3D Printing and Bioprinting to Model Bone Cancer: The Role of Materials and Nanoscale Cues in Directing Cell Behavior

Abstract

Bone cancer, both primary and metastatic, is characterized by a low survival rate. Currently, available models lack in mimicking the complexity of bone, of cancer, and of their microenvironment, 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 challenge 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 biomaterials 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.

3D bioprinted osteosarcoma model for experimental boron neutron capture therapy (BNCT) applications: Preliminary assessment

“…Notably, the use of 3D bioprinting technique to fabricate the proposed OS model provides versatility in 3D model design, creating complex structures by combining different biomaterials and cell lines (healthy and pathological). In addition, a capillary network can be designed to vascularize the OS model in the future 22 …”

In vitro models of breast cancer bone metastasis: analyzing drug resistance through the lens of the microenvironment

“…The emergence of more complex 3D models which more accurately mimic cell-ECM and cell-cell interactions thus seems to be a promising alternative ( 10 ). However, to this date most bone or bone marrow models are still focusing on the biofabrication of the scaffold and the microenvironment and very few have tried to add cancer cells to their model ( 137 ). Noteworthy, only a small fraction of them is focusing on drug resistance.…”

A bone-based 3D scaffold as an in-vitro model of microenvironment–DLBCL lymphoma cell interaction

“…Certainly, among the new strategies, the 3D-printed and bioprinted models can provide novel perspectives for reproducing the composition and architecture of bone which may be exploited in cancer studies. However, as the development of 3D models in this field is still at an early stage, our model based on native bone scaffold may help to provide insights into the complexity of the bone microenvironment ( 17 – 19 ).…”