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International Journal of Bioprinting Biomimetic biofabrication of tumors volume

Figure 5. Engineering 3D metastatic models. (a) Schematization of metastasis niche extravasation, migration, and homing, favoring the propagation of
tumor cells from the primary tumor to secondary sites. (b-i) A sketch of control and drugged capsules with epidermal growth factor (EGF) where the
directional migration of tumor cells was led by EGF gradients. (b-ii) A picture of a 3D-printed culture chamber for testing the guided cell migration.
(b-iii) Fluorescence images show the distribution of cells. The white circle is the control, and the red circles indicate the EGF capsules. (b-iv) The graph
shows the cellular fluorescence intensity of A549 cells normalized by intensity at day 0, and EGF release (red) was compared to no EGF release (black)
over time. (b-v) The plot illustrates the displacement of cells in the X-direction toward the EGF capsules, revealing the directional influence of EGF on cell
migration. Adapted with permissions from ref. [119] .

cancerous tissue (Figure 5). A multi-cellular TME is be used to allow cancer cells to achieve and maintain their
recreated using tumor cells and endothelial cell-lined native phenotypes and physiological functions. Moreover,
vascular conduits within a fibrin gel containing functional the absence of standardized bioinks in terms of polymeric
fibroblasts. 3D-printed microcapsules were loaded with composition and cell encapsulation density could lead to
growth factors and selectively disrupted with a laser source difficulties in the reproducibility of the experiments and in
to guide VEGF or EGF release. The effect of the released the correlation of the results. Furthermore, new features of
molecules influenced the TME progression, offering a new existing bioprinting platforms, innovative implementations,
tool to probe the spatiotemporal evolution of specific pro- and new technologies, such as microfluidic-assisted
metastatic tumors. bioprinting , co-extrusion, or multi-material bioprinting,
[34]
are promising tools to meet the need of multi-cellular and
5. Conclusion and future outlooks vascularized tumor models. Lastly, to overcome the use of
immortalized cell lines, the use of patient-derived primary
In the past decade, the advances in 3D bioprinting have
allowed the development of biomimetic 3D tumor models cells is promising for the development of biomimetic in vitro
that can mimic TMEs more accurately. Despite the platforms for personalized drug screening and therapies.
remarkable progresses, there are still several limitations The lack of cancer-specific models is a worrisome problem,
to solve to obtain physiologically relevant in vitro tumor which points to the urgent need to seek the assistance of
models. For instance, a high cell viability and long-term bioengineers and biologists to fabricate a model for the
cultures, or cell native phenotypes and functions, are still study of cancer progression and the test of new drugs
difficult to maintain within 3D-bioprinted platforms. Thus, against tumors.
3D biomimetic models are still far from recapitulating the
complexity of TMEs. Considering these challenges, the Acknowledgments
engineering of new bioinspired material inks, along with None.
the characteristics of the bioprinting technique and cell
sources, plays a pivotal role. Funding
Patient-derived ECM or biomaterials inks that This study was supported by funding from AIRC Aldi
accurately mimic the native ECM of specific tumors should Fellowship (GC) under grant agreement No. 25412.

Volume 9 Issue 6 (2023) 384 https://doi.org/10.36922/ijb.1022