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International Journal of Bioprinting 3D bioprinting in otorhinolaryngology

6.2. Nasopharynx would help to elucidate the metastatic potential of cancer
Nasopharyngeal carcinoma (NPC) is the most common cells and the influence of biological effects outside the
type of malignant tumor in otorhinolaryngology and is physical microenvironment on cancer metastasis (Figure
driven by chronic Epstein–Barr virus (EBV) infections. 8A and B). Zhang et al. found that in single-layer
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A recent randomized clinical trial revealed that even with platform, NP460 and NPC43 can migrate in the same
the best chemoradiotherapy, more than 30% of the most direction or randomly (Figure 8C). In two-layer 3D
advanced locoregional NPC patients relapsed and reported platforms, differences in cell morphology (including cell
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cancer progression. In recent years, an increasing shape, spreading, and protrusion) lead to the probability of
number of studies have focused on the NPC tumor crossing the platform. Using this property, cancer cells can
microenvironment and targeted immunotherapy through be separated from epithelial cells, and drugs can be targeted
correlation analysis of the microenvironment, suggesting to attack cancer cells focused on a specific platform. Hence,
the demand for highly reducible in vitro tumor models. method could potentially be utilized for the treatment of
NPC. Hence, this method could potentially be utilized for
In many in vitro NPC models, 3D organoids can 168
maintain the phenotype and heterogeneity of tumor the treatment of NPC.
tissue. In 2021, Ding et al. and Lucky et al. successfully 6.3. Nasal skull base
established NPC organoid models. 162,163 Recently, Wang et Transnasal skull base surgery is currently the most complex
al. established an in vitro NPC organoid model based on surgical procedure in the field of otolaryngology, and the
clinical NPC samples, and the model retained its tumor surgical outcome is often determined by the experience of
heterogeneity and pathophysiological characteristics. The the surgeon due to the complex anatomy and its adjacent
research team simulated the cellular microenvironment structures. The development of 3D bioprinting technology
by optimizing in vitro media, such as simulating the can be used to demonstrate the morphology of intracranial
involvement of Wnt/β-catenin signal transduction in the base diseases and the spatial relationship with adjacent large
regulation of NPC stem cell proliferation and self-renewal blood vessels and bones, thereby improving the success
in tissues. Besides that, collagen provides a scaffold of surgery. Shen et al. reported that a 3D-printed model
structure for tumor growth and can be used to guide of the skull was used in the reconstruction of pituitary
clinicians when providing individualized medication tumors for surgical planning and simulation. CT images
regimens for patients with refractory NPC and also obtain were initially used as original data, segmented, and edited
reliable drug susceptibility data. 164 using 3D software. The problems and details of the model
Tumor-on-a-chip is another prominent research construction process were also summarized. Subsequently,
concept. Park et al. recreated cancerous tissues in polylactide filament and melt deposition model methods
vitro by fabricating a hypoxic cancer chip using 3D were used to print the skull base and mold. For surgical
bioprinting, and the chip could induce central hypoxia, areas, bioprinting was performed using a spray method
the malignancy of conventional cancer, and the expression with plaster and adhesive. Finally, the surgical area was
of pathophysiological markers. The proposed chip could processed to provide a realistic simulation. The operation
bridge the gap between in vivo and in vitro models in simulation proved that the printed model had the same
several studies. Tumor-on-a-chip also facilitates drug characteristics as the real operation, and different invasion
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development and evaluations to test the pharmacological levels were accurately generated. Huang et al. performed
parameters and toxicology of drugs in subsequent 3D reconstructions of the skull using MRI and obtained
clinical trials. Liu et al. used a 3D biomimetic platform, a skull-based model using 3D bioprinting before the
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including ECM topography, porous interfaces, and operation. The 3D model restored the anatomical structure
underlying grooves, to investigate the cell migration of the sphenoid sinus and the vascular structure of the
behavior of an immortalized nasopharyngeal epithelial intracranial sella region, and the model was consistent
cell line (NP460) and NPC cell line (NPC43). It was with the intraoperative findings, thereby enabling the
observed that the cells were misaligned regardless of the surgeon to successfully plan the surgery. Ultimately, all
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presence of a porous substrate and a two-layer platform. patients recovered well without complications or death.
On a three-layer platform, NP460 cells did not exhibit However, the authors also indicated that the accuracy
of 3D bioprinting requires further refinement, and its
an orientation preference, whereas NPC43 cells migrated application in clinical surgery is limited due to the length
in the direction of the underlying groove. The top layer of time required for layer-by-layer bioprinting.
of NP460 cells migrated faster than that of NPC43 cells.
However, the migration rate of crossed NP460 cells was In addition, 3D bioprinting can play an important role
lower than that of NPC43 cells. Understanding how these in other therapeutic areas of the nasal skull base, such as
cells move in different ways on the designed platform individual skull base repair, intranasal skull base drug

Volume 10 Issue 4 (2024) 45 doi: 10.36922/ijb.3006