2. Academic Validation
  3. Implantable Electrical Stimulation at Dorsal Root Ganglions Accelerates Osteoporotic Fracture Healing via Calcitonin Gene-Related Peptide

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

  • Adv Sci (Weinh). 2022 Jan;9(1):e2103005. doi: 10.1002/advs.202103005.
Jie Mi 1 2,  Jian-Kun Xu 1,  Zhi Yao 1,  Hao Yao 1,  Ye Li 1,  Xuan He 1,  Bing-Yang Dai 1,  Li Zou 1,  Wen-Xue Tong 1,  Xiao-Tian Zhang 3,  Pei-Jie Hu 3,  Ye Chun Ruan 3,  Ning Tang 1,  Xia Guo 3,  Jie Zhao 2,  Ju-Fang He 4,  Ling Qin 1
Affiliations

Affiliations

  • 1 Musculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong, 999077, China.
  • 2 Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People's Republic of China.
  • 3 Department of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, 999077, Hong Kong.
  • 4 Departments of Neuroscience and Biomedical Sciences, City University of Hong Kong, Kowloon Tong, 999077, Hong Kong.
PMID: 34708571 DOI: 10.1002/advs.202103005
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.

Keywords

CGRP; bone regeneration; dorsal root ganglions; electrical stimulation.

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