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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
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