Page 152 - IJB-10-1

International Journal of Bioprinting 3D-printed micro-perfused culture device

of fabricating such microfluidic devices are usually by spheroids within an SLA-printed fluidic device. Knowlton
19
micro-machining, soft lithography, embossing, injection et al. have developed an SLA-printed microfluidic device
molding, and laser ablation. These fabrication techniques coupled with 3D cell encapsulation and spatial patterning
3
are often tedious, expensive, and complex and require within gelatin methacryloyl (GelMA) to provide a 3D cell
sophisticated cleanroom facilities with multiple assembly culture environment. Yang et al. developed a numerical
27
steps. Additive manufacturing or more commonly model, which enables the dynamic process modeling
4
known as three-dimensional (3D) printing was found to of cell capture to be used for organ-on-a-chip. The
28
be an attractive fabrication alternative due to its highly numerical model is able to predict cells capture efficiency
automated process, rapid design iterations, minimal device with various embedded microfluidic chip features, which
assembly (one-step fabrication tool) with the production is helpful to future microfluidic chip design.
of fine, and complex features. The prototyping via polymer More recently, Ma et al. introduced the concept of tuning
4
additive manufacturing techniques can be achieved at a the viscoelasticity of the extracellular matrix (ECM) to
lower infrastructure, equipment, and maintenance cost recapitulate time-dependent mechanic in cell environment
compared to conventional fabrication techniques. Among to regulate cell behavior and guide cell fate. Kim et al.
3,4
29
the many 3D printing techniques, stereolithography (SLA) attempted the partitioning of hydrogels to the center of
emerged as the most relevant technique for microfluidics the microfluidic chip where the high aspect ratio capillary
device fabrication, since it can produce features with channels prevented cross-channel convection transport but
5,6
less than 100 µm and offer biocompatible and clear allowed selective diffusion of molecules across the hydrogel
resins. The direct 3D printing of microfluidic device can barrier. The resultant platform has demonstrated the ability
also potentially avoid the need for multiple preassembly to selectively filter solutes to be diffused across. This SLA-
and bonding steps to incorporate additional functional printed device can be used for tissue engineering or organ-
components (e.g., sensors) into the microfluidic channel on-a-chip platform. Alternative 3D bioprinting of scaffold
30
networks. However, only the integration of physical has also been reported, e.g., microalgae–laden material
7-9
functional components into 3D-printed microfluidic enabled self-adaptive and sustained oxygen supply to thick
devices has been reported to date. In this paper, we report wound site. The embedded living microalgae produced
31
the integration of a biological functional component in the sustained oxygen under light illumination, which in turn
form of a 3D nanofibrous scaffold construct into an SLA- facilitated cell growth in low-oxygen condition. Another
printed microfluidic device for 3D perfusion cell cultures. reported work to improve vascularization to thick scaffold
To date, several studies have successfully demonstrated is through the incorporation of black phosphorous to
the use of 3D printing for the fabrication of cell microfluidic 3D-printed scaffold. The black phosphorus
32
culturing microfluidics devices 2,10,11 and their peripheral possesses photothermal properties that reversibly shrink
elements. 12-14 These include the development of 3D-printed and swell through near-infrared irradiation. This motion
molds for polydimethylsiloxane (PDMS) device facilitated the penetration of suspended cells into the
fabrication, 15,16 microfluidics cell culture platform, 17-19 scaffold channels and promotes pre-vascularization.
microfluidics gradient generator, 20,21 and reactionware. Among the many studies, the inclusion of 3D fibrous
22
Among the reported studies on cell culture in 3D-printed scaffold constructs to support cells in 3D-printed
microfluidic devices, the majority had adopted existing microfluidic devices has not yet been reported. 3D fibrous
designs for performing 3D cell cultures in conventional scaffolds have been developed by tissue engineers to
microfluidic perfusion culture systems. Since conventional mimic the native ECM, which comprises an interwoven
microfluidic fabrication and assembly techniques usually nanofibrous network of protein fibers, plays an essential
result in an enclosed microfluidic network, cells have to role in providing biophysical cues to the cells, and promotes
be dynamically seeded (i.e., perfused in with pump or essential cellular processes. Extensive studies have shown
33
manually with a pipette) into the device. Hence, the device that the surface topographical cues were beneficial in
architectures of many microfluidic 3D perfusion culture maintaining various cells phenotype. 34-37 While there are
systems are designed to be compatible with a dynamic cell studies which report the incorporation of membranes on
seeding workflow. These design configurations include microfluidic devices, they were either 2D flat substrate
either using micro-structures (e.g., micropillar arrays) to or non-fibrous in nature. 38,39 These do not truly represent
physically trap and pack cells into 3D cell aggregates 23,24 the actual physiological environment within a cell. 40
or patterning hydrogel precursors containing cells within Therefore, in this study, a 3D-printed micro-perfusion
the microfluidic device. 25,26 Similar approaches have been culture platform that supported the direct integration of a
adopted to develop 3D cultures. For instance, Ong et al. miniaturized 3D fibrous scaffold was explored. The setup,
have printed micro-structures to immobilize 3D tumor
which encompassed both the nanofibrous scaffold and

Volume 10 Issue 1 (2024) 144 https://doi.org/10.36922/ijb.0226