Antimicrobial devices, appliances and products, and methods of use thereof

Abstract

Provided are devices, appliances and products such as oral hygiene coated with polydopamine (PDA), a PDA derivative, or a multilayer PDA coating. Devices such as an antimicrobial tooth brush is provided, comprising a handle and a brush head attached thereto. Also provided are methods for providing a protective barrier against oral pathogens on a tooth surface and / or a gum surface and / or fixed or removable appliance in the oral cavity of a subject and methods for preserving integrity of enamel of a tooth surface in the oral cavity of a subject. Also provided are methods for reducing the persistence of oral microorganisms on a toothbrush post-brushing of teeth in an oral cavity of a subject and reducing re-contamination risk of the oral cavity.

Description

UCLA 2025-031 P-638957-PCANTIMICROBIAL DEVICES, APPLIANCES AND PRODUCTS, AND METHODS OF USE THEREOFCROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to U.S. provisional patent application serial no. 63 / 730,765, filed December 11, 2024, and is incorporated herein by reference in its entirety.FIELD OF THE INVENTION

[0002] The invention relates to a coated toothbrush and other devices, appliances and products, using mussel-inspired biomimetic materials, e.g., polydopamine, designed to combat a wide range of pathogens while ensuring no damage or wear to the tooth structure. The invention also relates to methods for reducing the persistence of oral microorganisms on a toothbrush post-brushing of teeth in an oral cavity comprising brushing teeth with the coated toothbrush. The invention further relates to methods for reducing the risk of physical wear and tear of a toothbrush comprising: coating bristles of the toothbrash with at least one layer of polydopamine.BACKGROUND OF THE INVENTION

[0003] Ninety five percent of tooth loss in humans is from dental caries and periodontal disease. Various micro-organisms play significant roles in the development and persistence of these oral conditions. Microbial transmission within the mouth can lead to the infection of previously treated areas, such as those addressed through scaling and root planning. Dental plaque, a soft tissue build-up on teeth, is a major contributor to various oral diseases. Thus, maintaining oral hygiene is crucial for combating this issue, often achieved through methods, such as regular toothbrush use.

[0004] Furthermore, research findings have highlighted the potential transmission of cariogenic and periodontopathic bacteria through various dental tools including dental instruments, dental floss, and toothbrashes. The persistence of microorganisms on toothbrashes post-brushing poses a potential risk for re-contamination of the oral cavity. Several studies have demonstrated that prolonged use of toothbrushes can lead to contamination by a range of microorganisms such as Streptococcus mutans, Staphylococcus, lactobacilli, Pseudomonas, Provetella gingingivalis, Escherichia coli, and Candida albicans. Additionally, microorganisms can infiltrate toothbrushes from both intraoral and externalUCLA 2025-031 P-638957-PC sources, including contaminated hands, aerosols generated from activities like toilet flushing, and bacteria thriving in moist bathroom environments. Consequently, toothbrushes act as reservoirs for various microorganisms, including bacteria, fungi, and viruses, thereby facilitating their potential transmission.

[0005] In recent years, the issue of toothbrush disinfection has gained importance. Toothbrush disinfection should be recommended as a routine practice for the patients. The use of chlorhexidine (CHX), LISTERINE®, and several dentifrices have shown varying degrees of efficacy, none are widely used as a home-based application. A possible reason for the noncompliance with these methods is that they are time-consuming and may result in unwanted product residues.

[0006] Recently, a few studies indicated that the use of microwaves and ultraviolet (UV) light are the most effective household methods to sanitize toothbrushes after contamination. Furthermore, due to the ease of use, these techniques may increase compliance with toothbrush bacterial decontamination. However, the extent of bacterial decontamination using a microwave and UV light has not been determined in a clinical setting.

[0007] Controlling the microbial load in the oral cavity is crucial for managing both oral and systemic diseases. Maintaining proper oral hygiene, including daily use of clean and decontaminated toothbrushes, plays a key role in achieving this goal. However, there is a significant lack of awareness among the public regarding toothbrush maintenance practices. Therefore, it is essential to educate the public about proper toothbrush storage, replacement, and disinfection methods. Accordingly, there remains a need for improved dental care devices, such as toothbrushes, which provide antimicrobial protection without compromising the integrity of the tooth structure or the biocompatibility of the dental care device.SUMMARY OF THE INVENTION

[0008] In one aspect, a device, appliance or product such as an oral hygiene device, appliance or product, is provided comprising a surface that contacts the teeth, gums, tongue, oral mucosa and / or any other body part for providing hygiene, wherein said surface comprises a coating of polydopamine (PDA) or a PDA derivative. In an embodiment, the device, appliance or product comprises a surface comprising a multilayer coating comprising: (a) a primary PDA or PDAUCLA 2025-031 P-638957-PC derivative layer and a (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment, the device, appliance or product comprises a surface comprising a multilayer coating comprising: (a) a primary PDA or PDA derivative layer; (b) a bioactive reservoir layer immobilized on the primary PDA or PDA derivative layer, said bioactive reservoir layer comprising an antimicrobial agent; and (c) a second PDA or PDA derivative layer, wherein said second PDA or PDA derivative layer encapsulates the bioactive reservoir layer and the primary PDA or PDA derivative layer. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green- synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises Salvadora persica. In certain embodiments, the antimicrobial agent comprises a mixture of Syzygium aromaticum and myrrh. In some embodiments, the device or product is an oral hygiene device, appliance or product such as a toothbrush, toothpick, dental floss, electric toothbrush head, interdental brush, orthodontic toothbrush or tongue cleaner. In some embodiments, the fitting surface of a fixed or removable dental appliance, such as a retainer, aligner, or night guard, a denture base / fitting surface, a crown or a bridge, or an appliance storage case for an oral hygiene, appliance device or product, comprises a coating of polydopamine (PDA) or a derivative of PDA. In some embodiments, the surface comprises bristles, filaments or a scraper. In some embodiments, the surface comprises a coating of about 20 nanometers to about 1 mm PDA or PDA derivative. In some embodiments, the PDA or PDA derivative coating, the primary PDA or PDA derivative layer, and / or the second PDA or PDA derivative layer may independently further comprises an additional agent, such as an antimicrobial agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, antibiotic, or any combination thereof, or an extended release form thereof. In some embodiments, any one or more or the PDA or PDA derivative coating or layers (e.g., the coating, the primary or the second) may comprise a single or plurality of PDA or PDA derivative layers. In some embodiments, each PDA or PDA derivative coating has a thickness of between about 20 nanometers and about 100 nanometers. In some embodiments, 50% to 100% of the surface is coated. In some embodiments, the device, appliance or product is or comprises a toothbrush, toothbrush bristles, toothbrush heads, toothbrush handles, protective caps, tongue cleaners, interdental sticks, toothpicks, denture fitting surfaces, retainers, aligners, night guards, appliance storage cases, sutures such as oral sutures, endoscope tubing, endoscope housings, CPAP ventilation tubing, reusable or non-reusable shaver heads, surgical robotic parts notUCLA 2025-031 P-638957-PC autoclavable, toilet seat components, bidet components, coffee machine water contact parts, infant teething toys, high-touch consumer grips such as used in a gym or transit vehicles, or door handles. In one aspect, a method is provided for reducing the persistence of oral microorganisms in the oral cavity, preserving integrity of enamel on a tooth surface, providing a protective barrier against oral pathogens on an oral surface or dental appliance, or any combination thereof, comprising using the oral hygiene device, appliance or product.

[0009] In one aspect, an antimicrobial toothbrush is provided comprising a handle and a brush head attached thereto by a neck portion extending between the brush head and the handle, the brash head comprising a top surface and a bottom surface, the top surface comprising a bundle of polydopamine (PDA)- or PDA derivative-coated bristles embedded in or fused into the top surface of the brush head. In an embodiment, the antimicrobial toothbrush comprises a bundle of polydopamine (PDA)- or PDA derivative-coated bristles comprise a multilayer coating comprising: (a) a primary PDA layer and (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment, the antimicrobial toothbrush comprises a bundle of polydopamine (PDA)- or PDA derivative-coated bristles comprise a multilayer PDA coating comprising: (a) a primary PDA layer; (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and (c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA layer. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises S. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In some embodiments, the bristles comprise a coating of about 20 nanometers to about 1 mm PDA or PDA derivative. In some embodiments, the PDA- or PDA derivative-coated bristles comprise at least one PDA coating. In some embodiments, the PDA- or PDA derivative- coated bristles comprise two PDA or PDA derivative coatings. In some embodiments, each PDA or PDA derivative coating has a thickness of between about 20 nanometers and about 100 nanometers. In some embodiments, 50% to 100% of the bristles are coated. In some embodiments, the PDA or PDA derivative coating further comprise an additional agent, such as an antimicrobial agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, antibiotic, or any combination thereof, or an extended release formUCLA 2025-031 P-638957-PC thereof. Tn some embodiments, the PDA or PDA derivative is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises S. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green-synthesized silver nanoparticles (“AgNP”). In some embodiments, the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to about 90 degrees from the perpendicular, or any combination thereof. In some embodiments, the brush head is permanently attached to the toothbrush by the neck portion. In some embodiments, the brush head is removably attached to the toothbrush by a removable neck portion. In some embodiments, the toothbrush is a manual toothbrush. In some embodiments, the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate. In some embodiments, the head and the handle of toothbrush are coated with one or several layers of coating.

[0010] In one aspect, a method for providing a protective barrier against oral pathogens on a tooth surface and / or a gum surface in the oral cavity of a subject is provided, the method comprising: brushing the tooth surface and / or the gum surface at least once or twice per day with an antimicrobial tooth brush comprising a handle and a brush head attached thereto by a neck portion extending between the brush head and the handle, the brush head comprising a top surface and a bottom surface, the top surface comprising a bundle of at least polydopamine (PDA)- or PDA derivative-coated bristles embedded in or fused into the top surface of the brush head, wherein brushing the tooth surface and / or the gum surface with the antimicrobial toothbrush generates reactive oxygen species thereby inducing oxidative stress in the oral pathogens.

[0011] In some embodiments, the method further comprises: rinsing the oral cavity with water; and rinsing the oral cavity with an antimicrobial mouthwash. In some embodiments, the oral pathogens are bacteria, fungi and / or viruses. In some embodiments, the bacteria are cariogenic and / or periodontopathic bacteria. In some embodiments, the bristles comprise a coating of about 20 nanometers to about 1 mm PDA. In some embodiments, the PDA- or PDA derivative-coated bristles comprise a first layer of a PDA or PDA derivative coating and optionally a second layerUCLA 2025-031 P-638957-PC of PDA or PDA derivative coating. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer coating, said multilayer PDA coating comprising: (a) a primary PDA layer and (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising: (a) a primary PDA layer; (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and (c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA layer. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green- synthesized metal nanoparticles. In some embodiments, the antimicrobial agent comprises 5. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green- synthesized silver nanoparticles (“AgNP”). In some embodiments, each PDA or PDA derivative coating has a thickness of between about 20 nanometers and about 100 nanometers. In some embodiments, 50% to 100% of the bristles are coated. In some embodiments, the PDA or PDA derivative coating further comprises an additional agent such as an antimicrobial agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, antibiotic, or any combination thereof, or an extended release form thereof. In some embodiments, the PDA or PDA derivative is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises S. persica, a mixture of S. aromaticum and myrrh and / or green- synthesized silver nanoparticles (“AgNP”). In some embodiments, the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to about 90 degrees from the perpendicular, or a combination thereof. In some embodiments, the brush head is permanently attached to the toothbrush by the neck portion. In some embodiments, the brush head is removably attached to the toothbrush by a removable neck portion. In some embodiments, the toothbrush is a manual toothbrush. In some embodiments, the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate.

[0012] In one aspect, a method is provided for preserving integrity of enamel of a tooth surface in the oral cavity of a subject, the method comprising:UCLA 2025-031 P-638957-PC brushing the tooth surface at least twice per day with an antimicrobial tooth brush comprising a handle and a brush head attached thereto by a neck portion extending between the brush head and the handle, the brush head comprising a top surface and a bottom surface, the top surface comprising a bundle of at least polydopamine (PDA)- or PDA derivative-coated bristles embedded in or fused into the top surface of the brush head, wherein brushing the tooth surface with the antimicrobial toothbrush creates a smooth hydrophilic interface with the tooth structure, thereby preserving the integrity of the enamel of the tooth surface.

[0013] In some embodiments, the method further comprise: rinsing the oral cavity with water; and rinsing the oral cavity with an antimicrobial mouthwash. In some embodiments, the bristles comprise a coating of about 20 nanometers to about 1 mm PDA or PDA derivative. In some embodiments, the PDA- or PDA derivative-coated bristles comprise a first layer of a PDA or PDA derivative coating and optionally a second layer of PDA or PDA derivative coating. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer coating, said multilayer PDA coating comprising: (a) a primary PDA layer and (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising: (a) a primary PDA layer; (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and (c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA layer. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green- synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises S. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green-synthesized silver nanoparticles (“AgNP”). In some embodiments, each PDA or PDA derivative coating has a thickness of between 20 nanometers and 100 nanometers. In some embodiments, 50% to 100% of the bristles are PDA or PDA derivative coated. In some embodiments, the PDA or PDA derivative coating further comprises an additional agent such as an antimicrobial agent, silver, silver nanoparticles, curcumin, antibiotic, or any combination thereof, or an extended release form thereof. In some embodiments, the PDA or PDA derivative is functionalized with an antimicrobialUCLA 2025-031 P-638957-PC agent. Tn an embodiment, the antimicrobial agent comprises S. persica, a mixture of S. aromaticum and myrrh and / or green- synthesized silver nanoparticles (“AgNP”). In some embodiments, the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to 90 degrees from the perpendicular, or a combination thereof. In some embodiments, the brush head is permanently attached to the toothbrush by the neck portion. In some embodiments, the brush head is removably attached to the toothbrush by a removable neck. In some embodiments, the toothbrush is a manual toothbrush. In some embodiments, the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate.

