Skip to main content
Download PDF

The use of oxymetazoline-based nasal solutions to remove bacteria-blood debris and eradicate Rothia dentocariosa: an artificial cavity model study

BMC Oral Health volume 25, Article number: 448 (2025) Cite this article

Abstract

Background

This study evaluated the antibacterial properties of a potential pulpal medicament, a nasal solution with oxymetazoline (NS-OXY, 0.05%), against a dentinal caries pathogen.

Methods

Using a disc diffusion susceptibility test (n = 6), Rothia dentocariosa was grown on brain–heart infusion (BHI) agar plates and exposed to OXY (0.05%), benzalkonium chloride (BKC-0.025%), OXY-NS (with OXY-0.05% and BKC), ferric sulfate (20%; ViscoStat), and distilled water (DI). This was followed by exposure of an artificial dental caries model with sheep blood to simulate the clinical pulpotomy procedure. An antibacterial broth inhibition test was conducted by adding the test samples in BHI broth at 37 ± 0.5 °C in an aerobic chamber.

Results

In the disc diffusion test, NS-OXY and BKC had the largest zone of inhibition (ZOI) measuring 14.42 mm (± 1.62) and 18.92 mm (± 4.14) respectively, indicating antibacterial activity. Ferric sulfate demonstrated a smaller ZOI, while OXY alone had no ZOI. The antibacterial broth test showed antibacterial effects with stable OD and pH levels for test samples containing BKC (0.025%) and diluted NS-OXY (0.01%) for up to 20 h. DI- and OXY-treated samples showed an increase in OD, indicating an increase in bacterial count and a concurrent drop in pH. BKC treatment statistically (P < 0.05) reduced polyP extracts, which may contribute to blood clot formation. NS-OXY demonstrated antibacterial properties, likely due to the addition of BKC to Rothia dentocariosa. NS-OXY showed concentration dependent biocompatibility with dental pulp stem cells while FS was cytotoxic at the same dilution.

Conclusion

These antimicrobial properties, together with OXY’s hemostatic effects, suggest the potential off-label use of NS-OXY during a pulpotomy procedure in primary and permanent teeth. This study provides support for potential future clinical trials of repurposing FDA-approved drugs consisting of oxymetazoline and benzalkonium chloride for dental and other similar applications.

Featured application

An over-the-counter nasal solution containing oxymetazoline has the potential to be used off-label to manage surgical bleeding from dental pulp exposures and provide antimicrobial properties against Rothia dentocariosa, a model gram-positive bacteria associated with deep dentinal caries.

Peer Review reports

Background

According to the literature, the oral microbiome and cavity biofilm is known to consist of more than 700 bacterial, fungal, and viral species [1]. For several decades, caries research into the etiology of caries initiation and progression mainly focused on gram-positive bacteria, such as Streptococcus mutans, Streptococcus sobrinus, and species of lactobacilli with known acidogenic and aciduric phenotypes [2]. However, with the advancements in technologies such as 16S rRNA, a more complete understanding of the oral microbiome is emerging with research studies examining additional factors contributing to dental caries and pulpal invasion. The uptake of orthophosphate and accumulation of polyphosphate (polyP) by aerobic species such as Rothia dentocariosa may have additional roles in caries progression [3,4,5,6,7]. In a clinical setting, the management of deep dental decay from bacteria such as Rothia dentocariosa, requires evaluating decay severity from the bacterial infection and associated patient symptoms. In most cases, the ideal method for managing deep dentinal caries is indirect pulp capping, where pulpal exposure is avoided [8]. In some cases, a pulp exposure occurs iatrogenically or due to a provider’s decision. The result is the exposure of pulp tissue that bleeds into the cavity preparation and has a risk of bacterial contamination by bacteria associated with the deep carious lesion, such as Rothia dentocariosa [9]. The peripheral pulp, especially near the pulp horns, has high blood flow, which makes hemostasis challenging in direct pulp capping [10]. In many situations, dental providers perform a pulpotomy to remove all the tissue within the pulp chamber. In both direct pulp capping and pulpotomies, hemostasis is necessary prior to the placement and final setting of a biocompatible pulp capping material [11,12,13].

One of the goals for surgical pulpal management is to create hemostasis. The current gold standard for hemostasis, especially in pediatric dentistry applications, is 20% ferric sulfate, which can limit the total blood clot formed at the exposure site [14]. The rationale for limiting blood clot volume is based on evidence that larger clot formations are associated with slower healing rates [15]. A blood clot becomes a degradable barrier between the pulp and the overlying biocompatible material. In addition to limiting the volume of blood clots, newer medicaments need to address other factors that may lead to lower success rates. Bacterial contamination is associated with blood clot formation, residual dentinal debris generated from the surgical procedure, and residual blood proteins, which may also contribute to lower or slower dental pulp healing rates [16].

Nasal solutions containing alpha-adrenergic agonists, such as the imidazoline derivative (ImD) oxymetazoline (OXY), are highly effective hemostatic agents [17, 18]. Nasal solutions with oxymetazoline (NS-OXY) are used in otolaryngology to manage nasal edema and establish hemostasis during surgery [19]. NS-OXY is also widely utilized by anesthesia teams to manage bleeding from intubation procedures [20]. Despite its widespread use in perioperative medical surgery and as an over-the-counter (OTC) product worldwide [21], NS-OXY has not been extensively examined for off-label hemostasis use in dentistry. One potential off-label hemostatic application in dentistry is the use of NS-OXY for pulpal management, such as direct pulp capping or pulpotomies in primary and permanent teeth [22].

OXY mimics catecholamines such as epinephrine and has a high affinity for alpha(α)−1 post-synaptic receptors [23]. These receptors are found in the nasal mucosa and dental pulp tissue [23, 24]. Autonomic nerves within dental pulp tissue are primarily part of the sympathetic nervous system, with vasoconstriction mediated by the activation of α−1 receptors [24, 25]. OXY initiates hemostasis via α−1 receptor activation, followed by profound vasoconstriction of smooth muscles lining arterioles and venules [26]. Vasoconstriction exceeds the activity of vasoconstriction induced by epinephrine [27]. An additional benefit of OXY over catecholamines is that ImDs have very little beta-adrenergic agonist activity, which stimulates systemic effects within tissues of the heart and lungs [28]. NS-OXY is safe for labeled use in children as both an OTC product and for surgical hemostasis. This selectivity adds to the safety profile of NS-OXY in children and adults for use as a nasal decongestant and hemostatic agent in surgery [29, 30]. The widespread use of NS-OXY and OTC designation suggests that the solution may be biocompatible with dental pulp tissue.

