Endogenous Electric Field‐Coupled PD@BP Biomimetic Periosteum Promotes Bone Regeneration through Sensory Nerve via Fanconi Anemia Signaling Pathway

Abstract

To treat bone defects, repairing the nerve-rich periosteum is critical for repairing the local electric field. In this study, an endogenous electric field is coupled with 2D black phosphorus electroactive periosteum to explore its role in promoting bone regeneration through nerves. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) are used to characterize the electrically active biomimetic periosteum. Here, the in vitro effects exerted by the electrically active periosteum on the transformation of Schwann cells into the repair phenotype, axon initial segment (AIS) and dense core vesicle (DCV) of sensory neurons, and bone marrow mesenchymal stem cells are assessed using SEM, immunofluorescence, RNA-sequencing, and calcium ion probes. The electrically active periosteum stimulates Schwann cells into a neuroprotective phenotype via the Fanconi anemia pathway, enhances the AIS effect of sensory neurons, regulates DCV transport, and releases neurotransmitters, promoting the osteogenic transformation of bone marrow mesenchymal stem cells. Microcomputed tomography and other in vivo techniques are used to study the effects of the electrically active periosteum on bone regeneration. The results show that the electrically active periosteum promotes nerve-induced osteogenic repair, providing a potential clinical strategy for bone regeneration.

Emerging roles of nerve‐bone axis in modulating skeletal system

“…The electroactive field stimulates SCs into a neuroprotective phenotype, induces neurotransmitter release, and promotes osteogenic transformation. 194 Other metal elements, such as copper (Cu), tantalum (Ta), and calcium (Ca), are also beneficial to neurovascularization and bone regeneration. Researchers found that GelMA containing Cu 2+ -modified germanium-phosphorus (GeP) nanosheets (GelMA/GeP@Cu) were able to enhance nerve differentiation, axon regeneration, angiogenesis, and eventually enhanced osteogenesis.…”

Black phosphorus, an advanced versatile nanoparticles of antitumor, antibacterial and bone regeneration for OS therapy

“…The nano-sheets with electric conduction released by BPNSs@mg and bioactive ions synergistically promote the migration and secretion of Schwann cell, which contributes to neural axon growth, and provide a new idea for neurogenic bone regeneration. Su et al ( Su et al, 2023 ) prepared a biomimetic periosteum using ordered coaxial electrospinning, and constructed an electrically active biomimetic periosteum by loading BPNSs onto the biomimetic periosteum via electrostatic action ( Figure 10 ). In this study, BP with excellent electrical conductivity was the main trigger to stimulate the efflux of nerve vesicles, then the PD@BP biomimetic periosteum mainly induces neurogenesis and osteogenesis through the Fanconi anemia pathway, providing a new strategy for bone regeneration.…”

“…(E) Detection of electrically active periosteal osteogenesis with micro-CT in vivo . (Copyright ( Su et al, 2023 )).…”

Advances in the Application of Black Phosphorus-Based Composite Biomedical Materials in the Field of Tissue Engineering

“…Several neuropeptides, which are secreted by sensory nerves, facilitate bone reconstruction [ 125 ]. Therefore, Su et al [ 126 ] utilized coaxial electrospinning technology to fabricate (core)–polycaprolactone (PCL)/s(shell)–DNM biomimetic periosteum(PD). BPNS combined with PD through electrostatic interactions, constructing an electrically active biomimetic bone membrane (BPNS/PD).…”