Harnessing functionalized polysaccharides: Tailoring biomacromolecules for varied tissue engineering and drug delivery applications

Polysaccharides are ubiquitous and versatile biomacromolecules that play vital roles across a wide range of biological systems. Found in everything from towering trees to microscopic bacteria, they serve as structural support, energy reserves, and even signalling molecules, showcasing nature’s ingenuity. Their multifaceted nature not only highlights their importance in natural ecosystems but also underscores their potential in various biotechnological and pharmaceutical applications. Recently, polysaccharides have emerged as pivotal materials in the fields of tissue engineering and drug delivery, owing to their biocompatibility, tuneable properties, and ability to mimic the extracellular matrix. In the form of hydrogels or nanohydrogels, they provide water-swollen networks able to create a stable environment for encapsulated drugs or suitable conditions for cell attachment, proliferation and differentiation. This thesis explores the diverse roles of these biomaterials as scaffolds for tissue regeneration and nanosystems for the controlled release of therapeutic agents. Despite their promising applications, several limitations persist, including insufficient mechanical strength, complex fabrication processes, and challenges in achieving precise control over degradation rates and drug release profiles. Through a comprehensive review of current literature and original experimental studies, this work aims to elucidate the interplay between polysaccharide chemistry, hydrogel and nanohydrogel formulation, and their properties in relation to biological responses. Additionally, strategies to overcome existing limitations, such as the introduction of external crosslinker and adhesive or targeting moieties, are presented. In conclusion, the polysaccharide-based hydrogels and nanohydrogels described in this thesis are attractive candidates for a wide range of pharmaceutical and biomedical applications, from bone tissue regeneration to cancer therapy and treatment of posterior segment eye diseases, paving the way for future clinical opportunities.