3d printing and bioprinting to model bone cancer: The role of materials and nanoscale cues in directing cell behavior

Bone cancer, both primary and metastatic, is characterized by a low survival rate. Cur-rently, available models lack in mimicking the complexity of bone, of cancer, and of their microen-vironment, leading to poor predictivity. Three-dimensional technologies can help address this need, by developing predictive models that can recapitulate the conditions for cancer development and progression. Among the existing tools to obtain suitable 3D models of bone cancer, 3D printing and bioprinting appear very promising, as they enable combining cells, biomolecules, and biomaterials into organized and complex structures that can reproduce the main characteristic of bone. The chal-lenge is to recapitulate a bone-like microenvironment for analysis of stromal–cancer cell interactions and biological mechanics leading to tumor progression. In this review, existing approaches to obtain in vitro 3D-printed and-bioprinted bone models are discussed, with a focus on the role of biomateri-als selection in determining the behavior of the models and its degree of customization. To obtain a reliable 3D bone model, the evaluation of different polymeric matrices and the inclusion of ceramic fillers is of paramount importance, as they help reproduce the behavior of both normal and cancer cells in the bone microenvironment. Open challenges and future perspectives are discussed to solve existing shortcomings and to pave the way for potential development strategies.