Leveraging solid-liquid interaction to fabricate drug-microsphere in site encapsulated bone-repair scaffolds

Drug-encapsulated scaffolds are crucial to treat challenging bone defects, but the approach for loading drugs into scaffolds is limited. Despite microspheres as carriers that improve drug efficacy and the therapeutic window, the traditional "first preparation - then encapsulation" in drug-microsphere encapsulated scaffolds remains complicated and time-consuming. Herein, we present a facile approach for fabricating drug-microsphere in site encapsulated bone-repair scaffolds (CHP@Drug), in which a solid-liquid interaction triggered by vortex oscillation can be leveraged to realize in site preparation and simultaneous encapsulation of drug-loaded microspheres, rapidly and uniformly. Owing to the induced collision, homogenized and reinforced shear stress from the solid-liquid interaction, CHP@Drug endowed a sustained drug release and an interconnected porous structure. As a proof of concept, CHP@Drugs, were loaded with three drugs respectively, demonstrating significantly enhanced healing of critical-sized, infected, and osteoporotic bone defects in vivo. This study offers a facile and universal way to load drugs into tissue-repair scaffolds, with in-clinic potential.