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Summary of dissertation

The limited predictive value of animal models has significantly impeded progress in drug development and regenerative medicine. While advances in biofabrication have enabled the creation of 3D cell-laden structures, replicating functional human tissue remains difficult, mainly due to the lack of suitable, dynamic biomaterials. This thesis focuses on the development of innovative, 4D-manipulable biomaterials that support cellular behaviour in realistic microenvironments and enable the fabrication of advanced tissue models via 3D bioprinting.

Chemically defined hydrogels were developed to allow precise spatiotemporal biofunctionalisation. Using volumetric bioprinting and photografting, bioactive molecules were incorporated without compromising their function, thereby enhancing cell coverage and invasion depth. To broaden accessibility, AddGraft, an off-the-shelf ready additive, was developed to enable 4D photografting in a wide range of acrylated hydrogels without altering their bulk properties. This facilitated mechanical tuning of cell-laden constructs in a biocompatible manner. Additionally, a thermally responsive strategy was introduced to overcome the limitations in bioprinting resolution. Larger channels could be seeded with cells and subsequently shrunk to physiological dimensions. To mimic tissue dynamics, a hybrid supramolecular hydrogel, HybriGel, was designed, combining high shape fidelity with improved cell migration, decoupling structural stiffness from cellular microenvironments. Lastly, combining HybriGel with AddGraft created a robust, modular platform offering precise control over both chemical and mechanical cues in space and time.

This work represents a paradigm shift: biomaterials are redefined as active, adaptive components that dynamically interact with their environment, laying the foundation for more realistic and functional in vitro tissue models.

If a candidate gives a layman's talk, the live stream will start 15 minutes earlier.