Matrix Vesicle–Inspired Lactoferrin-Loaded Mineralized Alginate Microspheres for Bone Defect Repair

Abstract Bone defects remain a major clinical challenge, creating a need for biomaterials that can simultaneously support osteogenesis, angiogenesis, and immune regulation. Here, we developed lactoferrin (Lf)-loaded mineralized alginate microspheres with integrated osteogenic, angiogenic, and immunomodulatory functions and evaluated their potential for bone defect repair both in vitro and in vivo. Lf-loaded alginate microspheres (ALG@Lf) were fabricated by electrospraying and subsequently mineralized in simulated body fluid to obtain M-ALG@Lf microspheres inspired by the mineral nucleation and deposition functions of matrix vesicles. The resulting microspheres exhibited sustained Lf release and provided a mineralized microenvironment favorable for bone regeneration. In vitro studies demonstrated that M-ALG@Lf promoted osteogenic differentiation, angiogenic activity, and favorable macrophage regulation. In vivo, M-ALG@Lf further enhanced new bone formation and mineralization in a rat femoral defect model. Overall, the integration of Lf-mediated biological activity with matrix vesicle-inspired mineralization endowed the microspheres with multiple regenerative functions, highlighting their potential as a multifunctional strategy for bone defect repair.