Reconstruction and Mechanics of the Middle Ear
The middle ear comprises the tympanic membrane (eardrum) and ossicular chain (bones of hearing), which are critical for hearing. Due to infections or trauma, these structures are frequently damaged. Tympanic membrane perforations are one example of damage to the middle ear and commonly result in chronic pain, dizziness, hearing loss, and decreased quality of life.
Healthy human eardrum Perforated human eardrum
Our research group focuses on studying tympanic membranes and ossicular chains that have been affected by disease. As surgeon-scientists, we are interested in better methods to reconstruct and rehabilitate the middle ear.
Specifically, we aim to:
- Study regenerative properties of the tympanic membrane and ossicular chain.
- Improve contemporary surgical approaches to repair the tympanic membrane and ossicular chain.
If you wish to contribute to Dr. Aaron Remenschneider's research, please contact Irene Hammer-Mclaughlin.
Tympanic Membrane Regeneration
While the structure and cellular composition of the normal tympanic membrane has been rigorously studied, little is known about the changes that occur in perforated eardrums. Tympanic membranes frequently heal spontaneously, however, in a significant number of pediatric and adult patients, the perforations persist causing significant hearing loss and impaired quality of life.
Our goal in studying the disease human tympanic membrane is to answer:
- What are the cellular and molecular factors that drive tympanic membrane regeneration?
- What local factors prevent effective tympanic membrane healing?
- How do graft materials used tympanic membrane reconstruction promote effective remodeling?
Low power view of the human temporal bone demonstrating the conical shape of the thin tympanic membrane.
High power H&E stain of the normal human tympanic membrane showing a thin epithelial layer with a middle, lamina propria of radial fibers and circular fibers.
To address these questions, our group uses otopathologic techniques to understand tympanic membrane regeneration and incorporation of graft materials. This research involves retrospectively studying the diseased human eardrum in archived otopathologic specimens, as well as prospectively investigating eardrums in patients undergoing tympanoplasty.
A deeper understanding of the environmental and biologic milieu, which influence tympanic membrane regeneration and repair, will have direct clinical impact on the more than 30 million individuals worldwide who suffer from tympanic membrane perforation each year. Indeed, we aim to improve materials and techniques used in surgical reconstruction of the eardrum, minimize procedure related morbidity, as well as improve audiometric outcomes and broaden access to treatment by decreasing cost.
Biomimetic Tympanic Membranes and Ossicular Prostheses
A biomimetic ear drum generated using 3-D printing techniques.
We apply novel 3-D printing technology to generate biomimetic graft materials with desirable biologic and mechanical properties to promote rapid healing, effective sound transmission, and resistance to recurrent middle ear disease.
Printed tympanic membrane scaffolds with different materials and designs. (A-C) Images of TM scaffolds composed of PDMS, PLA, and PCL filaments, respectively, with 8C/ 8R and 16C/16R filamentary architectures. The TMs in the first column of each box have a total diameter of 25 mm. The next two columns show higher magnification images, 50 with a scale bar of 1 mm and 100 with a scale bar of 500 mm, respectively. (D) Image of a representative printed scaffold highlighting design features. Kozin ED, Black NL, Cheng JT, Cotler MJ, McKenna MJ, Lee DJ, Lewis JA, Rosowski JJ, Remenschneider AK. Design, Fabrication and In Vitro Testing of Novel Three-Dimensionally Printed Tympanic Membrane Grafts. Hearing Research. 2016 Mar 16.
Laser Doppler Vibrometry allows measurement of sound induced membrane velocity.
In tympanic membrane reconstruction, traditionally used graft materials frequently fail to result in perforation closure, leaving patients with persistent hearing loss. Some patients who obtain closure of the perforation have poor audiometric outcomes or are left susceptible to recurrent disease. The structure of contemporary eardrum grafting materials does not resemble the native human tympanic membrane and is partly responsible for poor clinical outcomes.
Differences in normalized surface velocity among PLA-based tympanic membrane composite grafts and fascia. (A) Three separate fabricated 8C/8R PLA TM composite grafts have uniform surface velocity as measured by laser Doppler vibrometry. Velocity peaks are highly consistent. PDMS and PCL also have consistent velocities among graft samples. (Data not shown.) (B) Three separate human temporalis fascia samples harvested and prepared identically yield distinctly different velocity patterns. Kozin ED, Black NL, Cheng JT, Cotler MJ, McKenna MJ, Lee DJ, Lewis JA, Rosowski JJ, Remenschneider AK. Design, Fabrication and In Vitro Testing of Novel Three-Dimensionally Printed Tympanic Membrane Grafts. Hearing Research. 2016 Mar 16.
Digital opto-electronic holography (DOEH) fringe patterns of tympanic membrane grafts fabricated with different materials. DOEH results from TM composite grafts consisting of PDMS (top row), PLA (middle row) and PCL (bottom row) all with 8C/8R architecture are shown. Color bars are standardized at each frequency, displacement is normalized by sound pressure and units are dB re 1 mm/Pa. Kozin ED, Black NL, Cheng JT, Cotler MJ, McKenna MJ, Lee DJ, Lewis JA, Rosowski JJ, Remenschneider AK. Design, Fabrication and In Vitro Testing of Novel Three-Dimensionally Printed Tympanic Membrane Grafts. Hearing Research. 2016 Mar 16.
Our ‘biomimetic’ tympanic membrane graft designs are informed by the intricate fibrous structure of the normal human tympanic membrane, which we have shown is critical to effective sound transmission. The biodegradable materials used in our grafts are generated in house and possess unique properties to promote axial cellular ingrowth along the printed fibers. This results in regenerated eardrums with structure and function that mimics nature’s original design. Our laboratory utilizes a chinchilla animal model of chronic tympanic membrane perforation to evaluate hearing outcomes using auditory brainstem responses (ABR) and conduct acoustic and mechanical testing with laser Doppler vibrometry (LDV) and digital opto-electronic holography (DOEH).
3-D printed tympanic membrane under light microscopy. Fibroblasts avidly adhere and deposit collagen.
Cellular alignment of fibroblasts generate a biomimetic pattern on 3-D printed grafts.
The Remenschneider Lab works in concert with the Jennifer Lewis Lab of Harvard’s John A. Paulson School of Engineering and Applied Sciences and the John Rosowski and Jeffrey Cheng Laboratory within the Middle Ear Mechanics Unit at Mass. Eye and Ear.
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