NS-OXY may have additional benefits in addition to hemostasis. NS-OXY also contains antimicrobial preservatives such as benzalkonium chloride (BKC) and edetate disodium (EDTA) [22]. These preservatives protect the container bottle from bacterial overgrowth when using OTC with repeated dosing. The purpose of this study was to evaluate the antimicrobial effects of NS-OXY containing BKC and EDTA against Rothia dentocariosa, a highly prevalent bacterium associated with deep dentinal caries. Rothia dentocariosa was chosen for antimicrobial testing due to its association as a source of bacterial contamination during pulp exposures and its association with periapical periodontitis and pulpal necrosis [31, 32]. Rothia dentocariosa also synthesizes a known bacterial derived hemostatic factor, polyphosphate, which initiates blood clotting [33,34,35]. Additionally, this first ever study/investigation will evaluate whether NS-OXY, BKC, and OXY solutions effectively remove the bacterial load associated with dentinal debris and blood and reduce the presence of polyphosphate, thereby allowing the potential future repurposing of NS-OXY. Additionally, preliminary evidence is suggestive of NS-OXY biocompatibility with human dental pulp stem cells (hDPSCs) based on metabolic activity assay.

Materials and Methods

Materials

Commercially available NS with 0.05% OXY was purchased (Afrin® original, Bayer Healthcare) with a pH of 5.81. Oxymetazoline (OXY, 500 mg, 23,826) was purchased from Cayman chemical USA to make pure 0.05% OXY solution in distilled water (no additives, pH: 4.57). Benzalkonium chloride (synonyms: alkylbenzyldimethylammonium chloride, BKC, 12,060−100 g) was purchased from Millipore Sigma USA. Millipore Sigma specified that the BKC was a mixture of different chain length alkylbenzyldimethylammonium chlorides: ~ 70% benzyldime-thyldodecylammonium chloride CH3(CH2)11N(Cl)(CH3)2CH2C6H5., ~ 30% benzyldimethyltetradecylammonium chloride CH3(CH2)13N(Cl)(CH3)2CH2C6H5. Ferric sulfate syringes were purchased from Ultradent USA (ViscoStat™, ferric sulfate 20%, 1278) with a measured pH of 2.55. All the reagents were used as received or dilutions were prepared in distilled water. The BKC – 0.025% (pH = 4.7) and OXY – 0.05% (pH = 4.57) solutions were prepared in distilled water, stored at 4 °C, and brought to room temperature on the day of experiment. The diffusion assay discs (Cytiva Whatman™, 2017–006 Antibiotic Assay Paper, 6 mm Discs, 1000/pk) were obtained from Fisher Scientific USA. Sheep’s blood (SB, R54012, pack volume – 100 ml) was purchased from Fisher Scientific USA, which was used in lieu of human blood. Rothia dentocariosa (ATCC 17931) was purchased from ATCC USA and stored at − 80 °C prior to being brought into culture. The human dental pulp stem cells (hDPSCs, PT-5025) were purchased from Lonza Walkersville Inc. (Walkersville MD USA).

Methods

Disc inhibition and growth inhibition assays

The BHI growth media and all the solutions for the study were prepared in commercial distilled water to control/minimize inorganic phosphate contamination. Initial broth culture conditions of R. dentocariosa were grown aerobically at 37 °C in BHI media [4]. For the disc inhibition assay (n = 6), BHI-agar plates were prepared, and 300 µL of R. dentocariosa bacterial inoculum (OD, 0.5 at 600 nm) was spread using a disposable L-shaped spreader. Bacteria-BHI-agar plates were allowed to dry at room temperature for 10–15 min. Commercial formulations of NS-OXY (Afrin® original, Bayer Healthcare) and ferric sulfate (20%, ViscoStat™, Ultradent) were used in addition to the custom pure reagents, described above, OXY (0.05%) and BKC (0.025%). Discs (n = 6) were exposed to 20 µL of the respective reagent, allowed to dry for 10 min, and gently pressed against Bacteria-BHI-agar plates. All the plates were incubated at 37 °C in an aerobic chamber for 20 h to investigate the antibacterial properties of each reagent. A positive (1:10 dilution of commercial bleach; 5.0% sodium hypochlorite) and negative control (sterile distilled water) were used (n = 6) for assay validation. For the broth/growth inhibition assay (n = 6), OXY (0.05%) and BKC (0.025%), were prepared by pre-concentrating the custom reagents and adding to BHI media in a 1:5 dilution (25 ml). Ferric sulfate was incompatible with the broth inhibition assay because it interfered with the spectrophotometric measurement of the OD and was not evaluated in this specific study. R. dentocariosa were grown according to the initial conditions described above. A pre-calculated volume of bacterial suspension (overnight culture) was added to achieve an initial OD of ~ 0.1–0.15 at 600 nm in 50 ml centrifuge tubes. Bacterial cell suspensions were collected at different time intervals for OD and pH measurements. Commercial sterile (autoclaved) distilled water was used as a negative control.

Artificial cavity pulpal exposure model

After IRB approval (the study obtained pathological specimens of extracted teeth done during routine dental care without patient identifiers and was deemed by the University of Minnesota Institutional Review Board to be exempt from review based on USA Code of Federal Regulations 45CFR46104(4ii).), teeth were collected as pathological specimens after extractions performed in oral surgery during routine care. An artificial pulpal access cavity model (n = 6) was used, where cavity preparations were made using a #4 round bur with an approximate length, width, and depth of 3.94 mm (SD: 0.52) × 2.64 mm (SD: 0.62) × 3.5 mm. The final preparation was then exposed to the underlying dentin. Pulp chamber access was avoided because of the geometric variation of the pulp chamber. Standardized pulpal access cavity preparation was used to assess the ability of NS-OXY, OXY, BKC, FS, and sterile distilled water (control) to remove bacteria and blood debris, as described later.

R. dentocariosa were grown in BHI broth as previously described. After overnight incubation, the optical density (OD) at 600 nm was measured, and the bacterial suspension was used to inoculate the fresh 10 ml suspension with the prepared tooth with initial OD ~ 0.1–0.15 at 600 nm in 20 ml scintillation bottles. The bottles were placed overnight in an aerobic chamber with a shaker at 100 rpm for bacterial growth and biofilm development. The overnight teeth samples were then exposed to sheep blood (SB) for 5 min by placing a 30–50 µL volume in the tooth cavity. The standardized SB exposure simulated the pulp exposure scenario.

