Transient Hyperoxia‐Generating Interface Coupled with Mg 2+ Delivery Reprograms Osteoimmune Microenvironment for Enhancing Osseointegration

Abstract Implants fail due to aseptic loosening remains a critical challenge in orthopedic surgery. This condition arises from poor early‐stage osseointegration caused by the bioinert implant interface. Designing immune‐active implant coating to timely create a regenerative osteoimmune microenvironment is a recent approach to promote new bone formation. Here, the transient hyperoxia‐generating interface coupled with Mg 2+ delivery is developed for the titanium (Ti) to steer osseointegration. This design achieves strong adhesion (388.5 kPa) of the hydrogel coating, ensuring the interfacial stability. Under hypoxic conditions, the engineered interface mitigates cell death and promotes the shift from pro‐inflammatory M1 to regenerative M2 macrophages. This immune transition enhances osteogenesis of mesenchymal stem cells (MSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro. Meanwhile, this modified surface demonstrates superior osseointegration results, with histological evidence showing earlier M2 macrophage existence and coordinated bone‐vessel growth around the implants. By regulating natural bone healing phases—transient hyperbaric oxygen signaling synergies with Mg 2 ⁺ release for faster inflammation resolution—this platform creates a self‐sustaining regenerative niche without exogenous biologics. The results provide a clinically viable strategy to improve implant integration by modulating the osteoimmune microenvironment.