Antimicrobial and wound healing properties of nitric oxide-releasing xerogels and silica nanoparticles.

摘要

Indwelling medical devices continue to be plagued by the body's response to foreign materials and the ever-present threat of microbial infection. Endogenously-produced nitric oxide (NO) has been shown to play beneficial roles in both wound healing and the body's defense against infection. To exploit NO's favorable properties for biomaterials applications, previous studies have detailed the synthesis of xerogel polymers and silica nanoparticles capable of storing and releasing NO via diazeniumdiolate NO-donors. Here, the ability of NO-releasing materials to reduce bacterial adhesion under flow conditions, modulate the foreign body response, and kill microbial pathogens is described.;To more thoroughly characterize the antibacterial properties of NO-releasing xerogels, studies were conducted with Pseudomonas aeruginosa in a parallel plate flow cell. Xerogels modified to release NO reduced bacterial adhesion in a flux-dependent manner, with a NO flux of ∼21 pmol·cm -2·s-1 inhibiting P. aeruginosa adhesion by 65% compared to controls. Fluorescent viability probes indicated that bacteria adhered to NO-releasing xerogels were killed within 7 h of adhesion. In terms of tissue biocompatibility, the foreign body response was studied in an animal model at the site of subcutaneous implants coated with NO-releasing xerogels. Implant-derived NO reduced capsule thickness and the chronic inflammatory response by 50 and 30%, respectively, compared to controls. Additionally, 77% more blood vessels were observed in proximity to NO-releasing implants after 1 week compared to controls.;Along with their ability to reduce bacterial adhesion and mitigate the foreign body response, NO-releasing materials may prove useful for treating infections due to the broad-spectrum antimicrobial properties of NO. Recently, silica nanoparticles have been developed that release micromolar quantities of NO, and here the efficacy of such nanoparticles was examined against both planktonic and biofilm-based pathogens. Comparison of the antibacterial activity of NO-releasing 45 mol% AHAP3/TEOS nanoparticles to the small molecule NO donor PROLI/NO demonstrated greater bactericidal efficacy of nanoparticle-derived NO and reduced cytotoxicity to mammalian fibroblasts. Treatment of gram-negative, gram-positive, and fungal biofilms with 70 mol% MAP3/TEOS silica nanoparticles killed ≥99% of biofilm-based cells for each species tested, with the greatest efficacy (≥99.999% killing) against gram-negative biofilms.