Simultaneous Regeneration of Bone and Nerves Through Materials and Architectural Design: Are We There Yet?

Abstract

Bilateral communication between bone and nerves is crucial for optimal repair of large bone defects as well as repair of peripheral nerves within the skeleton. However, simultaneous regeneration of bone and nerves is an issue that has long been overlooked in prior literature. Incongruous or even contradictory requirements or regeneration environments for bone and nerves make simultaneous regeneration of multiple tissues challenging. The present review commences with introducing natural crosstalk between bone and nerves, highlighting the rationale for simultaneous regeneration of bone and nerves. These issues will pave the way for the development of inspirational materials design concepts that capitalize on the principles of osteoconduction, osteoinduction, neuroconduction, neuroinduction, and neuroattraction. Potential strategies based on selection of appropriate scaffolds, acellular biological factors and architectural design will be addressed.

Osteoporotic bone recovery by a bamboo-structured bioceramic with controlled release of hydroxyapatite nanoparticles

“…As the main inorganic mineral constituent of bone and teeth, hydroxyapatite nanoparticles (nHA) play an essential role in hard tissue engineering because of their superior bioactivity [ 23 ]. Synthetic nHA is now used extensively in the form of components or implant coatings to improve skeletal regeneration.…”

Copper Ion‐Modified Germanium Phosphorus Nanosheets Integrated with an Electroactive and Biodegradable Hydrogel for Neuro‐Vascularized Bone Regeneration

“…[ 44 ] Further, it has been reported that sensory nerve fibers with CGRP+ peptidergic receptors are the main ones healing calvarial defects; and they are thus, crucial to bone regeneration and homeostasis. [ 45 ] In brief, the CGRP produced by sensory nerves promotes bone formation, stimulates osteoblast differentiation, and inhibits osteoclast formation. [ 46 ] Figure A shows that nerve fibers expressing CGRP were located in areas with bone defects.…”

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.…”