Antibacterial, proangiogenic, and osteopromotive nanoglass paste coordinates regenerative process following bacterial infection in hard tissue

Abstract

Bacterial infection raises serious concerns in tissue repair settings involved with implantable biomaterials, devastating the regenerative process and even life-threatening. When hard tissues are infected with bacteria (called ‘osteomyelitis’), often the cases in open fracture or chronic inflammation, a complete restoration of regenerative capacity is significantly challenging even with highly-dosed antibiotics or surgical intervention. The implantable biomaterials are thus needed to be armored to fight bacteria then to relay regenerative events. To this end, here we propose a nanoglass paste made of ~200-nm-sized silicate-glass (with Ca, Cu) particles that are hardened in contact with aqueous medium and multiple-therapeutic, i.e., anti-bacterial, pro-angiogenic and osteopromotive. The nanoglass paste self-hardened via networks of precipitated nano-islands from leached ions to exhibit ultrahigh surface area (~300 m2/g), amenable to fill tunable defects with active biomolecular interactions. Also, the nanoglass paste could release multiple ions (silicate, calcium, and copper) at therapeutically relevant doses and sustainably (for days to weeks), implying possible roles in surrounding cells/tissues as a therapeutic-ions reservoir. The osteopromotive effects of nanoglass paste were evidenced by the stimulated osteogenic differentiation of MSCs. Also, the nanoglass paste promoted angiogenesis of endothelial cells in vitro and vasculature formation in vivo. Furthermore, the significant bactericidal effect of nanoglass paste, as assessed with E. coli and S. aureus, highlighted the role of copper played in elevating ROS level and destroying homeostasis, which salvaged tissue cells from co-cultivated bacteria contamination. When administered topically to rat tibia osteomyelitis defects, the nanoglass paste enhanced in vivo bone healing and fracture resistance. The developed nanoglass paste, given its self-setting property and the coordinated therapeutic actions, is considered to be a promising drug-free inorganic biomaterial platform for the regenerative therapy of bacteria-infected hard tissues.