Bioadhesive-Integrated 3D-Printed Multilayer Scaffolds Secure a Mechanically-Stable Osteoimmune Niche for Enhanced Bone Augmentation.

Early mechanical stabilization within the osteogenic niche is a key regulator of bone regeneration fate, and maintaining stability in material-driven repair remains a clinical challenge in dynamic, non-retentive, and anatomically complex bone defects, where implant materials are difficult to achieve stable fixation. However, most existing repair systems lack satisfactory strategies for addressing it. Here, this study reports an interfacial-fixation-centered scaffold design realized by a bioadhesive-integrated multilayer architecture fabricated via 3D-printing, comprising a soft-tissue-blocking barrier layer, a wet-adhesive interface, and a porous osteogenic framework. The scaffold exhibits rapid and robust adhesion to bone under blood-rich physiological conditions, enabling immediate stabilization of the osteogenic niche. In rabbit mandibular and tibial augmentation models, it significantly outperforms non-adhesive scaffolds and the specific guided-bone-regeneration-like comparator. Mechanistically, adhesive-mediated stabilization reduced scaffold micromotion and was associated with a pro-regenerative mechano-immune profile, including increased M2-like macrophage polarization and enhanced VEGF/BMP2-associated angiogenic-osteogenic coupling. By highlighting the interface-fixation-mediated mechanical stabilization of the osteogenic niche, this work offers a new framework for enhancing bone augmentation in dynamic and complex defect settings, provides insights into potential mechano-immune cues for mechanical-stability-secured bone augmentation, and demonstrates the scaffold's potential in bone repair.