Abstract
Initial implant-related infection and subsequent poor osseointegration are the main causes of implant placement failure. The extracellular microenvironment is an important mediator of behaviors of cell and bacteria; however, spontaneously dynamically regulating the microenvironment to match tissue integration processes remains a challenge. Here, we construct a multilayer film on polyetheretherketone (PEEK) surface with different inner and outer layers of magnesium oxide (MgO) degradation rates. This film can sequentially regulate surface ions and immune microenvironment to achieve sequential antibacteria and bone integration. In the early stage of bone implantation, the outer layer of MgO can rapidly degrade to produce a strong alkaline microenvironment and a large amount of magnesium (Mg) ions, disrupting the energy metabolism of adherent bacteria and inducing M1 polarization of macrophages to enhance their ability to engulf planktonic bacteria. In the later stage, the inner layer MgO can slowly release Mg ion for a long time, synergistically promoting the proliferation and differentiation of osteoblasts by directly stimulating osteoblasts and inducing M2 polarization of macrophages. The rat femoral implantation model confirms the good sequential immune-enhanced antibacteria and bone integration ability of the film in vivo. In addition, the film can control the polarization time of cells by adjusting the thickness of the outer layer to meet the needs of different scenarios. This study demonstrates that the synergistic induction of ion microenvironment and immune microenvironment is a promising and safe surface modification strategy for bone implants.