Abstract 2: Heat Generating Nanocomposite To Reduce Infection

Abstract

Purpose: To evaluate the combination of mild hyperthermia plus antibiotics for reducing Stapylococcus aureus biofilms associated with silicone materials. Methods: The additive effect of non-ablative hyperthermia with antibiotics was explored in a mouse model. Small disks of silicone with [4,4-bis(2-ethylhexyl)cyclopenta[2,1-b;3,4-b’]dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe) nanoparticles were inoculated with Xen29 S. aureus biofilms. These disks were implanted in the flanks of hairless, immunocompetent Crl:SKH1-hrBR mice, with each mouse receiving with 1 silicone disk on the left flank and 1 nanocomposite disk on the right flank. After 24 hours, the mice were imaged using IVIS to evaluate the infection using the bioluminescent signature from the Xen 29. Mice were treated with either 200µL 2mg/mL Gentamicin orIP Saline, with or without laser (3W, CW, 800nm, 25s) applied directly over the flank 1 hour afterinjection. Mice were imaged using IVIS 24 hours after treatment. The disks and surrounding infected tissue were extracted and homogenized. The homogenate was diluted and plated in triplicate to calculate the CFU /g per disk. The change in IVIS luminescence before and after treatment was compared. A total of 14 mice were implanted and treated. 2 mice received treatment of IP Gentamicin only, 4 mice received IP saline and laser therapy, and 8 mice received IP Gentamicin and laser therapy. Results: Only mice treated with Gentamicin and laser therapy demonstrated a decrease in luminescence on IVIS after treatment, representing a decrease in bacterial burden. These mice also demonstrated the greatest percent decrease (-65.8%) of CFU/g on the nanocomposite disk relative to the silicone disk. This was also the only treatment group which saw a significant decrease in bacterial burden on the nanocomposite disk relative to the silicone disk. Conclusion: Mice treated with the combined Gentamicin and laser therapy had the largest percent reduction in biofilm burden on the BSe-Si disk relative to the Si disk. This supports the hypothesis that joint heat and antibiotic therapy can be effective at reducing biofilms in vivo. Ultimately, this technology may have clinical utility towards treating biofilms on indwelling medical devices, mitigating a major burden of disease.