[0014] In one aspect, a method is provided for reducing the persistence of oral microorganisms on a tooth brush post-brushing of teeth in an oral cavity of a subject and reducing re-contamination risk of the oral cavity, the method comprising: a. brushing the teeth with a toothbrush comprising bristles coated with at least one layer of polydopamine (PDA) or PDA derivative; and b. rinsing the toothbrush with water and / or an antimicrobial mouthwash.

[0015] In some embodiments, the method further comprises sanitizing the toothbrush by exposing the PDA- or PDA derivative-coated bristles to ultraviolet light. In some embodiments, the oral microorganisms are bacteria, fungi and / or viruses. In some embodiments, the bacteria are cariogenic and / or periodontopathic bacteria. In some embodiments, the bristles comprise a coating of about 20 nanometers to about 1 mm PDA or PDA derivative. In some embodiments, the PDA- or PDA derivative-coated bristles comprise a first layer of a PDA or PDA derivative coating and optionally a second layer of PDA or PDA derivative coating. In an embodiment, the PDA- or PDA derivative- coated bristles comprise a multilayer PDA coating, said multilayer coating comprising: (a) a primary PDA layer and (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising: (a) a primary PDA layer; (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent: and (c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA layer. In an embodiment, the antimicrobial agentUCLA 2025-031 P-638957-PC comprises a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises . persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green- synthesized silver nanoparticles (“AgNP”). In some embodiments, each PDA or PDA derivative coating has a thickness of between 20 nanometers and 100 nanometers. In some embodiments, 50% to 100% of the bristles are PDA or PDA derivative coated. In some embodiments, the PDA or PDA derivative coating further comprises an additional agent such as an antimicrobial agent, silver, silver nanoparticles, curcumin, antibiotic, or any combination thereof, or an extended release form thereof. In some embodiments, the PDA or PDA derivative is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises 5. persica, a mixture of S. aromaticum and myrrh and / or green- synthesized silver nanoparticles (“AgNP”). In some embodiments, the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to 90 degrees from the perpendicular, or a combination thereof. In some embodiments, the brush head is permanently attached to the toothbrush by the neck portion. In some embodiments, the brush head is removably attached to the toothbrush by a removable neck portion. In some embodiments, the toothbrush is a manual toothbrush. In some embodiments, the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate.

[0016] In one aspect, a method is provided for reducing the risk of physical wear and tear of a toothbrush, the method comprising:(a) coating bristles of the toothbrush with a first layer of polydopamine (PDA) or PDA derivative; and(b) optionally coating the PDA- or PDA derivative-coated bristles of step (a) with a second layer of PDA or PDA derivative.

[0017] In some embodiments, the bristles comprise a coating of about 20 nanometers to about 1 mm PDA or PDA derivative. In some embodiments, the PDA- or PDA derivative-coated bristles comprise a first layer of a PDA or PDA derivative coating and optionally a second layer of PDA or PDA derivative coating. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer coating, said multilayer coating comprising: (a) a primary PDA layer andUCLA 2025-031 P-638957-PC(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising: (a) a primary PDA layer; (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and (c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA layer. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises 5. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green- synthesized silver nanoparticles (“AgNP”). In some embodiments, each PD.A or PDA derivative coating has a thickness of between 20 nanometers and 100 nanometers. In some embodiments, 50% to 100% of the bristles are PDA or PDA derivative coated. In some embodiments, the PDA or PDA derivative coating further comprises an additional agent such as an antimicrobial agent, silver, silver nanoparticles, curcumin, antibiotic, or any combination thereof, or an extended release form thereof. In some embodiments, the PDA or PDA derivative is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises 5. persica, a mixture of S. aromaticum and myrrh and / or green- synthesized silver nanoparticles (“AgNP”). In some embodiments, the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to 90 degrees from the perpendicular, or a combination thereof. In some embodiments, the brush head is permanently attached to the toothbrush by the neck portion. In some embodiments, the brush head is removably attached to the toothbrush by a removable neck portion. In some embodiments, the toothbrush is a manual toothbrush. In some embodiments, the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate.

[0018] Other features and advantages of the present invention will become apparent from the following detailed description examples and figures. It should be understood, however, that the detailed description and the specific examples while indicating preferred embodiments of the invention are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.UCLA 2025-031 P-638957-PCBRIEF DESCRIPTION OF THE DRAWINGS

[0019] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present disclosure, the inventions of which can be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.

[0020] Figure 1 shows PDA coated toothbrushes exhibited significantly higher (p<0.05) antimicrobial properties against S. mutans, C. albicans and S. aureus. The antimicrobial results show total biofilm density at 595 nm and intergroup comparison against S. mutans, C. albicans and S. aureus. Groups that do not share a letter are significantly different. Antimicrobial activity (biofilm and CFU) was tested on each species using uncoated toothbrushes (left bar), freshly coated brushes (center bar) and PDA-coated toothbrushes after a 4-month simulation of tooth brushing (right bar), considering that the typical recommendation is to replace a toothbrush every 3 to 4 months.

[0021] Figure 2 shows mean CFU against S. mutans.

[0022] Figure 3 shows mean values of inhibition zones (mm) showing intergroup comparison against P. gingivalis.

[0023] Figure 4 shows the mean viability of cells after exposure to coated and uncoated samples over 1 and 3 days.

[0024] Figure 5 shows the release of polydopamine from coated samples. No significant release was observed after different time intervals up to two months in water. Absorbance from 200-700 nm was measured.

[0025] Figure 6 shows enamel loss after 32,000 cycles of brushing with coated samples using overlapping of the 3D models and calculation of the enamel loss. Volumetric enamel wear loss after 32,000 cycles of brushing reported less than 0.01 mm3.

[0026] Figures 7A and 7B show the wear of an embodiment of the toothbrush of the present invention after 32,000 cycles of brushing against natural enamel. No significant wear of brush bristles was found after 32,000 cycles of brushing against natural enamel. Fig. 7A shows aUCLA 2025-031 P-638957-PC toothbrush of the present invention before 32,000 cycles of brushing against natural enamel. Fig. 7B shows a toothbrush of the present invention after 32,000 cycles of brushing against natural enamel.

[0027] Figure 8 shows the static contact angle measurements that quantified anti-adhesion behavior of (A) Control, (B) PDA, (C) PDA / Mix of plant extracts (“Mix”) and PDA / metal ions nanoparticles (“PDA / NPs”). Lower angles indicated a reduced likelihood of microbial adhesion.

[0028] Figure 9 shows the results of antifungal biofilm testing with C. albicans of (A) Control, (B) PDA 5 mg, (C) PDA / 5mg + plant extract (“SP”). Biofilm reduction was calculated relative to uncoated controls.

[0029] Figure 10 shows the results of antibacterial testing with S. aureus RN4220 of PDA / NPs / PD (triple layer of two PDA layers with metal ions nanoparticles therebetween), PDA (one layer), PD / PE / PD (triple coating of polydopamine (“PD”), plant extract (“PE”) and polydopamine) compared to a control. After incubation, adherent bacteria were quantified via colony-forming units (CFU / mL).

[0030] Figure 11 shows the results of antibacterial testing with Aggregatibacter actinomycetemcomitans ATCC 33383 of PDA / NPs / PD (triple layer of two PDA layers with metal ions nanoparticles therebetween), PDA (one layer), PD / PE / PD (triple coating of polydopamine (“PD”), plant extract (“PE”) and polydopamine) compared to a control. After incubation, adherent bacteria were quantified via colony-forming units (CFU / mL).

[0031] Figure 12 shows that cell viability remained >80% on all coated samples and demonstrates that the surfaces were safe and non-cytotoxic for prolonged oral exposure. MG-63 cells were cultured on coated substrates (PDA, PD / PE / PD and PD / NPS / PD) and uncoated substrates (Control). Metabolic viability was assessed using a colorimetric assay and normalized to control surfaces.DETAILED DESCRIPTION OF THE INVENTION

[0032] The present subject matter may be understood more readily by reference to the following detailed description which forms a part of this disclosure. It is to be understood that this inventionUCLA 2025-031 P-638957-PC is not limited to the specific products, methods, conditions, or parameters described and / or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed invention.

[0033] Polydopamine (PDA), a polymer formed through the oxidative self-polymerization of dopamine, has attracted attention for its unique properties, particularly its adhesion, remineralization, and antimicrobial activity. This versatile polymer adheres to a wide range of surfaces, forming a protective barrier with many properties. PDA's antimicrobial effect is driven by multiple mechanisms, including the generation of reactive oxygen species (ROS), which induces oxidative stress in microbial cells, and its pH-responsive behavior, which can enhance its antimicrobial activity in acidic environments. Additionally, PDA can be functionalized with antimicrobial agents, such as silver nanoparticles or antibiotics, providing a controlled release of these agents to further combat pathogens. In an embodiment, the antimicrobial agent comprises S. persica, a mixture of 5. aromaticum and myrrh and / or green- synthesized silver nanoparticles (“AgNP”). These characteristics make PDA an excellent candidate for coating medical devices, and dental equipment. The polymer’s unique combination of strong adhesion, biocompatibility, and antimicrobial properties opens the door to innovative applications in drug delivery systems and other medical technologies.

[0034] In light of these properties of PDA, the present invention provides various devices, appliances and products for oral hygiene or oral use, with such a PDA coating that provides such antimicrobial and other properties. In one non-limiting example, a toothbrush with poly dopamine- coated bristles aims to provide an antimicrobial toothbrush that effectively combats bacterial growth, thereby promoting better oral hygiene. Additionally, the herein provided PDA- coated toothbrush is designed to preserve enamel and dentin integrity by preventing tooth wear and reduce the overall wear and tear of the toothbrush itself. By incorporating PDA, the toothbrush aims to enhance oral health while ensuring durability and gentleness on the teeth. The invention also focuses on ensuring good biocompatibility with cells and maintaining a stable coating even after two months of use, as demonstrated through release tests. The innovative coatings are both biocompatible and highly effective, as demonstrated through cell viability testing, ensuring they are safe for use in the human body.UCLA 2025-031 P-638957-PC

[0035] Such uses may be achieved by the use of polydopamine (PDA) or by a derivative thereof, referred to herein as a polydopamine derivative or PDA derivative. Any iteration herein of polydopamine (PDA) alone is intended to refer to PDA or a derivative thereof.

[0036] Polydopamine (PDA) is a unique biomimetic polymer derived from the oxidative polymerization of dopamine, a compound that contains both catechol and amine functional groups, making it chemically versatile. The process begins with dopamine monomers (often used as dopamine hydrochloride), which oxidize under alkaline conditions (pH > 7.5) to form dopaminequinone. This undergoes intramolecular cyclization via a 1,4-Michael addition, producing leucodopaminechrome. Subsequent oxidation and rearrangement steps yield intermediate compounds such as 5,6-dihydroxyindole and 5,6-indolequinone. These intermediates can form dimers and higher oligomers through branching reactions at various positions on the aromatic rings (e.g., 2, 3, 4, and 7), eventually cross-linking into a polymeric structure. Various derivatives of PDA are also known, any of which may be used for in the products and for the uses disclosed herein. See, for example, Liu Y, Ai K, Lu L. Polydopamine and its derivative materials: synthesis and promising applications in energy, environmental, and biomedical fields. Chem Rev. 2014; 114(9):5057-l 15; Yu F, Chen S, Chen Y, Li H, Yang L, Chen Y, Yin Y. Experimental and theoretical analysis of polymerization reaction process on the polydopamine membranes and its coiTosion protection properties for 304 Stainless Steel. Journal of Molecular Structure. 2010; 982: 152-161 ; and Li Na, Qiuying Zhang, Lu Han, Juntong Huang, Xudong Luo and Xibao Li. Recent advances in polydopamine and its derivatives assisted electrocatalysis and photocatalysis. International Journal of Hydrogen Energy. 2023;48 :7004-7018. In one embodiment, a "polydopamine derivative" comprises a bioinspired poly(catecholamine) polymer (e.g., a melanin like polymeric coating) having catechol and / or quinone functionalities and capable of forming an adherent surface layer on a substrate. In some embodiments, the polydopamine derivative is a polymer comprising monomer units selected from 3,4-dihydroxy-L-phenylalanine, norepinephrine, 2-bromo-N-[2-(3,4-dihydroxyphenyl)ethyl]-2-methylpropanamide, 6- nitrodopamine, or any combination thereof. Such polymers may be formed via oxidative polymerization and / or deposition, and may provide surface properties that are substantially similar to polydopamine, including strong substrate adhesion and reactive catechol / quinone chemistry suitable for further functionalization, as illustrated in the Examples. In further embodiments, the poly(catecholamine) coating is optionally (i) morphology modified (e.g., increased roughness), (ii)UCLA 2025-031 P-638957-PC co-deposited with one or more additional polymers (e.g., polyamines), and / or (iii) post modified to introduce functional groups or coupled agents (e.g., PEG / polyether chains, sulfonated groups, quaternary ammonium antimicrobial moieties, antimicrobial peptides, or multilayer composites), while maintaining PDA like biointerface performance.

