In this work, fibrin-polysaccharide-based hydrogel and microgel systems were investigated as biomaterials for 3D cellular constructs. Fibrin is valued for its excellent cell compatibility, while the polysaccharides dextran and pectin contribute to mechanical stability. By strategically combining fibrin with polysaccharides, hydrogels with advantageous properties for potential tissue engineering applications can be produced. In the first chapter, fibrin-polysaccharide co-network hydrogels and fibrin-polysaccharide interpenetrating polymer network hydrogels were fabricated and characterized based on their mechanical and structural properties. For the fibrin-polysaccharide co-network hydrogels, varying amounts of functionalized polysaccharides were covalently cross-linked with fibrin and subsequently analyzed. In a second approach, two simultaneous networks composed of fibrin and functionalized polysaccharides with a crosslinker were generated to create interpenetrating fibrin-polysaccharide hydrogel networks. The addition of dextran-methacrylate (Dex-MA) to the fibrin-Dex-MA interpenetrating polymer network resulted in increased stiffness, tunable porosity, and slower degradation of the hydrogels. In the second chapter, fibrin-dextran-methacrylate-based microgels were synthesized via droplet-based microfluidics. Investigation of the mechanical properties of the microgels showed increased stiffness with higher Dex-MA concentrations. Additionally, a decrease in permeability and porosity of fibrin-Dex-MA microgels was observed with increasing Dex-MA content. The degradation and encapsulation of hepatocyte growth factors within fibrin-Dex-MA microgels were studied. Microgels with variable degradation times were obtained, enabling controlled release of hepatocyte growth factors. The biocompatibility of the hydrogels and microgels was confirmed by live/dead staining of cells cultured on these materials. The third chapter focused on the 3D printing of fibrin-Dex-MA hydrogels and microgels systems using two different methods, as well as on the encapsulation of oxygen-releasing calcium peroxide nanoparticles in fibrin-Dex-MA microgels. With the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) technique, hydrogels were successfully printed as 3D constructs. Pronounced shear-thinning properties were achieved by ‘jamming’ the microgels, which enabled the extrusion-based printing of microgels. Encapsulation of calcium peroxide demonstrated a controlled release of oxygen from the gel systems. In summary, fibrin-Dex-MA hydrogels and microgels with tunable stiffness, porosity, controlled degradation, biocompatibility, and printability were successfully fabricated. These favorable properties facilitate the formation of 3D cellular constructs and highlight their potential in tissue engineering applications.
Shannon Anna Jung (Wed,) studied this question.