Engineered Sensory Nerve Guides Self‐Adaptive Bone Healing via NGF‐TrkA Signaling Pathway

Abstract

The upstream role of sensory innervation during bone homeostasis is widely underestimated in bone repairing strategies. Herein, a neuromodulation approach is proposed to orchestrate bone defect healing by constructing engineered sensory nerves (eSN) in situ to leverage the adaptation feature of SN during tissue formation. NGF liberated from ECM‐constructed eSN effectively promotes sensory neuron differentiation and enhances CGRP secretion, which lead to improved RAOECs mobility and osteogenic differentiation of BMSC. In turn, such eSN effectively drives ossification in vivo via NGF‐TrkA signaling pathway, which substantially accelerates critical size bone defect healing. More importantly, eSN also adaptively suppresses excessive bone formation and promotes bone remodeling by activating osteoclasts via CGRP‐dependent mechanism when combined with BMP‐2 delivery, which ingeniously alleviates side effects of BMP‐2. In sum, this eSN approach offers a valuable avenue to harness the adaptive role of neural system to optimize bone homeostasis under various clinical scenario.

Nerve Growth Factor-Preconditioned Mesenchymal Stem Cell-Derived Exosome-Functionalized 3D-Printed Hierarchical Porous Scaffolds with Neuro-Promotive Properties for Enhancing Innervated Bone Regeneration

“…Moreover, neurotrophins and neurotransmitters are both key regulators of not only the nervous system but also the function of non-neuronal tissue, such as bone. Both neurotrophins and neurotransmitters are reported to manipulate a cascade of reparative processes including angiogenesis and osteogenesis during the process of fracture healing, and function as a kind of tight connection between peripheral nerve and the skeleton. ,,, In this section, to investigate the osteo-promotive capacities of N-Exos-stimulated neural cells, BMSCs were incubated with conditioned medium (CM) obtained from supernatants of exosome-treated DRG neuron/SC cocultures (Figure A and Figure S4, Supporting Information).…”

An Antibacterial Bionic Periosteum with Angiogenesis-Neurogenesis Coupling Effect for Bone Regeneration

“…48 Neurotransmitters, neuropeptides, axon guidance factors, and neurotrophic factors are secreted by peripheral nerves and are essential for processes involving bone formation and repair. 49 Wu et al utilized tissueengineered bones containing sensory nerve fibers to successfully repair large segmental bone defects. Their findings demonstrated that tissue-engineered bones implanted with cooperative sensory nerve fibers exhibited superior osteogenesis compared to those solely implanted with tissueengineered bones.…”

Anisotropic Microspheres–Cryogel Composites Loaded with Magnesium l-Threonate Promote Osteogenesis, Angiogenesis, and Neurogenesis for Repairing Bone Defects

“…The immunohistochemical staining of NGF showed that the 100MgT-MCS/GB group had the most positive cells at 6 weeks. It has been reported that NGF could effectively promote neuronal differentiation and improve osteogenic differentiation of BMSCs via enhanced CGRP secretion, 48 which is essential for bone regeneration. The immunohistochemical staining of OCN indicated that the 100MgT-MCS/GB group had the most positive cells, suggesting the coupling effect of osteogenesis-neurogenesis for bone regeneration.…”