Cleansing artificial model and biomass quantification

After teeth with R. dentocariosa and exposed with SB for 5 min, each treatment group was washed with respective reagent (sterile distilled water, NS-OXY, BKC, OXY, and FS) using 2.0 ml volume (500 µL aliquots, 10 s hold) followed by 2.0 ml water rinse. After the washing step, a crystal violet (CV) assay (n = 6) was used for biomass quantification. This assay was designed to test the ability of different agents to cleanse bacteria-blood from the cavity preparation. In brief, tooth cavities were exposed to 0.1% crystal violet (CV) solution in water for 10 min (500 µL, up-side down in 24 well plate) followed by a water rinse that ceased when no CV stain was observed in the water rinse. Then the teeth were placed up-side down in 24 well plate and 500 µL 1 M acetic acid solution was add-ed to dissolve the CV stain taken up by biomass complex in the tooth cavity. Following that 200 µL CV-acetic acid suspension was transferred to 96 well plates. The biomass quantification using CV assay was performed by capturing the OD at 600 nm using microplate spectrophotometer (Epoch, Biotek, VT, USA).

Inorganic phosphate and polyphosphate (polyP) quantification

To examine NS-OXY, BKC, and OXY effects on a hemostatic molecule, polyphosphate (polyP), that is derived from bacteria such as R. dentocariosa, the level of polyphosphate (polyP) (n = 3) accumulation was measured after NS-OXY, BKC, and OXY exposure using the previously published method [4]. At time 0 h and 8 h, the cell suspensions were collected and centrifuged at 5000 rpm 4 °C for 5 min to separate the cell pellet and BHI media. PolyP was isolated using a modified neutral phenol and chloroform protocol [36] with full details found elsewhere [4]. Importantly, a critical 2 h incubation step with DNAase (10 mg/ml) and RNAase (10 mg/ml) was used to reduce long chain polynucleotides contamination in the polyP extract. The dried polyP extract was eventually mixed with 4.2 M sulfuric acid (400 μL) and incubated for 24 h. This step hydrolyzed the phospho-anhydride bonds between individual orthophosphates. The polyP linear chain extract was converted into a mixture of free inorganic phosphate (PO43−). A 100 × dilution of the (PO43−) was performed and 100 μl samples were removed and added to 100 μl of ascorbic acid in a 96 well plate. The plate was incubated at room temperature for 15 min followed by spectrophotometer (Epoch, Biotek, VT, USA) absorbance reading at 880 nm. Inorganic PO43− values were determined through the use of a phosphate standardized curve [4].

Biocompatibility using alamarBlue™ assay

For biocompatibility assessment, NS-OXY, BKC, and OXY (n = 8) were diluted 1:5 and 1:10 in cell culture media and FS (n = 6) was diluted to 1:2.5 and 1:10 similarly. Human dental pulp stem cells (hDPSCs) were grown in a T75 flask in α-MEM media with 10% FBS and 1% Pen-Strep at 37 °C in a humidified incubator with 5% CO2 until cells were 90% confluent. When ready, the cells were trypsinised and plated in 24 well plates at cell density of 10,000 cells per well in serum supplemented media for 24 h to allow cell attachment before treatment. The reagents solutions at each dilution (NS-OXY, BKC, OXY, and FS) were freshly prepared and the cells were exposed for 10 min at ambient condition. After treatment time, the cells were washed with PBS and incubated in fresh media (α-MEM media with 10% FBS and 1% Pen-Strep) at 37 °C in a humidified air incubator with 5% CO2 for another 24 h. Metabolic activity as a measure of cell cytotoxicity was determined using alamarBlue™ (ThermoFisher Scientific, USA) following manufacturer’s instruction. Fluorescence intensity was measured at 540/590 excitation/emission wavelength on a multimode microplate reader (Synergy, HT, BioTek, USA). The percentage cell growth inhibition was determined using the equation: 1, where Asample is a metabolic activity for treatment group and Acontrol is for control untreated group.

$${\%reduction}=\left(1-\left(\frac{\text{Asample}}{\mathrm{Acontrol}}\right)\right)\times 100\;equation:1$$

Statistical analysis

The results in the study are composed of two independent experiments (triplicates, final n = 6), unless stated otherwise. The data was collected, and parametric analysis was performed by ANOVA using Prism (GraphPad, Boston, MA, USA). For post hoc testing for group differences, Holm-Sidak’s multiple comparison testing analysis was performed at significance level of P < 0.05.

Results

Disc and growth inhibition assay

Disc inhibition assays (n = 6) demonstrated that NS-OXY and BKC (0.025%) had higher antimicrobial activity after 20 h toward R. dentocariosa than ferric sulfate (20%) as shown in Fig. 1a. No difference was found between the antimicrobial effects of NS-OXY and BKC (Fig. 1b) with comparable activity as 1:10 dilution of bleach, sodium hypochlorite (5.0%, stock, data reported in supplemental information (SI) as Figure S1). Ferric sulfate had higher activity toward R. dentocariosa than OXY (Fig. 1b) and sterile distilled water (included in Figure S1, SI). Discs containing OXY and distilled water had no inhibition of the growth of R. dentocariosa on BHI-agar plates. The growth inhibition assay (n = 6) assessed how the treatment groups affected bacterial growth over 20 h in BHI media (Fig. 2). In the control samples (no treatment), R. dentocariosa planktonic cultures demonstrated a typical bacterial growth curve in BHI media with an increase in the optical density of the media over 20 h, which corresponds to the exponential growth phase of the bacteria. There was a corresponding decrease in pH from the fermentation of media carbohydrates (Fig. 2a). Since NS-OXY is a commercial formulation that could not be pre-concentrated, a diluted concentration was tested (0.01%). Both 0.01% NS-OXY and 0.025% BKC inhibited bacterial growth with little change in optical density and the original media pH was maintained at 6.98 (Fig. 2b, 2c). OXY (0.05%) had slightly less growth (P = 0.0009) but no found difference in pH to the negative control.

