Developing 3D cell cultures for synthetic bone models

Hill, Laurence (2023). Developing 3D cell cultures for synthetic bone models. University of Birmingham. Ph.D.

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Abstract

Bone is a difficult tissue type to investigate with much of the primary investigations performed in animals. While this can improve our understanding of the basic mechanisms of the tissue, the pace of research can be slow and have poor clinical translation from benchtop to clinic. Therefore, there is a need for an intermediate step, a synthetic tissue model that accurately recapitulates the biology of bone. This can be used as a substitute for animals in primary and investigatory research without the cost and ethical concerns associated with animal models. This thesis focused on the development of such models. A composite bioink formulation of alginate, collagen and hydroxyapatite was developed. A key feature of this bioink was fibrillar collagen formed within the alginate and in the presence of the hydroxyapatite mineral. To achieve the fibrillar collagen, low concentrations of alginate had to be used within the bioink that meant the printed constructs could not self-support. A suspended printing technique was incorporated and facilitated the 3D printing of the constructs, due to the low structural stability of the bioink, the constructs could not be removed from the bath. A novel in situ hybrid crosslinking 3D printing mechanism was developed to semi crosslink the constructs which allowed them to be retrieved. This mechanism was compatible with cell incorporation and fibril collagen formation.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):