3D printing of bio-instructive materials: Toward directing the cell

Fabrication of functional scaffolds for tissue engineering and regenerative medicine applications requires ma-
terial systems with precise control over cellular performance. 3D printing is a powerful technique to create highly
complex and multicomponent structures with well-defined architecture and composition. In this review paper,
we explore extrusion-based 3D printing methods (EBP, i.e., Near Field Electrospinning (NFES), Melt Electro-
writing (MEW), Fused Deposition Modeling (FDM), and extrusion bioprinting) in terms of their ability to produce
scaffolds with bio-instructive properties. These material systems provide spatio-temporal guidance for cells,
allowing controlled tissue regeneration and maturation. Multiple physical and biochemical cues introduced to
the EBP scaffolds are evaluated in their ability to direct cell alignment, proliferation, differentiation, specific
ECM production, and tissue maturation. We indicate that the cues have different impacts depending on the
material system, cell type used, or coexistence of multiple cues. Therefore, they must be carefully chosen based
on the targeted application. We propose future directions in bio-instructive materials development, including
such concepts as metamaterials, hybrid living materials, and 4D printing. The review gathers the knowledge
essential for designing new materials with a controlled cellular response, fabrication of advanced engineered
tissue, and developing a better understanding of cell biology, especially in response to the biomateria