Bioengineered <i>in vitro</i> bone scaffolds to investigate bone metastases: a systematic review of mechanical and biological model validation

One of the most common sites of cancer metastasis is the bone, with a large proportion of both breast cancer and prostate cancer patients who develop metastases having involvement of the skeleton. The prognosis for patients with bone metastases is poor as there are limited effective treatment options. The lack of reliable models to recapitulate the native bone micro-environment during the drug discovery process, has resulted in a poor understanding of the biological processes that enable and drive metastases, and difficulty evaluating potential treatments. Animal models that have been successful in the genesis of cutting-edge treatments for primary cancer have not been able to be used for treatments for metastases, in part due to their inability to accurately recapitulate the native human microenvironment. Consequently, the development and availability of drugs to treat and/or prevent bone metastases are lacking. The last decade has seen an increase in the development and use of three dimensional (3D) scaffolds in cell culture to investigate cancer, as these models have demonstrated similar cancer cellular growth and gene/protein expression to the native human microenvironment. The majority of 3D cell culture systems for studying cancer processes comprise a soft matrix, which fails to accurately replicate the rigidity and structural complexity of bone tissue, which further alters the behaviour of cells. This systematic literature review focuses on the research to date on the development and characterisation of solid scaffolds that have been used for the purpose of<i>in vitro</i>investigation of bone metastases. It highlights the importance of materials testing to characterise the models, ensuring they have a composition, structure and strength similar to bone, to give appropriate mechanical cues to cells, while also highlighting the biological validation completed to ensure the models are an accurate representation of the metastatic niche.