Antibacterial and Cytocompatible: Combining Silver Nitrate with Strontium Acetate Increases the Therapeutic Window

Abstract

Microbial infection and insufficient tissue formation are considered to be the two main causes of dental implant failure. Novel studies have focused on designing dual-functional strategies to promote antibacterial properties and improve tissue cell response simultaneously. In this study, we investigated the antibacterial properties and cytocompatibility of silver nitrate (AgNO3) and strontium acetate (SrAc) in a mono-culture setup for dental application. Additionally, we defined the therapeutic window between the minimum inhibitory concentration against pathogenic bacteria and maximum cytocompatible dose in the case of combined applications in a co-culture setup. Antibacterial properties were screened using Aggregatibacter actinomycetemcomitans and cell response experiments were performed with osteoblastic cells (MC3T3) and fibroblastic cells (NIH3T3). The osteoinductive behavior was investigated separately on MC3T3 cells using alizarin red staining. A therapeutic window for AgNO3 as well as SrAc applications could be defined in the case of MC3T3 cells while the cytocompatibility of NIH3T3 cells was compromised for all concentrations with an antibacterial effect. However, the combined application of AgNO3/SrAc caused an enhanced antibacterial effect and opened a therapeutic window for both cell lines. Enhanced mineralization rates could be observed in cultures containing SrAc. In conclusion, we were able to demonstrate that adding SrAc to AgNO3 not only intensifies antibacterial properties but also exhibits bone inductive characteristics, thereby offering a promising strategy to combat peri-implantitis and at the same time improve osseointegration in implant therapy.

Bacteria‐Epithelial Cell Interaction Influences Cytotoxicity and Antibacterial Effect of Silver‐Gold Alloy Nanoparticles on a Species‐Specific Level

“…For quantification, analyses were changed to standard plate counting for bacteria and fluorescence microscopy for cells, as quantification of metabolic activity would have been biased by mixed cells and bacteria, respectively. This experimental setup has already been used previously and reliably characterized silver and strontium salts’ antibacterial and cytotoxic effect [33] …”

“…This experimental setup has already been used previously and reliably characterized silver and strontium salts' antibacterial and cytotoxic effect. [33]…”

Effectiveness of strontium/silver-based titanium surface coatings in improving antibacterial and osteogenic implant characteristics: a systematic review of in-vitro studies

“…Our recent in vitro investigation reported similar findings, where the combination of Sr acetate with Ag nitrate resulted in a synergistic increase in the antibacterial effect against Aggregatibacter actinomycetemcomitans . However, so far, the mechanism is unclear ( Figure 3 ) as the synergistic effect might have different mechanism of action in killing bacteria than the individual substances ( Parizi et al, 2022 ). It might be hypothesized that the effect includes changes in environmental factors, like pH or increasing of membrane permeability.…”

“…Moreover, the coating accelerated the healing of bone defects and enhanced the expression of osteoblastic phenotype in vivo and in vitro respectively ( Cheng et al, 2016 ). Our recent study on the biological potential of Sr/Ag combination showed that Sr may not only partially compensate the cytoxicity of Ag facilitating bone formation but also exhibited a synergistic antibacterial effect when combined with Ag ( Parizi et al, 2022 ). Nevertheless, these are results of individual studies.…”

Silica-based silver nanocomposite 80S/Ag as Aggregatibacter actinomycetemcomitans inhibitor and its in vitro bioactivity

“… 8 Some efforts have been made for the antibacterial activity of silver against A. actinomycetemcomitans . 9 , 10 Parizi et al. reported a combination of silver nitrate with stomium acetate, with a lowered cytotoxicity to NIH3T3 cell line, a boosted antibacterial activity against A. actinomycetemcomitans , and thus, an increased therapeutical window for silver ion.…”