Current Advances in 3D Bioprinting for Cancer Modeling and Personalized Medicine

Abstract

Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.

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

“…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.…”

Recreating heterogeneity of bladder cancer microenvironment to study its recurrences and progression

“…These models can therefore constitute interesting platforms for the validation of drugs. Bioprinting offers a more controlled way to use hydrogels in the form of bioinks while providing the ability to establish complex 3D architectures that incorporate cellular heterogeneities (27,28). While this method suffers from the same downside as classical hydrogel from which the bioinks are derived from, it remains a method that is improving quickly and has been used to explore cancer related questions (29,30).…”

3D bioprinting and the revolution in experimental cancer model systems—A review of developing new models and experiences with in vitro 3D bioprinted breast cancer tissue-mimetic structures

“…There are several options for crosslinking: e.g., enzymatic (fibrinogen + thrombin = fibrin); ionic (alginate—CaCl 2 ); chemical (alginate—horseradish peroxidase); physical (gelatine-methacrylate—UV), or thermal (gelatine—high temperature) which can be performed either before or during or even after the printing process is finished ( 58 ). 3D bioprinting is a very effective tool, however, the standardisation of 3D bioprinting protocols is essential, and additionally, multi-faceted improvements are also required: 1) developing printing protocols, 2) standardising the materials used as bioinks, 3) creating novel biomaterials which have more sophisticated physical and biological properties, 4) improving the usability of 3D printed structures, as well as establishing test systems required for these ( 59 , 60 ).…”