Recently, tissue engineering and regenerative medicine studies have evaluated smart biomaterials as implantable scaffolds and their interaction with cells for biomedical applications. Porous materials have been used in tissue engineering as synthetic extracellular matrices, promoting the attachment and migration of host cells to induce the in vitro regeneration of different tissues. Biomimetic 3D scaffold systems allow control over biophysical and biochemical cues, modulating the extracellular environment through mechanical, electrical, and biochemical stimulation of cells, driving their molecular reprogramming. In this review, first we outline the main advantages of using polysaccharides as raw materials for porous scaffolds, as well as the most common processing pathways to obtain the adequate textural properties, allowing the integration and attachment of cells. The second approach focuses on the tunable characteristics of the synthetic matrix, emphasizing the effect of their mechanical properties and the modification with conducting polymers in the cell response. The use and influence of polysaccharide-based porous materials as drug delivery systems for biochemical stimulation of cells is also described. Overall, engineered biomaterials are proposed as an effective strategy to improve in vitro tissue regeneration and future research directions of modified polysaccharide-based materials in the biomedical field are suggested.