[0037] PDA can also be synthesized via enzymatic oxidation, using enzymes such as laccase or tyrosinase to catalyze dopamine oxidation, or through electropolymerization, which deposits PDA films directly onto conductive substrates. The presence of various functional groups, including catechol, quinone, and amine, enables PDA to chelate metal ions, react with nucleophiles, and participate in secondary functionalization. These properties allow for the formation of PDA derivatives with enhanced chemical functionality, suitable for applications in drug delivery, biosensing, catalysis, and advanced coating technologies (see Liu et al. 2014, op. cit; Yu et al, 2010, op. cit.; Li et al., 2023, op. cit.).

[0038] Thus, as described herein, an oral hygiene device or product may be coated with polydopamine (PDA), a polydopamine derivative (PDA derivative), or a mixture thereof. In embodiments in which two or more coatings are provided on a surface, any coating may be, independently, PDA, a PDA derivative, or a mixture thereof. In some embodiments, a PDA derivative is a mixture of PDA derivatives. In some embodiments, each coating of PDA derivative may comprise a different mixture of PDA derivatives. Thus, any one or more coatings may independently be PDA, a PDA derivative, a mixture of PDA and a PDA derivative, or a mixture of PDA derivatives. As used herein throughout, any recitation of PDA alone is intended to refer to polydopamine and / or a polydopamine derivative and / or a mixture of polydopamine and a polydopamine derivative and / or a mixture of polydopamine derivatives. And as embodied herein, the PDA or PDA derivative coating may be a single coating, or may be the first coating wherein an antimicrobial agent is provided in a second coating (e.g., a two layer coating), and in further embodiments, such first PDA or PDA derivative coating and an antimicrobial coating thereon may be further coated with a PDA or PDA derivative coating (e.g., a three later coating). Moreover, as noted herein, each coating may comprise multiple layers of the same coating. And each PDA or derivative coating may independently further comprise an additional agent such as an antimicrobial agent. As referred to herein, a PDA or PDA derivative coated toothbrush or any otherUCLA 2025-031 P-638957-PC appliance as described herein is intended to mean comprising any one of the coating formats herein described, e.g., a single, two or three layered format.

[0039] While a PDA or PDA derivative coated toothbrush is described herein in further detail, such properties, methods of making, methods of using, methods for recharging, and additional agents present with a PDA coating are equally applicable to any and all oral hygiene products, dental appliances and devices embraced herein including but not limited to a toothpick, dental floss, electric toothbrush head, interdental brush, orthodontic toothbrush, tongue cleaner, fitting surface of a fixed or removable dental appliance such as a denture base, crown or bridge. Guidance from the present disclosure will make it readily apparent how the PDA or PDA derivative coating can be applied to and used in any and all such products, appliances and devices to achieve the desirable properties disclosed herein. Non-limiting examples of other products, appliances and devices that may comprise any of the coatings described herein include CPAP / ventilation tubing, endoscope tubing I housing, a reusable or non-reusable shaver head or grooming tool surface, a surgical robotic component which is not autoclave safe, a toilet / bidet surface, a coffee machine water contact part, a high-touch consumer grip (such as a gym grip or a transit vehicle grip), an infant teething toy, or a door handle. Features described herein imparted by the PDA or derivative coating or coatings, in any format embodied herein, apply to all products, appliances or devices exemplified herein. Moreover, such coatings are particularly useful for products, appliances and devices that cannot be heat sterilized or autoclaved. Moreover, such devices, appliances and products may contact or be used in contact with any external or internal body part in addition to those in the oral cavity, such as but not limited to the skin, face, fingers, hands or feet. Such devices, appliances or products provide a hygienic surface with reduced microbial growth, contamination, and other benefits, and in particular for devices, appliances and products that cannot be heat sterilized or autoclaved. Such devices, appliances and products are useful where contact with microorganisms is prevalent, such as areas in or the body, and in high traffic areas where such devices, appliances or products are exposed to multiple individuals.

[0040] The toothbrush coating of the present invention is designed to resist microbial growth, providing a protective barrier against common oral bacteria and other pathogens that can lead to infections. Moreover, the coating ensures a smooth hydrophilic interface with the tooth structure, reducing the risk of physical wear and tear. The stability of the coatings has been proven throughUCLA 2025-031 P-638957-PC extended-release tests, showing that the protective properties remain intact for at least two months. This novel PDA or PDA derivative coating system provides a significant advancement in oral care, offering enhanced antimicrobial protection without compromising the integrity of the tooth structure or the biocompatibility of the dental care device.

[0041] The terms PDA-coated toothbrush and PDA-coated bristles referring to a toothbrush are used interchangeably herein, referring to the PDA coating on the bristles of a toothbrush, which as is generally known comprises a handle to hold the brush for facile contact with the teeth. As noted herein, the PDA coating may be applied to or is present on bristles and the toothbrush head. The PDA coating may be applied to or is present on the entire toothbrush. The terms toothbrush and tooth brush are also used interchangeably and have the same meaning. Various syntactic and other variants of such terminaology is not meant to be limiting and embraces the concept disclosed herein. Moreover, any PDA-coated bristles for application to teeth but not in a traditional “toothbrush” configuration is also fully embraced herein. The term PDA is intended to embrace PDA and PDA derivatives.

[0042] The teachings herein may be applied to any device or product used for oral hygiene, typically for home use but may be used by oral healthcare professionals. Non-limiting examples of such products include tooth brushes, toothpicks, dental floss, electric toothbrush heads, interdental brushes, orthodontic tooth brushes, tongue cleaners, single-use, travel or disposable toothbrushes and tooth cleaners, and the like.

[0043] Preparing a polydopamine (PDA) coated surface such as a bristle or on dental appliance can employ any of a wide range of variable conditions that can be tailored to achieve desired properties. By way of non-limiting example, a PDA coating is prepared under wide range of alkaline pH conditions (e.g., about 7.5-9.5) using buffers such as but not limited to Tris. PBS, carbonate or others, though neutral or acidic pH can be employed for slower polymerization. Temperatures ranging from about 4°C to about 60°C may be used, with higher temperatures accelerating polymerization and lower ones offering more controlled deposition. Dopamine precursor concentrations between about 0.5-10 mM are common, but also higher concentrations may be used as they yield thicker coatings and lower concentrations producing more uniform layers. Reaction times span from minutes for thin coatings to 24 hours for thicker deposits. Aqueous solvents are standard, though organic solvents, mixed solvent systems and ionic liquidsUCLA 2025-031 P-638957-PC can be used to modify deposition properties. Additives such as metal ions or nanoparticles may be incorporated to enhance functionality, and substrates including metals, ceramics, polymers, natural substances, antiseptic, biological surfaces and others, affect deposition behavior. Different oxygen availability may be provided, as it influences polymerization, with reduced oxygen or inert atmospheres altering the PDA structure. Static or agitated conditions (from 0 to about 500 rpm) can further control coating uniformity, and dopamine derivatives can be substituted to produce PDA-like materials with unique characteristics. As noted herein, any of the PDA or derivative coatings may be built up from multiple individual layers of the same or similar solution.

[0044] Preparation of a surface PDA coating on any device, appliance, bristle, filament or other surface may be performed manually, such as at the time of a dental professional visit or on a particular appliance prepared for a patient, or the surface may be applied in an automated process, such as for the mass production of oral hygiene products e.g., toothbrushes, tongue cleaners, etc. By way of example, nylon cord or filament used for manufacturing toothbrush bristles may be coated with PDA by passing the cord through one of multiple baths of PDA solution for preparing the coating; after coating and drying, the cord rewound and then used for toothbrush manufacture. As noted herein, the variables of PDA precursor concentration, solvent, temperature, speed of application, time of polymerization, and number of coatings will be governed by the desired properties of the finished product. Guidance provided herein on the variables to achieve the desired PDA coating, as well as the number of layers applied, will be readily determinable by the teachings herein, and are fully embraced herein.

[0045] The PDA coating on any surface as described herein may further comprise one or more additional agents, such as an antimicrobial agent. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises S. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green- synthesized silver nanoparticles (“AgNP”). In some embodiments, the additional agent is a metal ion. In some embodiments, the additional agent is non-metal ions. In some embodiments, the additional agent is silver. In some embodiments, the additional agent is zinc oxide. In some embodiments, the additional agent is a mineral. In some embodiments, the additional agent is an antiseptic. In some embodiments, the additional agent isUCLA 2025-031 P-638957-PC nanoparticles. In some embodiments, the additional agent is chlorhexidine. In some embodiments, the additional agent is curcumin. In some embodiments, the additional agent is neem. In some embodiments the additional agent is a plant extract such as phenols or polyphenols. In some embodiments, the additional agent is an essential oil. In some embodiments, the additional agent is a probiotic. In some embodiments, the additional agent is a natural or synthetic antifungal agent such as chitosan, nystatin or amphotericin B. In some embodiments, the additional agent is an antifouling agent such as a zwitterionic polymer. In some embodiments, the additional agent is a flavoring agent. In some embodiments, the additional agent is a green synthesized nanoparticle. In some embodiments, the additional agent is an antibiotic. In some embodiments, the additional agent is a sugar alcohol or sugar alcohol derivative such as xylitol and erythritol. In some embodiments, the additional agent is a remineralizing agent such as fluoride, bioglass or calcium phosphate. In certain embodiments of the antimicrobial toothbrush, the PDA is functionalized with an antimicrobial agent. In certain embodiments herein, the PDA can be refreshed after coating, or recharged to add more of the additional agent. In an embodiment, the antimicrobial agent comprises S. persica, a mixture of S. aromaticum and myrrh and / or green- synthesized silver nanoparticles (“AgNP”). In some embodiments, the antimicrobial agent (e.g., antibiotic, antifungal, antiseptic, etc.) comprises an extended release antimicrobial agent. In some embodiments, the antimicrobial agent comprises silver nanoparticles or an antibiotic In some embodiments, the additional agent may be incorporated during the PDA coating process, or in other embodiments, it may be loaded onto the surface of the PDA coating after the PDA coating is applied. Any of the forgoing embodiments of additional agents with the PDA may be applied to any surface as embraced herein, such as but not limited to a toothbrush, toothpick, dental floss, electric toothbrush head, interdental brush, orthodontic toothbrush, tongue cleaner, fitting surface of a fixed or removable dental appliance such as a denture base, crown or bridge.

[0046] In one aspect, the present invention provides an antimicrobial tooth brush comprising a handle and a brush head attached thereto by a neck portion extending between the brush head and the handle, the brush head comprising a top surface and a bottom surface, the top surface comprising a bundle of polydopamine (PDA) coated-bristles embedded in or fused into the top surface of the brush head. In some embodiments, the bristles comprise at least one PDA coating. In some embodiments, the bristles comprise two PDA coatings. In some embodiments, the bristles comprise three or more PDA coatings.UCLA 2025-031 P-638957-PC

[0047] In one embodiment of the antimicrobial toothbrush, the PDA coated-bristles comprise a first layer of a PDA coating. In one embodiment of the antimicrobial toothbrush, the PDA coated- bristles comprise a first layer of a PDA coating and a second layer of a PDA coating. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer coating, said multilayer coating comprising: (a) a primary PDA layer and (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising: (a) a primary PDA layer; (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and (c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA layer. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green- synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises S. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green-synthesized silver nanoparticles (“AgNP”). In some embodiments, each coating of PDA may be from about 20 nm to 100 nm thick. In some embodiments, the PDA coating has a total thickness of not more than about 1 mm. However, the specific PDA coating thickness is not so limiting. For example, depending on the method of manufacture of the toothbrush, concentration of PDA in the coating solution, time, temperature, pH, etc, and whether the bristle material is precoated with PDA before fabrication of bristles, or the finished toothbrush is coated, variation in the PDA thickness and method of application may be varied, but are entirely within the teaching of the disclosure. In various embodiments of the antimicrobial toothbrush, 50% to 100% of the bristles are PDA coated. The disclosure is not limited by the coating thickness or coverage of the bristles or components of other oral hygiene products, and such variables will be selected for ease and reproducibility of manufacture to achieve the desired effectiveness of the manufactured product. As noted herein, any one or more coatings may independently be PDA, a PDA derivative, a mixture of PDA and a PDA derivative, or a mixture of PDA derivatives.

[0048] Similarly with other oral care products provided with a PDA coating on the entire product or the portion that contacts any part of the oral cavity, the thickness of the PDA coating and methodUCLA 2025-031 P-638957-PC for application (e.g., single application or coating, two or more applications or coatings, etc.) may be selected for ease of manufacture, and the thickness of the total PDA coating is not limited.

[0049] As noted herein, a PDA coating may be provided on the fitting surface of a fixed or removable dental appliance such as a denture base, crown or bridge. Such coating may be applied following the guidance provided herein, and may be applied during the making of the appliance, such as at a custom dental laboratory or in a dentist’s office, and / or may be applied by the dental professional while fitting the appliance into the patient’s mouth, and / or training the patient on how to fit e.g. a removable appliance. As noted herein, the PDA coating may also be applied by the patient at home, e.g., to replenish a coating on a temporary appliance or oral hygiene product after a period of time or indication (e.g., visual indicator) that the coating should be restored. The disclosure embraces kits for professional and for home use comprising the PDA precursors, buffers, other materials and instructions on preparing the surface if necessary before applying or reapplying the PDA coating. Instructions may also comprise methods for determining the remaining useful life of a coating before it should be restored, and also methods for determining or assuring that the coating has been properly applied. As noted elsewhere herein, provided are methods for restoring any additional agent provided with or on the PDA coating; such restoring of the PDA or the additional agent may be done at the same or independent times, on a schedule or on an indication (e.g., visual indicator) that the PDA and / or the additional agent should be recharged or restored. In some embodiments, the additional agent is a prescription or off-the-shelf antiseptic mouth rinse or solution (e.g., chlorhexidine) that the user can soak the PDA-coated toothbrush or other device, following instructions provided.

