Bringing the first prosthetic eardrum to market

Each year there are millions of eardrum (tympanic membrane) perforations worldwide.  They can be the result of trauma, barotrauma, drugs, infection or genetic causes.

Most small, acute perforations will heal independently, but larger, more complex or chronic perforations require surgical intervention (tympanoplasty).  Tympanoplasty is the repair of the tympanic membrane using autologous graft material (temporalis fascia, cartilage or perichondrium).

Chronic middle ear disease leading to eardrum perforation is one of the major causes of hearing loss in indigenous populations in Western Australia and across the world. Our innovation will change the way the tympanic membrane is repaired and enhance the treatment and quality of life of patients worldwide.

Cleardrum Pty Ltd

ClearDrum Pty Ltd is a spinout from the Ear Science Institute Australia, leveraging over 10 years of research and development.

More than US$5 million has been invested to complete early-stage development, final prototyping, and pre-clinical testing.

The ClearDrum device was developed to provide an off-the-shelf implant that addresses the difficulties with current treatments in a single, straightforward surgical procedure. We partnered with Deakin University’s Future Fibers Hub to develop a prototype based on silk fibroin biomaterial and started the pre-clinical phase of development.

Technology and Innovation

Silk is an ideal biomaterial for tympanic membrane surgical repair

Silk fibroin from Bombyx Mori is an FDA-approved natural protein, renowned for its:

  • Biocompatibility
  • Tunable degradation
  • Mechanical strength
  • Good material supply, and
  • Easily scalable production

Biocompatibility of ClearDrum materials

Tested on tympanic membrane related human cell lines:

  • Human tympanic membrane keratinocytes (hTMk; primary cell lines)
  • Human dermal fibroblast (NHDF)
  • Human epithelial middle ear cells (HMEE)

ClearDrum supports the growth of the tympanic membrane cells, promoting tissue regeneration.

Silk biomaterials manufacturing

Publications

Valente F, Hepburn MS, Chend J, Aldanae AA, Allardyce BJ, Shafeid S, Doyle BJ, Kennedy BF, Dilley RJ.
Bioprinting silk fibroin using two-photon lithography enables control over the physico-1 chemical material properties and cellular response.
Bioprinting. 25:e00183; 2022. 10.1016/j.bprint.2021.e00183

Valente F, Simoni E, Gentilin E, Martini A, Zanoletti E, Marioni G, Nicolai P, Astolfi L.
Liquid crystalline nanoparticles conjugated with dexamethasone prevent cisplatin ototoxicity in vitro.
International Journal of Molecular Sciences. 23:14881; 2022. 10.3390/ijms232314881

Aldana AA, Valente F, Dilley R, Doyle B.
Development of 3D bioprinted GelMA-alginate hydrogels with tunable mechanical properties.
Bioprinting. 21: e00105; 2020. 10.1016/j.bprint.2020.e00105

Chambre L, Parker RN, Allardyce B, Valente F, Rajkhowa R, Dilley RJ, Wang X, Kaplan DL.
Tunable biodegradable silk-based memory foams with controlled release of antibiotics.
ACS Applied Bio Materials. 3(4):2466–2472; 2020. 10.1021/acsabm.0c00186

Liang Y, Allardyce BJ, Kalita S, Remadevi R, Uddin MG, Shafei S, Batchelor W, Dilley RJ, Wang X, Rajkhowa R.
Protein paper from exfoliated silk nano fibers. Biomacromolecules.
21(3):1303-1314; 2020. 10.1021/acs.biomac.0c00097

Liew LJ, Wang AY, Dilley RJ.
Isolation of epidermal progenitor cells from rat tympanic membrane.
In: Progenitor Cells: Methods and Protocols”in the lab protocol series “Methods in Molecular Biology”, Springer Nature. 10.1007/978-1-4939-9631-5_19; 2020.

Valente F, Allardyce BJ, Hepburn M, Wijesinghe P, Redmond SL, Chen J, Kennedy BF, Rajkhowa R, Atlas MD, Wang X, Dilley RJ.
Enhancing resistance of silk fibroin material to enzymatic degradation by cross-linking both crystalline and amorphous domains.
ACS Biomaterials Science & Engineering. 6(4):2459–2468; 2020.

Tan HE, Santa Maria PL, Wijesinghe P, Kennedy B, Allardyce BJ, Eikelboom RH, Atlas MD, Dilley RJ.
Optical Coherence Tomography of the Tympanic Membrane and Middle Ear: A Review. Otolaryngology – Head and Neck Surgery.
159(3):424-438; 2018.  First published online: May 22, 2018.

