Promotion of osteointegration by silk fibroin coating under diabetic conditions on 3D printed porous titanium implants via ROS-mediated NF-κB pathway.

The clinical evidence indicates the compromised application of titanium implants (TI) in diabetics, associated with reactive oxygen species (ROS) overproduction at the bone-implant interface. Silk fibroin has exerted impressive biocompatibility in application of biomedical material and optimal anti-diabetic effect as oriental medicine. We proposed that SF coated titanium implant (STI) could alleviate diabetes-induced compromised osteointegration, which had been rarely reported before. To confirm the hypothesis and explore the underlying mechanisms, rat osteoblasts cultured on 3-dimensional (3D) printed TI and STI were subjected to normal serum (NS), diabetic serum (DS), DS with NAC (a ROS inhibitor) or SN50 (a NF-κB inhibitor). In vivo study was performed on diabetic sheep implanted with TI or STI into the bone defect on crista iliaca. Results demonstrated that ROS overproduction induced by diabetes lead to osteoblast dysfunctions and cellular apoptosis on TI substrate, associated with activation of NF-κB signaling pathway in osteoblasts. Importantly, STI substrate significantly attenuated ROS production and NF-κBp65 phosphorylation, through which the osteoblast biological dysfunctions were ameliorated. These results were further confirmed in vivo by the improved osteointegration of STI evidenced by Micro-CT and histological examinations compared with TI. These results demonstrated that ROS-mediated NF-κB signaling pathway played a crucial role in diabetes-induced implant destabilization. Importantly, SF coating as a promising material for biomaterial-engineering markedly improved clinical treatment effect of TI under diabetic conditions, possibly associated with the suppression of NF-κB pathway.