Mimicking the Human Tympanic Membrane: The Significance of Scaffold Geometry

Abstract

The human tympanic membrane (TM) captures sound waves from the environment and transforms them into mechanical motion. The successful transmission of these acoustic vibrations is attributed to the unique architecture of the TM. However, a limited knowledge is available on the contribution of its discrete anatomical features, which is important for fabricating functional TM replacements. This work synergizes theoretical and experimental approaches toward understanding the significance of geometry in tissue-engineered TM scaffolds. Three test designs along with a plain control are chosen to decouple some of the dominant structural elements, such as the radial and circumferential alignment of the collagen fibrils. In silico models suggest a geometrical dependency of their mechanical and acoustical responses, where the presence of radially aligned fibers is observed to have a more prominent effect compared to their circumferential counterparts. Following which, a hybrid fabrication strategy combining electrospinning and additive manufacturing has been optimized to manufacture biomimetic scaffolds within the dimensions of the native TM. The experimental characterizations conducted using macroindentation and laser Doppler vibrometry corroborate the computational findings. Finally, biological studies with human dermal fibroblasts and human mesenchymal stromal cells reveal a favorable influence of scaffold hierarchy on cellular alignment and subsequent collagen deposition.

Development of electrospun, biomimetic tympanic membrane implants with tunable mechanical and oscillatory properties for myringoplasty

“…Previous works that focused on the biomimetic design of possible TM implants such as ref. 27 and 28 have already underlined the importance of radially and circumferentially oriented fibers in achieving mechanical and oscillatory behavior close to that of human TMs. However, in these works, this fiber orientation was achieved by generating skeletons with filament sizes in the tens of microns by melt electrowriting or fused deposition modeling, such that the filament diameters far exceeded the natural filament diameters of the human TM.…”

“…The structure seems to affect the vibration behavior in such a way that the first resonance frequency is much more prominent in comparison with the vibration properties here. In the work of Anand et al , 27 PEOT/PBT scaffolds with mimicking radial filaments (Case II) produced by electrospinning combined with fused deposition modeling have the lowest first resonance frequency. A similar case is represented by the PCL scaffold with collagen fibers (4L45°d10w250) prepared by melt electrowriting in the work of Witzleben et al 28 The TM implants in this study made using a one-step electrospinning process were able to achieve comparable acoustic behavior by tuning of the electrospinning solution and process parameters.…”

“…low resistance for dynamic pressure up to about 1 Pa (acoustic behavior), but a high resistance for large static pressures (mechanical stability) comparable with that of the human TM. Therefore, the static mechanical properties of the TM implant were investigated and compared with the results of human 27 and 4L45°d 10w250 28 ).…”

“…Previous works have already shown the significance of structural mimicry of the fiber orientation of the TM to generate functional implants. 27,28 These works primarily focus on membrane design, especially structures mimicking radial and circumferential fibers in the microscale by e.g. melt electrowriting or fused deposition modeling in combination with electrospinning or collagen coating to close macroscale pores.…”

“…Fig.10The acoustic vibration curves of (A) TM implants developed in this study that have a comparable behaviour to human TM; (B) comparison of the vibration with the data from the literature (Case II27 and 4L45°d 10w25028 ).…”