Fig. 1
figure 1

a Disc inhibition assay against Rothia dentocariosa after 20 h where zone of inhibition is identified by the translucency around the disc indicating an absence of bacterial growth surrounding the disc. b The diameter of the zone was measured for each plate (n = 6). There was no statistical difference found (ns) between NS-OXY and 0.025% BKC, both groups had larger zones of inhibition over FS and OXY alone

Full size image
Fig. 2
figure 2

Rothia dentocariosa growth (n = 6) measured by optical density (solid) and media pH (dotted) in (a) BHI (control) over 20 h (b) BHI with 0.01% NS-OXY (c) BHI with 0.025% BKC (d) BHI with 0.05% OXY. ANOVA with post-hoc Tukey’s multiple comparison testing show group factor (P < 0.05) difference

Full size image

Inorganic phosphate and polyP quantification using ascorbic acid assay

Control and OXY samples demonstrated a reduction in media free phosphate via bacteria uptake over the course of the first 8 h (early log growth) as reported in Fig. 3a. Free phosphate in the media was statistically higher for both 0.01% NS-OXY and 0.025% BKC over no treatment controls (Fig. 3a). Control and OXY sample also had isolated polyP. BKC treatment statistically (P < 0.05) reduced polyP extracts found in R. dentocariosa. The diluted NS-OXY (0.01%) did not have a measurable effect on reducing the bacterial derived hemostatic molecule of polyP as shown in Fig. 3b.

Fig. 3
figure 3

Inorganic phosphate and polyP quantification for Rothia dentocariosa (n = 3) (a) Media phosphate changes after 8 h of Rothia dentocariosa growth and (b) polyphosphate isolates per treatment group. ANOVA with post-hoc Tukey’s multiple comparison testing show group factor (P < 0.05) difference

Full size image

Artificial cavity model representing pulpotomy procedure

In the artificial dental cavity model (n = 6) where bacteria are grown inside tooth cavity preparations and then exposed to Sheep’s blood, Fig. 4a demonstrates the steps of the assay and results from exposure to bacteria-Sheep’s blood after rinsing with water. NS-OXY (full strength), BKC, and OXY had favorable results in removing the bacteria-blood biomass from the cavity preparation. FS left visually noticeable residual biomass. Crystal violet staining and quantification revealed that FS had a substantial and statistically higher residual biomass after water rinsing than NS-OXY, BKC, and OXY as reported in Fig. 4b.

Fig. 4
figure 4

Artificial cavity model and biomass quantification (n = 6): A with exposure to Rothia dentocariosa in BHI overnight followed by exposure to Sheep’s blood for 5 min, and after rinsing with treatment groups. B Residual biomass was quantified with crystal violet and quantified with a spectrophotometer at 880 nm. FS had statistically higher biomass than other treatments (ANOVA, Holm-Sidak’s, **** = P < 0.001)

Full size image

Biocompatibility with dental pulp stem cells

The effect of different concentrations of washing agents (NS-OXY, BKC, OXY, and FS) on hDPSCs was determined by measuring metabolic activity of the cells. The alamarBlue™ fluorescence intensity was measured for different treatment groups and normalized to untreated controls hDPSCs, based on reduced a resazurin-based molecule (as reported in Fig. 5). Different compounds showed different effects on metabolic activity of hDPSCs in a dose-dependent manner. Both FS and BKC demonstrated significantly lower reduction in cell metabolic activity (< 15%) relative to untreated control at different tested dilutions confirming their cytotoxicity. However, when hDPSCs were treated with NS-OXY at 1:1 and 1:5 dilutions, low metabolic activity was observed which was significantly improved to approximately 78% of untreated controls when the dilution factor was increased to 1:10. On the other hand, hDPSCs treated with OXY at 0.025% and 0.0125% also showed relatively higher metabolic activity had a higher cellular reducing capacity (more than 60% which improved upto 80% at high dilution). These results confirm that both NS-OXY at 1:10 and OXY at 0.025% and 0.0125% were well tolerated by cells as suggested by alamarBlue™ assay (Fig. 5).

Fig. 5
figure 5

Analysis of alamar blue assay with hDPSCs. The cell viability assay measures reduction of a resazurin-based molecule by hDPSCs exposed to NS-OXY, BKC, OXY, and FS at different dilutions (n = 8). Values are presented as a percentage of alamarBlue™ reduction normalized to the untreated PBS controls. ANOVA, post hoc Tukey–Kramer, was performed across all pairwise with close differences shown. Figure assembled with BioRender.com

Full size image

Discussion

This study confirms the antimicrobial activity of NS-OXY against Rothia dentocariosa. NS-OXY is colorless and odorless with a biocompatible pH (5.81). NS-OXY had superior antimicrobial effects than the current standard of care option for dental pulp management, 20% FS, against R. dentocariosa. FS inhibition may be due to its low pH (2.55). Results of this study demonstrate that the main active ingredient of NS-OXY, oxymetazoline (OXY) showed no bactericidal activity and during the exposure in broth culture media had very minor difference between negative (sterile distilled water) controls. One of the main inactive ingredients in NS-OXY is BKC, which exhibited higher antimicrobial activity than FS. The results of this study indicate that the antimicrobial action of NS-OXY is partially the result of the addition of BKC since OXY did not possess any effects. In the labeled usage of NS-OXY, BKC is added to the container to reduce bacterial overgrowth from nasal bacteria contamination. This is necessary since the bottle is repeatedly used for individual use. In the case of dental off-label use, such as for the dental pulp management, NS-OXY would be dripped extra orally onto a small, dampened dish similar to the application of formocresol or bonding agents. The presence of BKC and OXY in the NS-OXY would harness the properties of both the ingredients independently during the potential pulp management procedure. BKC will work as an antibacterial/bactericidal agent by minimizing the bacterial contamination and sterilizing the area, and OXY may work as a hemostatic agent controlling the bleeding [22, 37, 38].

In this application, the bottle does not get contaminated across patients but can be applied to a cavity access preparation as a result of dental decay with bacteria ingress. This study suggests that BKC adds antimicrobial activity toward R. dentocariosa to NS-OXY if used as a pulp medicament, but direct clinical studies are needed. Additional studies may also examine the activity of NS-OXY on other oral bacteria and its residual effects on oral bacteria pathogens. In past studies, BKC has been added to dental materials for its residual antimicrobial effects and anti-matrix metalloproteinase activity [38,39,40,41,42]. These past studies, and the present study, are in agreement with medical-based studies demonstrating BKC broad antimicrobial effects. BKC is a cationic organic quaternary ammonium compound where membrane disruption is the primary mechanism of action [43]. BKC has been shown to be safe up to 0.1% for short-term use in humans [44]. Concentrations of BKC in all commercial nasal sprays range from 0.00045% to 0.1% and our test concentration was 0.025%. BKC is actually not a single compound but a mixture of alkyl benzyl dimethylammonium chlorides (ABAC).

