Abstract
Mesoporous bioactive glass nanoparticles (MBGNs) are emerging biomaterials for bone repair/regeneration, considering their favorable pro-osteogenic and proangiogenic activities. To further improve their therapeutic effects, the endowment of MBGNs with additional antioxidant properties is of particular interest to target oxidative stress related to bone remodeling and diseases. To this end, we developed antioxidant cerium-containing MBGNs (Ce-MBGNs) (particle size of 100–300 nm) by using a postimpregnation strategy to incorporate Ce, through which the shape, pore structure, and dispersity of the nanoparticles were preserved. The incorporated amount of Ce could be tailored by adjusting the concentration of the Ce precursor solution. When impregnated at a relatively low temperature (20 °C), Ce-MBGNs containing either 1.8 or 2.8 mol% of Ce were produced, while the formation of by-product cerium oxide nanoparticles (nanoceria) could be avoided. In both developed Ce-MBGNs, the concentration of Ce4+ was higher than that of Ce3+, while the relative molar percentage of Ce4+ was similar (∼74%) in both Ce-MBGNs. The obtained Ce-MBGNs were evidenced to be non-cytotoxic against fibroblasts at the concentration of 1 mg/mL. Moreover, the incorporation of Ce into MBGNs significantly reduced the expression of oxidative stress–related genes in macrophages (J774a.1). Particularly in the presence of pro-oxidation agents, Ce-MBGNs could downregulate the expression of oxidative stress–related genes in comparsion with the polystyrene plates (control). When cultured with Ce-MBGNs, the expression of proinflammatory-related genes in macrophages could also be downregulated in comparsion with MBGNs and the control. Ce-MBGNs also exhibited pro-osteogenic activities through suppressing pro-osteoclastogenic responses. The obtained results highlight the great potential of the developed Ce-MBGNs in a variety of biomedical applications, particularly in treating bone defects under inflammatory conditions, considering their antioxidant, anti-inflammatory, and pro-osteogenesis activities.
Highlights
Bioactive glasses (BGs) are versatile multifunctional biomaterials, suitable for numerous biomedical applications, for example, from bone regeneration and wound healing to cancer treatment [1,2]
We aimed to develop Ce-mesoporous bioactive glass nanoparticles (BGNs) (MBGNs) with improved chemical homogeneity and dispersity, which could act as drug delivery carriers or bioactive fillers for bone repair/regeneration applications
Ce-MBGNs were synthesized by using a two-step strategy, where MBGNs were first synthesized using a microemulsion-assisted sol-gel method as reported in the literature [40], followed by a postimpregnation approach to incorporate Ce into MBGNs
Summary
Bioactive glasses (BGs) are versatile multifunctional biomaterials, suitable for numerous biomedical applications, for example, from bone regeneration and wound healing to cancer treatment [1,2] Depending on their chemical composition and morphology, BGs can induce osteogenesis, angiogenesis, or antibacterial action to different extents [3]. Mesoporous BGNs (MBGNs), given their large specific surface area (SSA) and tunable pore structure (e.g., pore volume, pore size) [7,8], are attractive carriers for the codelivery of drugs (e.g., antibiotics, growth factors) [9] and biologically active ions (e.g., Cu ions) [8] Such a codelivery of ions and biomolecules has been reported to be able to induce synergistic effects toward enhanced therapeutic outcomes (e.g., osteogenesis, angiogenesis) [10,11]. MBGNs are attracting increasing attention in tissue regeneration and nanomedicine, given their desired morphological and compositional characteristics [8,9,10,11,12]
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