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Priyadarshini, et al.
biomedical, pharmaceutical, food, wastewater bioreactors with microfluidic networks. The
treatment, chemical, and fermentation . This compartmentalized microfluidic devices with
[5]
review focuses on biological applications in detail. interconnected microchannels created cellular
environments confined in a culture vessel that
1.2 Three-dimensional (3D)-printed bioreactor directed fluid flow through the cell culture [12,13] .

Conventional bioreactors grant operators the In addition, these devices were shown to emulate
convenience of controlling the environment and physiological relevance by creating in vitro
experimental manipulation of two-dimensional microenvironments on the same scale of cells.
tissue models . However, their incompatibility However, devices with challenging functionalities
[6]
with in vivo systems and their inability to and dimensional specifications, such as channel
reflect true cell traits and tissue morphology has height and aspect ratio, are difficult to achieve
necessitated 3D systems which exhibit better by conventional microfluidic techniques. Recent
spatial distribution and structurally complex advancements have led to the development of
tissue architecture. Nevertheless, it is challenging 3D-microfluidics with intricate detailing, greater
[14]
to produce 3D bioreactors with complex geometry accuracy, and better resolution using 3D-
using conventional manufacturing methods . printing techniques.
[7]
Additive manufacturing (AM), also known 1.3 Methods for fabricating 3D-printed
as 3D-printing technology, has shown enormous bioreactors
potential in the fabrication of complex, low-cost,
and custom-designed structures constructed Features of 3D-printed devices rely primarily on
by depositing a layer on top of earlier printed the chosen printing method. Some applications
layers . Over the past three decades, several only 3D-printed the substrate in cell culture for
[5]
3D-printing strategies have been established in vitro analysis, whereas other applications
with a focus on the fabrication of bioreactors of embedded living cells into biocompatible
various shapes and sizes [8,9] . Through 3D-printing, printable materials (bio-inks) [15] . In this review,
specialized bioreactors can be engineered with we primarily focus on the 3D-printed bioreactors
high performance in terms of experimental for in vitro studies, not including the direct
throughput, liquid controllability, and stability . printing of cells. Various 3D-printing methods
[10]
3D-printing not only grants freedom to optimize have been used to fabricate 3D structures and
new bioreactor designs but also enhances cellular devices based on various printing techniques
functionality and suitability of bioreactor for including selective laser melting (SLM),
specific applications such as in vitro culturing and direct metal laser sintering (DMLS), fused
testing . deposition modeling (FDM), fused filament
[11]
In view of this article, any 3D-printed culture fabrication (FFF), inkjet, PolyJet, material
apparatus, including chip, culture chamber, jetting, stereolithography (SLA), digital light
or filters that directly contact the cells, are processing (DLP), micro-SLA (µSLA), and
considered as 3D-printed bioreactors. Moreover, multiphoton lithography, each with their own
various customized components and accessories advantages and disadvantages [16] . These 3D-
of bioreactors such as culture tube holders, test printing processes are also used to fabricate
parts, chamber inserts, and sensors fabricated bioreactors. However, none of these 3D-
with various 3D-printing modalities have been printing processes are ideal due to their specific
discussed. Several bioreactor models were limitations such as biocompatibility issues,
designed to encourage the flow of culture medium difficulty in removing support materials, low
for even distribution of nutrients throughout the printing resolution, poor dimensional accuracy,
culture vessel. The fluid flow in bioreactors could and rough surface texture [17-19] . Considerations
be manipulated at the micro-level by coupling for the choice of 3D-printing methods are shown

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