[0050] Thus, the description of PDA coatings and additional agents, and methods for applying them to any oral hygiene product, are applicable to any and all dental care devices, appliances and products embraced herein. As noted herein, the additional agents may be independently provided in any one or more of the PDA coatings disclosed herein, such as present in a single PDA or PDA derivative coating, and / or present in a coating over the PDA or PDA derivative coating, and / or present in a second PDA or PDA derivative coating over the prior coating. Any such formats are embodied herein.UCLA 2025-031 P-638957-PCIn certain embodiments, the PDA coated bristles comprise at least one additional agent, such as an antimicrobial agent. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises S. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In one embodiment, the antimicrobial agent comprises green-synthesized silver nanoparticles (“AgNP”). In some embodiments, the additional agent is silver. In some embodiments, the additional agent is curcumin. In some embodiments, the additional agent is chlorhexidine. In some embodiments the additional agent is a plant extract such as phenols or polyphenols. In some embodiments, the additional agent is a green synthesized nanoparticle. In some embodiments, the additional agent is an antibiotic. In certain embodiments of the antimicrobial toothbrush, the PDA is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises S. persica, a mixture of S. aromaticum and myrrh and / or green- synthesized silver nanoparticles (“AgNP”). In an embodiment of the antimicrobial toothbrush, the antimicrobial agent comprises an extended release antimicrobial agent. In some embodiments, the antimicrobial agent comprises silver nanoparticles or an antibiotic In some embodiments, the additional agent may be incorporated during the PDA coating process, or in other embodiments, it may be loaded onto the surface of the PDA coating after the PDA coating is applied.

[0051] An additional agent provided with the PDA coating may include a visual indicator that the user can check to determine whether the PDA coating is maintained or needs to be recharged (or the device discarded and replaced). Such indicator may also be provided for any additional agent with the PDA. Such indicator(s) may be a dye or other visible materials that can be observed by the user (e.g., the intensity or density of a color), and may be present in or on the entire PDA coating or at a specific location, e.g., an opaque overcoat over a pre-printed symbol which when becomes visible, indicates the PDA coating has worn.

[0052] In some embodiments, the additional agent may be provided on the PDA coated toothbrush (or other oral hygiene device, appliance or product) and / or may be provided to be added to the toothbrush as a first coating and / or as a recoating process, such that the toothbrush user can maintain the effectiveness of the additional agent on the toothbrush by recharging the additional agent coating. In some embodiments, a recharging station is provided such that the user canUCLA 2025-031 P-638957-PC recharge the toothbrush with the additional agent e.g., soaking overnight or between toothbrush uses. In some embodiments, a dye or other visible component indicates when the user should recharge the toothbrush with the additional agent.

[0053] In various embodiments of the antimicrobial toothbrush, the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle, or a combination thereof. In one embodiment of the antimicrobial toothbrush, the brush head is permanently attached to the toothbrush by the neck portion. In an embodiment, the brush head is removably attached to the toothbrush by a removable neck portion. In some embodiments, the toothbrush is a manual toothbrush. In certain embodiments the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate. In some embodiments, the brush head is detachable.

[0054] In some embodiments, the bristles are coated with the one or more PDA coatings, and optionally other agents, before assembly of the toothbrush. In some embodiments, the bristles are coated with the one or more PDA coatings before assembly of the toothbrush, then coated thereafter with the additional agent. In some embodiments, one or more PDA coatings are provided on the bristles before toothbrush assembly, then at least one further PDA coating is applied after assembly. In an embodiment, bristles are coated with a multilayer coating, said multilayer coating comprising: (a) a primary PDA layer and (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment, bristles are coated with a multilayer PDA coating, said multilayer PDA coating comprising: (a) a primary PDA layer; (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and (c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA layer. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises 5. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green- synthesized silver nanoparticles (“AgNP”). Additional one or more additional agents may be applied before or after toothbrush assembly, or both, for at least one or more additional agents.UCLA 2025-031 P-638957-PC

[0055] In another aspect, the present invention provides a method for providing a protective barrier against oral pathogens on a tooth surface and / or a gum surface in the oral cavity of a subject, the method comprising: brushing the tooth surface and / or the gum surface at least once per day or at least twice per day with an antimicrobial tooth brush comprising a handle and a brush head attached thereto by a neck portion extending between the brash head and the handle, the brash head comprising a top surface and a bottom surface, the top surface comprising a bundle of polydopamine (PDA) coated-bristles embedded in or fused into the top surface of the brash head, wherein brushing the tooth surface and / or the gum surface with the antimicrobial toothbrash generates reactive oxygen species thereby inducing oxidative stress in the oral pathogens. In some embodiments, the bristles comprise at least one PDA coating. In some embodiments, the bristles comprise two PDA coatings. In some embodiments, the bristles comprise three or more PDA coatings. In an embodiment, the bristles comprise a multilayer coating, said multilayer coating comprising: (a) a primary PDA layer and (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment, the bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising: (a) a primary PDA layer; (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and (c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA layer,. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises . persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green- synthesized silver nanoparticles (“AgNP”). In an embodiment of the herein provided method, the method further comprises: (a) rinsing the oral cavity with water; and (b) rinsing the oral cavity with an antimicrobial mouthwash. In some embodiments of said method, the oral pathogens are bacteria, fungi and / or viruses. In an embodiment, the bacteria are cariogenic and / or periodontopathic bacteria. In various embodiments, the cariogenic and / or periodontopathic bacteria is a Streptococcus bacteria, a Staphylococcus bacteria, a Porphyromonas bacteria, a Pseudomonas bacteria, a Prevotella bacteria, an Escherichia species, a Lactobacillus species and / or a combination thereof. In a particular embodiment, the cariogenic and / or periodontopathic bacteria is Streptococcus mutans, Staphylococcus aureus, Porphyromonas gingivalisUCLA 2025-031 P-638957-PC or Escherichia coli. Tn some embodiments, the oral pathogen is a fungus such as Candida albicans. Tn certain embodiments, the cariogenic and / or periodontopathic bacteria is Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus rhamnosus, Lactobacillus casei / paracasei, Pseudomonas aeruginosa, Prevotella intermedia. In some embodiments, the oral pathogen is a virus such as herpes simplex virus. In some embodiments of said methods, the PDA coated-bristles comprise a first layer of a PDA coating and a second layer of PDA coating. In various embodiments of said methods, the PDA coating has a thickness of between 100 nanometers and 1 mm. In some embodiments of said methods, 50% to 100% of the bristles are PDA coated.

[0056] In certain embodiments, the PDA coated bristles comprise at least one additional agent, such as an antimicrobial agent. In an embodiment, the antimicrobial agent comprises a plant- derived antimicrobial extract(s) and / or green- synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises S. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green-synthesized silver nanoparticles (“AgNP”). In some embodiments, the additional agent is silver. In some embodiments, the additional agent is curcumin. In some embodiments, the additional agent is an antibiotic, antiseptic, fluoride, natural plant extracts, polyphenols, or green synthesised nanoparticles. In certain embodiments of the antimicrobial toothbrush, the PDA is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises S. persica, a mixture of S. aromaticum. and myrrh and / or green-synthesized silver nanoparticles (“AgNP”). In an embodiment of the antimicrobial toothbrush, the antimicrobial agent comprises an extended release antimicrobial agent. In some embodiments, the antimicrobial agent comprises silver nanoparticles or an antibiotic. As noted herein, the additional agent may be provided on or within the PDA coating, and may be recharged onto the PDA coating by the user. In an embodiment of the herein provided methods, the PDA is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises S. persica, a mixture of S. aromaticum and myrrh and / or green- synthesized silver nanoparticles (“AgNP”). In some embodiments, the antimicrobial agent comprises an extended release antimicrobial agent. In certain embodiments, the antimicrobial agent comprises silver nanoparticles or an antibiotic. In some embodiments, the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to about 90 degrees from the perpendicular, such as at an angle of from 0 degrees to about 50 degrees fromUCLA 2025-031 P-638957-PC the perpendicular, or any combination thereof. In an embodiment of said methods, the brash head is permanently attached to the toothbrush by the neck portion. In some embodiments, the brash head is removably attached to the toothbrush by a removable neck portion. In an embodiment, the toothbrush is a manual toothbrush. In various embodiments of said methods, the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate.

[0057] In one aspect, the present invention provides a method for preserving integrity of enamel of a tooth surface in the oral cavity of a subject, the method comprising: brushing the tooth surface at least twice per day with an antimicrobial tooth brush comprising a handle and a brash head attached thereto by a neck portion extending between the brash head and the handle, the brash head comprising a top surface and a bottom surface, the top surface comprising a bundle of polydopamine (PDA) coated-bristles embedded in or fused into the top surface of the brush head, wherein brushing the tooth surface with the antimicrobial toothbrush creates a smooth hydrophilic interface with the tooth structure, thereby preserving the integrity of the enamel of the tooth surface. In an embodiment of said method, the method further comprises: (a) rinsing the oral cavity with water; and (b) rinsing the oral cavity with an antimicrobial mouthwash. In some embodiments of said methods, the PDA coated-bristles comprise a first layer of a PDA coating and a second layer of a PDA coating. In an embodiment of said method, the PDA coated-bristles comprise a multilayer coating, said multilayer coating comprising: (a) a primary PDA layer and (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment of said method, the PDA coated-bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising: (a) a primary PDA layer; (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and (c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA layer. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises S. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green-synthesized silver nanoparticles (“AgNP”). In an embodiment of said methods, the PDA coating has a thickness of between 20 nanometers and 1 mm. In some embodiments of said methods, 20-50% to 100% of the bristles are PDA coated. In one embodiment, at least 50%, preferably at least 60%,UCLA 2025-031 P-638957-PC more preferably at least 70%, even more preferably at least 80%, and still more preferably at least 90% or up to 100% of the bristles, or of the surface of the device, are coated with PDA, wherein it is also contemplated that less than 50% of the bristles or of the surface of the device are PDA-coated, provided that the beneficial effect associated with fully coated bristles or a fully coated device as demonstrated in the Examples is substantially maintained or at least in part. In certain embodiments, the PDA coated bristles comprise at least one additional agent, such as an antimicrobial agent. In some embodiments, the additional agent is silver. In some embodiments, the additional agent is curcumin. In some embodiments, the additional agent is an antibiotic. In certain embodiments of the antimicrobial toothbrush, the PDA is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises S. persica, a mixture of S. aromaticum and myrrh and / or green-synthesized silver nanoparticles (“AgNP”). In an embodiment of the antimicrobial toothbrush, the antimicrobial agent comprises an extended release antimicrobial agent. In some embodiments, the antimicrobial agent comprises silver nanoparticles or an antibiotic. In an embodiment of said methods, the PDA is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises S. persica, a mixture of S. aromaticum and myrrh and / or green-synthesized silver nanoparticles (“AgNP”). In some embodiments of said methods, the antimicrobial agent comprises an extended release antimicrobial agent. In some embodiments, the antimicrobial agent comprises silver nanoparticles or an antibiotic. In an embodiment, the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to about 90 degrees from the perpendicular, such as at an angle of from 0 degrees to about 50 degrees from the perpendicular, or any combination thereof. In some embodiments, the brush head is permanently attached to the toothbrush by the neck portion. In an embodiment of said methods, the brush head is removably attached to the toothbrush by a removable neck portion. In some embodiments, the toothbrush is a manual toothbrush. In some embodiments of said methods, the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate.

