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

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.

Automated summary

The role of sensory innervation in bone homeostasis is often overlooked in bone repair strategies. This study proposes a neuromodulation approach that uses engineered sensory nerves (eSN) to optimize bone defect healing by leveraging the adaptive capabilities of sensory neurons. The release of NGF from ECM-constructed eSN promotes sensory neuron differentiation and enhances CGRP secretion, leading to improved mobility of RAOECs and osteogenic differentiation of BMSCs. The eSN approach effectively drives ossification in vivo through the NGF-TrkA signaling pathway, accelerating the healing of critical size bone defects. It also suppresses excessive bone formation and promotes bone remodeling by activating osteoclasts via a CGRP-dependent mechanism when combined with BMP-2 delivery, mitigating the side effects of BMP-2. Overall, this eSN approach offers a valuable avenue for optimizing bone homeostasis in various clinical scenarios by harnessing the adaptive role of the neural system.