Abstract
The development of tissue models and replacements that closely mimic native biological structures is a central goal in tissue engineering and biofabrication. These models aim to reduce animal testing and improve the relevance and translatability of experimental results. A key step is the transition from simple two-dimensional cultures to three-dimensional systems that better reflect the architecture of the extracellular matrix. Replicating the hierarchical organization of native tissues is essential, particularly the fibrous networks mainly composed of collagen, which regulate cell alignment, migration, proliferation, and differentiation. Incorporating such structures has proven highly effective and often necessary to induce cell behaviors resembling those in vivo. This review first examines the cellular mechanisms that govern interactions with fibrous microenvironments. It then outlines key design parameters for fiber-based substrates, including chemical composition, diameter, surface topography, and alignment. These factors can be tuned to guide cell organization and function. Strategies for translating these principles into three-dimensional fiber-reinforced constructs and bioinks are then discussed, with a focus on current approaches for creating biomimetic environments. The article concludes with future perspectives, highlighting the potential of fibrous scaffolds and advanced fabrication techniques to enable next-generation tissue models and regenerative therapies.