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3D-printed bioreactors for in vitro modeling and analysis
uniform metal structures with distinct cavities, and been fabricated with 3D-printing to study the
precisely control geometric parameters down to response of these cells to the smallest details of their
several hundred microns using laser power as low local environments such as substrate geometric
as 90 W [22,23] . Extrusion printing and its common arrangement, chemistry, and mechanics [28,29] .
variants such as FDM and FFF extrude molten Much of our understanding of fundamental
polymer in a layer-by-layer manner to construct cellular mechanisms is garnered from the aberrant
3D objects [17,24] . This 3D-printing technique is cost- interactions of cells on 2D substrates. As we move
effective and could be easily adopted as a viable toward more-compliant microenvironment, it is
manufacturing option to create 3D constructs vital to demystify exactly what factors are operative
with high resolution, structural integrity, and in 3D systems rather than simply considering a
transparency. Jetting-based methods, including dimensionality factor at play . The increased
[30]
inkjet, PolyJet, and material jetting deposit fluidic capabilities of 3D-printers have resulted in well-
materials in a controlled fashion through a nozzle architecture constructs with fine features and
onto a 3D platform and are used to create highly application-specific geometries. The key challenge
complex constructs . These direct cell printing here lies in achieving the geometry that provides
[25]
techniques will not be discussed in this review. the correct degree of biomimicry, mechanical
Another widely used 3D-printed method is the and chemical cues needed for sufficient cell-cell
vat photopolymerization, including SLA and signaling, cell development, and gene expression.
DLP, which prints by curing photosensitive resins Indeed, surface parameters such as porosity,
with ultraviolet light [17,26] . SLA uses a laser beam roughness, and curvature are tunable according
that scans line-by-line to cure the photosensitive to experimental needs, and their effect on the
resin, whereas DLP uses a digital light projector collective cell behavior including adhesion, growth,
to cure each layer of photoreactive resin in one alignment, proliferation, and differentiation has
go. Compared to DLP, SLA-based printers offer been demonstrated as well. Ideally, the role of 3D-
a higher spatial resolution, resulting in structures printing is to provide cells a suitable environment
with dimensions <10 µm. µSLA-based systems supporting their transition into functional tissue in
that utilize two-photon optics further improve vitro. With 3D-printing, we are able to fabricate
the resolution to submicrons . The resulting bioreactors of different sizes and shapes and
[17]
ultrafine features may influence the mechanistic introduce cells into the bioreactors post-printing for
properties of cells in tissues. Nevertheless, resins in vitro testing. Overall, this article aims to cover
used for SLA printers often contain methacrylate 3D-printed bioreactors for the in vitro study of both
and/or acrylate monomers that have a reputation mammalian and bacterial cell culture.
to be cytotoxic .
[17]
2.1 3D-printed bioreactor for mammalian cell
2 3D-printed bioreactor for biological culture
applications
3D-printed bioreactors used in mammalian
3D-printing is a rapidly evolving technology that cell culture applications for assessment of cell
provides an opportunity to fabricate complex 3D viability, cell encapsulation, cell/tissue models,
structures for biological applications [5,27] . It is cell imaging, testing of therapeutics, and organ-
an important tool for translational research that on-chip applications are discussed below and
focuses on the in vitro biology and disease models summarized in Table 1.
in bioreactors. The increasing accessibility to 2.1.1 Cell viability in 3D-printed bioreactors
3D-printing has spurred substantial efforts toward
many creative developments of 3D-printed Bioreactors are an indispensable tool for
bioreactors for the cultivation of mammalian as maintaining cellular microenvironment to
well as microbial cells. Various bioreactors have promote cell viability, growth, and proliferation.

84 International Journal of Bioprinting (2020)–Volume 6, Issue 4