Novel, bioinspired 3D bone models to simulate prostate cancer bone metastases

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Date
2024
Authors
Dozzo, Annachiara
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University College Cork
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Abstract
Prostate cancer (PC) ranks first amongst the types of cancer affecting the male population. There is a lack of effective drug treatments for patients diagnosed with metastatic spread of PC (mPC) to the bone and their prognosis is poor. The development of 3D, in vitro, models offers exciting opportunities to recapitulate the native tissue environment in vitro, to better understand diseases such as cancer, to reduce the overreliance on animal models in drug development and to develop more effective drug treatments. However, the number of 3D scaffold models of bone is limited, and many lack structural relevance to the hierarchy characterising the native bone tissue. While very few have been used to model mPC spread to the bone. The work presented in this aims to address these limitations by providing several scaffolds for deployment as models of mPC in the bone. The first models were produced using conventional techniques (CO2 foaming/porogen leaching), while additive manufacture (AM) methods including fused deposition modelling (FDM) and stereolithography (SLA) were used to produce advanced models based on a novel and versatile CAD design (iMARS), which was conceived as part of the work in the thesis. The different scaffolds proposed were physically and mechanically characterised and used as testbeds for drug studies with docetaxel to investigate their clinical correlation capabilities. Additive manufacture of scaffolds according to the novel and versatile iMARS design enabled reproducible scaffold production. In general, it was shown that scaffold type, the methodology applied to produce it and the blend of materials chosen, impacted the physicochemical properties of the scaffolds and influenced the behaviour of osteoblast cells, hFOB 1.19 in mono- or co-culture with prostate cancer cells, PC-3, and the cellular response to chemotherapeutics. The use of the biodegradable, PLGA copolymer either blended or coated with hydroxyapatite and/or collagen altered the scaffold’s microenvironmental cues, and enhanced the malignant profile of PC-3 cells at the expense of hFOB 1.19 cells contributing to the development of clinically relevant niches of mPC in the bone.
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Keywords
Prostate cancer , 3D scaffolds , Metastases , CAD , 3D printing , FDM , SLA
Citation
Dozzo, A. 2024. Novel, bioinspired 3D bone models to simulate prostate cancer bone metastases. PhD Thesis, University College Cork.
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