Advances in 3D Bioprinting for Cancer Biology and Precision Medicine: From Matrix Design to Application

Abstract

The tumor microenvironment is highly complex owing to its heterogeneous composition and dynamic nature. This makes tumors difficult to replicate using traditional 2D cell culture models that are frequently used for studying tumor biology and drug screening. This often leads to poor translation of results between in vitro and in vivo and is reflected in the extremely low success rates of new candidate drugs delivered to the clinic. Therefore, there has been intense interest in developing 3D tumor models in the laboratory that are representative of the in vivo tumor microenvironment and patient samples. 3D bioprinting is an emerging technology that enables the biofabrication of structures with the virtue of providing accurate control over distribution of cells, biological molecules, and matrix scaffolding. This technology has the potential to bridge the gap between in vitro and in vivo by closely recapitulating the tumor microenvironment. Here, a brief overview of the tumor microenvironment is provided and key considerations in biofabrication of tumor models are discussed. Bioprinting techniques and choice of bioinks for both natural and synthetic polymers are also outlined. Lastly, current bioprinted tumor models are reviewed and the perspectives of how clinical applications can greatly benefit from 3D bioprinting technologies are offered.

Generation of a Perfusable 3D Lung Cancer Model by Digital Light Processing

“…The proliferation, metabolism, and invasive potential of cancer cells are largely determined by the tumor microenvironment. The composition of stromal cells, such as fibroblasts, adipocytes, endothelial cells, and pericytes, as well as the extracellular matrix, needs to be modeled to fully recapitulate the characteristics of a biological tumor [ 19 ]. Furthermore, several studies have used decellularized extracellular matrix as a natural cell environment in the bioink [ 56 , 57 ].…”

“…A particularly promising strategy to produce models with higher relevance for human (patho-)physiology is the generation of organ models by 3D bioprinting, which allows the arrangement of different types of (human) cells of an organ with high spatial resolution [ 16 , 17 , 18 ]. Cancer biology is one of the research fields in which bioprinting holds the most promise [ 19 , 20 ]. Due to its high flexibility, the technology allows the adjustment of the stiffness of the extracellular environment, the combination of various cell types, and the design of desired 3D arrangements.…”

Trends in Photopolymerizable Bioinks for 3D Bioprinting of Tumor Models

“…This model mimicked increased drug resistance in multicellular tumor spheroids (MCTSs) compared to individual cell spheroids of MCF7 and L929 cells (Figure c) . Matrigel-based spheroids are well explored for clinical drug screening, but these models lack in human relevant biochemical and mechanical cues provided by the ECM in vivo . High throughput spheroid formation approaches involving photopolymerizable decellularized ECM-based bioinks can provide an advanced means to maintain tumor heterogeneity for patient-derived organoid drug screening.…”

The three-dimension preclinical models for ferroptosis monitoring

“…This technique has gradually become the most promising cell research model. 3D cultures, including spheroids, are nowadays recognized as a better model of the in vivo environment, whereas rare detailed cell death (including ferroptosis) assays are available for 3D cultures (Jung et al, 2022;Yan et al, 2022). Robin Demuynck's (Demuynck et al, 2020) employed 3D cells culture technology to demonstrate an assay that can effectively identify diverse types of cell death, including ferroptosis, and quantitatively assess cell death in tumor spheroids, the 3D Cell Death Assay (3DELTA).…”