Micro-nano scale Mg-containing SrTiO3 nanofilm spacially sustained release platform promotes bone regeneration by stereoscopic repair of immune-vasculature network

In the physiological process of bone tissue regeneration, osteogenesis relies heavily on vasculature network because of the transport of oxygen, nutrients and metabolites. Unfortunately, the disordered inflammatory response provoked by multiple factors impairs the smooth repair progress including vascularization and lymphangiogenesis, which eventually leads to implant loosening and failure. In this study, a novel micro-nano scale ion-sustained (Mg 2+ and Sr 2+ ) release platform (RTMS) is designed to improve osteogenesis around implants via enhancing vasculature system repair through immune regulation. Firstly, samples are fabricated through sandblasting, acid etching and hydrothermal synthesis orderly, realizing the sustained release of bioactive ions. Then the macrophages seeded on RTMS polarize towards M2 subtype and the subsequent promotion of angiogenesis and lymphangiogenesis is observed, suggesting the promising anti-inflammation effects and the stereoscopic vasculature regeneration actuated by micro-nano morphological and the sustained Mg 2+ as well as Sr 2+ . Additionally, owing to the polarization towards M2 macrophages and good vessel network repair, bone regeneration in the RTMS group presents a significant increasing trend. RTMS promoted osteogenesis via activating ERK-Osterix pathway and regulating immune-vascular crosstalk. This study provides a basis and reference direction for orthopedic implant modification in the future.