Cobalt ions-derived nanoenzyme array for endosseous neural network reconstruction and osseointegration
Xinmei Cai, Meng Yu, Bo Li, Yingang Zhang, Yong Han
Abstract
Interactions between bone cells and neurocytes are crucial for endosseous nerve and ensuing bone regeneration. However, absence of neural stem cells in bone makes the innervation of implant osseointegration a major challenge. Herein, a nanorod-like array of sodium hydrogen titanate (ST) co-doped with Co 2+ and Co 3+ , namely STC h that behaves as a reactive oxygen species (ROS)-scavenging enzyme, was hydrothermally formed on Ti substrate. We show that the doped Co 2+ and Co 3+ locate at TiO 6 octahedral interlayers and within octahedra of STC h lattice, appearing releasable and un-releasable, respectively, leading to an increase in Co 3+ /Co 2+ ratio and enzyme activity of the array with immersion. The nanoenzyme-released Co 2+ triggers macrophages (MΦs) towards M1 phenotype, then the nanoenzyme scavenges extracellular ROS inducing M1-to-M2 transition. The neurogenic factors secreted by STC h -regulated MΦs, in combination with the released Co 2+ , promote mesenchymal stem cells to differentiate into neurons and Schwann cells compared to sole Co 2+ and ST. STC h array greatly enhances nerve reconstruction, type-H capillary formation and ensuing osseointegration in normal rat bone, and antibacteria via engulfing S. aureus by MΦs and osteogenesis in infective case. This nanoenzyme provides an alternative strategy to orchestrate endosseous nerve regeneration for osseointegration without loading exogenous neurotrophins in implants. • Co 2+ and Co 3+ co-doped arrays (STC h ) behaves as a ROS-scavenging enzyme. • STC h shifts MΦ M1-to-M2 switch via Co 2+ release and later ROS scavenging. • STC h promotes BMSC neural differentiation via conditioned MΦs-derived neurotrophins. • STC h enhances nerve reconstruction, capillary formation and osseointegration in vivo.