Neurofunctional MOF nanoparticles integrated with extracellular matrix hydrogel for neuro-Vascularized bone regeneration

The neural and vascular systems are the basic elements of bone. Neurovascular networks are widely distributed throughout the periosteum, cortical bone, and cancellous bone, which is highly significant for bone regeneration and remodeling. Reconstruction of the neurovascular network has been proposed as a therapeutic approach for bone defects. Here, a neuropeptide substance P-loaded nano-MOF combined with a double network hydrogel (PM@PS hydrogel) was applied to the bone regeneration environment to promote neuroangiogenesis by modulating Schwann cells (SCs) and human umbilical vein endothelial cells (HUVECs). It further enhances the osteogenic differentiation of bone marrow stromal cells (BMSCs) by activating the Wnt signaling pathway. In vivo experiments also demonstrate that functionalized hydrogels promote nerve ingrowth and vascularization, leading to neurovascular-driven bone regeneration. These findings emphasize the important role of the neurovascular network in bone regeneration and provide a new therapeutic strategy to facilitate the repair of critical-size bone defects.