For NS-OXY, the chain length distribution of ABAC and concentration used is proprietary. Also, the NS-OXY used during the study had EDTA as an additive that may have an improved BKC membrane disruption efficacy and allowed a lower BKC concentration used in our custom concentration [43]. We chose the BKC from Sigma to have ideal water solubility with 70% benzyldimethyldodecylammonium chloride CH3(CH2)11N(Cl)(CH3)2CH2C6H5 and ~ 30% benzyldimethyltetradecylammonium chloride. Future studies can investigate changes to these concentrations and their effect on antimicrobial activity. Investigation into BKC is complex given that BKC is a mixture of ABAC with different chain lengths that can lead to differing antimicrobial activity, solubility, debris removal, and tissue compatibility. Importantly, BKC is most efficacious as an antimicrobial at higher pH values that are closer to physiological pH, and NS-OXY used in this study had a pH of 5.86.

In this study, in addition to the antimicrobial effects, we prepared an artificial cavity model to investigate the washing and debris removing potential of compounds in the study creating similar conditions during the pulp management procedure. The artificial model closely translates steps such as caries excavation, pulp exposure and bleeding, controlling the bleeding by applying a medicament moistened cotton pellet, and finally applying the adhesive and composite layers and preparing for final enamel restoration [45]. The limitation of this study is that it accomplishes examining an artificial model without the use of an animal model where current standards are to reduce animal investigations. In addition, the advantage of using an artificial model is to control and tailor the model as needed for clinical evaluation and that these types of clinical investigations (biomass removal and antimicrobial activity) are difficult to test using an in vivo model. Our use of positive and negative control provides relative comparison between different agents. NS-OXY has superior biomass debris removal than the current clinical standard of ferric sulfate (FS). In the current study, when bacteria colonies were mixed with Sheep’s blood and then treated with FS and subsequently rinsed with water, a residual biomass was left on the tooth. Also, with a pH of 2.55 the biocompatibility of FS with pulpal tissue remains questionable and a possible irritant. The results of the study show that ferric sulfate’s poor biofilm and debris removal, leaving possible residual iron-protein deposits behind, maybe a potential reason for radiographic resorption found in clinical studies [46,47,48,49,50]. As an important aside, since this paper is discussing NS-OXY potential off-label use in pulp management, FS is FDA approved for gingival retraction. FS is currently used as a pulp medicament off label.

NS-OXY ubiquitous use in the nasal cavity with limited complication is suggestive of its biocompatibility [17, 18, 21, 51]. NS-OXY was found to be non-toxic in animal models [52] and human gingival fibroblasts [53]. In the present study, NS-OXY had improved hDPSC viability at 1:5 and 1:10 dilutions compared to the full commercial concentration. NS-OXY, BKC, OXY, and FS had a deleterious effect on the cellular metabolic activity of hDPSCs. Up to a 1:10 dilution, FS was cytotoxic, with less than 14% viability compared to the untreated control samples. This concurred with previous work that demonstrated that FS can reduce cellular metabolic activity more than aluminum sulfate solutions, and the difference in the magnitude of effect may be attributed to the lower pH and high viscosity of FS [30]. When accounting for the fact that FS is more likely to leave a residue than other agents after rinsing, the use of FS may cause residual cytotoxic effects. Previous studies examining OXY alone as a retraction agent have shown that OXY is non-toxic to human gingival fibroblasts [5]. In that study, NS-OXY did not alter the intracellular arrangement and intensity of fibronectin [5]. This previous study also found an elevated degree of reactive oxygen species in gingival fibroblasts exposed to NS-OXY, which warrants further investigation into effects on dental pulp cells. BKC has shown short term use safety (up to 0.1%) in humans [31]. NS-OXY was found to be non-toxic toward sensitive auditory hair cells in an animal model [32]. From the results of the present study, the cytotoxicity of NS-OXY on hDPSCs along with the established antimicrobial activity can be inferred to be from BKC. The results of the present work suggest that clinical application should consider rinsing the cavity with water to improve biocompatibility after establishing hemostasis with NS-OXY. It is noteworthy that diffusion of NS-OXY into the tissue will dilute the agent and more work is needed to examine effects on 3D tissue models where additional connective tissue may protect hDPSCs. This may allow for absorbance and clearance in the pulpal tissue, thus improving biocompatibility, similar to its nasal application. As a pulpal medicament, it is estimated that 0.05 ml of 0.05% NS-OXY delivered via cotton ball or micro-brush is needed for hemostasis during a primary molar pulpotomy procedure [6]. This is a fraction of the 1–2 ml that has been associated with serious adverse events in children 5 and younger. The low volume, and low concentration of added BKC, should also be considered in future investigations when investigating anaphylaxis risk, found with some medical applications of BKC, but extremely rare in cases of nasal spray application [54].

Future dental investigations that would study NS-OXY off-label use as a pulp medicament could be informed by the specifics of this study and the proposed NS-OXY mechanisms (Fig. 6). Future studies are needed to examine the substantivity of NS-OXY applied to the dentin and effects of bacteria within dentinal tubules. We found that a BKC concentration of 0.025% had similar antimicrobial and biomass cleansing effects as NS-OXY, and this concentration also reduced the microbial hemostatic agent of polyP in Rothia dentocariosa. Microbial polyP can mimic the polyP secreted by platelets to accelerate blood clotting [33, 34]. PolyP has been found to strongly activate factor XII [55]. The microbial polyP clotting effect has been found in other oral bacteria such as Porphyromonas gingivalis [35]. Given that NS-OXY mainly achieves hemostasis via α−1 receptor activation, which reduces blot clot formation, the additional benefit of limiting polyP formation requires further investigation. However, multi-mechanism approaches to achieve optimal clotting while avoiding excessive blot clot formation may be warranted because large clots have been associated with failure of pulp procedures [56]. It is important to point out that a dental application of NS-OXY may have improved efficacy over nasal surgical applications since hemostasis is achieved through multiple modes including chemical based hemostasis initial pressure hemostasis, and the application of a pulp capping material that provides long-term clot stabilization. These principles are currently being applied to future nasal surgical bleeding investigations [3, 57]. Additional studies, including clinical investigations and trials, are needed to confirm the potential applications, safety, and repurposing of drugs consisting of OXY and BKC to harness their properties.

