Nanosilver in BMP-2-PLGA Composite Grafts Efficaciously Repairs Bone in Infected Segmental Defects

The regeneration of contaminated bone defects in organisms that display multi-antibiotic resistance has proven to be a clinical challenge. Recently, antiseptic silver, which is an efficient yet less toxic antimicrobial with a reduced potential of inducing bacterial resistance, has received greater attention. We hypothesize that silver in nanocrystalline form has bactericidal effects that can be combined with bone morphogenetic protein 2 (BMP-2) to treat contaminated segmental bone defects. We performed in vitro microplate proliferation assays of 20-40 nm nanocrystalline silver particles (nanosilver). MC3T3-E1 pre-osteoblasts were cultured on 0, 1, and 2% nanosilver coupled poly(lactic-co-glycolic acid) (PLGA) scaffolds to measure levels of toxicity. Nanosilver PLGA scaffolds + BMP-2 or PLGA only scaffolds + BMP-2 were implanted into 6mm rat femoral defects contaminated with 10^8 S. aureus Mu50 to determine effects of BMP-2 osteoinductivity in vivo. Nanosilver demonstrated strong bactericidal properties in vitro and in vivo. Nanosilver particles did not influence the osteoinductivity of BMP-2. Moreover, nanosilver particles-PLGA composite grafts failed to inhibit adherence, proliferance, alkaline phosphatase activity, and mineralization of ongrowth MC3T3-E1 pre-osteoblasts when compared with PLGA controls. Unlike BMP-2 coupled PLGA control grafts, which failed to regenerate with the introduction of bacterial colonies, infected femoral defects that were injected with BMP-2 coupled 2.0% nanosilver particles-PLGA composite grafts recovered in 12 weeks without residual bacteria. These findings reaffirm the antibacterial and non-cytotoxicity property of nanosilver while also implicating nanosilver as a promising antimicrobial for bone regeneration in infected wounds.