Neuro–bone tissue engineering: emerging mechanisms, potential strategies, and current challenges

Abstract

The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells. Peripheral nerve endings release neurogenic factors and sense skeletal signals, which mediate bone metabolism and skeletal pain. In recent years, bone tissue engineering has increasingly focused on the effects of the nervous system on bone regeneration. Simultaneous regeneration of bone and nerves through the use of materials or by the enhancement of endogenous neurogenic repair signals has been proven to promote functional bone regeneration. Additionally, emerging information on the mechanisms of skeletal interoception and the central nervous system regulation of bone homeostasis provide an opportunity for advancing biomaterials. However, comprehensive reviews of this topic are lacking. Therefore, this review provides an overview of the relationship between nerves and bone regeneration, focusing on tissue engineering applications. We discuss novel regulatory mechanisms and explore innovative approaches based on nerve–bone interactions for bone regeneration. Finally, the challenges and future prospects of this field are briefly discussed.

Establishing stable and highly osteogenic hiPSC-derived MSCs for 3D-printed bone graft through microenvironment modulation by CHIR99021-treated osteocytes

“…The successful integration of bone grafts and the regeneration of bone tissue rely crucially on their vascularisation and neuralisation activities, which provide nutrients and oxygen, remove waste, and perceive environmental changes, thereby facilitating bone healing [ [70] , [71] , [72] ]. Current strategies to achieve vascular/neuro-bone tissue engineering involve scaffold materials incorporating endothelial cells/Schwann cells or acellular active factors [ [73] , [74] , [75] , [76] ], which face challenges in effectiveness and side effects. In vivo and in vitro evidence suggests that MSCs can support both angiogenesis and neurogenesis [ 20 , 77 ].…”

Smart responsive in situ hydrogel systems applied in bone tissue engineering

“…Bone is a hierarchical hard tissue that is mineralized and neurovascularized, supports the skeleton, and has many functions, including immunoregulation, growth, movement, hematopoiesis, and organ protection ( Sun W. et al, 2023 ; Wang P. et al, 2024 ). The homeostasis regulation of bone tissue is primarily relayed in the microenvironment of the ECM.…”

Bone-nerve crosstalk: a new state for neuralizing bone tissue engineering—A mini review

“…Peripheral nerve fiber subtypes have a specific function within the bone ( 2 ). However, it has recently begun to be in the spotlight on the regulatory role of the bone and nervous system, which has been examined for many years ( 3 – 6 ).…”