Mimicking the Human Tympanic Membrane: the Significance of Geometry
The human tympanic membrane (TM) captures sound waves reaching the outer ear from the environment and transforms them into mechanical motion. The successful transmission of these acoustic vibrations in varying frequency ranges is attributed to the structural architecture of the TM. However, a limited knowledge is available on the contribution of its discrete anatomical features, which is important to fabricate functional biomimetic 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 were chosen to decouple some of the dominant structural attributes, such as, the radial and circumferential alignment of the collagen fibrils. In silico models suggested a geometrical dependency of their mechanical and acoustical responses, where the presence of radially aligned fibers was observed to have a more prominent effect compared to their circumferential counterparts. Following which, a hybrid fabrication strategy combining electrospinning and additive manufacturing was optimized to manufacture hierarchical scaffolds within the dimensions of the native TM. The experimental characterizations conducted using macro-indentation and laser Doppler vibrometry were in line with the computational models. Finally, biological studies performed with human dermal fibroblasts and human mesenchymal stromal cells, revealed a favorable influence of scaffold hierarchy on cellular alignment and subsequent collagen deposition. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/383299v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@16b3653org.highwire.dtl.DTLVardef@1bbc47forg.highwire.dtl.DTLVardef@619ad8org.highwire.dtl.DTLVardef@1fd1071_HPS_FORMAT_FIGEXP M_FIG Graphical abstract. Schematic diagram illustrating the overall flowchart of the work. 3D: three-dimensional; ES: electrospinning; FDM: fused deposition modeling; TM: tympanic membrane. C_FIG