Page 57 - IJB-9-4

International Journal of Bioprinting Machine learning and 3D bioprinting

Figure 1. Bioprinting technologies. Abbreviations: DBB, droplet-based bioprinting; EBB, extrusion-based printing; EHD, electrohydrodynamic printing.

workload when researchers are trying to optimize printing and easy crosslinking mechanisms. Bioprinted constructs
materials and process parameters and evaluate their impacts may have weak mechanical and structural integrity.
on bioprinted constructs. For example, biomaterial/bioink Moreover, the dispensing process induces cell damage
should be formulated with the desired performance, the at substantial levels, which places additional limitations
printing process should be quantified with consistent printing when fabricating cell-laden structures.
results, and the performance of bioprinted constructs should As shown in Figure 1b, EBB uses a pressure-controlled
be purposely linked to the material, structure, and process. reservoir and nozzle to spatially pattern hydrogel
It is extremely difficult to conduct these studies by merely constructs layer by layer with varied pore sizes and
using mathematical models or experimental equations. compositional gradients [2,3] . The combination of relevant
To cope with such complicated scenarios, both traditional printing parameters including needle diameter, extrusion
machine learning (ML) and deep learning (DL) methods rate, printer head speed, and temperature of the nozzle and
have been adopted, which could potentially provide cost- material-related factors, such as viscoelastic properties and
effective solutions.
curing mechanism, play critical roles in determining the
In the following section, we overview the working shape fidelity and biocompatibility of constructs [8,9] . As
principles of the most popular bioprinting technologies, low-viscosity materials are used for extrusion, EBB cannot
such as droplet-based bioprinting (DBB), extrusion-based be used to fabricate high-resolution bioprinted constructs.
printing (EBB) and electrohydrodynamic printing (EHD),
and their printed constructs. In addition, general strategies During EHD bioprinting (Figure 1c), a high voltage is
for applying traditional ML and DL methods to make applied between the nozzle and the collecting substrate to
bioprinting more powerful for fabricating custom-made electrically eject biomaterial/bioink flows. EHD bioprinting
structures are discussed. uses viscous synthetic polymer solutions or melts to produce
well-oriented structures with precisely stacked micro/
[4]
1.1. Bioprinting technologies for construct nanoscale fibers . The polymer inks adopted include poly-
[12]
fabrication ε-caprolactone (PCL) [6,10,11] , polylactic acid (PLA) , and
[13]
Printing technologies such as DBB, EBB, stereolithography, polyethylene oxide (PEO) . EHD bioprinting can produce
EHD bioprinting, and laser-assisted bioprinting can be fibers ranging from hundreds of nanometers to a few
used to fabricate constructs with micro/nanoscale features micrometers, which can regulate cellular behaviors [3,14,15] . This
for 3D cell culture systems to establish in vitro models [1-5] . process is controlled by the properties of the biomaterial ink
These technologies have been fully investigated and many (viscosity, surface tension, and electrical conductivity), the
commercial machines have been launched [6,7] . environmental factors (temperature and humidity), and the
process parameters (nozzle-to-substrate distance, solution
As shown in Figure 1a, DBB dispenses droplets from a feeding rate, and nozzle dimensions). EHD bioprinting can
nozzle using thermal, pneumatic, or sonic actuation. This be disturbed by environmental factors or inhomogeneous
technology can precisely control the volume and position of material properties and then becomes unstable during the
biomaterial/bioinks, growth factors, and drugs to produce stacking of printed fiber structures . In addition to printing
[15]
microstructures for tissue engineering, regenerative fiber structures, EHD bioprinting can also be used to pattern
medicine, high-throughput screening, and cancer 2D structures. For example, a drop-on-demand EHD
research . This technology is only applicable to a narrow inkjet can use low-viscosity solutions to print droplets with
[1]
range of printable materials with good biocompatibility
organized patterns and form micro/nanoscale dot arrays.

Volume 9 Issue 4 (2023) 49 https://doi.org/10.18063/ijb.717