Polysaccharide hydrogels have become increasingly studied as matrices in soft tissue engineering. Main advantages of these materials are their known cytocompatibility and the possibility to tailor the material properties chemical modification of the educts. In this work cross-linkable polysaccharide methacrylates based on dextran, amino dextrans, and hyaluronan were synthesized and their transformation into stable hydrogels were studied. In comparison to hyaluronan-based materials, the dextran gels showed a reduced water incorporation, better form stability, mechanical strength, and longer durability. The formed gels had no cytotoxic effects against CHO and 3T3 cells, but cells could only adhere inefficiently in long term experiments. Smooth gel surfaces, fibronectin addition and the use of mixed gels improved the adherence of cells. Different scaffold architectures usable as matrices for soft tissue engineering were studied in vitro including porous and perforated gels and a layer-by-layer assembly in which each layer was overgrown with cells. Embedding of cells between two layers inhibited their aggregation to spheroids and cells kept attached at the support. Selected hydrogels were examined in a rabbit model in vivo to study their biocompatibility, stability, and degradation. No signs of inflammation were seen and with prolonged duration the material was degraded and lacunas were formed obviously by immigrating or ingrowing cells. Additionally, in dextran gels an ingrowth of cells from the surrounding into little channels could be observed similar to the sprouting of small vessels. Optimizing their mechanical properties, the dextran hydrogels represent promising candidates as matrices for soft tissue reconstruction.