[0058] In another aspect, the present invention provides a method for reducing the persistence of oral microorganisms on a tooth brush post-brushing of teeth in an oral cavity of a subject and reducing re-contamination risk of the oral cavity, the method comprising: brushing the teeth with a toothbrush comprising bristles coated with at least one layer of polydopamine (PDA); and rinsing theUCLA 2025-031 P-638957-PC toothbrush with water and / or an antimicrobial mouthwash. In an embodiment of said methods, the method further comprises sanitizing the toothbrush by exposing the PDA-coated bristles to ultraviolet light. In some embodiments of said methods, the method further comprises storing the toothbrush in a PDA-coated case. In some embodiments, the PDA-coated toothbrush or other oral hygiene product can be stored in a case containing an antimicrobial or other agent to recharge onto the PDA. In an embodiment of said methods, the PDA coated-bristles are further coated with a layer of PDA. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer coating, said multilayer coating comprising: (a) a primary PDA layer and (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment, the PDA - or PDA derivative -coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising: (a) a primary PDA layer; (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and (c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA layer. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises S. persica. In certain embodiments, the antimicrobial agent comprises a mixture of .S'. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green-synthesized silver nanoparticles (“AgNP”). In some embodiments, the PDA coating has a thickness of between 100 nanometers and 1 mm. In certain embodiments 50% to 100% of the bristles are PDA coated. In certain embodiments, the PDA coated bristles comprise at least one additional agent, such as an antimicrobial agent. In some embodiments, the additional agent is silver. In some embodiments, the additional agent is curcumin. In some embodiments, the additional agent is an antibiotic. In certain embodiments of the antimicrobial toothbrush, the PDA is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises 5. persica, a mixture of S. aromaticum and myrrh and / or green-synthesized silver nanoparticles (“AgNP”). In an embodiment of the antimicrobial toothbrush, the antimicrobial agent comprises an extended release antimicrobial agent. In some embodiments, the antimicrobial agent comprises silver nanoparticles or an antibiotic. In some embodiments of said methods, the PDA is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises S. persica, a mixture of S. aromaticum and myrrh and / or green-synthesized silver nanoparticles (“AgNP”). InUCLA 2025-031 P-638957-PC some embodiments of said methods, the antimicrobial agent comprises an extended release antimicrobial agent. In an embodiment of said methods, the antimicrobial agent comprises silver nanoparticles or an antibiotic. In some embodiments of said methods, the oral microorganisms are bacteria, fungi and / or viruses. In certain embodiments of said methods, the bacteria are cariogenic and / or periodontopathic bacteria. In various embodiments, the cariogenic and / or periodontopathic bacteria is a Streptococcus bacteria, a Staphylococcus bacteria, a Porphyromonas bacteria, a Pseudomonas bacteria, a Prevotella bacteria, an Escherichia species, a Lactobacillus species and / or a combination thereof. In a particular embodiment, the cariogenic and / or periodontopathic bacteria is Streptococcus mutans, Staphylococcus aureus, Porphyromonas gingivalis or Escherichia coli. In some embodiments, the oral pathogen is a fungus such as Candida albicans. In certain embodiments, the cariogenic and / or periodontopathic bacteria is Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus rhamnosus, Lactobacillus casei / paracasei, Pseudomonas aeruginosa, Prevotella intermedia. In some embodiments a pathogenic virus is herpes simplex vims.

[0059] In still another aspect, the present invention provides a method for reducing the risk of physical wear and tear of a toothbrush, the method comprising: (a) coating bristles of the toothbrush with at least a first layer of polydopamine (PDA); and optionally coating the PDA coated-bristles of step (a) with a second layer of PDA. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer coating, said multilayer coating comprising: (a) a primary PDA layer and (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent. In an embodiment, the PDA- or PDA derivative-coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising: (a) a primary PDA layer; (b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and (c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA layer. In an embodiment, the antimicrobial agent comprises a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles. In an embodiment, the antimicrobial agent comprises S. persica. In certain embodiments, the antimicrobial agent comprises a mixture of S. aromaticum and myrrh. In an embodiments, the antimicrobial agent comprises green- synthesized silver nanoparticles (“AgNP”). In an embodiment of said methods, the PDA coating has a thickness of between 100 nanometers and 1 mm. In some embodiments of said methods, 50% to 100% of the bristles are PDA coated. In certain embodiments, the PDAUCLA 2025-031 P-638957-PC coated bristles comprise at least one additional agent, such as an antimicrobial agent. In some embodiments, the additional agent is silver. In some embodiments, the additional agent is curcumin. In some embodiments, the additional agent is an antibiotic. In certain embodiments of the antimicrobial toothbrush, the PDA is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises S. persica, a mixture of S. aromaticum and myrrh and / or green-synthesized silver nanoparticles (“AgNP”). In an embodiment of the antimicrobial toothbrush, the antimicrobial agent comprises an extended release antimicrobial agent. In some embodiments, the antimicrobial agent comprises silver nanoparticles or an antibiotic. In another embodiment of said methods, the PDA is functionalized with an antimicrobial agent. In an embodiment, the antimicrobial agent comprises S. persica, a mixture of S. aromaticum and myrrh and / or green-synthesized silver nanoparticles (“AgNP”). In an embodiment of said methods, the antimicrobial agent comprises an extended release antimicrobial agent. In some embodiments, the antimicrobial agent comprises silver nanoparticles or an antibiotic.

[0060] Thus, in some embodiments, the additional agent is an antimicrobial agent. Non-limiting examples of antimicrobial agents include S. aromaticum, S. persica, myrrh, silver nanoparticles including green-synthesized silver nanoparticles (“AgNP”), a metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, neem, an essential oil, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, silver, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof. Other additional agents include a re-mineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, an essential oil, probiotic, an antifouling agent such as a zwitterionic polymer, a flavoring agent, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

[0061] In one embodiment, the oral hygiene device, appliance or product of the present invention comprising a surface that contacts the teeth, gums, tongue and / or oral mucosa, wherein said surface comprises a coating of polydopamine (PDA) or a derivative thereof, is free of any additional functional agent and in particular does not comprise any antimicrobial agent.UCLA 2025-031 P-638957-PC

[0062] The following examples are presented in order to more fully illustrate the preferred embodiments of the invention. They should in no way be construed, however, as limiting the broad scope of the invention.EXAMPLE 1 Methods a. Coating of toothbrush bristles

[0063] To apply a double polydopamine (PDA) coating on a toothbrush, first, the brush heads were sonicated in fresh distilled water for 10-15 minutes. Next, a Tris buffer solution (10 mM, pH 8.5) was prepared as a base for the dopamine solution, with the alkaline pH initiating the selfpolymerization of dopamine to form the PDA layer. Dopamine hydrochloride was dissolved in the Tris buffer at a concentration of 2.5 mg / mL, with continuous stirring to ensure complete dissolution. The cleaned brush bristles were then submerged in the dopamine solution, and the brush heads were allowed to incubate in the dopamine solution with shaking at 300 rpm for 24 hours at 37 C, during which time dopamine gradually polymerized, forming a uniform PDA coating on the bristles and brush head surface.

[0064] After the first layer was applied, the heads were carefully removed from the dopamine solution and rinsed with distilled water to eliminate any loosely bound particles. To enhance the coating’s thickness and functionality, a second layer of PDA was added. This step was carried out by preparing a fresh dopamine solution in Tris buffer and submerging the brush heads again with shaking at 300 rpm for an additional 24 hours. The double-coating procedure strengthened the PDA layer, allowing it to serve as a robust base for additional biomolecules or nanoparticles if desired. Once the double coating was complete, the bristles were thoroughly rinsed with distilled water and allowed to air-dry. The coating’s presence and quality were verified using techniques such as FTRI to detect PDA-specific absorbance peaks and Scanning Electron Microscopy (SEM) to assess coating thickness and uniformity. b. Tooth brushing simulation

[0065] The brushing experiment was conducted using a setup designed to simulate long-term use with both control (uncoated) and PDA-coated toothbrushes. Coated and uncoated samples wereUCLA 2025-031 P-638957-PC mounted against natural teeth in a specially designed wear machine at the Department of Oral Technology, University of Bonn, Germany. The toothbrushes underwent a specified number of brushing cycles per minute, with artificial saliva used as a lubricant at a flow rate of 10 mL / min. This setup was designed to reflect the ADA recommendation for toothbrush use, which is 2 minutes of brushing twice daily, resulting in a total of 4 minutes of use per day. Natural adult anterior teeth or premolars were selected for testing, with the buccal or occlusal surfaces of each tooth serving as the brushing area.

[0066] During the brushing simulation, specimens were rinsed with tap water for 30 seconds every 1 h and the brushing force was maintained at 2 N, with the brushing motion confined to horizontal strokes along the buccal surfaces. Following the final brushing cycle, all specimens were rinsed and stored for post-experimental analysis.Testing procedures1. Antimicrobial properties

[0067] The antimicrobial activity of the toothbrushes was assessed by measuring colony forming units (CFU) and biofilm formation against S. mutans, C. albicans and S. aureus. Toothbrushes were divided into two main groups: the uncoated control group and the PDA coated group. The coated group was further subdivided into two sets: one set of coated toothbrushes was immediately investigated for antimicrobial activity, while the other set underwent a simulated brushing procedure.

[0068] The brushing experiment was conducted using a setup designed to simulate long-term use with both control (uncoated) and experimental coated toothbrushes. Each toothbrush was subjected to 56,000 brushing cycles at a rate of 120 strokes per minute (equivalent to 4 months of full mouth tooth brushing), with artificial saliva used as a lubricant at a flow rate of 10 mL / min. Two extracted adult natural anterior teeth were selected for testing, with the buccal surface of each tooth representing the brushing area. After the simulation, the toothbrushes were analyzed for colonyforming units (CFU) and biofilm formation to evaluate the impact of the brushing simulation on the antimicrobial effectiveness of the coating. For comparison, uncoated toothbrushes underwent the same brushing simulation (56.000 cycles), and their CFU and biofilm formation were alsoUCLA 2025-031 P-638957-PC assessed (Oliveira DC, Salomao PM, Martinelli de Lima A, et al. In vitro Streptococcus mutans adhesion and biofilm formation on different esthetic orthodontic archwires. Angle Or-thod. 2021; 91(6)1786-793; Feres MFN, Nunes LP, Morais IPD, et al. Streptococcus mutans adherence to conven-tional and self-ligating brackets: an in vitro study. Dent Press J Orthod. 2021; 26: e212019).2. Wear of enamel and toothbrush

[0069] To provide clinical context, the 32,000 brushing cycles used in this study correspond to approximately 266 minutes of continuous brushing. Assuming typical twice-daily oral hygiene routines, this represents around two months of regular full-mouth use. When localized to a single tooth surface, the exposure reflects several years of brushing wear. These values are approximate and based on simplified assumptions, as no standardized conversion model for brushing simulations currently exists.Enamel wear

[0070] Enamel wear following brushing simulation involved measuring volumetric enamel loss using micro-CT scanning and Mimics software. Intact human premolars were obtained and thoroughly cleaned using an ultrasonic scaler. They were then embedded in cold-curing resin (Technovit 4004, Kulzer GmbH, Werheim, Germany), ensuring that the full crown remained exposed. Each tooth was meticulously inspected under magnification, and any defective teeth were excluded and replaced. To aid in the alignment of 3D images, a round indentation was created on each tooth surface to serve as guiding marks for the overlapping process. The teeth were then carefully mounted to allow for consistent brushing simulation (see Fouda AM, Atta O, Kassem AS, Desoky M, Bourauel C. Wear behavior and abrasiveness of monolithic CAD / CAM ceramics after simulated mastication. Clin Oral Investig. 2022; 26(l l);6593-6605).

[0071] Before the brushing simulation, each tooth was scanned using a high-resolution micro-CT scanner (Skyscan 1174; Skyscan, Belgium). The scanning parameters were set as follows; 11.5 pm voxel size, 50 kVp energy, 800 pA intensity, 1 mm aluminum filter, 9500 ms integration time, a 360° rotation angle, and a 0.3° angular step. Micro-CT images were converted into virtual 3D models using Mimics Research software (Materialise HQ, Leuven, Belgium), and then imported into 3-Matic software (Materialise HQ, Leuven, Belgium). In 3-Matic, the worn and non-wornUCLA 2025-031 P-638957-PC models were aligned using guiding marks. Boolean subtraction was subsequently applied to isolate the worn area, allowing for the calculation of its volume. These initial scans served as the baseline for the analysis, providing detailed images of the enamel surface and volume prior to any brushing simulation. After the baseline scans, the toothbrushes either coated with PDA or uncoated were subjected to a brushing simulation using artificial saliva as a lubricant using above mentioned procedure (see Fouda et al.. 2022, op. cit.).

[0072] After completing the brushing simulation, the teeth were washed with distilled water and re-scanned using the same micro-CT protocol to capture the post-simulation enamel surface. The pre- and post-simulation scans were then analyzed using Mimics software to calculate the volumetric enamel loss. This was done by subtracting the post-simulation enamel volume from the pre- simulation volume, allowing for precise measurement of enamel wear.Toothbrush wear

[0073] The degree of wear of the toothbrushes used in the investigation of enamel wear was evaluated on a 5-point scale by two different operators as follows (from Van Leeuwen MPC, Van der Weijden FA, Slot DE, Rosema MAM. Toothbrush wear in relation to toothbrushing effectiveness. Int J Dent Hyg. 2019; 17(l):77-84):Grade 0: New / Unwom.Grade 1 : Mild Wear.Grade 2: Moderate Wear.Grade 3: Severe Wear.Grade 4: Very Severe Wear.Grade 5: Total Wear / Unsafe

[0074] Almost all samples were classified as grade 2 after the respective brushing simulations.3. Stability of Coating

[0075] The stability of the coatings on toothbrush bristles was assessed by immersing the coated bristles in distilled water and monitoring the release of the coating over time. The bristles were placed in separate containers filled with distilled water and maintained at 37°C. At predeterminedUCLA 2025-031 P-638957-PC intervals over a period of up to two months, water samples were collected for analysis. The released coating material was quantified using UV-Vis spectrophotometry. Distilled water served as a reference. The scanning speed for the samples in the range of 200 to 700 nm was 475 nm / min. The optical path was 1 cm at room temperature. These absorbance values were used to calculate the concentration of the released coating. By tracking the cumulative release over time, the stability of the coating was evaluated, providing insight into its durability and resistance to leaching under simulated use conditions.EXAMPLE 2 Antimicrobial Properties

[0076] Antimicrobial properties against Streptococcus mutans. Streptococcus aureus and Candida albicans by the polydopamine (PDA) coated tooth brushes was determined (see Oliveira DC, Salomao PM, Martinelli de Lima A, et al. In vitro Streptococcus mutans adhesion and biofilm formation on different esthetic orthodontic archwires. Angle Orthod. 2021; 91(6)1786-793; Feres MFN, Nunes LP, Morais IPD, et al. Streptococcus mutans adherence to conventional and selfligating brackets: an in vitro study. Dent Press J Orthod. 2021; 26: e212019). The PDA coated and uncoated toothbrushes (control group) were co-cultured and incubated at 37 °C for 24 h under agitation (120 rpm). After this time, the microorganisms were harvested by centrifugation at 8000 rpm for 5 min at 1 °C. washed twice and resuspended with phosphate-buffered saline (PBS; pH 7.0) to a concentration of 107cells / mL by adjusting the optical density OD0.951 at 530 nm using a spectrophotometer. Additionally, the antimicrobial properties were further investigated by the enumeration of colony-forming units (CFUs). The data (Figs. 1 and 2) showed that PDA coated toothbrushes exhibited signifyingly higher (p<0.05) antimicrobial properties against S. mutans, S. aureus and C. albicans. The antimicrobial results show total biofilm density at 595 nm and intergroup comparison against S. mutans, C. albicans and 5. aureus. Groups that do not share a letter are significantly different. Fig. 2 shows mean CFU against S. mutans.

