Bio-inspired Janus microcarriers with sequential actives release for bone regeneration

Growth factor therapy is an effective treatment strategy for bone repair. Research in this field aims to develop functional biomaterials for delivering multiple growth factors in a temporally controllable way and thus improving the therapeutic effect. Herein, inspired by natural bone healing mechanisms that involves early-stage angiogenesis and later-stage osteogenesis, we develop a novel type of Janus microcarriers with sequential actives release ability from microfluidic electrospray for bone regeneration. The Janus microcarriers contain two distinct hemispheres consisting of hyaluronic acid methacryloyl (HAMA) and gelatin methacryloyl (GelMA) hydrogel, respectively. Vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) are compartmentalized in different hemispheres of the microcarriers and released sequentially, in a way mimicking the natural bone repair process. In addition, magnetic Fe3O4@SiO2 nanoparticles are doped in the microcarriers to facilitate magnetic enrichment and localization of the microcarriers in the bone defect site. Moreover, the GelMA hemisphere facilitates cell migration to the defect site, and the HAMA hemisphere reduces the risk of tissue adhesion. In vivo experiments demonstrate that the Janus microcarriers can effectively promote bone regeneration by coordinating angiogenesis and osteogenesis. We believe this work provides a new approach for the development of novel smart drug vehicles and treatment of bone defects.