Developing and evaluating a microsphere laden neural tissue model using 3D bioprinting and microfluidics

Date

2022-12-22

Authors

Kirsch, Rebecca

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Abstract

3D bioprinting is a form of additive manufacturing that deposits a bioink composed of biomaterials, small molecules, and cells in a layer-by-layer fashion, creating a 3D structure. The constructs created with 3D bioprinting can be used as disease models for drug development and testing. To create a proper 3D constructs representative of native tissues, the biological, mechanical, and rheological properties of the bioink components and the final 3D model must be analyzed. Adding small structures like microspheres or nanofibers can alter the mechanical and rheological properties of the tissue as well as deliver drugs or growth factors. Microspheres can be created in several methods, including batch stirring or microfluidics, with microfluidics offering additional benefits such as better control over the shapes and sizes of particles. This thesis overviews the development of tools that can be employed to create a healthy or diseased neural tissue model using 3D bioprinting. First, Chapter 1 includes an introduction on common types of 3D bioprinting, biomaterials, micro- and nanomaterials, and mechanical and rheology properties. In Chapter 2, a neural tissue model was developed using a microfluidic printhead-based bioprinter, and the mechanical and rheological properties of the tissue with and without microspheres was investigated. Next, in Chapter 3 a flow-focusing microfluidic platform was used to create cargo-loaded microspheres with controllable sizes and morphology. Furthermore, Chapter 4 overviews a detailed protocol on preparing a fibrin-based bioink, alginate-gelatine bioink, printing set-up, and printing on Cellink’s BIO X is described. Altogether, the approaches used in this thesis offer information on developing a particle-laden neural tissue model using 3D extrusion bioprinting.

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Keywords

3D bioprinting, controlled drug delivery, microspheres, microfluidics, neural progenitor cells

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