Allardyce B, Rajkhowa R, Redmond S, Altas M, Dilley R, Wang X.
Glycerol-plasticised silk membranes made from formic acid are ductile, transparent and degradation-resistant.
Materials Science and Engineering C. C 80: 165-173.

Liew LJ, Day R, Dilley RJ.
3D tympanic membrane organ culture using cell culture well inserts engrafted with tympanic membrane tissue explants.
Biotechniques. 62(3): 109-114; 2017.

Ong HT, Redmond S, Marano R, Atlas MD, von Unge M, Aabel P, Dilley RJ.
Paracrine Activity from Adipose-Derived Stem Cells on in vitro Wound Healing in Human Tympanic Membrane Keratinocytes. Stem Cells and Development.
26(6):405-418; 2017. doi: 10.1089/scd.2016.0204. 

Santa Maria PL, Gootlieb P, Santa Maria C, Kim S, Puria S, Yang YP.
Functional Outcomes of Heparin-Binding Epidermal Growth Factor-Like Growth Factor for Regeneration of Chronic Tympanic Membrane Perforations in Mice.
Tissue Engineering Part A. 23(9-10):436-444;2017

Allardyce BJ, Rajkhowa R, Dilley RJ, Xie Z, Campbell L, Keating A, Atlas MD, von Unge M, Wang X.
Comparative acoustic performance and mechanical properties of silk membranes for the repair of chronic tympanic membrane perforations.
Journal of the Mechanical Behavior of Biomedical Materials. 64:65-74; 2016. doi: 10.1016/j.jmbbm.2016.07.017

Shen Y, Teh BM, Dilley RJ.
Response to Tympanic Membrane Repair Using Silk.
The Laryngoscope. Published online: 1 March 2016. doi: 10.1002/lary.25935

Wang A, Shen Y, Liew LJ, Wang JT, von Unge M, Atlas MD, Dilley RJ.
Rat model of chronic tympanic membrane perforation: Ventilation tube with mitomycin C and dexamethasone.
International Journal of Pediatric Otorhinolaryngology. 80(1):61-68; 2015. doi: 10.1016/j.ijporl.2015.11.010

Tan HE, Santa Maria PL, Anandacoomaraswamy K, Eikelboom RH, Atlas MD.
A meta-analysis of myringoplasties.
Otology & Neurotology. 37(7):838-46; 2016. doi: 10.1097/MAO.0000000000001099.

Tan HE, Santa Maria PL, Eikelboom RH, Atlas MD.
Type I Tympanoplasty Meta-analysis: A single variable analysis of more than 26 thousand adults and children from 214 studies.
The Journal of Laryngology & Otology, 130(S3):S64-S65. doi: 10.1017/S0022215116002966

Allardyce BJ, Rajkhowa R, Dilley RJ, Atlas MD, Kaur J, Wang X.
The impact of degumming conditions on the properties of silk films for biomedical applications.
Textile Research Journal, 0040517515586166; 2015.

Wang AY, Shen Y, Liew LJ, Wang JT, von Unge M, Atlas MD, Dilley RJ.
Searching for a rat model of chronic tympanic membrane perforation: Healing delayed by mitomycin C/dexamethasone but not paper implantation or iterative myringotomy.
International Journal of Pediatric Otorhinolaryngology. 79(8):1240-7; 2015. doi: 10.1016/j.ijporl.2015.05.020.

Allardyce BJ, Rajkhowa R, Atlas MD, Dilley RJ, Wang X. 
Silk films as a robust support to repair large perforations of the tympanic membrane.
Proceedings of The 89th Textile Institute World Conference, 2-6 Nov 2014, Wuhan, China.

Wang AY, Shen Y, Wang JT, Eikelboom RH, Dilley RJ.
Animal models of chronic tympanic membrane perforation. In response to: Plasminogen initiates and potentiates the healing of acute and chronic tympanic membrane perforations in mice. Clinical and Translational Medicine.
3:1-5; 2014. doi: 10.1186/2001-1326-3-5. PubMed PMID: 24669846; PubMed Central PMCID: PMC3987050.

