Tympanic Membrane Project

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Chronic eardrum perforations are most commonly caused by ear infection, mechanical trauma or a pressure blast injury from a slap or a nearby explosion. Sometimes referred to as a ‘burst eardrum’ in laymans terms, a perforation is a hole in the thin layer of skin that makes the drum membrane.   

When a perforation occurs, most will repair themselves with no medical intervention required, like a normal skin wound. However some don’t heal and they can form chronic eardrum perforations, which can cause problems for many years in some patients.  They are considered a serious medical problem due to the middle ear being exposed to infection and the significant impact on a patient’s hearing. As such, chronic eardrum perforations are usually treated with a surgical procedure to close the hole within the eardrum.

Over centuries (even mummies have been shown to have perforated eardrums), surgeons have developed varied and complex treatments to repair the eardrum. The current surgical procedures used for repairing perforated eardrums involve making grafts from the patient’s own tissues and using specialised and delicate microsurgery techniques applying them to the eardrum to close the hole. The patient quite often is required to return to surgery for further procedures due to failure of the complex procedure  or to ongoing effects of their ear conditions on the graft.

One of the most common graft materials used for the surgery is the patient’s own cartilage. It is retrieved from part of their outer ear and very thinly sliced to provide a graft then microsurgically implanted over or under the eardrum to close the hole and prevent infection.  A significant number require repeat surgery and even those where the surgery is adequate, the drum doesn’t return to normal function because the graft has inherently different tissue properties to the drum. Due to the opaque nature of the cartilage, this stops medical professionals being able to see through the normally clear eardrum, inhibiting the view of any infection or abnormal tissue growth behind the eardrum. 

In order to improve this procedure and its outcomes, the Ear Science research team has been investigating new graft materials which may provide a better option for surgeons to use to close chronic eardrum perforations. The team has developed a world-first model for studying perforations, aiding in their ability to test new graft materials as successful replacement treatments for cartilage.

The research team has used 3D printing to create grafts with the same shape as a human eardrum and made from biological materials. The grafts have been trialled in our lab and evaluated for their ability to provide an optimal approach for chronic eardrum perforations.

The most exciting results have come from a silk-based membrane (shown on the right) designed by Ear Science and Deakin University in a combined effort to identify a solution. It has received international accolades and is destined for clinical trials.

To get the device to this level has involved a lengthy process of design, manufacturing, testing and analysis. With a considerable amount of work and time being spent on perfecting material properties like transparency and mechanical properties. 

The end result is silk-based membrane grafts with specific mechanical and acoustic properties that we know provide strength and vibration properties that suit healthy and diseased human ear. In addition, the surgical properties and ability for medical professionals to see through the device, could establish it as the new industry-leader for chronic eardrum perforation surgeries.

Clinical trials will be conducted to provide evidence of the device’s abilities and we continue to refine the device for this purpose.

If you would like to support this project and others like it please see below:

For financial support, please click here

For PhD and Post-Doc students, please register your interest by emailing research@earscience.org.au.

Lead Investigator:

Winthrop Professor Marcus Atlas, Ear Science Institute Australia

Research Investigators:

Professor Xungai Wang, Institute for Frontier Materials – Deakin University

Professor Rodney Dilley, Ear Science Institute Australia

Publications:

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

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

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.2015.05.020t.

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.

Shen Y, Redmond S, Papadimitriou J, Teh BM, Yan S, Atlas MD, Marano RJ, Dilley RJ. The biocompatibility of silk fibroin and acellular collagen scaffolds for tissue engineering in the ear. Biomedical Materials. 9(1):015015; 2014.

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. http://dx.doi.org/10.1017/S002221511200166.

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.

Marano RJ, Redmond SL. In vitro cultured primary cells from a human utricle explant possesses hair cell like characteristics. Journal of Molecular Histology of Neurology. 42(4):365-70; 2011.

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.

Shen Yi, Teh BM, Friedland PL, Eikelboom RH, Atlas MD. To pack or not to pack? Laryngoscope. 121(5):1040-8; 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):6https://www.ncbi.nlm.nih.gov/pubmed/?term=Utilising+a+Silk+Fibroin+Scaff...(Review+Article)53-64; 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 (2005) Utilisation of fresh human tympanic membranes for structural analysis and cytokeratins immunocytochemistry implementing resin techniques, ACTA Oto-laryngologica, 126(2):149-53.