Initial therapeutic evidence of a borosilicate bioactive glass (BSG) and Fe₃O₄ magnetic nanoparticle scaffold on implant-associated <i>Staphylococcal aureus</i> bone infection.

Abstract

Implant-associated <i>Staphylococcus aureus</i> (<i>S. aureus</i>) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for <i>S. aureus</i> osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe₃O₄) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related <i>S. aureus</i> tibial infection rabbit model, we evaluated its antibacterial performance <i>in vivo</i>. RNA transcriptome sequencing demonstrated that BSG + 5%Fe₃O₄ enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe₃O₄ upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) <i>in vitro</i>. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-β1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1β) among macrophages. <i>In vivo</i> CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe₃O₄ + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of <i>S. aureus</i> osteomyelitis. Further investigations will focus on the <i>in vivo</i> biosafety and biological mechanism of this scaffold within infectious microenvironment.