Advancing biomimetic bone Scaffolds: From electrospun 2D membranes to functional 3D nanofiber constructs

Advancing beyond traditional electrospun two-dimensional (2D) membranes, functional three-dimensional (3D) nanofiber constructs represent a transformative approach. Unlike planar 2D structures, these advanced 3D constructs uniquely integrate essential biomimetic nanotopography with hierarchical porosity, offering mechanical adaptability and spatial guidance for cell infiltration, proliferation, and extracellular matrix (ECM) remodeling—critical for functional bone regeneration. This review systematically examines fabrication strategies enabling the transition from 2D electrospun membranes to 3D architectures, including gas foaming, short nanofiber assembly, and 3D printing. It emphasizes the synergistic advantages of organic/inorganic composites achieved through electrospinning's material versatility, effectively replicating native bone's collagen (COL)/hydroxyapatite (HAp) composition. Furthermore, the interconnected porous networks inherent to these 3D constructs enhance their functionality as carriers for bioactive molecules and stem cells, enabling spatiotemporally controlled osteogenesis. Targeted modification with osteoinductive and angioinductive functionalization further augments their efficacy in promoting bone tissue regeneration. In conclusion, this review provides valuable insights into the development and clinical potential of these advanced biomimetic scaffolds.