Abstract
During the healing and repair of bone defects, uncontrolled inflammatory responses can compromise bone regeneration. Biomaterials with anti-inflammatory activity are favorable for bone tissue regeneration processes. In this work, multifunctional Zn-containing mesoporous bioactive glass nanoparticles (Zn-MBGs) exhibiting favorable osteogenic and anti-inflammatory activities were produced employing a sol-gel method. Zn-MBGs exhibited a mesoporous spherical shape and nanoscale particle size (100 ± 20 nm). They were degradable in cell culture medium, and could release Si, Ca, and Zn in a sustained manner. Zn-MBGs also exhibited a concentration-dependent cellular response. The extract of Zn-MBGs obtained by incubation at 0.1 mg/mL (in culture medium) for 24 h could enhance in vitro mineralization, alkaline phosphatase activity, the expression of osteogenesis-related genes, and the production of intracellular protein osteocalcin of rat bone marrow stromal cells (BMSCs). Moreover, the extract of Zn-MBGs at 0.1 mg/mL could significantly downregulate the expression of inflammatory genes and the production of inducible nitric oxide in RAW 264.7 cells, particularly under stimulation of inflammatory signals interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Zn-MBGs also inhibited the pro-inflammatory M1 polarization of RAW264.7 cells induced by LPS and IFN-γ. In summary, we successfully synthesized Zn-MBGs with concentration-dependent osteogenic and anti-inflammatory activities. Zn-MBGs show their great potential in immunomodulation strategies for bone regeneration, representing a multifunctional biomaterial that can be applied to regenerate bone defects under inflammatory conditions.
Highlights
Repair of bone defects caused by tumor, trauma, or bacterial infection remains a challenging healthcare issue
We evaluated the cytotoxicity of Zn-containing mesoporous bioactive glass nanoparticles (Zn-mesoporous bioactive glass nanoparticles (MBGs)) and MBGs against bone marrow stromal cells (BMSCs) and RAW264.7 cells by using the Cell Counting Kit-8 (CCK-8) assay
Our results showed that Zn-MBGs at the tested concentrations (0.5, 1, and 5 mg/mL) were noncytotoxic against BMSCs and macrophages, which suggest that Zn-MBGs could be used in osteoimmunomodulation strategies for bone regeneration [7]
Summary
Repair of bone defects caused by tumor, trauma, or bacterial infection remains a challenging healthcare issue. Bone implants or bone tissue engineering scaffolds (e.g., bioceramics, biodegradable metals) with antibacterial, osteoconductive and osteoinductive properties have been used to repair and regenerate bone defects [1,2,3]. When biomaterials are implanted in vivo, they can trigger immune responses that may compromise or delay bone regeneration. Appropriate immune responses can promote bone defect healing and repair [4,5]. Biomaterials able to mitigate undesired inflammatory responses or modulate immune responses are emerging as part of novel strategies to enhance bone tissue regeneration [6,7]. Interactions between biomaterials and immune cells are key in immunomodulatory approaches toward enhanced tissue regeneration [5]. Macrophages are considered to be a primary immunomodulatory
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