Fig. 6
figure 6

a NS-OXY have potential to be used off-label to manage pulp exposures in dental applications. b Literature studies support the mechanism of OXY creating vasoconstriction of pulp tissue by activating α−1 receptors found in pulp tissue (c) Results of this current study support direct antimicrobial effects of NS-OXY against Rothia dentocariosa and a key ingredient benzalkonium chloride (BKC) which has biomass removing effects and limits the presence of residual polyP, which is a known pro-coagulant that may have residual effects. Figure adapted from Jones 2021 and created with BioRender.com

Full size image

Conclusions

Based on the disc diffusion assay, NS-OXY (stock) and pure BKC (0.025%) showed identical antimicrobial properties, as suggested by the similar zones of inhibition values. In response to our study, we can conclude that the antimicrobial activity of BKC combined into NS-OXY may be helpful in removing residual bacteria and blood debris during pulpal management. BKC provides immediate antimicrobial activity but has low biocompatibility. Oxymetazoline alone was highly biocompatible at higher dilution with human dental pulp stem cells. NS-OXY was more biocompatible with hDPSCs than FS. NS-OXY is a potential pulpal medicament due to hemostasis properties of oxymetazoline as an alpha(α)−1 receptor agonist.

Data availability

The data that support the findings will be available in the searchable Data Repository for University of Minnesota (DRUM), https://hdl.handle.net/11299/269154.

Abbreviations

ABAC:

Alkyl benzyl dimethylammonium chlorides

BHI:

Brain-heart infusion

BKC:

Benzalkonium chloride, pure compound

CV:

Crystal violet

DI:

Distilled water

EDTA:

Edetate disodium

FS:

Ferric sulfate (ViscoStat™)

hDPSCs:

Human dental pulp stem cells

ImD:

Imidazoline derivative (ImD)

NS:

Nasal solution

NS-OXY:

OTC NS containing OXY (Afrin®)

OD:

Optical density (absorbance)

OXY:

Oxymetazoline, pure compound

OTC:

Over-the-counter

PolyP:

Polyphosphate (polyP)

Rd:

Rothia dentocariosa

SB:

Sheep blood

ZOI:

Zone of inhibition

References

  1. Kroes I, Lepp PW, Relman DA. Bacterial diversity within the human subgingival crevice. Proc Natl Acad Sci U S A. 1999;96:14547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Nishikawara F, Nomura Y, Imai S, Senda A, Hanada N. Evaluation of cariogenic bacteria. Eur J Dent. 2007;01:031.

    Article  Google Scholar 

  3. Wake N, Asahi Y, Noiri Y, Hayashi M, Motooka D, Nakamura S, Gotoh K, Miura J, Machi H, Iida T, Ebisu S. Temporal dynamics of bacterial microbiota in the human oral cavity determined using an in situ model of dental biofilms. NPJ Biofilms Microbiomes. 2016;2(1):1–9.

    Article  Google Scholar 

  4. Kumar D, Mandal S, Bailey JV, Flood BE, Jones RS. Fluoride and gallein inhibit polyphosphate accumulation by oral pathogen Rothia dentocariosa. Lett Appl Microbiol. 2023;76:ovad017.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Baijal K, Downey M. Targeting polyphosphate kinases in the fight against pseudomonas aeruginosa. mBio. 2021;12:10.

    Article  Google Scholar 

  6. Rao NN, Gómez-García MR, Kornberg A. Inorganic polyphosphate: essential for growth and survival. Annu Rev Biochem. 2009;78(1):605–47.

    Article  CAS  PubMed  Google Scholar 

  7. Kornberg A, Rao NN, Ault-Riché D. Inorganic polyphosphate: a molecule of many functions. Annu Rev Biochem. 1999;68:89.

    Article  CAS  PubMed  Google Scholar 

  8. Farooq NS, Coll JA, Kuwabara A, Shelton P. Success rates of formocresol pulpotomy and indirect pulp therapy in the treatment of deep dentinal caries in primary teeth. Pediatr Dent. 2000;22(4):278–86.

    CAS  PubMed  Google Scholar 

  9. Sonmez D, Duruturk L. Success rate of calcium hydroxide pulpotomy in primary molars restored with amalgam and stainless steel crowns. Br Dent J. 2010;208(9):E18-.

    Article  CAS  PubMed  Google Scholar 

  10. Meyer MW, Path MG. Blood flow in the dental pulp of dogs determined by hydrogen polarography and radioactive microsphere methods. Arch Oral Biol. 1979;24(8):601–5.

    Article  CAS  PubMed  Google Scholar 

  11. Caicedo R, Abbott PV, Alongi DJ, Alarcon MY. Clinical, radiographic and histological analysis of the effects of mineral trioxide aggregate used in direct pulp capping and pulpotomies of primary teeth. Aust Dent J. 2006;51:297–305.

    Article  CAS  PubMed  Google Scholar 

  12. Accorinte MLR, Loguercio AD, Reis A, Muench A, Araújo VC. Response of human pulp capped with a bonding agent after bleeding control with hemostatic agents. Oper Dent. 2005;30:147.

    PubMed  Google Scholar 

  13. Hilton TJ, Ferracane JL, Mancl L. Comparison of CaOH with MTA for direct pulp capping: a PBRN randomized clinical trial. J Dent Res. 2013;92(7_suppl):S16-22.

    Article  PubMed Central  Google Scholar 

  14. Bandi M, Mallineni SK, Nuvvula S. Clinical applications of ferric sulfate in dentistry: a narrative review. J Conserv Dentist. 2017;20:278–81.

    Article  CAS  Google Scholar 

  15. Schröder U. Effect of an extra-pulpal blood clot on healing following experimental pulpotomy and capping with calcium hydroxide. Odontol Revy. 1973;24(3):257–68.

  16. Hørsted P, El Attar K, Langeland K. Capping of monkey pulps with Dycal and a Ca-eugenol cement. Oral Surg, Oral Med, Oral Pathol. 1981;52:531.

