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International Journal of Bioprinting Nozzle geometry for enhanced cell viability

fitting a modified expression for cell damage under shear in modulating mechanical stresses that affect cells.
and extensional stresses. These expressions consider an Optimizing these parameters can minimize extensional
exponential dependence on Ca , Ca , and τ : s stress, thereby improving post-printing viability.
e
s
The findings indicate that extensional stress, rather
b c
D 1 e aCa s s (XI) than shear stress, is a primary cause of cell damage,
s
particularly in the contraction region of the nozzle. Based
on the results, it is recommended that nozzle designs with
intermediate θ (30–60°) be used to balance extensional and
D 1 e dCa e e (XII) shear stresses, thus optimizing cell viability. Furthermore,
e
reducing capillary length and d can decrease exposure
2
time to mechanical stress, thereby improving cell survival.
where a, b, c, d, and e are fitting parameters determined These parameters should be prioritized when designing
by fitting Equations XI and XII to all experimental data. nozzles for sensitive or high-density cell bioinks.
As illustrated in Figure 7B, an increase in Ca resulted The proposed model helps to understand the
e
in a higher D for a given τ . This is consistent with the relationship between nozzle geometry and stress-induced
t
s
understanding that higher values of Ca correspond to cellular damage, offering another perspective that can
e
greater cell deformation in extensional flows, leading to guide future nozzle designs to improve bioprinting results.
increased cell damage. The color gradient representing τ s From an application standpoint, engineering customized
further highlights that lower residence times are associated nozzles with optimized geometries holds great promise
with reduced fractions of damaged cells. for enhancing bioprinting outcomes, ultimately advancing
In Figure 7A, the effect of increasing τ is apparent, regenerative medicine and tissue engineering. The findings
s
with transitions between nearly parallel planes in the from this study provide critical insights that can inform
parameter space of Ca , Ca , and τ . Conversely, the impact the design of next-generation bioprinters capable of
s
s
e
of shear stress was significantly less pronounced, as shown producing high-fidelity, cell-rich constructs with enhanced
in Figure 7C. The data reveal a weak dependence of D on biological functionality.
t
Ca for a given τ . However, an increase in τ still leads to In conclusion, this study highlights the crucial role of
s
s
s
a notable increase in cell damage. This weak correlation nozzle design in bioprinting. By systematically refining
between D and Ca can explain the observed behavior of nozzle geometry, it can reduce mechanical stress, enhance
t
s
D with varying d , as seen in Figure 5. A reduction in d cell viability, and improve the overall quality of bioprinted
2
t
2
increases Ca and, consequently, the shear stress. However, tissues, bringing bioprinting closer to clinical applications
s
this increase in shear stress is relatively ineffective in in regenerative medicine. With the rise of innovative
deforming and damaging cells, as shown in Figure 7C. bioprinting techniques—such as printing within a self-
Simultaneously, a decrease in d reduces the residence time healing support bath that can be subsequently washed
2
in the capillary, thereby limiting the exposure of cells to away to enable the fabrication of complex structures—it
shear stress and ultimately reducing cell damage.
would be highly beneficial to develop long needles capable
The non-linear dependence of cell deformability on of penetrating deeply into the support material. Long
Ca , Ca , and τ is highly influenced by the specific response needles—whose extended capillary length could increase
e
s
s
of cells to these flow conditions, making accurate modeling cell exposure to mechanical stress—are increasingly
challenging. The introduction of fitting parameters helps necessary for support-bath-based printing strategies.
address this complexity. Notably, the greater effectiveness The current findings on the role of needle length offer a
of extensional flows in deforming particles compared to valuable starting point for optimizing such designs.
shear flows has been previously highlighted by Grace,
19
also emphasizing the importance of exposure time to shear Acknowledgments
conditions in determining particle deformation.
None.
4. Conclusion Funding
This study comprehensively examines the influence of
nozzle design on cell viability in extrusion-based 3D None.
bioprinting. Through experimental observations and Conflict of interest
theoretical modeling, it is demonstrated that nozzle
geometry—particularly θ and d —plays a critical role The authors declare they have no competing interests.
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Volume 11 Issue 4 (2025) 325 doi: 10.36922/IJB025190182