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International Journal of Bioprinting 3D bioprinting in otorhinolaryngology

they would have their respective limitations. Bioinks are cartilage-specific markers. Olol-Moya et al. designed a
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commonly formulated by combining different materials to chondroinductive alginate-based hydrogel with graphene
obtain optimal formulations. Hong et al. used silk fibroin oxide, and the hydrogel was developed via bioconjugation
with glycidyl methacrylate (silk-GMA) as a bioink culture of photo-linkable alginate with gelatin and chondroitin
for 3D bioprinting. The silk-GMA hydrogel maintained sulfate. The scaffold exhibited high cytocompatibility and
the viability of the encapsulated cells and induced cell chondrogenic effects on human adipose tissue-derived
proliferation and chondrogenic differentiation in vitro for mesenchymal stem cells (hADMSCs), coupled with
up to 4 weeks. Subsequently, the 3D-printed silk-GMA improved printability and anisotropic structure compared
hydrogel was transplanted into rabbit models with partial with the alginate-only scaffolds. 82
tracheal loss, and new cartilage and epithelial tissues were Several studies have also developed other
identified around the graft thereafter. polysaccharide-based hydrogels. Microgel-based inks
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3.2. Polysaccharide-based hydrogels undergo structural changes in response to external
Alginate is derived from the natural polysaccharides stimuli and could reportedly exhibit shear-thinning and
of brown algae and has poor biological activity, poor self-healing properties that allow extrusion of the inks
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printability, uncontrollable biodegradability, and unstable through a nozzle and rapid stabilization after printing.
structure and mechanism. However, researchers have Likewise, Hinton et al. developed the free-form reversible
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recently noticed that alginate has good water solubility embedding of suspended hydrogels (FRESH) technique
and a rapid crosslinking effect. Crosslinking of alginate that prints soft bio-precipitates (i.e., hydrogels) in a gelatin
occurs when divalent cations, such as Ca , Ba , or Sr , microparticle support bath. The gelatin support bath
2+
2+
2+
interact with α-l-guluronic acid in alginate to form ionic facilitated the free-forming production of hydrogels, which
bonds between the different polymer chains (i.e., with α-l- could be removed from the gelatin bath by increasing
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guluronic acid and β-D-mannuronic acid). Crosslinking temperature to 37°C. Above all, polysaccharide materials
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does not require any other crosslinking agents and is have excellent properties and attracted extensive research
non-toxic to humans, indicating its promising use in interest. Moreover, the performance and usage of bioinks
tissue engineering. However, alginate lacks an adhesive based on polysaccharide will be improved in the future
to adhere to cells. At present, the most common solution researches.
is to incorporate other biomaterials into the mixed ink 3.3 Decellularized extracellular
formulation to promote cell–material interactions. Ilhan matrix-based bioinks
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et al. prepared artificial tympanic membrane patches by A decellularized extracellular matrix (dECM) can be
adding CS and sodium alginate (SA) to a PLA scaffold, obtained via the complete removal of cellular components
and the patches displayed good biocompatibility and could from an extracellular matrix (ECM), and it is considered
be used in patients with significant hearing loss due to one of the most promising bioink formulations produced
tympanic membrane defects. In this study, the authors used in recent years, particularly for the construction of
seven different concentrations of bioinks for bioprinting. human grafts (Figure 3A). Numerous methods have
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Low concentrations of CS (1 wt%) and SA (1 wt%) been proposed to remove the cellular components,
reduced the viscosity and density of the solution when including non-ionic, ionic, zwitterionic, enzymatic, and
mixed with PLA as the printed lines were dispersed and physical means. 85
the porous structures on the support were damaged. High
concentrations of CS (5 wt%) and SA (5 wt%) increased The use of dECM can stimulate specific signal
the viscosity and density of the solution when mixed with transduction pathways to regulate the differentiation and
PLA, thereby blocking the tip of the dispensing needle functions of different tissue structures. Studies have
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and damaging the structure of the support. In addition, displayed that dECM can be used to produce tissues, such
different concentrations and pore sizes affected cell as bone, skin, blood vessels, and muscle. Additionally,
nutrition and proliferation, as well as the ductility of the 3D bioprinting with dECM can produce highly porous
bioinks. Hence, a suitable concentration of bioinks should structures, conducive to the diffusion of oxygen and
be selected to mimic the properties of natural eardrum. nutrients, as opposed to traditional two-dimensional
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In a study by Schwarz et al., 3D reticular structures were (2D) technologies that are more suitable for the formation
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bioprinted using two crosslinking techniques with alginate- of tissues and blood vessels. Pati et al. designed a novel
dialdehyde (ADA) and gelatin as the bioink components, dECM bioink from several tissue types, and the bioink
and the reticular structures were embedded with human displayed a favorable reductive microenvironment for
nasal septal chondrocytes in ADA-gelatin. This approach reconstructing cellular structures and restoring their
successfully mediated cell viability and the expression of corresponding functions. Moreover, the open, porous

Volume 10 Issue 4 (2024) 34 doi: 10.36922/ijb.3006