    Article  PubMed  Google Scholar 

  17. Higgins TS, Hwang PH, Kingdom TT, Orlandi RR, Stammberger H, Han JK. Systematic review of topical vasoconstrictors in endoscopic sinus surgery. Laryngoscope. 2011;121:422.

    Article  PubMed  Google Scholar 

  18. Rodríguez Valiente A, Roldán Fidalgo A, Laguna Ortega D. Bleeding control in endoscopic sinus surgery: a systematic review of the literature. Rhinology. 2013;51:298.

    Article  PubMed  Google Scholar 

  19. Cartabuke RS, Anderson BJ, Elmaraghy C, Rice J, Tumin D, Tobias JD. Hemodynamic and pharmacokinetic analysis of oxymetazoline use during nasal surgery in children. Laryngoscope. 2019;129:2775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Katz RI, Hovagim AR, Finkelstein HS, Grinberg Y, Boccio RV, Poppers PJ. A comparison of cocaine, lidocaine with epinephrine, and oxymetazoline for prevention of epistaxis on nasotracheal intubation. J Clin Anesth. 1990;2(1):16–20.

    Article  CAS  PubMed  Google Scholar 

  21. Deckx L, De Sutter AI, Guo L, Mir NA, van Driel ML. Nasal decongestants in monotherapy for the common cold. Cochrane Database Syst Rev. 2016;10(10):CD009612.

  22. Jones RS. Conceptual model for using imidazoline derivative solutions in pulpal management. J Clin Med. 2021;10:1212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Haenisch B, Walstab J, Herberhold S, Bootz F, Tschaikin M, Ramseger R, Bönisch H. Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol. 2010;24:729–39.

    Article  CAS  PubMed  Google Scholar 

  24. Olgart L. Neural control of pulpal blood flow. Crit Rev Oral Biol Med. 1996;7:159.

    Article  CAS  PubMed  Google Scholar 

  25. Edwall L, Kindlová M. The effect of sympathetic nerve stimulation on the rate of disappearance of tracers from various oral tissues. Acta Odontol Scand. 1971;29:387–400.

    Article  CAS  PubMed  Google Scholar 

  26. Johnson DA, Hricik JG. The pharmacology of α‐adrenergic decongestants. Pharmacotherapy: J Hum Pharmacol Drug Ther. 1993;13:110S.

    Article  CAS  Google Scholar 

  27. Chou AK, Chiu CC, Zhu GC, Wang JJ, Chen YW, Hung CH. Naphazoline and oxymetazoline are superior to epinephrine in enhancing the cutaneous analgesia of lidocaine in rats. Fundam Clin Pharmacol. 2023;37:296–304.

    Article  CAS  PubMed  Google Scholar 

  28. Minyan W, Dunn WR, Blaylock NA, Chan SLF, Wilson VG. Evidence for a non-adrenoceptor, imidazoline-mediated contractile response to oxymetazoline in the porcine isolated rectal artery. Br J Pharmacol. 2001;132:1359–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Riegle EV, Gunter JB, Lusk RP, Muntz HR, Weiss KL. Comparison of vasoconstrictors for functional endoscopic sinus surgery in children. Laryngoscope. 1992;102:820–3.

    Article  CAS  PubMed  Google Scholar 

  30. Cartabuke R, Tobias JD, Jatana KR. Topical nasal decongestant oxymetazoline: Safety considerations for perioperative pediatric use. Pediatrics. 2021;148(5):e2021054271.

  31. Zahran S, Mannocci F, Koller G. Assessing the iatrogenic contribution to contamination during root canal treatment. J Endod. 2022;48(4):479–86.

    Article  PubMed  Google Scholar 

  32. Korona-Glowniak I, Piatek D, Fornal E, Lukowiak A, Gerasymchuk Y, Kedziora A, Bugla-Płoskonska G, Grywalska E, Bachanek T, Malm A. Patterns of oral microbiota in patients with apical periodontitis. J Clin Med. 2021;10(12):2707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Smith SA, Choi SH, Davis-Harrison R, Huyck J, Boettcher J, Reinstra CM, Morrissey JH. Polyphosphate exerts differential effects on blood clotting, depending on polymer size. Blood. 2010;116:4353–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Travers RJ, Smith SA, Morrissey JH. Polyphosphate, platelets, and coagulation. Int J Lab Hematol. 2015;37:31–5.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Neilands J, Kinnby B. Porphyromonas gingivalis initiates coagulation and secretes polyphosphates — a mechanism for sustaining chronic inflammation? Microb Pathog. 2022;162:104648.

    Article  CAS  PubMed  Google Scholar 

  36. Bru S, Jiménez J, Canadell D, Ariño J, Clotet J. Improvement of biochemical methods of polyP quantification. Microbial Cell. 2017;4:6.

    Article  CAS  Google Scholar 

  37. Bondurant S, McKinney T, Bondurant L, Fitzpatrick L. Evaluation of a benzalkonium chloride hand sanitizer in reducing transient Staphylococcus aureus bacterial skin contamination in health care workers. Am J Infect Control. 2020;48:522–6.

    Article  CAS  PubMed  Google Scholar 

  38. Yamamoto M, Inokoshi M, Tamura M, Shimizubata M, Nozaki K, Takahashi R, Yoshihara K, Minakuchi S. Development of 4-META/MMA-TBB resin with added benzalkonium chloride or cetylpyridinium chloride as antimicrobial restorative materials for root caries. J Mech Behav Biomed Mater. 2021;124:104838. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.jmbbm.2021.104838.

  39. Tezvergil-Mutluay A, Mutluay MM, Gu LS, Zhang K, Agee KA, Carvalho RM, Manso A, Carrilho M, Tay FR, Breschi L, Suh BI, Pashley DH. The anti-MMP activity of benzalkonium chloride. J Dent. 2011;39(1):57–64.

    Article  CAS  PubMed  Google Scholar 

  40. Alovisi M, Pasqualini D, Mandras N, Roana J, Costamagna P, Comba A, Cavalli R, Luganini A, Iandolo A, Cavallo L, Scotti N. Confocal laser scanner evaluation of bactericidal effect of chitosan nanodroplets loaded with benzalkonium chloride. J Clin Med. 2022;11(6):1650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kurt A, Tüzüner T, Baygın Ö. Antibacterial characteristics of glass ionomer cements containing antibacterial agents: an in vitro study. Eur Arch Paediatr Dent. 2021;22:49.

