Three-Dimensional Electrospun Nanofiber Scaffolds: Fabrication Methods and Biomedical Applications

Amid the rapid advancement in tissue engineering and regenerative medicine, 3D nanofiber scaffolds have attracted significant interest in the biomedical field for their ability to mimic the structure and function of the natural extracellular matrix (ECM). Their biomimetic nature stems not only from the morphological resemblance between the nanofiber topology and that of the ECM but, more importantly, from their capacity to replicate the complex functional properties of the ECM-such as mechanical signaling and biochemical communication-through multi-material composition, gradient design, and multi-scale structural engineering. Compared with their conventional 2D counterparts, these architectures provide an enhanced microenvironment that promotes cellular infiltration, vascularization, and functional tissue regeneration. This review systematically outlines fabrication strategies for 3D electrospun scaffolds, highlighting advanced electrospinning techniques and the underlying theories of structure formation, including multi-axial setups, dynamic collectors, sacrificial templates, ceramic nanofiber aerogels, and hybrid manufacturing approaches. The properties of commonly employed materials and their effects on the mechanical behavior, biocompatibility, and degradation profiles of the scaffolds are discussed in detail. Finally, future directions and practical challenges related to novel bioactive materials, multifunctional integration, and personalized medicine are presented to provide a translational framework for the clinical implementation of 3D electrospun scaffolds.