Bio – Matrices Interaction : From Microstructured Hydrogel Volumes and Hydrogel Surfaces

In vivo cellular behavior is highly relevant to understand for various diseases and future tissue engineering but challenging to study using traditional in vitro cell growth methods: Many cellular mechanism functions differently when cells are grown in three-dimensional (3D) conditions similar to in vivo conditions as in traditional 2D culture techniques. As it is known for some time that 2D cell cultures and their mechanical properties influence the cellular behavior, this is also true for the 3D environment. Especially for the stability of the nucleus, the subcellular compartment responsible for storing the main part of our DNA, the 3D environment, and the mechanical and structural properties of it are highly valuable. Considering an implant inside the body’s soft tissue, the mechanical and structural properties will mediate the cell-matrix interaction. Recent advances in biomaterial research have enabled both cell growth in 3D and increased control of the cell-matrix interaction on an artificial substrate, e.g., as with structured PDMS channels. Despite these advances, there remain challenges in this field. An essential challenge until now is the creation of 3D structured samples that display the properties of the extracellular matrix in a controllable manner. These properties are hydration for the diffusive exchange of nutrition, controllable variability of the mechanical properties, and highly controllable biofunctionalization in 3D. In this thesis, novel means of growing cells in 3D environments with defined mechanical properties, creating new bio-crosslinker and investigating substance release from hydrated matrices showing the power of biomaterial-cell interactions for life sciences and biomedical research are presented In the first part of this work, the 3D cell-matrix interactions are discussed using fibrosarcoma cells grown in 3D-microstructured hydrogel matrices with a range of controlled mechanical properties. With the tuning of the matrix stiffness, cell behavior was affected, creating a preference for specific positions within the structured environment. Interestingly, the mechanical properties of the matrix were also found to impact the nucleus, affecting the stability of the nuclear envelope, and the intracellular position of the nucleus during cell migration. The second part of this thesis focuses on two different approaches for cell-matrix interactions in two dimensions (2D). In the first approach, the focus is on the compliance of miniaturized biosensors to primary endothelial cells. In the second approach, a chemically engineered bio-crosslinker is presented for enhanced biofunctionalization and cell adhesion. For studying the new bio-crosslinker (BCL) effectiveness, cells were grown on pHEMA, a protein-inert hydrogel. Once inserted inside the pHEMA precursor mixture, the pHEMA hydrogels included free reactive groups and can be biofunctionalized with fibronectin instantly to support cell adhesion. In the final part of this thesis, I present a study of hydrogel matrices, which release different drugs. I demonstrate the influence of the drug solution on hydrogel swelling and its release for an anti-seizure drug. The possibility of matrix degradation within the incubation time is also investigated. Initial studies have shown that the substances were released over several days, attesting to the high suitability for indirect drug administration. In the second approach, an anti-inflammatory drug release from swollen hydrogel matrices is investigated. The aim here was to create an anti-inflammatory soft substratum for future tissue cuts. The results of the investigations presented in this work have also highlighted three essential features of biomaterials: matrix structural size, matrix topography or architecture, and dimensionality. Each element played a key role in the studies presented in this work, clearly demonstrating the importance of each when designing, and working with biomaterials.


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