p = 0.31) with control healing rates. HB-EGF (p = 0.000001) showed a significant difference for healing. The HB-EGF healed TMs showed layers similar to a normal TM, whereas the other groups showed a lack of epithelial migration.

Conclusion: This study confirms the advantage of HB-EGF over two other commonly used growth factors and is a promising nonsurgical treatment of chronic TM perforations.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Chronic Disease
  • Drug Delivery Systems
  • Epidermal Growth Factor / therapeutic use*
  • Fibroblast Growth Factor 2 / therapeutic use*
  • Heparin-binding EGF-like Growth Factor / administration & dosage
  • Heparin-binding EGF-like Growth Factor / therapeutic use*
  • Hydrogels
  • Male
  • Mice
  • Mice, Inbred CBA
  • Polymers
  • Tympanic Membrane Perforation / drug therapy*
  • Tympanic Membrane Perforation / psychology
  • Wound Healing / drug effects


  • Heparin-binding EGF-like Growth Factor
  • Hydrogels
  • Polymers
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor