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International Journal of Bioprinting 3D cell culture model for neural cell analysis

negative control. These findings suggest that the 3D model controlled in bioprinting through synchronized light
used in this study offers improved stability and reliability, exposure or temperature regulation, leading to reproducible
allowing for a more accurate evaluation of neural cell and structurally stable constructs. This controlled
responses to CoCrMo particles. The distinct responses of environment results in higher fidelity in model architecture
C6 astrocyte-like and NG108-15 cells to CoCrMo particles and better mimics the native tissue microenvironment.
likely stem from their differing sensitivities to foreign Despite the valuable insights gained, one of the limitations
materials. Astrocytes, known for their structural support of the current study was the use of commercially available
and role in tissue repair within the central nervous system, model particles, not clinically representative wear-simulated
exhibit greater resilience to such exposure. In contrast, the particles, particularly in terms of size, morphology, and
more sensitive NG108-15 cells are less equipped to tolerate chemical composition. As these particles differ from those
foreign materials. These findings highlight the need for typically generated in clinical settings, future studies should
further research to understand the cellular mechanisms aim to replicate these experiments with clinically relevant
behind these responses, which is essential for improving particles to better understand neural cell responses in vitro
the safety and effectiveness of spinal implants and within the same 3D-bioprinted GelMA hydrogel model.
minimizing neural tissue damage. No significant oxidative Moreover, examining the cumulative or synergistic effects
stress or DNA damage was detected in C6 astrocyte-like of multiple biomaterial wear particles, such as those from
or NG108-15 cells following 24 h of exposure to model metals, ceramics, and polymers, could provide deeper
CoCrMo particles. This contrasts with findings by Lee et insights into the overall impact on neural tissue, particularly
al., who reported significant DNA damage in primary in the context of multi-material spinal implants. Expanding
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astrocytes under similar conditions. The discrepancy the scope in these areas will enhance the clinical relevance
may stem from differences in cell models, particle of the findings and support the development of safer,
characteristics, or experimental conditions, underscoring more effective biomaterials for spinal and neural tissue
the need for further research to clarify the varying cellular applications. While no significant difference in cell viability
responses to CoCrMo particles. The discrepancies between was observed between the 2D and 3D cultures, this is a
this study and Lee et al.’s investigation can be attributed positive outcome, as cell viability often decreases in 3D
to key differences in the experimental models, particularly systems due to limited nutrient diffusion. The ability of
the type and size of CoCrMo particles used. our 3D-bioprinted model to maintain comparable viability
suggests good biocompatibility and supports its use for
In the current study, we developed a novel 3D-bioprinted
spinal cord model integrating neural cells with spinal further physiological studies. Future work will focus on
evaluating neural-specific functions and comparing cell
implant wear particles and biomaterials, establishing the behavior in this model to native tissue to further validate
first in vitro platform of its kind to assess the biological its physiological relevance. Another limitation of this study
effects of wear debris. While the 3D constructs in this study was the use of cell lines (C6 and NG108-15), which do not
were deposited in droplet format, the use of a bioprinter was fully represent the functionality and cellular heterogeneity
essential for ensuring precise and reproducible placement, of the spinal cord, particularly due to the absence of
volumetric consistency, and homogeneous distribution microglia. These cell lines were chosen to establish a robust
of cells and particles across replicates. Unlike manual and reproducible 3D-bioprinted model and to assess the
pipetting, the bioprinter allowed for controlled deposition of feasibility of incorporating spinal implant biomaterial-
defined volumes and bioink compositions, which is critical derived particles in the 3D-bioprinted system. Future
when evaluating cellular responses to different biomaterial work should focus on incorporating primary or induced
particles. Additionally, bioprinting supports future scalability pluripotent stem cell (iPSC)-derived neural cells, including
and integration into more complex architectures, which microglia, to enhance the physiological relevance of
aligns with our longer-term aim of developing advanced the model.
neural tissue models. Compared to traditional casting,
bioprinting offers superior control over the distribution 5. Conclusion
and organization of cells and particles within hydrogels.
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In casting, sedimentation and uneven mixing often lead to This study established a 3D-bioprinted spinal cord cellular
heterogeneous distribution, whereas bioprinting ensures model that integrates neural cells with spinal implant wear
uniform dispersion by precisely depositing cell-particle- particles. It represents the first in vitro platform designed
laden hydrogels. Bioprinting also applies minimal and to investigate the biological effects of wear debris in a
consistent mechanical stress on cells during fabrication, physiologically relevant context. By incorporating model
reducing unintended shear forces common in casting or particles with diverse morphologies (ranging from irregular
manual handling. Additionally, gelation can be finely to spherical), sourced from different biomaterials, and
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Volume 11 Issue 4 (2025) 273 doi: 10.36922/IJB025180174