Printing the Pathway Forward in Bone Metastatic Cancer Research: Applications of 3D Engineered Models and Bioprinted Scaffolds to Recapitulate the Bone–Tumor Niche

SIMPLE SUMMARY: Breast cancer commonly migrates to the skeleton. Once patients have breast cancer in their bones, their quality of life is poor. Research has shown that the environment and structure of bone helps support metastatic breast cancer cell growth. Current models used in laboratories to study breast cancer that has migrated to bone do not include all the components of what happens in the human body. This is because technology in the past was limiting. Now, however, a new technology exists, called three-dimensional (3D) bioprinting, that “prints” living cells in geometries like the ones within the human body, to replicate a more realistic environment. In cancer research, 3D bioprinting allows researchers to more closely replicate events that occur when cancer cells migrate from a primary location to a secondary site, as well as model events in the environment of the secondary site. 3D bioprinting may also be used instead of animal models in some cases, and may speed up new drug discovery for cancer treatment. ABSTRACT: Breast cancer commonly metastasizes to bone, resulting in osteolytic lesions and poor patient quality of life. The bone extracellular matrix (ECM) plays a critical role in cancer cell metastasis by means of the physical and biochemical cues it provides to support cellular crosstalk. Current two-dimensional in-vitro models lack the spatial and biochemical complexities of the native ECM and do not fully recapitulate crosstalk that occurs between the tumor and endogenous stromal cells. Engineered models such as bone-on-a-chip, extramedullary bone, and bioreactors are presently used to model cellular crosstalk and bone–tumor cell interactions, but fall short of providing a bone-biomimetic microenvironment. Three-dimensional bioprinting allows for the deposition of biocompatible materials and living cells in complex architectures, as well as provides a means to better replicate biological tissue niches in-vitro. In cancer research specifically, 3D constructs have been instrumental in seminal work modeling cancer cell dissemination to bone and bone–tumor cell crosstalk in the skeleton. Furthermore, the use of biocompatible materials, such as hydroxyapatite, allows for printing of bone-like microenvironments with the ability to be implanted and studied in in-vivo animal models. Moreover, the use of bioprinted models could drive the development of novel cancer therapies and drug delivery vehicles.