[0077] Moreover, the antibacterial properties of the PDA coated toothbrush against periodontitis causing bacteria ( . gingivalis') was analyzed. After 5 days, qualitative analysis of the antimicrobial properties of the PDA coated tooth brushes on a biofilm layer of P. gingivalis, MTT assay indicated decreased viability of P. gingivalis on all PDA coated samples (Fig 3). Fig. 3 shows mean values of inhibition zones (mm) showing intergroup comparison against P. gingivalis.UCLA 2025-031 P-638957-PCEXAMPLE 3 Biocompatibility

[0078] A live-dead assay was utilized and confirmed the biocompatibility of the PDA coated toothbrushes when co-cultured with human dental pulp stem cells (hDPSCs). Fig. 4 shows mean viability of cells after exposure to coated and uncoated samples over 1 and 3 days. No difference was observed (p>0.05) between the PDA coated toothbrush and the control group (Fig. 4).EXAMPLE 4 Stability of PDA Coating

[0079] Moreover, the release profile of PDA was evaluated from the PDA coated samples using a nanodrop machine (Thermo Fisher). Fig. 5 shows release of polydopamine from coated samples. The data confirmed that no significant amounts of PDA were released for up to two months after immersion in distilled water solution (Fig. 5).EXAMPLE 5 Wear

[0080] The effects of PDA coated toothbrushes on human enamel loss was analyzed. In vitro wear test was conducted using an UAB chewing simulator for 32, 000 cycles. Results showed minimal enamel wear against PDA coated that was comparable to the control group (p>0.05) (Fig. 6). Fig. 6 shows enamel loss after 32,000 cycles of brushing with coated samples using overlapping of the 3D models and calculation of the enamel loss. Volumetric enamel wear loss after 32,000 cycles of brushing reported less than 0.01 mm3.

[0081] Additionally, no significant wear of brush bristles was observed after 32,000 cycles of brushing against natural enamel (Figs. 7A-7B). Figs. 7A and 7B show wear of a toothbrush of the present invention after 32,000 cycles of brushing against natural enamel. No significant wear of brush bristles was found after 32,000 cycles of brushing against natural enamel. Fig. 7A shows a toothbrush of the present invention before 32,000 cycles of brushing against natural enamel. Fig. 7B shows a toothbrush of the present invention after 32,000 cycles of brushing against natural enamel.EXAMPLE 6UCLA 2025-031 P-638957-PCSurface Preparation, Coating Fabrication and Performance Evaluation of a Multilayer Polydopamine-based System for Coating Oral Hygiene DevicesMethods Materials and Methods1. Substrate Preparation

[0082] Polymeric substrate discs representative of oral hygiene device components were ultrasonically cleaned to remove surface contaminants, then rinsed and air-dried under dust-free laboratory conditions and subjected to a surface activation process to enhance adhesion affinity.2. Fabrication of Multilayer Polydopamine (PDA) Coating

[0083] A multi-layer polydopamine-based encapsulation architecture was fabricated using sequential solution-based deposition, i.e., immersion steps, consisting of three functional layers: a. Layer 1 — Primary Adhesion Layer

[0084] A first polydopamine (PDA) layer was deposited on the polymer surface under oxidative polymerization conditions, forming a strongly adherent and uniformly conformal interface.

[0085] Dopamine hydrochloride was dissolved in Tris-HCl buffer (10 mM, pH —8—8.5) at 2 mg / mL concentration. Substrates were immersed in the solution for 24 hours to form a uniform conformal PDA layer developed. Coated samples were rinsed with deionized water to remove unreacted residues and dried.

[0086] This layer served as a robust primer for subsequent functionalization due to catechol- mediated adhesion. b. Layer 2 — Bioactive Reservoir Layer

[0087] A bioactive reservoir layer comprising two different antimicrobial systems, namely, plant- derived antimicrobial extract(s) and / or green- synthesized metal nanoparticles, was immobilized over the primary PDA layer, forming an inner antimicrobial reservoir.(i) Polyphenol-Rich Plant Extract CoatingUCLA 2025-031 P-638957-PC

[0088] Extracts from two selected medicinal plants were prepared using suitable solvent extraction. The extracts were combined at a defined ratio, diluted to the working concentration, and applied via dip-coating for certain period of time. Samples were dried at the incubator to allow film formation.

[0089] In one example, 5. aromaticum and myrrh were prepared separately and then mixed together and used to coat the primary PDA layer.

[0090] In another example, S. persica alone was applied in a two-layer coating (i.e., PDA and polyphenol-rich plant extract coating). The two-layer coating was applied for biofilm testing, as described below in Biofilm Quantification, but not for thermocycling.(ii) Green-Synthesized Silver Nanoparticles (“AgNP”)

[0091] The same plant extract mixture as in (i) acted as both the reducing and stabilizing agent for environmentally friendly AgNP synthesis. The AgNP was applied onto PDA-coated substrates by dip-coating, followed by drying. c. Layer 3 — Polydopamine Encapsulation Layer

[0092] A secondary PDA layer was deposited, i.e., polymerized, over the bioactive reservoir to function as a cross-linked encapsulation barrier to regulate release of the antimicrobial agents, strengthen the coating against wear and brushing forces and also for biocompatability, i.e., resist mechanical abrasion, improve chemical stability and minimize leaching, and enhance long-term biological, i.e.. antimicrobial, effectiveness, e.g., enhance antifungal performance on polymeric hygiene surfaces. In some instances, no Layer 3 was included.

[0093] To ensure optimal coating thickness and adhesion robustness, the polydopamine layers were applied using different deposition concentrations and / or coating parameters across the first and second PDA layers. This configuration prevents chipping or delamination and maintains coating integrity during repeated oral hygiene contact. Coated samples underwent thermocycling equivalent to simulate several months of oral hygiene exposure to assess long-term performance. All functional testing was conducted after durability simulation.UCLA 2025-031 P-638957-PC

[0094] An adjusted concentration of dopamine hydrochloride, i.e., of 2 mg / ml for only 2 hours, was dissolved in Tris-HCl buffer (10 mM, pH -8-8.5) at and used for the outer layer to ensure optimal encapsulation and prevent mechanical damage such as chipping or cracking.3. Durability Simulation

[0095] Coated substrates underwent thermocycling to simulate several months of consumer brushing-related exposure including alternating immersion in cool and warm aqueous environments, representing intraoral temperature fluctuations during daily hygiene, e.g., rinsing, brushing, saliva contact. All biological testing was performed after durability simulation.4. Performance Evaluations a. Hydrophilicity - Contact Angle Measurement

[0096] Surface wettability was evaluated using static water contact angle analysis (n=10). A 10 pL distilled water droplet was dispensed onto each leveled disc surface, and the droplet profile was recorded using a macro-lens camera setup positioned horizontally. Images captured shortly after droplet deposition were analyzed with ImageJ (Contact Angle plugin) to determine the contact angle at equilibrium. All sample groups were tested, with multiple measurements taken on each disc. The mean values were used for comparison.

[0097] The static water contact angles were measured to quantify anti-adhesion surface behavior. Lower angles indicate reduced likelihood of microbial adhesion. b. Colony Forming Unit (CFU) Analysis

[0098] Coated and control discs were incubated in Aggregatibacter spp. and Staphylococcus aureus suspensions (~1 x 107CFU / mL, BHI medium) at 37 °C. After gentle PBS rinsing, adherent bacteria were detached by standardized vortexing and brief ultrasonication. Serial dilutions were plated on blood agar in duplicate and incubated; viable colonies (CFU / mL) were counted. Results are reported as mean CFU / mL from at least three discs per group.UCLA 2025-031 P-638957-PC c. Biofilm Quantification (Crystal Violet Assay) on PDA-coated discs loaded with Salvadora persica extract (2 layers)

[0099] To evaluate antifungal performance, discs preloaded with Candida albicans were incubated to allow biofilm formation. After incubation, each disc was gently rinsed with PBS to remove non-adherent cells. The remaining surface biofilm was stained using crystal violet, followed by thorough washing to eliminate unbound dye. The retained stain was then solubilized with acetic acid, and optical density was measured at OD 595 nm to quantify biofilm biomass. Biofilm reduction was calculated relative to uncoated controls. All measurements were performed in triplicate. d. Cytocompatibility Evaluation (MTT Assay)

[0100] Sterile coated and uncoated discs were placed in culture plates, and MG-63 osteoblast-like cells were seeded onto their surfaces. After incubation under standard cell culture conditions (37 °C, 5% CO2), cell viability was evaluated using the MTT assay. The formed formazan crystals were dissolved, and absorbance was measured at -570 nm. Viability (%) was calculated relative to uncoated controls. e. Coating Adhesion and Integrity Evaluation

[0101] The adhesion strength and surface integrity of the multilayer coating were assessed using a standard tape-test. A pressure-sensitive adhesive tape was firmly applied onto the coated surface, ensuring full contact, and then removed at a consistent angle and speed. The coating was visually examined before and after tape removal for any evidence of peeling, cracking, or delamination. Each group included at least three discs. Coating continuity and adhesion quality were confirmed, indicating stable attachment of the PDA-based multilayer architecture to the substrate.

[0102] Statistical analysisData are presented as mean / median ± SD. Normality and variance were checked before analysis. Parametric data were analyzed by one-way ANOVA with Tukey’s post hoc test; non-parametric data used Kruskal-Wallis with Dunn’s test. Statistical significance was set at p < 0.05.5. ResultsUCLA 2025-031 P-638957-PC a. Hydrophilicity

[0103] Figure 8 shows the static contact angle measurements in degrees that quantified antiadhesion behavior of (A) Control, (B) PDA, (C) PDA / Mix of plant extracts (“Mix”) and PDA / metal ions nanoparticles (“PDA / NPs”). Lower angles indicated improved hydrophilicity. A or B vs. C, p < 0.05. c. Biofilm

[0104] Figure 9 shows the results of antifungal total biofilm (optical density (OD) at 595 nm) against C. albicans of (A) Control, (B) PDA, (C) PDA / SP + plant extract (“SP”). Biofilm reduction was calculated relative to uncoated controls. d. CFU

[0105] Figure 10 shows the CFU / ml results of antibacterial testing against S. aureus RN4220 of 2 PDA / NPs (triple layer of two PDA layers with metal ions nanoparticles therebetween), PDA (one layer), 2PD / PE (triple layer of polydopamine (“PD”), plant extract (“PE”) and polydopamine) compared to a control. After incubation, adherent bacteria were quantified via colony-forming units (CFU / mL).

[0106] Figure 11 shows the CFU / ml results of antibacterial testing with Aggregatibacter actinomycetemcomitans ATCC 33383 of 2PDA / NPs (triple layer of two PDA layers with metal ion nanoparticles therebetween), PDA (one layer), 2PD / PE (triple layer of polydopamine (“PD”), plant extract (“PE”) and polydopamine) compared to a control. After incubation, adherent bacteria were quantified via colony-forming units (CFU / mL). e. Cell Viability

[0107] Cell viability remained >80% on all coated samples. (Figure 12) These resiults demonstrate the safety and non-cytotoxicity of the coated single PDA- and triple- PD / PE / PD or PD / NPS / PD layer surfaces for prolonged oral exposure. f. Coating IntegrityUCLA 2025-031 P-638957-PC

[0108] The testing of coating integrity confirmed the mechanical robustness essential for consumer hygiene devices: no delamination was demonstrated, high adhesion was confirmed by a tape-test, and function of the coated surfaces was retained after mechanical stress tests.EXAMPLE 7Providing a protective antimicrobial barrier against oral pathogens on a tooth surface, a gum surface and / or a fixed or removable appliance surface in the oral cavity of a subject using an oral hygiene device comprising an antimicrobial agent-coated one PDA layer surface

[0109] In an embodiment, an oral hygiene device, appliance or product comprising a surface that contacts the teeth, gums, tongue and / or oral mucosa is fabricated, wherein said surface comprises a coating of polydopamine (PDA) or a derivative thereof, and the PDA coating (PDA layer) further comprises an additional agent, such as an antimicrobial agent, wherein said antimicrobial agent is a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles, and said antimicrobial agent is immobilized on / over the PDA layer. In another embodiment, the PDA coating is mixed with said antimicrobial agent and the mixture is applied to a surface of the device.

[0110] In some embodiments, the antimicrobial agent comprises an S. persica or any other plant extract or polyphenol coating on the PDA or a derivative thereof coating (single PDA layer) on a surface of the device.

