Development of an ultrasound-sensitive antimicrobial platform for reducing infection after spinal stabilization surgery

Abstract

Infection arises in 8.5% of primary and 12% of secondary spinal fusion surgeries. Because many of these infections are marked by the formation of biofilms, which are difficult to treat with systemic antibiotics, treatment options are often limited to revision surgery. In order to prevent infection, we are developing antibiotic-loaded vessels for localized ultrasound mediated drug delivery. Macro-porous PEEK pucks were loaded with methylene blue (MeB) and coated in poly(lactic acid). In vitro samples were submerged in 200 ml of saline solution and ultrasound was applied for 30 minutes (5 MHz, 3 MPa). Surrounding media was sampled over 8 days and the concentration of MeB measured via spectrophotometry. The release from sonicated samples was compared to unsonicated controls. In parallel, a single-reservoir ABS clip design was also loaded with a combination of VAN and MeB and coated with either one or two layers of PLA. Release was observed while samples were submerged in 200 ml of saline solution. No immediate release of MeB was observed after suspension of the loaded porous PEEK pucks, demonstrating complete coating. Solutions from the non-insonated control group showed a 26 % increase in MeB concentration 2 days after suspension, and then remained stable. Solution from the insonated (experimental group) showed a 757 % increase in MeB concentration relative to baseline levels over an 8-day period. Finally, porous PEEK vessels loaded with vancomycin (VAN), were implanted in a cadaverous bunny to test their efficacy in situ. Two sites were inoculated with 104 CFU S. aureus and another two sites were wrapped in plastic to capture released drug. Surgical sites in the cadaverous rabbit showed a 10x reduction in the concentration of bacteria, while sites wrapped in plastic caught 50% of the released drug. ABS clip prototype single-coated samples showed immediate leakage and complete release of drug after 48 hours. Double-coated samples completely retained drug after 48 hours. Thus, feasibility of an ultrasound mediated drug delivery system was demonstrated in vitro and ex vivo.