Sequential Regulation of Neurovascular Bone Regeneration in Large Bone Defects Using Black Phosphorus‐Europium Nanosheet Integrated TPMS Biomimetic Scaffold with Photo‐Controlled Ion Release

ABSTRACT Titanium alloy scaffolds (Ti–6Al–4 V) are widely used to repair bone defects. However, conventional titanium‐based implants lack customized functional surface interfaces that promote coordinated local nerve and blood vessel regeneration, thereby limiting bone regeneration and long‐term stability. To address this limitation, we utilize a topologically optimized triple‐periodic minimal surface (TPMS) porous titanium (Ti) scaffold. Polydopamine (PDA) surface engineering is used to stably immobilize europium ions (Eu 3+ )‐coordinated black phosphorus (BP) nanosheets onto the surface, forming a Ti–PDA@(BP+Eu) (TPBE) scaffold with photothermal‐ionic synergistic release to coordinate early neurovascular reconstruction and subsequent bone regeneration. In vitro studies demonstrate that under periodic near‐infrared irradiation, the TPBE scaffold enables on‐demand release of Eu 3 + /phosphate ions (PO 4 3− ), thereby promoting adhesion, migration, differentiation, and gene expression of neural, vascular, and osteogenic cells. Further, activating the PI3K/Akt pathways enhances neurite outgrowth and axonal regeneration of rat adrenal pheochromocytoma cells. In vivo large‐segment bone defect models demonstrate that TPBE scaffolds combined with mild photothermal therapy increases neurovascular network density and upregulate osteogenic–neuro–vascular coupling factors, thereby accelerating bone regeneration. This study presents an innovative method for the fabrication of Ti‐based implant materials capable of cascade regeneration of nerve, vascular, and bone tissues, establishing the basis for the exploration of multitissue regenerative biomaterials.