Crosstalk between Bone and Nerves within Bone

Abstract

For the past two decades, the function of intrabony nerves on bone has been a subject of intense research, while the function of bone on intrabony nerves is still hidden in the corner. In the present review, the possible crosstalk between bone and intrabony peripheral nerves will be comprehensively analyzed. Peripheral nerves participate in bone development and repair via a host of signals generated through the secretion of neurotransmitters, neuropeptides, axon guidance factors and neurotrophins, with additional contribution from nerve‐resident cells. In return, bone contributes to this microenvironmental rendezvous by housing the nerves within its internal milieu to provide mechanical support and a protective shelf. A large ensemble of chemical, mechanical, and electrical cues works in harmony with bone marrow stromal cells in the regulation of intrabony nerves. The crosstalk between bone and nerves is not limited to the physiological state, but also involved in various bone diseases including osteoporosis, osteoarthritis, heterotopic ossification, psychological stress‐related bone abnormalities, and bone related tumors. This crosstalk may be harnessed in the design of tissue engineering scaffolds for repair of bone defects or be targeted for treatment of diseases related to bone and peripheral nerves.

Large-sized bone defect repair by combining a decalcified bone matrix framework and bone regeneration units based on photo-crosslinkable osteogenic microgels

“…Finally, the combined BRUs and DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired large-sized bone defects of rabbit tibia. Although some questions (such as larger bone defect repair in a large animal model, preparation of engineered bone with complicated and precise 3D shape, as well as evaluation of biosafety) and mechanism (such as mechanical induction and signal transduction of intrabony nerves) [ 50 , 51 ] still need to be investigated in future, the current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.…”

Construction of developmentally inspired periosteum-like tissue for bone regeneration

“…In addition to being highly vascularized, the periosteum is also abundantly innervated. 54 , 55 Abundant periostin emerged in the PTs, indicating that the generation of PTs may be regulated by nerves to some extent.…”

Bioprinted Constructs that Mimic the Ossification Center Microenvironment for Targeted Innervation in Bone Regeneration

“…Bone is richly innervated by peripheral sensory and motor nerves, transporting different excitation signals and conveying information to target cells and tissues. [34] Studies on humans and animal species have shown that innervation often occurs before osteogenic differentiation and mineralization, indicating that nerves play an essential role in bone development and repair. [35,36] Although the role of nervous system in bone regeneration has been demonstrated in some studies, current implants lack nerve-guiding activity and innervation is slow.…”