Abstract
In vitro cancer 3D models are valuable tools to provide mechanistic insight into solid tumor growth, invasion, and drug delivery. The 3D spheroid model of solid tumors has been the most popular cancer model in use until now. However, previous studies have shown that these spheroid models lack sufficient morphological parameters, which may affect their response to chemicals. In this work, we proposed the fabrication of miniaturized 3D cancer models using collagen type I-based bioprintable bioinks. In the context of a mimicking model for advanced neuroblastoma studies, we showed that cancer cells contained in bioprintable bioinks formed Homer Wright-like rosettes, maintained their proliferative capacities and produced an equivalent Vimentin-rich matrix unlike that of non-bioprintable bioinks which made for poorer models. In addition, bioprintable bioinks were successfully bioprinted as compartmentalized 3D models in the centimeter scale, which was not feasible using non-bioprintable bioinks. In contrast to non-bioprintable hydrogels, we did not observe contraction in their bioprintable counterparts, which is an advantage for prospective 3D bioprinted models that should attain stable rheological and mechanical properties after bioprinting. By adopting this proposed system for the use of patient-derived primary tumor cells, the approach could be introduced as a first line strategy in precision medicine for testing the response of neuroblastoma cells to drugs, especially when disease progresses rapidly or patients do not respond to actual therapy regimens.
Highlights
In vitro cancer 3D models are valuable tools to provide mechanistic insight into solid tumor growth, invasion and drug delivery
Cell-free 0.5% AG-0.2% COL bioprintable bioink was printed with a resembling architecture as as proposed in Figure 1, in order to show the potential of a drop-on-demand bioprinting strategy proposed in Figure 1, in order to show the potential of a drop-on-demand bioprinting strategy to to create 3D miniaturized cancer models
The creation of 3D cancer models using drop-on-demand bioprinting involves the use of hydrogels, which are biocompatible, and succeed in mimicking in vitro
Summary
In vitro cancer 3D models are valuable tools to provide mechanistic insight into solid tumor growth, invasion and drug delivery They are slowly replacing the use of conventional 2D in vitro cell culture as the main method of adherent cell growth that has been practiced for decades in determining complex cellular and biological processes that occur during tumorigenesis. In order to recreate the tumor microenvironment, researchers have created tumor–microvessel models which incorporate a microvessel into an extracellular environment consisting of a hydrogel-like fibrin or collagen type I [8,9]. This type of approach is used to study interactions between cancer cells, their microenvironment and the tumor vasculature. We compared cell interactions in the form of co- and tricultures in a non-bioprintable biological hydrogel (type I collagen) with a bioprintable bioink (agarose-type I collagen) as a potential microenvironment for cancer modeling using bioprinting
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