[0111] In another embodiment, the antimicrobial agent comprises a layer of green- synthesized silver nanoparticles (“AgNP”) coating on the coating of PDA or a derivative thereof (single PDA layer) on a surface of the device.

[0112] In an embodiment, the additional agent is a metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a re-mineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.UCLA 2025-031 P-638957-PC

[0113] In certain embodiments, the device, appliance or product is a toothbrush, toothpick, dental floss, electric toothbrush head, interdental brush, orthodontic toothbrush, tongue cleaner, or a fixed or removable dental appliance, denture base, crown or bridge, wherein the device comprises a surface that contacts the teeth, gums, tongue and / or oral mucosa, wherein said surface comprises a coating of polydopamine (PDA) or a derivative thereof and an antimicrobial agent or an additional agent, as described above.

[0114] It is expected that brushing teeth, gums, tongue and / or oral mucosa with the antimicrobial agent-coated one PDA layer coated device, appliance or product, including but not limited to a toothbrush, toothpick, dental floss, electric toothbrush head, interdental brush, orthodontic toothbrush, tongue cleaner, or a fixed or removable dental appliance, such as a retainer (e.g., orthodontal retainer), aligner, or night guard, a denture base / fitting surface, a crown or a bridge, or an appliance storage case for an oral hygiene, appliance device or product, will reduce the persistence of oral microorganisms in the oral cavity of the subject, preserve the integrity of enamel on a tooth surface of the subject, provide a protective barrier against oral pathogens on an oral surface of the subject, wherein the oral surface is a tooth surface and / or a gum surface of the subject.

[0115] In another embodiment, it is envisaged that the coating of polydopamine (PDA) or a derivative thereof, wherein the PDA coating (PDA layer) / derivative thereof further comprises an additional agent, such as an antimicrobial agent, will reduce the persistence of oral microorganisms on the device, such as a tooth brush, post-brushing of teeth in an oral cavity of the subject and reduce re-contamination risk of the oral cavity with oral pathogens, and further that said device, e.g., a tooth brush, will have a reduced risk of physical wear and tear.EXAMPLE 8Providing a protective antimicrobial barrier against oral pathogens on a tooth surface, a gum surface and / or a fixed or removable appliance surface in the oral cavity of a subject using an oral hygiene device comprising two layers of PDA coated on the surface

[0116] In another embodiment, an oral hygiene device, appliance or product comprising a surface that contacts the teeth, gums, tongue and / or oral mucosa is fabricated, wherein said surface comprises a coating of two layers of polydopamine (PDA) or a derivative thereof and one or bothUCLA 2025-031 P-638957-PC of the two PDA coatings (PDA layers) further comprises an additional agent, such as an antimicrobial agent, wherein said antimicrobial agent is a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles, and said antimicrobial agent is immobilized on / over the PDA layer. In another embodiment, one or both of the two PDA coatings (PDA layers) is mixed with said antimicrobial agent and the mixture is applied to a surface of the device.

[0117] In an embodiment, the antimicrobial agent comprises an S. persica coating on the PDA or a derivative thereof coating (single PDA layer) on a surface of the device.

[0118] In some embodiments, the antimicrobial agent comprises a layer of green- synthesized silver nanoparticles (“AgNP”) coating on the PDA or a derivative thereof coating (single PDA layer) on a surface of the device.

[0119] In certain embodiments, the additional agent is a metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a re-mineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

[0120] In certain embodiments, the device, appliance or product is a toothbrush, toothpick, dental floss, electric toothbrush head, interdental brush, orthodontic toothbrush, tongue cleaner, or a fixed or removable dental appliance, such as a retainer (e.g., orthodontal retainer), aligner, or night guard, a denture base / fitting surface, a crown or a bridge, or an appliance storage case for an oral hygiene, appliance device or product, wherein the device comprises a surface that contacts the teeth, gums, tongue and / or oral mucosa, wherein said surface comprises a coating of two layers of polydopamine (PDA) or a derivative thereof and one or both of the two PDA coatings (PDA layers) further comprises an additional agent, such as an antimicrobial agent, as described above.

[0121] It is expected that brushing teeth, gums, tongue and / or oral mucosa with the antimicrobial agent-coated two PDA layers coated device, appliance or product, including but not limited to a toothbrush, toothpick, dental floss, electric toothbrush head, interdental brash, orthodontic toothbrush,UCLA 2025-031 P-638957-PC tongue cleaner, or a fixed or removable dental appliance, such as a retainer (e.g., orthodontal retainer), aligner, or night guard, a denture base / fitting surface, a crown or a bridge, or an appliance storage case for an oral hygiene, appliance device or product, will reduce the persistence of oral microorganisms in the oral cavity of the subject, preserve the integrity of enamel on a tooth surface of the subject, provide a protective barrier against oral pathogens on an oral surface of the subject, wherein the oral surface is a tooth surface and / or a gum surface of the subject.

[0122] In another embodiment, it is envisaged that the two coatings of PDA or a derivative thereof, wherein one or both of the PDA coatings (PDA layers / / derivative thereof further comprises an additional agent, such as an antimicrobial agent, will reduce the persistence of oral microorganisms on the device, such as a tooth brush, post-brushing of teeth in an oral cavity of the subject and reduce re-contamination risk of the oral cavity with oral pathogens, and further that said device, e.g., a tooth brush, will have a reduced risk of physical wear and tear.EXAMPLE 9Providing a protective antimicrobial barrier against oral pathogens on a tooth surface, a gum surface and / or a fixed or removable appliance surface in the oral cavity of a subject using an oral hygiene device, comprising a bioactive reservoir layer encapsulated between two layers of PDA on the device surface

[0123] In one embodiment, an oral hygiene device, appliance or product comprising a surface that contacts the teeth, gums, tongue and / or oral mucosa is manufactured, wherein said surface comprises a multilayer PDA coating comprising a primary PDA layer / coating, a bioactive reservoir layer, such as an antimicrobial agent (but not limited thereto), immobilized on the primary PDA layer, and a second PDA layer, i.e., an encapsulation layer, which encapsulates the bioactive reservoir layer between the primary PDA layer and the PDA encapsulation layer.

[0124] In an embodiment, the additional agent is an antimicrobial agent, wherein said antimicrobial agent is a plant-derived antimicrobial extract(s) and / or green- synthesized metal nanoparticles, and said antimicrobial agent is immobilized on / over the primary PDA layer.

[0125] In certain embodiments, the antimicrobial agent comprises S. persica.UCLA 2025-031 P-638957-PC

[0126] In an embodiment, the antimicrobial agent comprises a layer of green-synthesized silver nanoparticles (“AgNP”).

[0127] In some embodiments, the additional agent is a metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a re-mineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

[0128] In particular embodiments, the device, appliance or product is a toothbrush, toothpick, dental floss, electric toothbrush head, interdental brush, orthodontic toothbrush, tongue cleaner, or a fixed or removable dental appliance, such as a retainer (e.g., orthodontal retainer), aligner, or night guard, a denture base / fitting surface, a crown or a bridge, or an appliance storage case for an oral hygiene, appliance device or product, wherein the device comprises a surface that contacts the teeth, gums, tongue and / or oral mucosa, wherein said surface comprises a multilayer PDA coating comprising a primary PDA layer / coating, a bioactive reservoir layer, such as, but not limited to, an antimicrobial agent, immobilized on the primary PDA layer, and a second PDA layer, i.e., an encapsulation layer, which encapsulates the bioactive reservoir layer between the primary PDA layer and the PDA encapsulation layer. In an embodiment, the antimicrobial agent is a plant- derived antimicrobial extract(s) and / or green- synthesized metal nanoparticles.

[0129] In some embodiments, the antimicrobial agent comprises S. persica.

[0130] In certain embodiments, the antimicrobial agent comprises a layer of green-synthesized silver nanoparticles (“AgNP”).

[0131] In some embodiments, device, appliance or product comprises an additional agent, wherein the additional agent is a metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a re-mineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agentUCLA 2025-031 P-638957-PC such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

[0132] It is expected that brushing teeth, gums, tongue and / or oral mucosa with the device, appliance or product comprising on a surface thereof the antimicrobial agent-multilayer PDA coating comprising a primary PDA layer, a bioactive reservoir layer immobilized on the primary PDA layer, and a second PDA layer, i.e., an encapsulation layer, wherein the bioactive reservoir layer comprises an antimicrobial agent, wherein the coated device, appliance or product, includes but is not limited to a toothbrush, toothpick, dental floss, electric toothbrush head, interdental brush, orthodontic toothbrush, tongue cleaner, or a fixed or removable dental appliance, such as a retainer (e.g., orthodontal retainer), aligner, or night guard, a denture base / fitting surface, a crown or a bridge, or an appliance storage case for an oral hygiene, appliance device or product, will reduce the persistence of oral microorganisms in the oral cavity of the subject, preserve the integrity of enamel on a tooth surface of the subject, provide a protective barrier against oral pathogens on an oral surface of the subject, wherein the oral surface is a tooth surface and / or a gum surface of the subject.

[0133] In another embodiment, it is envisaged that the device, appliance or product comprising on a surface thereof the antimicrobial agent-multilayer PDA coating comprising a primary PDA layer, a bioactive reservoir layer immobilized on the primary PDA layer, and a second PDA layer, i.e., an encapsulation layer, wherein the bioactive reservoir layer comprises an additional agent, such as an antimicrobial agent, will reduce the persistence of oral microorganisms on the device, such as a tooth brush, post-brushing of teeth in an oral cavity of the subject and reduce re-contamination risk of the oral cavity with oral pathogens, and further that said device, e.g., a tooth brush, will have a reduced risk of physical wear and tear.EXAMPLE 10Non-sterilizable, Biofilm-prone Oral / Dental Hygiene Devices Coated with One Antimicrobial Agent- PDA layer, Two Antimicrobial Agent PDA Layers or a Multilayer Coating Comprising PDA-antimicrobial-PDA on Surfaces of the DevicesUCLA 2025-031 P-638957-PC

[0134] In an embodiment, a non-sterilizable, biofilm-prone device that is applied for dental hygiene and / or is contacted with the oral cavity, and is at risk of biofilm growth thereon, is manufactured with an antimicrobial PDA-layer, two antimicrobial PDA-layers or multilayer PDA coating / layers comprising a bioactive reservoir layer comprising an antimicrobial agent or an additional agent. The PDA layer may be on an inner and / or outer surface of the device. In some embodiments, the device includes but not limited to a removable dental appliance, such as a retainer (e.g., orthodontal retainer), aligner, or night guard, a denture base / fitting surface, a crown or a bridge, or an appliance storage case for an oral hygiene, appliance device or product.

[0135] In some embodiments, the one antimicrobial PDA-layer, two antimicrobial PDA-layers or multilayer PDA layers of the multilayer PDA coating / layers comprise an additional agent, wherein the additional agent is a metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a re-mineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

[0136] In some embodiments, said additional agent is immobilized on a surface of the (1) one PDA layer, (2) two PDA layers or (3) said additional agent is immobilized on the first PDA layer of the multilayer PDA coating, and is encapsulated by a second PDA layer of the multilayer PDA coating, and the one PDA, two PDA or multilayer PDA coating comprising the additional agent is coated on a surface of the device.

[0137] In an embodiment, the bioactive reservoir layer (the additional agent) comprises a mixture of 5. aromaticum and myrrh coating on (1) the PDA or a derivative thereof coating (single PDA layer) on a surface of the device, (2) one or both of the two layer PDA coatings on a surface of the device, or (3) the primary PDA layer of the multilayer PDA coating, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer.

[0138] In some embodiments, the bioactive reservoir layer (the additional agent) comprises an . persica coating on (1) the PDA or a derivative thereof coating (single PDA layer) on a surfaceUCLA 2025-031 P-638957-PC of the device, (2) one or both of the two layer PDA coatings on a surface of the device, or (3) the primary PDA layer of the multilayer PDA coating, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer.

[0139] In another embodiment, the bioactive reservoir layer (the additional agent) comprises a layer of green-synthesized silver nanoparticles (“AgNP”) coating on (1) the PDA or a derivative thereof coating (single PDA layer) on a surface of the device, (2) one or both of the two layer PDA coatings on a surface of the device, or (3) the primary PDA layer of the multilayer PDA coating, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer.

[0140] It is expected that the one antimicrobial-PDA layer, two antimicrobial-PDA layer or multilayer PDA layer coatings comprising the antimicrobial agent coated on one or more surfaces of a non- sterilizable, biofilm-prone device that is applied to an oral cavity of a subject for dental hygiene and / or is contacted with the oral cavity of a subject will reduce the persistence of oral microorganisms in the oral cavity, prevent fungal and / or bacterial infection in the oral cavity of a subject treated with the dental hygiene device, i.e., to who the non-sterilizable, biofilm-prone device is applied in the oral cavity thereof and / or whose oral cavity is contacted with said PDA coated device non-sterilizable, biofilm-prone. In some embodiments, the PDA coated device is a removable dental appliance, such as a retainer (e.g., orthodontal retainer), aligner, or night guard, a denture base / fitting surface, a crown or a bridge, or an appliance storage case for an oral hygiene, appliance device or product.

[0141] In an embodiment, the non-sterilizable, biofilm-prone device comprises a coating of polydopamine (PDA) or a derivative thereof on a surface thereof (a single PDA layer). In particular embodiments, the PDA coating (PDA layer) further comprises an additional agent, such as an antimicrobial agent, wherein said antimicrobial agent is a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles, and said antimicrobial agent is immobilized over the PDA layer. In another embodiment, the PDA coating is mixed with said antimicrobial agent and the mixture is applied to a surface of the non-sterilizable, biofilm-prone device.

