Bifunctional biomaterials for bone metastasis and relevant models to evaluate these new materials

Breast and prostate cancer patients have a high chance of developing bone metastasis. Such lesions are very painful and current treatments do not suffice. Especially resection of the tumor is not preferred, as cancer cells often remain in the defect, and now there is a critical sized bone defect which needs some type of graft to heal the bone. Thus, researchers have been developing bifunctional biomaterials, which can kill remaining cancer cells and then help regenerating bone. However, these materials have always been tested separately for these two functionalities in either in vitro or in vivo. This research aimed on developing new models for evaluating these bifunctional biomaterials. First, differences in 2D to 3D cultures was explored for which the same viability read out was used for both the 2D and 3D cultures was used. Confocal imaging showed that the penetration of the chemotherapeutic drug into the spheroids is time and concentration dependent. Secondly, a bone metastatic spheroid model was developed. These spheroids bone metastasis could be feasibly modelled, while still remaining relevancy due to the 3D and direct co-culture. Confocal imaging showed that the spheroids were more robust to chemotherapeutic treatment than 2D co-cultures of the same cells. This was confirmed in metabolic activity and MMP-9 concentration measurements in supernatants of these cultures. Thirdly, the bone metastatic spheroid model was utilized to evaluate the effects of cisplatin loaded hydroxyapatite nanoparticles (nHAcis), a bifunctional biomaterial. First confocal imaging and metabolic activity measurements showed that cancer cells were not affected by nHA supplementation. However, with these same methods and MMP-9 concentration measurements an anti-cancer effect of nHAcis was observed. Lastly, when these spheroids were then subjected to osteogenic stimulation some new mineral depositions were observed by calcein staining. Lastly, a novel humanized bone metastasis model was developed with either ex vivo or in vivo applications. For this human bone discs were loaded with cancer cells to evoke bone metastasis. Bioluminescent tracking allowed for cancer cell detection, and with histology cancer cells as well as bone (cells) could be investigated. The data in this collection contain: protocols, images (brightfield, confocal laser scanning, digital, bioluminescent, fluorescent), subsequent quantifications, viability readouts, metabolic readouts, supernatant MMP-9 measurements, data related to physicochemical quantifications, and supporting files.