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

Simple item page
dc.check.chapterOfThesisChapter 3-5en
dc.check.date2027-12-31
dc.check.infoPartial Restriction
dc.contributor.advisorRyan, Katie
dc.contributor.advisorO'Driscoll, Caitriona M.
dc.contributor.authorDozzo, Annachiaraen
dc.date.accessioned2024-09-23T11:05:33Z
dc.date.available2024-09-23T11:05:33Z
dc.date.issued2024
dc.date.submitted2024
dc.descriptionPartial Restriction
dc.description.abstractProstate 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.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDozzo, A. 2024. Novel, bioinspired 3D bone models to simulate prostate cancer bone metastases. PhD Thesis, University College Cork.
dc.identifier.endpage352
dc.identifier.urihttps://hdl.handle.net/10468/16419
dc.language.isoen
dc.publisherUniversity College Corken
dc.rights© 2024, Annachiara Dozzo.
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectProstate canceren
dc.subject3D scaffoldsen
dc.subjectMetastasesen
dc.subjectCADen
dc.subject3D printingen
dc.subjectFDMen
dc.subjectSLAen
dc.titleNovel, bioinspired 3D bone models to simulate prostate cancer bone metastasesen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
Files
Original bundle
Now showing 1 - 4 of 4
Thumbnail Image
Name:
DozzoA_PhD2024.docx
Size:
27.08 MB
Format:
Microsoft Word XML
Description:
Full Text E-thesis (Word)
Thumbnail Image
Name:
DozzoA_PhD2024.pdf
Size:
29.87 MB
Format:
Adobe Portable Document Format
Description:
Full Text E-thesis
Thumbnail Image
Name:
DozzoA_Submission for examination Form.pdf
Size:
408.24 KB
Format:
Adobe Portable Document Format
Thumbnail Image
Name:
DozzoA_PhD2024_Partial.pdf
Size:
20.03 MB
Format:
Adobe Portable Document Format
Description:
Partial Restriction
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
5.2 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Research Theses
College of Medicine and Health - Doctoral Theses
Pharmacy - Doctoral Theses