Advancing 3D scaffold models for metastatic prostate cancer in bone: Materials, manufacture, and future perspectives.

The metastatic spread of prostate cancer to the bone is debilitating for patients and is associated with a poor prognostic outlook. Gaining a deeper insight into the pathophysiology of prostate cancer and its metastatic spread using advanced, in vitro, 3D models could enhance disease understanding and the successful development of new drug treatments. The in vitro replication of prostate cancer metastasisation to bone is challenging and has received little research attention. The 3D scaffold models investigated to date exhibit different physical characteristics and utilise a diverse range of materials, and manufacturing methods. This variability is likely driven by the lack of standardisation and guidance. Herein, we review the scaffold models used as in vitro bone niches of prostate cancer metastases and examine the different physical (e.g. porosity, pore geometry) and material criteria that guide the design and production of artificial 3D bone aliases. We critically review different manufacturing techniques ranging from standard techniques (e.g. freeze drying) to more advanced additive manufacturing strategies that enable the production of more intricate and controlled structures. Ultimately, we provide insights and future directions to guide researchers investigating this poorly studied field.