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Osteocompatibility of biofilm inhibitors.

Rawson M, Haggard W, Jennings JA - Open Orthop J (2014)

Bottom Line: Farnesol and dFBr induced cytotoxic responses within the reported biofilm inhibitory concentration range and low doses of dFBr were found to inhibit osteoblast differentiation.At high concentrations, such as those that may be present after local delivery, many of these biofilm inhibitors can have effects on cellular viability and osteoblast function.Concentrations at which negative effects on osteoblasts occur should serve as upper limits for delivery to orthopaedic trauma sites and guide development of these potential therapeutics for orthopaedics.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Engineering, University of Memphis, 330 Engineering Technology Building, Memphis, TN 38152, USA.

ABSTRACT
The demand for infection prevention therapies has led to the discovery of several biofilm inhibitors. These inhibiting signals are released by bacteria, fungi, or marine organisms to signal biofilm dispersal or disruption in Gram-positive, Gram-negative, and fungal microorganisms. The purpose of this study was to test the biocompatibility of five different naturally-produced biofilm chemical dispersal and inhibition signals with osteoblast-like cells: D-amino acids (D-AA), lysostaphin (LS), farnesol, cis-2-decenoic acid (C2DA), and desformyl flustrabromine (dFBr). In this preliminary study, compatibility of these anti-biofilm agents with differentiating osteoblasts was examined over a 21 days period at levels above and below concentrations active against bacterial biofilm. Anti-biofilm compounds listed above were serially diluted in osteogenic media and added to cultures of MC3T3 cells. Cell viability and cytotoxicity, after exposure to each anti-biofilm agent, were measured using a DNA assay. Differentiation characteristics of osteoblasts were determined qualitatively by observing staining of mineral deposits and quantitatively with an alkaline phosphatase assay. D-AA, LS, and C2DA were all biocompatible within the reported biofilm inhibitory concentration ranges and supported osteoblast differentiation. Farnesol and dFBr induced cytotoxic responses within the reported biofilm inhibitory concentration range and low doses of dFBr were found to inhibit osteoblast differentiation. At high concentrations, such as those that may be present after local delivery, many of these biofilm inhibitors can have effects on cellular viability and osteoblast function. Concentrations at which negative effects on osteoblasts occur should serve as upper limits for delivery to orthopaedic trauma sites and guide development of these potential therapeutics for orthopaedics.

No MeSH data available.


Related in: MedlinePlus

Microscopic images (4X magnification) taken at day 21 of the control groups (a-c) and the highest sub-toxic concentrations of eachtest group (d-h) stained with Alizarin Red-S to show calcium deposits in dark red-brown. A 20X magnification of cells exposed to dFBr (i)shows the rounded morphology of these cells.
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Figure 2: Microscopic images (4X magnification) taken at day 21 of the control groups (a-c) and the highest sub-toxic concentrations of eachtest group (d-h) stained with Alizarin Red-S to show calcium deposits in dark red-brown. A 20X magnification of cells exposed to dFBr (i)shows the rounded morphology of these cells.

Mentions: For focused analysis of mineralization response, the highest concentrations that supported viability were selected for reporting differentiation and mineralization markers (Table 2). In general, biocompatible concentrations of farnesol, D-AA, LS, and C2DA remained confluent and elongated similar to control groups, but dFBr was an exception. dFBr test samples changed morphology from the elongated fibroblast-like spindle shape form to a cuboidal form, similar to that of epithelial cells instead of osteoblast-like cells (Fig. 2h, i) [15]. Significant staining for mineral deposits in osteogenic control groups became apparent by day 14 (Fig. 2b, c).


Osteocompatibility of biofilm inhibitors.

Rawson M, Haggard W, Jennings JA - Open Orthop J (2014)

Microscopic images (4X magnification) taken at day 21 of the control groups (a-c) and the highest sub-toxic concentrations of eachtest group (d-h) stained with Alizarin Red-S to show calcium deposits in dark red-brown. A 20X magnification of cells exposed to dFBr (i)shows the rounded morphology of these cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260234&req=5

Figure 2: Microscopic images (4X magnification) taken at day 21 of the control groups (a-c) and the highest sub-toxic concentrations of eachtest group (d-h) stained with Alizarin Red-S to show calcium deposits in dark red-brown. A 20X magnification of cells exposed to dFBr (i)shows the rounded morphology of these cells.
Mentions: For focused analysis of mineralization response, the highest concentrations that supported viability were selected for reporting differentiation and mineralization markers (Table 2). In general, biocompatible concentrations of farnesol, D-AA, LS, and C2DA remained confluent and elongated similar to control groups, but dFBr was an exception. dFBr test samples changed morphology from the elongated fibroblast-like spindle shape form to a cuboidal form, similar to that of epithelial cells instead of osteoblast-like cells (Fig. 2h, i) [15]. Significant staining for mineral deposits in osteogenic control groups became apparent by day 14 (Fig. 2b, c).

Bottom Line: Farnesol and dFBr induced cytotoxic responses within the reported biofilm inhibitory concentration range and low doses of dFBr were found to inhibit osteoblast differentiation.At high concentrations, such as those that may be present after local delivery, many of these biofilm inhibitors can have effects on cellular viability and osteoblast function.Concentrations at which negative effects on osteoblasts occur should serve as upper limits for delivery to orthopaedic trauma sites and guide development of these potential therapeutics for orthopaedics.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Engineering, University of Memphis, 330 Engineering Technology Building, Memphis, TN 38152, USA.

ABSTRACT
The demand for infection prevention therapies has led to the discovery of several biofilm inhibitors. These inhibiting signals are released by bacteria, fungi, or marine organisms to signal biofilm dispersal or disruption in Gram-positive, Gram-negative, and fungal microorganisms. The purpose of this study was to test the biocompatibility of five different naturally-produced biofilm chemical dispersal and inhibition signals with osteoblast-like cells: D-amino acids (D-AA), lysostaphin (LS), farnesol, cis-2-decenoic acid (C2DA), and desformyl flustrabromine (dFBr). In this preliminary study, compatibility of these anti-biofilm agents with differentiating osteoblasts was examined over a 21 days period at levels above and below concentrations active against bacterial biofilm. Anti-biofilm compounds listed above were serially diluted in osteogenic media and added to cultures of MC3T3 cells. Cell viability and cytotoxicity, after exposure to each anti-biofilm agent, were measured using a DNA assay. Differentiation characteristics of osteoblasts were determined qualitatively by observing staining of mineral deposits and quantitatively with an alkaline phosphatase assay. D-AA, LS, and C2DA were all biocompatible within the reported biofilm inhibitory concentration ranges and supported osteoblast differentiation. Farnesol and dFBr induced cytotoxic responses within the reported biofilm inhibitory concentration range and low doses of dFBr were found to inhibit osteoblast differentiation. At high concentrations, such as those that may be present after local delivery, many of these biofilm inhibitors can have effects on cellular viability and osteoblast function. Concentrations at which negative effects on osteoblasts occur should serve as upper limits for delivery to orthopaedic trauma sites and guide development of these potential therapeutics for orthopaedics.

No MeSH data available.


Related in: MedlinePlus