Biofabrication strategies in otosurgery: from the outer to the inner ear

Ear physiology occurs via minute highly-specialized and histodiverse tissue components with a shape-dependent function, which ultimately allow a fine hearing. Such an anatomic site is thus a challenging application for tissue-engineers in which microfabrication techniques can make a difference. The aim of this study was to develop specific biofabrication strategies to replace the ear tissues, which could be useful in otologic surgery. 3D fiber deposition (3DF) was used as an additive manufacturing technique to obtain ear bone replacements, such as outer auditory canal wall and ossicular chain (OC), based on poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT) copolymer. These scaffolds were cultured with human mesenchymal stromal cells entrapped in fibrin clots as a biological nanofibrous matrix. After 21–27 days of osteodifferentiation, cell viability, bone markers and microCT were performed to assess appropriate mineralization. The measured acoustic response of OC constructs was superior to those of commercial prostheses in the hearing ranges: 250–8.000 Hz frequencies and 50–100 dB sound pressures. The tympanic membrane is a flexible and though connective tissue apt for vibration. Electrospinning was used in combination with 3DF to produce biomimetic PEOT/PBT dual and triple scale scaffolds provided with over-impressed patterning (radial, circular and reticular) able to localize cells and their synthesized biomolecules as in the native eardrum. The possibility of producing electrospun meshes that enable cell alignment was also investigated via a radial collector. Finally, other biofabrication strategies were investigated to produce thin ceramic/polymer composite scaffolds able to support the inner ear function, including spin coating, hot-press, and co-axial electrospinning.