Latte Bovio, Claudia (2024) Biomimetic dendritic microstructures for cell-chip coupling. [Tesi di dottorato]

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Abstract

In the cutting-edge fields of tissue engineering and bioelectronics, neuromorphic materials are revolutionizing our approach to replicating the intricate architecture and functionality of neurons. These groundbreaking materials are designed to mimic the physiological environment of native neuronal tissue, paving the way for advanced biomedical applications. By harnessing the power of biomimetic micro and nanostructures, researchers can craft physical scaffolds that provide crucial support and directional guidance for neurons, facilitating the extension of their intricate processes. The aim of integrating neuromorphic materials into bioelectronic devices is to create sophisticated chip-based platforms capable of both monitoring and stimulating neuronal networks with unparalleled precision. These platforms hold immense potential for a wide range of applications, from fundamental neuroscience research to innovative therapeutic interventions for neurological disorders. However, two major challenges must be overcome to fully unlock the potential of neuromorphic materials. The first challenge is achieving precise control over the morphology of these materials. The shape, size, and spatial arrangement are critical factors that dictate how these materials interact with neuronal cells. Fine-tuning these parameters is essential for optimizing the performance and functionality of the resulting bioelectronic devices. The second challenge is developing a deep understanding of how neuromorphic materials influence neural network development throughout various outgrowth phases. This requires studying the dynamic interactions between neurons and materials, including their effects on processes such as adhesion, endocytosis, polarity establishment, and overall network development. To address these challenges, we have developed bespoke biomimetic microstructure arrays using two-photon polymerization. This method allows us to create intricate structures that closely resemble the diverse morphologies and spatial arrangements of neuronal dendritic spines. By carefully designing these microstructures, we aim to provide an environment that supports and guides neuronal growth in a manner that closely mirrors natural conditions. We characterized the cell responses to these platforms, focusing on key processes at the neuronal-material interface. This includes cellular adhesion, where neurons attach to the material; endocytosis, where cells internalize material components; polarity establishment, which is crucial for proper cell function and organization; and the overall development and maturation of neuronal networks. Our findings demonstrate that these innovative biomimetic platforms significantly enhance the interaction between biomaterials and neurons. This improved coupling has the potential to transform neuroengineering, providing more effective tools for monitoring and stimulating neuronal activity. By addressing the current challenges and leveraging the unique properties of neuromorphic materials, we are paving the way for the development of bioelectronic devices with unprecedented capabilities in both research and clinical settings

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