Haversian-inspired hierarchical scaffold for vascularized bone repair

To overcome delayed vascularization and wet-state mechanical deterioration in critical-sized bone defect repair, we developed a composite scaffold inspired by the natural Haversian system. The scaffold features longitudinally interconnected primary channels surrounded by anisotropic micropores, forming a hierarchical network that enhances directional mass transport, tissue infiltration, and vascular ingrowth. Rather than adopting a uniform composition, we engineered a spatially heterogeneous distribution of inorganic components. While brushite and hydroxyapatite are integrated into the initial chitosan matrix, calcium phosphate is deposited via subsequent mineralization on the internal surfaces of the scaffold, providing widespread interfaces for cell adhesion and osteogenesis. Conversely, a tightly integrated silica-rich layer is selectively localized along the mechanically vulnerable primary-channel walls. This localized silica reinforcement, combined with the coordinated incorporation of calcium phosphates, significantly reinforces the scaffold's mechanical reliability in the wet state. Concurrently, the sustained release of bioactive calcium, phosphorus, and silicon species provides robust osteogenic and angiogenic cues. In vitro and in vivo evaluations demonstrated that this synergy of enhanced mass transport, localized mechanical reinforcement, and spatially programmed biochemical signals effectively promotes coupled vascularized bone regeneration. This study establishes an integrated compositional and structural design strategy, wherein spatially programmed simple constituents reconcile permeability, wet-state mechanical support, and biological activity for advanced bone repair.