Hierarchically Micro-Nano Porous Electrospun PBLG Mineralized Scaffolds: A Biomimetic Triune Platform Orchestrating...

The natural bone matrix is a heterogeneous three-dimensional mineralized fiber network structure composed of inorganic components (mainly hydroxyapatite) and organic components (collagen-І), endowing natural bone with excellent biological and mechanical properties. To replicate the critical role of natural bone's heterogeneous mineralized fiber network in guiding cell behavior, synthetic matrices that mimic both its composition and fibrous architecture are highly desirable. This study proposes a strategy for constructing mineralized electrospun poly-(γ-benzyl-L-glutamate) (PBLG) fiber scaffolds with biomimetic nano- and micro- structures. In this work, two-dimensional (2D) electrospun PBLG fiber membranes were transformed into three-dimensional (3D) porous scaffolds using NaBH₄ as a gas foaming agent. The resulting 3D scaffolds maintained the nanotopography and long-fiber structure while achieving macropores (>300 µm) and significantly improved porosity. Scaffolds were functionalized via solvent welding and in situ formation of copper-substituted nano-hydroxyapatite (n-CuHA), enhancing mechanical properties and bioactivity. The biomimetic fibrillar architecture, combined with bisphosphonates (BP) and n-CuHA, synergistically promoted osteogenic differentiation of MC3T3-E1 cells and angiogenic differentiation of endothelial cells while simultaneously inhibiting osteoclast activity. As expected, the biomimetic multifunctional PBLG scaffolds significantly enhanced femoral condyle defects regeneration and vascularization in rats while inhibiting osteoclast activity, which validated their potential in bone tissue engineering.