Effects of Innervation on Angiogenesis and Osteogenesis in Bone and Dental Tissue Engineering

The repair and regeneration of critical-sized bone defects remain an urgent challenge. Bone tissue engineering represents an exciting solution for regeneration of large bone defects. Recently, the importance of innervation in tissue-engineered bone regeneration has been increasingly recognized. The cross talk between nerve and bone provides important clues for bone repair and regeneration. Furthermore, the promotion of angiogenesis by innervation can accelerate new bone formation. However, the mechanisms involved in the promotion of vascular and bone regeneration by the nervous system have not yet been established. In addition, simultaneous neurogenesis and vascularization in bone tissue engineering have not been fully investigated. This article represents the first review on the effects of innervation in enhancing angiogenesis and osteogenesis in bone and dental tissue engineering. Cutting-edge research on the effects of innervation through biomaterials on bone and dental tissue repairs is reviewed. The effects of various nerve-related factors and cells on bone regeneration are discussed. Finally, novel clinical applications of innervation for bone, dental, and craniofacial tissue regeneration are also examined. Impact statement Innervation and vascularization are highly important in order for bone tissue engineering to be successful. However, there is still a lack of summary that correlates all three key concepts: osteogenesis, angiogenesis, and innervation. This article reviews the cutting-edge researches on the roles of innervation in promoting both angiogenesis and osteogenesis through biomaterials in bone and dental tissue engineering. In addition, the potential clinical application of innervation in bone, dental, and craniofacial tissue regeneration is also represented.