Tailoring time-varying alkaline microenvironment on titanium for sequential anti-infection and osseointegration

Initial implant-associated infection and later poor osseointegration are the main obstacles for bone implant success. Therefore, it is essential to endow implants with sequential antibacterial and osteogenic properties. However, bacteria and host cells share similar response mechanisms to external environments, so up to now, designing such implants remains a challenge. Here, we proposed a novel strategy of tailoring a time-varying surface alkaline microenvironment for sequential anti-infection and osteointegration, which was realized by constructing a two-layer hierarchical coating on the titanium with Ca-O-Ti as the inner layer and MgO as the outer layer. At the early stage of bone implantation, the outer MgO film rapidly generates a local strong alkaline microenvironment that disrupts bacterial energy metabolism and kills bacteria; at the later stage, the inner Ca-O Ti layer maintains a long-term local weak alkaline microenvironment, which promotes stem cell adhesion, proliferation, and osteogenic differentiation to achieve successful osteointegration. The results of an in vivo experiment using a rat osteomyelitis model confirmed that the hierarchical coating inhibited infection and promoted the formation of new bone. This study demonstrates the potential of tailoring a time-varying alkaline microenvironment for sequential anti-infection and osteointegration, as a promising and safe strategy for the surface modification of bone implants.