Wang AY, Shen Y, Wang JT, Friedland PL, Atlas MD, Dilley R.
Animal Models of Chronic Tympanic Membrane Perforation: a ‘Time-Out’ to Review Evidence and Standardize Design.
International Journal of Pediatric Otorhinolaryngology. 78(12):2048-2055; 2014; 10.1016/j.ijporl.2014.10.007

Shen Y, Redmond S, Teh B, Yan S, Wang Y, Zhou L, Budgeon C, Eikelboom RH, Atlas MD, Dilley RJ, Zheng MH, Marano RJ.
Scaffolds for tympanic membrane regeneration in rats.
Tissue Engineering Part A. 19:657-668; 2013. doi: 10.1089/ten.tea.2012.0053

Shen Y, Redmond SL, Teh BM, Yan S, Wang Y, Atlas MD, Dilley RJ, Zheng M-H, Marano RJ.
Tympanic membrane repair using silk fibroin and acellular collagen scaffolds.
Laryngoscope. 123(8):1976-82; 2013. doi: 10.1002/lary.23940.

Teh BM, Marano RJ, Shen Y, Friedland PL, Dilley RJ, Atlas MD.
Tissue Engineering of the Tympanic Membrane.
Tissue Engineering Part B. 19(2):1-17; 2013. doi:10.1089/ten.teb.2012.0389

Teh B, Redmond S, Shen Y, Atlas MD, Marano R, Dilley R.
TGF-α/HA complex promotes tympanic membrane keratinocyte migration and proliferation via ErbB1 receptor.
Experimental Cell Research. 319(6):790-199; 2013.

Levin B, Redmond SL, Rajkhowa R, Eikelboom RH, Marano RJ, Atlas MD.
Utilising silk fibroin membranes as scaffolds for the growth of tympanic membrane keratinocytes and their application to myringoplasty surgery.
Journal of Laryngology and Otology. 127(Suppl 1): S13-20; 2012.

Teh B, Shen Y, Friedland P, Atlas M, Marano R.
A review on the use of hyaluronic acid in tympanic membrane wound healing.
Expert Opinion on Biological Therapy. 12(1):23-36; 2012.

Rajkhowa R, Levin B, Redmond SL, Li LH, Wang L, Kanwar JR, Atlas MD, Wang X.
Structure and properties of biomedical films prepared from aqueous and acidic silk fibroin solutions.
Journal of Biomedical Materials Research Part A. 97A:37-45; 2011.

Redmond SL, Levin B, Heel KA, Atlas MD, Marano R.
Phenotypic and genotypic profile of human tympanic membrane derived cultured cells.
J Molecular Histology. 42(1):15-25; 2011.
Winner Valerie Alder Research Prize for the best hearing-related scientific paper in 2011.

Santa Maria PL, Redmond SL, McInnes RL, Atlas MD, Ghassemifar R.
Tympanic membrane wound healing in rats as assessed by transcriptome profiling.
Laryngoscope. 121(5):1040-8; 2011.

Santa Maria PL, Redmond SL, Atlas MD, Ghassemifar R.
Keratinocyte growth factor 1, fibroblast growth factor 2 and 10 in the healing tympanic membrane following perforation in rats assessed by transcriptome profiling and immunohistochemistry.
Journal of Molecular Histology. 42(1):47-58; 2011.

Levin B, Redmond SL, Rajkhowa R, Marano RJ, Atlas MD.
Preliminary results of the application of a silk fibroin scaffold to otology.
Otolaryngology Head and Neck Surgery. 142:S33-35; 2010.

Santa Maria PL, Redmond SL, Atlas MD and Ghassemifar R.
Histology of the healing tympanic membrane following perforation in rats.
The Laryngoscope. 120:2061-2070; 2010.

Santa Maria PL, Redmond SL, Atlas MD and Ghassemifar R.
The role of epidermal growth factor in the healing tympanic membrane following perforation in rats.
Journal of Molecular Histology. 42(6):309-314; 2010.

Levin B, Rajkhowa R, Redmond S, Atlas M.
Grafts in Myringoplasty:  Utilising a Silk Fibroin Scaffold as a Novel Device (Review Article).
Expert Rev Med Devices. 6(6):653-64; 2009.

Santa Maria PL, Atlas MD, Ghassemifar R.
Chronic tympanic membrane perforation: a better animal model is needed.
Wound Repair Regen. 2007 Jul-Aug;15(4):450-8.

Anandacoomaraswamy KS, Dutton N, Rajan GP, Eikelboom RH, Atlas MD, Robertson T.
Utilisation of fresh human tympanic membranes for structural analysis and cytokeratins immunocytochemistry implementing resin techniques.
ACTA Oto-laryngologica, 126(2):149-53; 2005.