The aim of tissue engineering (TE) is the production of live and functional tissues by combining a biomaterial scaffold, living cells, and a relevant bioactive stimulus. The engineering of soft tissues, such as brain and heart, requires a scaffold material that represents the natural tissue, meaning that it needs to be soft, elastic, flexible, and possibly strain hardening. Additionally, a scaffold material must allow the diffusion of nutrients and the penetration of migrating cells inside the microstructure. Furthermore, the scaffold must provide the encapsulated cells with enough attachment sites to ensure the cells can function in their natural way.

Hydrogels are promising scaffold candidates for soft tissue engineering applications. They are crosslinked, hydrophilic polymer networks with a high water content in the structure. Hydrogels can be produced from a large variety of natural or synthetic polymers by implementing a variety of physical and chemical crosslinking strategies. Here, hydrogels based on the polysaccharide gellan gum are studied in a conclusive manner from both the materials science and biological perspective. The gelation process and chemistry of modified hydrogel-forming biopolymers are characterized. The mechanical properties of the hydrogels as well as their microstructure and the effects of different functionalization strategies on these characteristics are studied in detail. Novel imaging methods are applied for the analysis of hydrogel microstructure. Similarly, the mechanical properties of the hydrogels are studied using methods that have never before been applied to gels in hydrated form. Then, the newly developed hydrogel formulations are used with human cells for the soft tissue engineering of the two most vital and poorly regenerating organs of the human body – the central nervous system and the heart.

The developed gellan gum-based hydrogels have biomimicking mechanical properties with adjustable stiffness corresponding to either brain or heart muscle tissue, depending on the exact composition used. The elasticity of the hydrogel network enables the spontaneous beating of human induced pluripotent stem cell-derived cardiomyocytes in three-dimensional culture. The polymer network creating the hydrogels is loose enough so that the cells can grow inside and that nutrients and waste products of cell metabolism can also be transported in and out of the hydrogel. The functionalization of gellan gum with extracellular matrix proteins, such as laminin and collagen-derived gelatin, enhances the cytocompatibility, growth, and elongation of cells cultured in the novel three-dimensional microenvironments.