Explore the vast range of titles available.

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.

Background Recent physiological and experimental data highlight the role of the sensory nervous system in bone repair, but its precise role on angiogenesis in a bone regeneration context is still unknown. Our previous work demonstrated that sensory neurons (SNs) induce the osteoblastic differentiation of mesenchymal stem cells, but the influence of SNs on endothelial cells (ECs) was not studied. Methods Here, in order to study in vitro the interplay between SNs and ECs, we used microfluidic devices as an indirect co-culture model. Gene expression analysis of angiogenic markers, as well as measurements of metalloproteinases protein levels and enzymatic activity, were performed. Results We were able to demonstrate that two sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were involved in the transcriptional upregulation of angiogenic markers (vascular endothelial growth factor, angiopoietin 1, type 4 collagen, matrix metalloproteinase 2) in ECs. Co-cultures of ECs with SNs also increased the protein level and enzymatic activity of matrix metalloproteinases 2 and 9 (MMP2/MMP9) in ECs. Conclusions Our results suggest a role of sensory neurons, and more specifically of CGRP and SP, in the remodelling of endothelial cells extracellular matrix, thus supporting and enhancing the angiogenesis process. 2_7KgRKy4YATrqDcNKG8uB Video abstract