The Yin and Yang of Immunomodulatory Magnesium-Enriched Graphene Oxide Nanoscrolls Decorated Biomimetic Scaffolds in Promoting Bone Regeneration

Tissue regeneration driven by immunomodulatory agents has emerged as a potential solution for repairing bone defects. However, the therapeutic benefits are compromised by disturbances in the pro- and anti-inflammatory balance. Here, using magnesium nanoparticles (MgNPs) as a template, magnesium-enriched graphene oxide nanoscrolls (MgNPs@GNSs) designed for combinational modulation of the inflammatory response are reported. First, the different effects of graphene oxide (GO) and magnesium ions (Mg2+) on Raw264.7 macrophage phenotype transformation are screened. The results reveal that GO activates inflammatory M1 macrophages, and that Mg2+ facilitates repolarization of M1 macrophages to the pro-healing M2 phenotype. With sustained release of Mg2+, the MgNPs@GNS nanoplatform can orchestrate harmonious type 1 and type 2 inflammatory responses. Mg2+ decrease the internalization of GO and downregulate the nuclear factor kappa-B pathway, which is profoundly involved in the inflammatory process. A series of experiments show that the ordered inflammatory response induced by MgNPs@GNSs stimulates in vitro angiogenesis and osteogenesis through chemotactic, mitogenic, and morphogenic actions. Obvious vascularized bone regeneration is achieved in a rat cranial bone defect model via MgNPs@GNS deposited decellularized bone matrix scaffold. Therefore, the potential of using inherently therapeutic nanomedicine to modulate biomaterial-induced immune responses and thus enhance bone regeneration is demonstrated.

Automated summary

This study demonstrates the successful use of magnesium nanoparticles and graphene oxide nanoscrolls for combinational modulation of inflammatory response to promote vascularization and bone regeneration. The orchestrated type 1 and type 2 inflammatory responses induced by the nanoplatform stimulate angiogenesis and osteogenesis, leading to significant vascularized bone regeneration.