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International Journal of Bioprinting Biomimetic biofabrication of tumors volume
volumes in the form of droplets which are dispensed by EBB platforms. Nevertheless, specific physicochemical
thermal or mechanical processes. IBB is a relatively low- parameters must be optimized prior to extrusion. For
cost technique and provides high cell viability with instance, hydrogels with high viscosity inevitably expose
[53]
elevated speed and high resolution . IBB has been cells to high shear stress at the nozzle and also to increased
[54]
extensively employed during the last decade for the pressure in the syringe during printing, both of which can
recapitulation of TMEs. Despite the numerous benefits, greatly impact cell viability [61,62] .
there are also several limitations, such as the use of However, EBB is a low-cost, simple and highly
polymer solutions with low concentration and the lack flexible technology that has been adapted to house multi-
[9]
of droplet stability and directionality during ejection. material and co-extrusion printing [63,64] . Harnessing the
Nevertheless, IBB has been recently proven efficacious for EBB functionality, 3D in vitro cancer models used for
the high-throughput patterning of cancerous micro-tissues investigating tumor progression and anti-cancer drug
for the rapid screening of therapeutics . Overcoming resistance have been recently fabricated. For instance,
[55]
the above-mentioned limitations and by harnessing the 3D matrices printed through EBB can function as ideal
rapid planar displacement of IBB technology, cancer platforms to promote the formation of tumor spheroids
microenvironments could be modeled accurately by and offer long-term proliferation cell culture.
patterning tumor cells with nanoliter precision.
Ultimately, EBB is a popular 3D bioprinting platform
3.2.2. Laser-induced forward transfer bioprinting to develop 3D tumor models not only because of the
Laser-induced forward transfer (LIFT) is a non-contact, associated low-cost and simple utilization but also by the
nozzle-free technique that uses a pulsating laser as the energy virtue of flexibility and suitability for implementations (e.g.,
[34]
source to irradiate a donor slide, causing the formation of co-extrusion, microfluidic-assisted bioprinting ). On the
microbubbles that propel the biomaterial onto the receiving other hand, the choice of biomaterial ink is subjected to
slide in droplet form . Tuning the laser energy source and strict requisites and determined parameters (e.g., viscosity),
[56]
printing speed , high-resolution 3D structures can be which could significantly impact cell viability.
[57]
printed, reaching single-cell droplet accuracy . However, the latest advancement of engineering
[58]
In addition to the high resolution and precision of the technologies has greatly facilitated the customization of
constructs, a great advantage of laser-based technologies EBB set-up to accommodate the fabrication of functional
for 3D bioprinting applications is the absence of the nozzle tumor models. Thus, a variety of novel approaches, such as
[65]
that allows for fabrication with no concern for viscosity the direct printing of cell, spheroid, organoid printing ,
[66]
or clogging during printing. However, there are several as well as the engineering of new vascularized structure ,
limitations, such as the lower cellular viability or the have been attempted lately. Typically, the low resolution
[59]
higher cost of the system, compared to other printing (>100 μm) cannot allow to create highly detailed structure,
technologies. The exploration of the potential use of LIFT but recent effort has been focused on functionalizing
in cancer modeling has been ongoing in recent years, EBB-fabricated tissues with cancer spheroids to improve
uncovering new ways of patterning high-throughput ultimate functionality of the model to validate and test new
[67]
[60]
platforms for drug screening studies . The ability of cancer anti-cancer drugs .
tissue to resist thermal and mechanical stresses is fostering
the use of laser-assisted bioprinting technologies to fabricate 4. 3D bioprinting bioinspired tumor models
new biomimetic models, facilitating the engineering of new
multi-cellular cancer microenvironments. Biofabrication is currently shaping cancer research, coming
to the fore as a high-throughput screening platform to
3.2.3. Extrusion-based bioprinting test the safety and efficacy of new drugs, while replicating
Extrusion-based bioprinting (EBB) is currently the most pathophysiological processes and events in vitro. Therefore,
widely used bioprinting platform in developing 3D tumor the unparalleled ability of bioprinted and bioinspired
models. Biomaterial inks, used in EBB, are loaded in models to recapitulate aggressive and deadly primary
cartridges and extruded through a nozzle by pneumatic or (breast and brain) and secondary (lung and bone) tumors
mechanical forces, which allows for continuous deposition and biological processes has been recently harnessed for
of the material in a predetermined 3D structure. Among its the fabrication of novel biomimetic models. Here, we
many advantages, EBB can rely on high printing speed and list the most recent work on tissue-specific bioprinted
the possibility to print constructs with high cell density cancer models, providing a comprehensive library for
and good viability. Hydrogel-based materials are the most 3D-bioprinted tumor tissue replicas (Figure 4) with a
reliable inks to be used in conjunction with living cells with classification that can be found in Table 1.
Volume 9 Issue 6 (2023) 378 https://doi.org/10.36922/ijb.1022

