3D printing of functional scaffolds for neural interfaces

Hakan Gürbüz*

*Corresponding author for this work

Research output: Book/ReportPh.D. thesis

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Abstract

Various systems have recently been developed to mimic the native morphologies and characteristics of tissues into three-dimensional (3D)-based tissue engineering systems using 3D biofabrication methods. These methods can be used for patterning materials with high fidelity and precision by finetuning physical geometries, mechanical features, and locating cellular cues. Moreover, they enable the creation of new biomaterial interfaces that better replicate complex tissues by precise control of the 3D positioning of cells. This dissertation aimed to investigate biomaterials that can be applied in biofabrication using 3D printing principles to create 3D scaffolds for application as neural interfaces. Within this frame, the Felix BIOprinter with two print heads was developed as a commercialized product with a high degree of modularity to enable easy exchange of print head units. The BIOprinter was designed with extrusion-based print heads, having heating/cooling on both the print heads and the bioprinter build plate, and a UV curing unit, which enables its use for a wide range of 3D printing applications. One of the Felix BIOprinter prototypes was used to fabricate polycaprolactone (PCL) scaffolds for culturing brain organoids. The engineered flat brain organoid (efBO) protocol demonstrated a shapeshift from normal spherical to flat brain organoids. By tuning the size and pattern of the scaffold, the common necrotic tissue core problem was solved, enabling the diffusion of oxygen and nutrients to the whole tissue, and moreover led to intrinsic gyrification, which is reported in brain organoids for the first time. After the commercialization of the Felix BIOprinter, it was used for embedded free-form 3D printing of SU8-derived pyrolytic carbon scaffold for application as a neuron-electrode interface. First, the ability to free-form 3D print SU8 photoresist in different granular gel mediums was investigated. Then, the optimized printing parameters were used for the 3D printing of SU8 with its subsequent pyrolysis to produce 3D pyrolytic carbon electrode scaffolds. The physical characterization showed that micro flower-like structures were formed on the surface of the carbon scaffold. The scaffold electrodes were tested electrochemically and further used as a support for differentiation of human neural stem cells into dopaminergic neurons, which subsequently were stimulated chemically and optically to see if the dopamine released from exocytosis could be detected electrochemically by the carbon scaffold electrodes.
Original languageEnglish
Place of PublicationKgs. Lyngby, Denmark
PublisherDTU Bioengineering
Number of pages218
Publication statusPublished - 2021

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