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International Journal of Bioprinting Biomimetic biofabrication of tumors volume

components of the TME and other relevant features, such biochemical, mechanical, and physical cues. Therefore, it is
as the supporting vasculature and the fluid dynamics. of utmost importance that the specific biomaterial mimics
Lastly, to overcome the disadvantages of MCTS the physiochemical characteristics of the native ECM [17,47] .
models, tumor-on-a-chip platforms have emerged as Particularly, for 3D bioprinting applications, biomaterials
[42]
[48]
microfluidics cell culture devices designed to recapitulate which can be adopted for use as biomaterial inks are
the tumor physiology by mimicking a dynamic TME, properly named bioinks following the addition of living
cells
. Specifically, when designing a biomaterial ink,
[49,50]
including and providing fluid flow, perfusion, and the mechanical and biochemical properties of the ink are
chemical gradients. Comprehensive reviews on 3D-printed needed to be taken into consideration for the printability
tumor-on-a-chip have been recently released with detailed and the biocompatibility of the constructs . Therefore, the
[51]
insights and information [43,44] .
limitations imparted by the material itself and the choice of
However, although these approaches may serve as useful the bioprinting technology inevitably narrow the range of
tools to understand the roles of biochemical and physical biomaterials available to engineer a 3D-bioprinted cancer
cues in tumor initiation and progression, these strategies model. Typically, biocompatible hydrogel material inks
lack the ability to control the location and organization of (>90% w/v water) can be synthesized from a wide array of
multiple cells in a complex system such as the TME. naturally derived and synthetic polymers.
In the last decade, tremendous efforts and progresses Naturally derived polymers are obtained from natural
have been made in the development of 3D culture models sources and can form hydrogels that usually demonstrate
that can more accurately resemble the in vivo tumor good biocompatibility and biodegradability. Naturally
milieu. To this purpose, 3D bioprinting technologies and derived polymers could be further classified based on
advanced biomaterials are gaining more interest because the native source. Indeed, polymers such as alginate,
of the potential to form more complex and well-organized agarose, or gellan gum are obtained from plant-based or
constructs and to better control the distribution of the cells living organisms like algae or seaweeds and lack specific
[45]
within the 3D structure . Moreover, 3D bioprinting relies motifs for cell adhesion, whereas others, such as collagen,
on the capability of building a full range of large-scale gelatin, fibrin, and even decellularized tissue-specific ECM
tumor models with multiple biomaterials, various cell materials, are derived from xenogeneic sources (generally
types, and perfusable networks with high resolution and vertebrates), which exhibit the inherent ability to foster cell
reproducibility (Figure 2). adhesion. Despite the elevated biocompatibility and ECM-
[46]
like properties, hydrogels formed from naturally derived
3.1. Biomaterial inks polymers have some limitations, such as their weak
The biomaterials used to engineer a 3D cancer model should mechanical properties (compared to synthetic hydrogels)
be selected to resemble the native TME, providing cells not or batch-to-batch variability , which may lead to low
[52]
only with a scaffolding structure, but also with appropriate reproducibility and consistency.

Figure 2. The evolution of cancer modeling. Standard pre-clinical cancer models often lack versatility and accuracy, making them inadequate for
replicating complex biological diseases, such as cancer. Conventional cancer models, such as two-dimensional (2D) cultured cancer cell lines and animal
models, struggle to accurately reproduce patient-specific cancerous tissue, compromising drug testing and significantly limiting further development.
Thus, inherent physiological differences with humans, resulting in altered drug response, remain crucial considerations for the final testing of cancer
therapeutics. Safe and effective pre-clinical cancer models are needed for drug screening and a better understanding of cancer growth and metastasis
mechanisms. 3D bioprinting is emerging as a key technology for the rapid and reliable engineering of cancer-like tissue.

Volume 9 Issue 6 (2023) 376 https://doi.org/10.36922/ijb.1022