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International Journal of Bioprinting                                3D bioprinted vascularized tissue models




































            Figure 4. 3D bioprinting of vascularized tumor models. (A) Sacrificial bioprinting strategy to engineer a complex GBM model consisting of tumor/
            stroma compartment and perfusable vascular channel in the penta-culture system. (B) Sacrificial bioprinting strategy to establish a biomimetic GBM
            model combining perfusable vascular channels and patient-derived GBM spheroids. Figure 4A and 4B from ref. (60) licensed under Creative Commons
            Attribution NonCommercial License 4.0 (CC BY-NC). (C) Coordinated patterning approach to produce a spatially-defined 3D in vitro metastatic model.
            Reproduced with permission from Meng F, Meyer CM, Joung D, et al., Adv Mater, Copyright © 1999-2023 John Wiley & Sons  . (D) A combination of
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            embedding and coaxial bioprinting strategies to construct a tissue-level cancer-vascular platform composed of a metastatic cancer unit and a perfusable
            vascular system  and to develop an advanced blood-lymphatic integrated system with melanoma heterospheroids.  Reproduced with permission from Cao
            X, Ashfaq R, Cheng F, et al., Adv Funct Mater, Copyright © 1999-2023 John Wiley & Sons. (E) Both for modeling metastatic melanoma from ref.  licensed
                                                                                                      [66]
            under Creative Commons Attribution 4.0 International (CC BY 4.0).
            models exhibited several tumorigenic characteristics (i.e.,   of 3D-bioprinted tumor constructs for the volumetric
            growth kinetics, drug response, and genetic signature) that   alteration of tumor mass and drug response assessment.
            were more similar to the murine in vivo tumor setting than
            the 2D culture model. 3D-bioprinted in vitro cancer models   Metastasis is the process by which cancer cells
            with increased complexities in structure and biology of   spread from a primary site to other  parts of the body
            GBMs may likely serve as a rapid and personalized drug   moving through the vascular system. Thus, establishing
            screening platform. For drug delivery studies, Ozturk    a  vascular  network  plays  a  crucial role  in  modeling
            et al.  developed a 3D-bioprinted GBM model combining   metastasis progression. Meng et al.  created a spatially-
               [61]
                                                                                           [62]
            perfusable vascular channels using sacrificial bioprinting   defined 3D in vitro metastatic model via 3D bioprinting
            (Figure 4B). To establish the GBM model, the two gelatin   where the tumor cell droplet as the primary tumor and
            channels were integrated into the collagen layers, followed   endothelialized micro-channels were assembled within
            by liquefying the gelatin and seeding the ECs into fluidic   the  fibroblast-laden  fibrin  matrix  as  tumor  stroma  to
            channels to form the lumen structure. Meanwhile, patient-  mimic the key aspects of metastasis, including invasion,
            derived GBM spheroids (>400  μm in diameter) were   intravasation, and angiogenesis (Figure 4C). Furthermore,
            placed between the vascular channels, permitting GBM   a spatiotemporal gradient of growth factors (e.g., epidermal
            invasion and an extended life span of the tumor for up to 70   growth factor and vascular endothelial growth factor) was
            days. Following temozolomide treatment, GBM spheroids   achieved using programmable release capsules (triggered
            revealed regressing tendency; however, some GBM    by laser irradiation) to reproduce the biochemical features
            cells survived and resumed their active invasion despite   of the TME. In the emulated metastasis model, lung
            continued drug treatment, implying long-term therapeutic   cancer cell invasion and intravasation into the engineered
            resistance. In particular, their novel 3D imaging modality   vasculature were observed under the guidance of signaling
            enabled the efficient, long-term, non-invasive imaging   molecule gradients. The study confirmed the suitability


            Volume 9 Issue 5 (2023)                         27                         https://doi.org/10.18063/ijb.748
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