期刊
ADVANCED HEALTHCARE MATERIALS
卷 10, 期 2, 页码 -出版社
WILEY
DOI: 10.1002/adhm.202000631
关键词
decellularized bone matrix; graphene oxide; inflammation; magnesium; nanomedicines; regenerative medicines
资金
- National Natural Science Foundation of China [81901050, 81671839, 81771042]
- Shanghai Sailing program [19YF1426300]
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.
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.
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