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International Journal of Bioprinting 3D bioprinting in otorhinolaryngology

5.3. Inner ear modeling ear, hearing aids oftentimes require customization
The inner ear is the deepest and most complex part of the according to the different conditions of the patient. 3D
ear. Hence, the diagnosis and treatment of many inner ear bioprinting has improved the manufacturing process of
diseases are still limited and challenging. 3D bioprinting hearing aids, reducing production costs and enhancing
is a promising method for constructing in vitro inner developments related to their miniaturization, flexibility,
ear models. and customization. The integration of 3D bioprinting
into manufacturing processes enables the production
Vestibular hair cells (V-HCs) play a key role in
maintaining balance in the inner ear. However, once of smaller equipment with better functionality and
V-HCs are destroyed, they cannot regenerate, leading implantability, as well as improving production
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to vestibular dysfunction. The ongoing research efficiency. A variety of materials has been evaluated for
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into the differentiation of pluripotent stem cells into the 3D bioprinting of customized hearing aids. Fu et al.
V-HCs through in vitro organoid culture is expected modeled the patient’s ear and printed different models
to elucidate the differentiation mechanisms occurring of in-ear hearing aids using acrylonitrile-butadiene-
in the inner ear. Ueda et al. recently established the styrene (ABS), PLA, and nylon materials according to
SOX2-2A-ntdTomato human ESC line using CRISPR/ the measurement model. The research team then studied
Cas9 technology, and single-cell RNA sequencing the different user experiences based on different product
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analysis of Sox2-positive cells was performed at parameters in subsequent follow-up assessments.
various differentiation time points. Different cellular Vivero-Lopez et al. used 3D bioprinting technology
origins were identified for different hair cell (HC) with digital light processing to fabricate a polymer resin
types, as well as the enrichment of different genes in hearing aid loaded with two antibiotics, ciprofloxacin
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different cells. However, 2D tissue culture often lacks and fluocinolone. In subsequent experiments, the
structural reduction and gene expression, highlighting hearing aid demonstrated good mechanical properties
the importance of 3D bioprinting in this field of and excellent biocompatibility, and allowed for the
research. Osaki et al. reported that EB in 3D cultures sustained release of antibiotics for more than 1 week,
induced higher levels of HC-related markers when while inhibiting the growth of Pseudomonas aeruginosa
compared with 2D in vitro culture, indicating that 3D and Staphylococcus aureus on the device surface (Figure
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culture combined with the use of V-CM can effectively 6A and B).
induce the growth of V-HCs, validating the higher Cochlear implants can release electrical stimulation
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value of organoids from in vitro cultures. Despite the to local tissues to restore nerve functions in the tissues
application of 3D bioprinting in otorhinolaryngology- and hearing. 151,152 A traditional cochlear implant is an
related organoids, the approach has its corresponding electrode array that directly instills current into the
limitations. surrounding tissue, and the current diffuses into the
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fluid within the cochlea to produce excitation, which
Salmon et al. 3D-printed custom microfluidic chips
with organized vascular networks of germinated HGSC- is susceptible to the influence of the surrounding
environment. Sarreal et al. developed and miniaturized
derived pericytes and endothelial cells. Brain organoids a 3D-printed micro-coil for the micro-magnetic
were then employed as a model system to explore the stimulation of neurons in the cochlea and reported a
interactions with newly generated blood vessels, and narrower diffusion range and was less susceptible to
the results indicated good compatibility and spatial interference from the surrounding environment.
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interactions between organoids and blood vessels. Thus, However, the cochlear implant was embedded in the
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it could be imagined that the structure of the inner ear can temporal bone, and the resulting electrophysiology
be reproduced by combining the 3D-bioprinted stem cells made it difficult to quantify. To address this issue, Lei
with an organoid culture and subsequently enabling the et al. established a cochlear model library using 3D
study of related physiological and pathological conditions bioprinting for robust modeling of clinical cochlear
using in vitro models. In this regard, the combination of 3D implant test data to decipher the current propagation
bioprinting and organoid development will be a promising properties of implanted cochlear implants and infer
tool for future research.
patient-dependent cochlear tissue resistivity. An aerosol
5.4. Hearing aids and cochlear implants spray of 3D-printed micro-coil was used to implant
Approximately 5% of the world’s population has the cochlear implant into the micro-coil array to form
disabling hearing loss, most of which requires a compound depolarization-hyperpolarizing region to
hearing aids or cochlear implants. Owing to the avoid the electrical conductivity of the perilymph in
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unique anatomical structure of each person’s external traditional cochlear implants (Figure 6C). 154

Volume 10 Issue 4 (2024) 42 doi: 10.36922/ijb.3006