Versatile multi-component (bio)ink platform for advanced biofabrication

The thesis aims to advance tissue engineering through bioprinting, addressing the need for innovative solutions to restore tissue function and tackle organ shortages. Bioprinting, which integrates 3D printing with biological materials to create "bioinks," has significant potential but is hindered by technological and regulatory challenges that limit its clinical application. The thesis begins with a comprehensive literature review that examines the state of the art in the clinical adoption of bioprinting, identifying key challenges and roadblocks to its translation. Drawing inspiration from the shorter approval pathways of equivalent medical devices, such as the FDA's 510(k) process, the research focuses on developing versatile bioinks that could facilitate regulatory approval. Two strategies were explored to enhance the adaptability of alginate-based bioinks for various bioprinting techniques and applications: (1) functionalizing alginate with tyramine for dityrosine crosslinking, creating a multicrosslinking platform with ionic, enzymatic, and photo-crosslinking capabilities, and (2) using norbornene functionalization to enable thiol-ene click chemistry, allowing precise control over the hydrogel's mechanical and biological properties. The results demonstrated that the multicrosslinking approach could be adapted across different bioprinting methods, including extrusion-based and microfluidic techniques, though further optimization was required to improve biological compatibility. In contrast, the thiol-ene click chemistry approach provided fine-tuning of the hydrogel properties, resulting in enhanced biological performance. It enabled the successful bioprinting of complex structures, such as endothelialized and epithelialized tubules, showcasing its potential for diverse tissue engineering applications. The final chapter summarizes the main findings and discusses future perspectives, highlighting directions for further advancing the field.