    Article  CAS  PubMed  Google Scholar 

  42. Torres-Garcia ML, Llavore LD, Bungay A, Sarol JD, Pineda RR, Delas Penas K. Benzalkonium chloride in an orthodontic adhesive: Its effect on rat enamel demineralization using color-based image analysis. Am J Orthod Dentofacial Orthop. 2019;155:88–97.

    Article  PubMed  Google Scholar 

  43. Richards RM, Cavill RH. Electron microscope study of effect of benzalkonium chloride and edetate disodium on cell envelope of Pseudomonas aeruginosa. J Pharm Sci. 1976;65(1):76–80.

    Article  CAS  PubMed  Google Scholar 

  44. Marple B, Roland P, Benninger M. Safety review of benzalkonium chloride used as a preservative in intranasal solutions: an overview of conflicting data and opinions. Otolaryngol Head Neck Surg. 2004;130(1):131–41.

    Article  PubMed  Google Scholar 

  45. Gill K, Stevenson RG. Navigating through caries excavation and pulp capping techniques in permanent teeth. Dent Rev. 2024;4:100078.

    Article  Google Scholar 

  46. Smith NL, Seale NS, Nunn ME. Ferric sulfate pulpotomy in primary molars: a retrospective study. Pediatr Dent. 2000;22:192.

    CAS  PubMed  Google Scholar 

  47. Vargas KG, Packham B. Radiographic success of ferric sulfate and formocresol pulpotomies in relation to early exfoliation. Pediatr Dent. 2005;27(3):233–7.

    PubMed  Google Scholar 

  48. Aksoy B, Güngör HC, Uysal S, Gonzales CD, Ölmez S. Ferric sulfate pulpotomy in primary teeth with different base materials: a 2-year randomized controlled trial. Quintessence Int. 2022;53(9):782–9.

    PubMed  Google Scholar 

  49. Akman H, Surme K. Retrospective analysis of ferric sulfate and sodium hypochlorite pulpotomy procedures in primary molars. J Dent Res Dent Clin Dent Prospects. 2023;17:182.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Brar KA, Kratunova E, Avenetti D, Da Fonseca MA, Marion I, Alapati S. Success of biodentine and ferric sulfate as pulpotomy materials in primary molars: a retrospective study. J Clin Pediatr Dent. 2021;45:22.

    Article  PubMed  Google Scholar 

  51. Randall DA. Simplified management of epistaxis. J Am Assoc Nurse Pract. 2021;33:1024–9.

    Article  PubMed  Google Scholar 

  52. Isaacson G, Buttaro BA, Mazeffa V, Li G, Frenz DA. Oxymetazoline solutions inhibit middle ear pathogens and are not ototoxic. Ann Otol Rhinol Laryngol. 2005;114:645–51.

    Article  PubMed  Google Scholar 

  53. Nowakowska D, Saczko J, Szewczyk A, Michel O, Ziętek M, Weżgowiec J, Więckiewicz W, Kulbacka J. In-vitro effects of vasoconstrictive retraction agents on primary human gingival fibroblasts. Exp Ther Med. 2020;19(3):2037–44.

  54. Mezger E, Wendler O, Mayr S, Bozzato A. Anaphylactic reaction following administration of nose drops containing benzalkonium chloride. Head Face Med. 2012;8:1–3.

    Article  Google Scholar 

  55. Weitz JI, Fredenburgh JC. Platelet polyphosphate: the long and the short of it. Blood. 2017;129(12):1574–5.

    Article  CAS  PubMed  Google Scholar 

  56. Schröder U. A 2-year follow-up of primary molars, pulpotomized with a gentle technique and capped with calcium hydroxide. Eur J Oral Sci. 1978;86:273.

    Article  Google Scholar 

  57. Mylonas S, Skoulakis C, Nikolaidis V, Hajiioannou J. Epistaxis treatment options: literature review Indian. J Otolaryngol Head Neck Surg. 2023;75:2235.

    Google Scholar 

Download references

Acknowledgements

The authors would like to thank Jake Bailey who was co-PI for partial funding on this work but was not directly involved in the study. The figures were created or assembled using “BioRender.com”. In memoriam, Prof. Isha Mutreja, whose insights and generosity were instrumental in this study.

Funding

This study was funded by NIH grant R01 DE027669 and R25 DE032529 training grant (MP funding PI K Mansky).

Author information

Authors and Affiliations

  1. Division of Basic Sciences, Department of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, 55455, USA

    Dhiraj Kumar

  2. North Carolina Agricultural and Technical State University, Greensboro, NC, 27411, USA

    Morgan Pride

  3. Division of Pediatric Dentistry, Department of Developmental & Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, 55455, USA

    Morgan Pride, Kaushik Mukherjee, Gaurav Jain & Robert S. Jones

  4. Division of Biomaterials, Department of Restorative Sciences, MDRCBB, University of Minnesota, Minneapolis, 55455, USA

    Isha Mutreja

Authors
  1. Dhiraj Kumar
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Morgan Pride
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Kaushik Mukherjee
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Gaurav Jain
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Isha Mutreja
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Robert S. Jones
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

All authors have read and agreed to the published version of the manuscript. All authors made substantial effort on this work: Conceptualization, RSJ, DK; methodology, RSJ, DK, IM; formal analysis, RSJ, DK, IM; investigation, KM, MP, GJ; data curation, DK, IM; writing—original draft preparation, RSJ, DK; writing—review and editing, RSJ, DK, IM; visualization, KM, MP, RSJ, DJ; supervision, RSJ, DK; project administration, RSJ, DK.

Corresponding authors

Correspondence to Dhiraj Kumar or Robert S. Jones.

Ethics declarations

Ethics approval and consent to participate

Institutional Review Board Statement: Note: “Clinical trial number: not applicable.” This study obtained pathological specimens of extracted teeth done during routine dental care without patient identifiers and was deemed by the University of Minnesota Institutional Review Board to be exempt from review based on USA Code of Federal Regulations 45CFR46104(4ii).

Consent for publication

The authors give consent for this manuscript publication.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, D., Pride, M., Mukherjee, K. et al. The use of oxymetazoline-based nasal solutions to remove bacteria-blood debris and eradicate Rothia dentocariosa: an artificial cavity model study. BMC Oral Health 25, 448 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12903-025-05791-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12903-025-05791-z

Keywords

BMC Oral Health

ISSN: 1472-6831

Contact us