Osteogenic and Antibacterial Response of Levofloxacin-Loaded Mesoporous Nanoparticles Functionalized with N-Acetylcysteine

<b>Background/Objectives</b>: Bone infection is one of the most prevalent complications in orthopedic surgery. This pathology is mostly due to bacterial pathogens, among which <i>S. aureus</i> stands out. The formation of a bacterial biofilm makes systemic treatment with antibiotics ineffective. Herein we propose a nanosystem composed of mesoporous bioactive glass nanoparticles (MBGN) loaded with levofloxacin and functionalized with N-acetylcysteine (NAC), aiming to offer an alternative to current treatments. These nanoparticles would present antibacterial activity able to disintegrate the biofilm and regenerate the peri-implantar osseous tissue. <b>Methods</b>: MBGN of composition 82.5 SiO₂-17.5 CaO have been synthesized, loaded with levofloxacin, and functionalized with NAC (MBGN-L-NAC). The antimicrobial activity against mature <i>S. aureus</i> biofilms and bioactivity of the nanosystem have been evaluated, as well as its biocompatibility and ability to promote murine pre-osteoblastic MC3T3-E1 differentiation. <b>Results</b>: MBGNs exhibited high surface areas and radial mesoporosity, allowing up to 23.1% (% <i>w/w</i>) of levofloxacin loading. NAC was covalently bound keeping the mucolytic thiol group, SH, available. NAC and levofloxacin combination enhances the activity against <i>S. aureus</i> by disrupting mature biofilm integrity. This nanosystem was biocompatible with pre-osteoblasts, enhanced their differentiation towards a mature osteoblast phenotype, and promoted bio-mimetic mineralization under in vitro conditions. MBGN-L-NAC nanoparticles induced greater osteogenic response of osteoprogenitor cells through increased alkaline phosphatase expression, increased mineralization, and stimulation of pre-osteoblast nodule formation. <b>Conclusions</b>: MBGN-L-NAC exhibits a more efficient antibacterial activity due to the biofilm disaggregation exerted by NAC, which also contributes to enhance the osteoinductive properties of MBGNs, providing a potential alternative to conventional strategies for the management of bone infections.