Isoeugenol-functionalized nanogels inhibit peri-implantitis associated bacteria in vitro

Obligate and facultative anaerobic bacteria adhering to dental implants are a major cause for peri-implant inflammation, which, if left untreated, can lead to implant loss. Previously, our group developed a new route for the synthesis of isoeugenol-functionalized aqueous nanogels for implant coatings. Here, the antimicrobial activity of several new nanogels differing in spacer length (n = 6, 9, 44), radius (60–200 nm), and amount of isoeugenol functional substance (1–20 mol%) was tested against the following peri-implantitis-associated species: Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, Escherichia coli, Actinomyces viscosus, Enterococcus faecalis, Staphylococcus aureus, Streptococcus oralis, S. parasanguinis, and the yeast Candida albicans. The minimal bactericidal concentration (MBC) and fungicidal concentration (MFC) were determined for each combination. In addition, transmission electron microscopy (TEM) and fluorescence microscopy after live-dead-staining (LD-S) were performed to visualize nanogel-microbe interactions. Two nanogels, NG9-3 and NG9-4 (colloids of 80–150 nm, with a spacer length of n = 9 and feeding between 5 and 10 mol% isoeugenol), had an inhibitory effect on all Gram-positive species and on P. gingivalis and P. intermedia with MBC ≥31.25 μg/ml. TEM and LD-S images showed that cellular adhesion and uptake of nanogels resulted in swelling, shedding, or even complete detachment of the cell wall and then to bursting (see graphical abstract). Functional nanogels can be used as building blocks in the design of bioactive coatings on implants to prevent infection and accelerate tissue regeneration, but the concentrations required are higher than for antibiotics. [Display omitted] •Isoeugenol (IE)-functionalized nanogels were produced in twelve different varieties.•The antimicrobial effect was spacer (n) -, particle size- and IE mol%-dependent.•Nanogels NG9 (n = 9) inhibited all 5 Gram-positive species tested.•NG9 inhibited Porphyromonas gingivalis and Prevotella intermedia.•Functional nanogels can be potentially used as bioactive implant coatings.