Fine-grained titanium mediates the biointerfacial and bioenergetic remodeling of macrophage for optimized osseointegration

The remodeling of macrophages mediated by biomaterials is an important step in osseointegration. The biointerfacial characteristics shaped by implants and the bioenergetic state derived from macrophages are considered the key to macrophage reprogramming. In this study, the integrated Ti/Zn composites with optimized morphology and bioactive phase were prepared by friction stir processing, which could meet the multi-biofunctional requirements in the application of narrow-diameter implants. The severe plastic deformation and the hindrance of Zn particles to grain growth promote grain refinement, resulting in enhanced mechanical properties. The cell interfacial adhesion mediated by the grain boundary collaborated the energy metabolism reprogramming induced by the released Zn ion, promoting jointly anti-inflammatory cascade in macrophages and favorable osteogenesis in bone marrow mesenchymal stem cells (BMSCs). This study provides a new simultaneous approach of morphology and composition modification for titanium implants, and reveals the important role of grain size and bioactive element in the reversion of macrophage fate as well.