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Bioprinting of novel gelatin methacryloyl hydrogel: bioink design, printing optimization by machine learning, and applications in cell protection under oxidative stress
Dissertation   Open access

Bioprinting of novel gelatin methacryloyl hydrogel: bioink design, printing optimization by machine learning, and applications in cell protection under oxidative stress

Zhouquan Fu
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2023
DOI:
https://doi.org/10.17918/00001915
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Abstract

Bioinks Bioprinting GelMA Colloids Minocycline Machine Learning
The rapid advancement in modern biofabrication technologies is driven by escalating demands across various key areas of biomedical research and application. Central to these developments is three-dimensional (3D) bioprinting, a technology that enables the precise deposition of cells, biomaterials, and biofactors in 3D space. This technique is crucial for constructing complex biological models and engineered living systems. It plays a pivotal role in biofabrication, with various applications in tissue engineering, disease modeling and etiology, drug screening, and personalized medicine. However, many significant challenges still persist in bioprinting. One major hurdle is the bioprinting of biomimetic constructs that reproduce the complexity, mechanical properties, resolution, and functionality of natural tissues. As the size of bioprinted constructs increases, maintaining their structural integrity and achieving high resolution becomes increasingly difficult. Another fundamental challenge lies in maintaining a balance between high-quality printability with bioinks and ensuring high cell viability throughout the printing process. Gelatin methacryloyl (GelMA) based bioink has been explored in numerous application settings owing to its favorable biochemical characteristics, there is still a lack of understanding regarding how GelMA synthesis parameters influence the material properties of GelMA and how its time and temperature dependent rheological properties, as well as batch differences further impact its applications in extrusion-based bioprinting. The tunable mechanical properties, high water content, and photocrosslinking capabilities of GelMA highlight its potential for localized drug delivery applications, such as in wound dressings or drug-loaded implants that require customization in shape and size. Previous research has shown success in incorporating minocycline (MH) into GelMA scaffolds for therapeutic applications but achieving prolonged and sustained release of MH is challenging due to its small molecular size. Furthermore, the current limitations in speed, precision, and reproducibility necessitate labor-intensive and iterative experiments in 3D bioprinting research. These experiments involve intricate tasks such as Computer-aided design (CAD) model creation, formulation of suitable bioinks, fine-tuning printer parameters, ensuring consistent printability, and assessing cytocompatibility. As a result, the costs and investments associated with bioink development remain significant. The objective of this thesis research is to develop novel GelMA hydrogel bioinks and explore their applications in 3D bioprinting and cellular protection under oxidative stress. We have systematically investigated the impact of synthesis reaction parameters on the properties of GelMA, such as its degree of substitution and molecular weight, and further examined how these properties influence printability. The second objective involves the application of machine learning techniques to optimize the bioprinting process, with a focus on enhancing efficiency and reducing costs. Finally, the third objective of this research is to develop an accessible bioprinted in vitro model utilizing GelMA bioink. This model is specifically designed to assess the effectiveness of minocycline, released from nanoparticle complexes embedded within GelMA scaffolds, in providing cellular protection under oxidative stress conditions. By addressing existing challenges and venturing into novel applications of GelMA based bioinks, this research seeks to contribute significantly to the advancement of 3D bioprinting technology and its potential in various biomedical applications.

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