Implantable Electrical Stimulation at Dorsal Root Ganglions Accelerates Osteoporotic Fracture Healing via Calcitonin Gene-Related Peptide

Jie Mi, Jian Kun Xu, Zhi Yao, Hao Yao, Ye Li, Xuan He, Bing Yang Dai, Li Zou, Wen Xue Tong, Xiaotian Zhang, Peijie Hu, Yechun Ruan, Ning Tang, Xia Guo, Jie Zhao, Ju Fang He, Ling Qin

Research output: Journal article publicationJournal articleAcademic researchpeer-review

4 Citations (Scopus)

Abstract

The neuronal engagement of the peripheral nerve system plays a crucial role in regulating fracture healing, but how to modulate the neuronal activity to enhance fracture healing remains unexploited. Here it is shown that electrical stimulation (ES) directly promotes the biosynthesis and release of calcitonin gene-related peptide (CGRP) by activating Ca2+/CaMKII/CREB signaling pathway and action potential, respectively. To accelerate rat femoral osteoporotic fracture healing which presents with decline of CGRP, soft electrodes are engineered and they are implanted at L3 and L4 dorsal root ganglions (DRGs). ES delivered at DRGs for the first two weeks after fracture increases CGRP expression in both DRGs and fracture callus. It is also identified that CGRP is indispensable for type-H vessel formation, a biological event coupling angiogenesis and osteogenesis, contributing to ES-enhanced osteoporotic fracture healing. This proof-of-concept study shows for the first time that ES at lumbar DRGs can effectively promote femoral fracture healing, offering an innovative strategy using bioelectronic device to enhance bone regeneration.

Original languageEnglish
JournalAdvanced Science
DOIs
Publication statusPublished - 28 Oct 2021

Keywords

  • bone regeneration
  • CGRP
  • dorsal root ganglions
  • electrical stimulation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this