Nanoscale manipulation of material surfaces can create extraordinary properties, holding great potential for modulating the implant–bio interface for enhanced performance. In this study, a green, simple and biocompatible nanosurfacing approach based on weak alkalinity-activated solid-state dewetting (AAD) was for the first time developed to nano-manipulate the Ti6Al4V surface by atomic self-rearrangement. AAD treatment generated quasi-periodic titanium oxide nanopimples with high surface energy. The nanopimple-like nanostructures enhanced the osteogenic activity of osteoblasts, facilitated M2 polarization of macrophages, and modulated the cross-talk between osteoblasts and macrophages, which collectively led to significant strengthening of in vivo bone–implant interfacial bonding. In addition, the titanium oxide nanopimples strongly adhered to the Ti alloy, showing resistance to tribocorrosion damage. The results suggest strong nano–bio interfacial effects, which was not seen for the control Ti alloy processed through traditional thermal oxidation. Compared to other nanostructuring strategies, the AAD technique shows great potential to integrate high-performance, functionality, practicality and scalability for surface modification of medical implants.

Nanotopography can promote osseointegration, but how bone marrow mesenchymal stem cells (BMMSCs) respond to this physical stimulus is unclear. Here, we found that early exposure of BMMSCs to nanotopography (6 h) caused mitochondrial fission rather than fusion, which was necessary for osseointegration. We analyzed the changes in mitochondrial morphology and function of BMMSCs located on the surfaces of NT100 (100 nm nanotubes) and ST (smooth) by super-resolution microscopy and other techniques. Then, we found that both ST and NT100 caused a significant increase in mitochondrial fission early on, but NT100 caused mitochondrial fission much earlier than those on ST. In addition, the mitochondrial functional statuses were good at the 6 h time point, this is at odds with the conventional wisdom that fusion is good. This fission phenomenon adequately protected mitochondrial membrane potential (MMP) and respiration and reduced reactive oxygen species. Interestingly, the MMP and oxygen consumption rate of BMMSCs were reduced when mitochondrial fission was inhibited by Mdivi-1(Inhibition of dynamin-related protein 1 fission) in the early stage. In addition, the effect on osseointegration was significantly worse, and this effect did not improve with time. Taken together, the findings indicate that early mitochondrial fission plays an important role in nanotopography-mediated promotion of osseointegration, which is of great significance to the surface structure design of biomaterials.

The homeobox gene Goosecoid (GSC), which is known to regulate craniofacial development, is activated by mono-ubiquitination; however, the deubiquitylase responsible for GSC deubiquitination and inhibition has yet to be identified. In the present study, we constructed the recombinant plasmid pFlag-CMV-2-GSC and the SRY (sex-determining region Y)-box 6 (Sox6) reporter gene system to identify deubiquitylases that regulate GSC expression. We demonstrate that the ubiquitin carboxyl-terminal hydrolase 21 (USP21) regulates the deubiquitination of GSC negatively, as demonstrated by its inhibition of Sox6 reporter gene transcription. USP21 interacted with GSC to promote GSC deubiquitination while having no effect on GSC protein stability. Cell viability, migration, and function in ATDC5 cells were probably influenced by USP21 through GSC. These findings suggest that USP21 modulates GSC function through deubiquitination.

HA nanorods reduce Zn²⁺ releasing from Zn alloy, significantly enhancing the response of osteoblasts and endothelial cells in vitro and early osteointegration in vivo.