Cobalt ions-derived nanoenzyme array for endosseous neural network reconstruction and osseointegration

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 Co²⁺ and Co³⁺, namely STC_h that behaves as a reactive oxygen species (ROS)-scavenging enzyme, was hydrothermally formed on Ti substrate. We show that the doped Co²⁺ and Co³⁺ locate at TiO₆ octahedral interlayers and within octahedra of STC_h lattice, appearing releasable and un-releasable, respectively, leading to an increase in Co³⁺/Co²⁺ ratio and enzyme activity of the array with immersion. The nanoenzyme-released Co²⁺ 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 Co²⁺, promote mesenchymal stem cells to differentiate into neurons and Schwann cells compared to sole Co²⁺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.