Neurovascular coupling in bone regeneration: Mechanisms, advanced biomaterials and challenges

Abstract Neurovascular interaction plays a central role in bone development, repair and regeneration. The coordinated activity between nerves and blood vessels not only ensures the delivery of oxygen, nutrients, and regulatory signals but also modulates skeletal cell behavior and immune responses. However, traditional therapeutic strategies, such as autografts and allografts, and synthetic scaffolds often fail to replicate the native neurovascular microenvironment, limiting their regenerative efficacy. This review outlines the regulatory mechanisms of neurovascular coupling in bone regeneration. Neural inputs, mediated through neurotrophic factors and neurotransmitters, regulate bone homeostasis by influencing the activity of osteoblasts and osteoclasts, while vascular networks supply essential oxygen and nutrients to support bone maintenance and repair. We then summarize recent advances in neurovascularized biomaterials, including neurotrophic factor‐loaded scaffolds, electroconductive composites, ion‐releasing ceramics, and endogenous electroactive materials, which enable synchronous neural, vascular, and osteogenic regeneration. In addition to functional materials, cell‐ and molecule‐based approaches further enhance neurovascularized bone repair. Together, these strategies represent a shift from passive fillers to multifunctional scaffolds capable of fulfilling complex repair processes. This review aims to bridge mechanistic understanding with material design, offering insights for next‐generation bone tissue engineering.