[0142] In some embodiments, the additional agent is a metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a re- mineralizing agent such as fluoride, bioglass andUCLA 2025-031 P-638957-PC calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

[0143] In another embodiment, the non-sterilizable, biofilm-prone device comprises two coatings of polydopamine (PDA) or a derivative thereof on a surface thereof. In particular embodiments, the two PDA coatings (two PDA layers) further comprises an additional agent, such as an antimicrobial agent, wherein said antimicrobial agent is / are a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles, and said antimicrobial agent is immobilized over the two PDA layers. In certain embodiments, the PDA coating(s) is / are mixed with said antimicrobial agent and the mixture is applied to a surface of the device twice.

[0144] In still another embodiment, the non-sterilizable, biofilm-prone device comprises a coating of multilayer PDA coating comprising a primary adhesion layer of PDA (a first PDA layer), a PDA encapsulation layer (a second PD layer) and a bioactive reservoir layer between the first and second PDA layers. In an embodiment, the multilayer PDA coating comprises an antimicrobial agent, wherein said antimicrobial agent is / are a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles, as descried in Example 6.

[0145] In some embodiments, each of the two layer PDA or the multilayer PDA coating / layers coated on a surface of the non-sterilizable, biofilm-prone device comprises an additional agent, wherein the additional agent is a metal ion. non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a re-mineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof. In some embodiments, said additional agent is immobilized on a surface of the two PDA layers or said additional agent is immobilized on the first PDA layer of the two PDA layers of the multilayer PDA coating, and said two PDA layers comprising the immobilized additional agent orUCLA 2025-031 P-638957-PC said multilayer PDA coating comprising the additional agent therebetween is coated on a surface of the non- sterilizable, biofilm-prone device.

[0146] In an embodiment, the bioactive reservoir layer (the additional agent) comprises a mixture of . aromaticum and myrrh coating on (1) the PDA or a derivative thereof coating (single PDA layer) on a surface of the non-sterilizable, biofilm-prone device, (2) one or both of the two layer PDA coatings on a surface of the non-sterilizable, biofilm-prone device, or (3) the primary PDA layer of the multilayer PDA coating, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer, coated on a surface of the non-sterilizable, biofilm-prone device.

[0147] In some embodiments, the bioactive reservoir layer (the additional agent) comprises an S. persica coating on (1) the PDA or a derivative thereof coating (single PDA layer) on a surface of the device, (2) one or both of the two layer PDA coatings on a surface of the device, or (3) the primary PDA layer of the multilayer PDA coating, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer coated on the non-sterilizable, biofilm-prone device.

[0148] In another embodiment, the bioactive reservoir layer (the additional agent) comprises a layer of green- synthesized silver nanoparticles (“AgNP”) coating on (1) the PDA or a derivative thereof coating (single PDA layer) on a surface of the device. (2) one or both of the two layer PDA coatings on a surface of the device, or (3) the primary PDA layer of the multilayer PDA coating, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer, coated on a surface of the non-sterilizable, biofilm-prone device.

[0149] It is expected that the one antimicrobial-PDA layer, two antimicrobial-PDA layer or multilayer PDA layer coatings comprising the antimicrobial agent coated on one or more surfaces of the non-sterilizable. biofilm-prone device that is applied to an oral cavity of a subject for dental hygiene and / or is contacted with the oral cavity of a subject will reduce the persistence of oral microorganisms in the oral cavity, prevent fungal and / or bacterial infection in the oral cavity of a subject treated with the dental hygiene device, i.e., to who the device is applied in the oral cavity thereof and / or whose oral cavity is contacted with said PDA coated device comprising (1) a single PDA layer on a surface of the device, (2) one or both of the two layer PDA coatings on a surface of the device, or (3) the primary PDA layer of the multilayer PDA coating, i.e., encapsulatedUCLA 2025-031 P-638957-PC between the primary PDA layer and the PDA encapsulation layer, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer, coated on a surface of the non-sterilizable, biofilm-prone device.

[0150] In some embodiments, the PDA coated non-sterilizable, biofilm-prone device is a removable dental appliance, such as a retainer (e.g., orthodontal retainer), aligner, or night guard, a denture base / fitting surface, a crown or a bridge, or an appliance storage case for an oral hygiene, appliance device or product.EXAMPLE 11Non-sterilizable, Biofilm-prone Devices Coated with One Antimicrobial Agent-PDA layer, Two Antimicrobial Agent PDA Layera or a Multilayer Coating Comprising PDA- antimicrobial-PDA on Surfaces of the Devices

[0151] In still another embodiment, a non-sterilizable, biofilm-prone device that is applied to or is contacted with the oral cavity or with a skin surface of a subject, and said device is at risk of biofilm growth thereon, is manufactured with an antimicrobial PDA-layer. The PDA layer may be on an inner and / or outer surface of the device. In some embodiments, the device includes but not limited to, CPAP / ventilation tubing, an endoscope tubing I housing, a reusable or non-reusable shaver head or grooming tool surface, a surgical robotic component which is not autoclave safe, a toilet / bidet surface, a coffee machine water contact part, a high-touch consumer grip (such as a gym grip or a transit vehicle grip), an infant teething toy, or door handles.

[0152] In an embodiment, the device, e.g., CPAP / ventilation tubing, an endoscope tubing I housing, a reusable or non-reusable shaver head or grooming tool surface, a surgical robotic component which is not autoclave safe, a toilet / bidet surface, a coffee machine water contact part, a high-touch consumer grip (such as a gym grip or a transit vehicle grip), an infant teething toy or a door handle, comprises a coating of polydopamine (PDA) or a derivative thereof on a surface thereof (a single PDA layer). In particular embodiments, the PDA coating (PDA layer) further comprises an additional agent, such as an antimicrobial agent, wherein said antimicrobial agent is a plant-derived antimicrobial extract(s) and / or green- synthesized metal nanoparticles, and saidUCLA 2025-031 P-638957-PC antimicrobial agent is immobilized over the PDA layer. In another embodiment, the PDA coating is mixed with said antimicrobial agent and the mixture is applied to a surface of said device.

[0153] In some embodiments, the additional agent is a metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a re-mineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

[0154] In another embodiment, the device, such as CPAP / ventilation tubing, an endoscope tubing I housing, a reusable or non-reusable shaver head or grooming tool surface, a surgical robotic component which is not autoclave safe, a toilet / bidet surface, a coffee machine water contact part, a high-touch consumer grip (such as a gym grip or a transit vehicle grip), an infant teething toy or a door handle, comprises two coatings of polydopamine (PDA) or a derivative thereof on a surface thereof. In particular embodiments, the two PDA coatings (two PDA layers) further comprises an additional agent, such as an antimicrobial agent, wherein said antimicrobial agent is / are a plant-derived antimicrobial extract(s) and / or green- synthesized metal nanoparticles, and said antimicrobial agent is immobilized over the two PDA layers. In certain embodiments, the PDA coating(s) is / are mixed with said antimicrobial agent and the mixture is applied to a surface of the device twice.

[0155] In still another embodiment, the device, such as CPAP / ventilation tubing, an endoscope tubing / housing, a reusable or non-reusable shaver head or grooming tool surface, a surgical robotic component which is not autoclave safe, a toilet / bidet surface, a coffee machine water contact part, a high-touch consumer grip (such as a gym grip or a transit vehicle grip), an infant teething toy, or a door handle, comprises a coating of multilayer PDA coating comprising a primary adhesion layer of PDA (a first PDA layer), a PDA encapsulation layer (a second PD layer) and a bioactive reservoir layer between the first and second PDA layers. In an embodiment, the multilayer PDA coating comprises an antimicrobial agent, wherein said antimicrobial agent is / are a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles, as descried in Example 6.UCLA 2025-031 P-638957-PC

[0156] In some embodiments, each of the two layer PDA or the multilayer PDA coating / layers of a surface thereof, e.g., CPAP / ventilation tubing, an endoscope tubing / housing, a reusable or non-reusable shaver head or grooming tool surface, a surgical robotic component which is not autoclave safe, a toilet / bidet surface, a coffee machine water contact part, a high-touch consumer grip (such as a gym grip or a transit vehicle grip), an infant teething toy, or a door handle, comprises an additional agent, wherein the additional agent is a metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a re-mineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof. In some embodiments, said additional agent is immobilized on a surface of the two PDA layers or said additional agent is immobilized on the first PDA layer of the two PDA layers of the multilayer PDA coating, said two PDA layers comprising the immobilized additional agent or said multilayer PDA coating comprising the additional agent therebetween is coated on a surface of the device, such as CPAP / ventilation tubing, an endoscope tubing I housing, a reusable or non-reusable shaver head or grooming tool surface, a surgical robotic component which is not autoclave safe, a toilet / bidet surface, a coffee machine water contact part, a high-touch consumer grip (such as a gym grip or a transit vehicle grip), an infant teething toy, or a door handle.

[0157] In an embodiment, the bioactive reservoir layer (the additional agent) comprises a mixture of S. aromaticum and myrrh coating on (1) the PDA or a derivative thereof coating (single PDA layer) on a surface of the device, (2) one or both of the two layer PDA coatings on a surface of the device, or (3) the primary PDA layer of the multilayer PDA coating, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer. In particular embodiments, the device is CPAP / ventilation tubing, an endoscope tubing / housing, a reusable or non-reusable shaver head or grooming tool surface, a surgical robotic component which is not autoclave safe, a toilet / bidet surface, a coffee machine water contact part, a high-touch consumer grip (such as a gym grip or a transit vehicle grip), an infant teething toy. or a door handle.UCLA 2025-031 P-638957-PC

[0158] In some embodiments, the bioactive reservoir layer (the additional agent) comprises an . persica coating on (1) the PDA or a derivative thereof coating (single PDA layer) on a surface of the device, (2) one or both of the two layer PDA coatings on a surface of the device, or (3) the primary PDA layer of the multilayer PDA coating, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer.

[0159] In another embodiment, the bioactive reservoir layer (the additional agent) comprises a layer of green- synthesized silver nanoparticles (“AgNP”) coating on (1) the PDA or a derivative thereof coating (single PDA layer) on a surface of the device, (2) one or both of the two layer PDA coatings on a surface of the device, or (3) the primary PDA layer of the multilayer PDA coating, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer, i.e., encapsulated between the primary PDA layer and the PDA encapsulation layer.

[0160] It is expected that the one antimicrobial-PDA layer, two antimicrobial-PDA layer or multilayer PDA layer coatings comprising the antimicrobial agent coated on one or more surfaces of non- sterilizable, biofilm-prone device, such as CPAP / ventilation tubing, an endoscope tubing I housing, a reusable or non-reusable shaver head or grooming tool surface, a surgical robotic component which is not autoclave safe, a toilet / bidet surface, a coffee machine water contact part, a high-touch consumer grip (such as a gym grip or a transit vehicle grip), an infant teething toy, or a door handle, wherein said device is contacted with the oral cavity or with a skin surface of a subject, will reduce the persistence of oral microorganisms in the oral cavity and / or on the skin of said subject, prevent fungal and / or bacterial infection in the oral cavity and / or on the skin of a subject treated with the dental hygiene, i.e., to who the device is applied in the oral cavity thereof and / or whose oral cavity or skin is contacted with said PDA coated device. In some embodiments, the PDA coated device is a CPAP / ventilation tubing, an endoscope tubing I housing, a reusable or non-reusable shaver head or grooming tool surface, a surgical robotic component which is not autoclave safe, a toilet / bidet surface, a coffee machine water contact part, a high-touch consumer grip (such as a gym grip or a transit vehicle grip), an infant teething toy, or a door handle. Having described certain embodiments of the invention with reference to the accompanying drawings, it is to be understood that the invention is not limited to the precise embodiments, and that various changes and modifications may be effected therein by those skilled in the art without departing from the scope or spirit of the invention as defined in the appended claims.

Claims

UCLA 2025-031 P-638957-PCWHAT IS CLAIMED IS:

1. A device, appliance or product comprising a surface that contacts the teeth, gums, tongue oral mucosa, and / or other body part, wherein said surface comprises a coating of polydopamine (PDA) or a derivative thereof.

2. The device, appliance or product of claim 1, wherein the device, appliance or product is an oral hygiene device or holds an oral hygiene device, such as a toothbrush, toothpick, dental floss, electric toothbrush head, interdental brush, orthodontic toothbrush, tongue cleaner, or a fixed or removable dental appliance, such as a retainer, aligner, or night guard, a denture base / fitting surface, a crown or a bridge, or an appliance storage case for an oral hygiene, appliance, device or product.

3. The device, appliance or product of claim 1 or 2, wherein the surface comprises bristles, filaments or a scraper.

4. The device, appliance or product of any one of claims 1-3, wherein the surface comprises a coating of about 20 nanometers to about 1 mm PDA or the derivative thereof.

5. The device, appliance or product of any one of claims 1-3, wherein the PDA coating or PDA derivative coating further comprises an additional agent, such as an antimicrobial agent, such as a plant-derived antimicrobial extract(s) and / or green-synthesized metal nanoparticles, metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a remineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, green synthesized nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

6. The device, appliance or product of any one of claims 1-3, wherein the surface comprises at least one PDA coating or PDA derivative coating.

7. The device, appliance or product of claim 6, wherein the surface comprises two PDA coatings or PDA derivative coatings.UCLA 2025-031 P-638957-PC8. The device, appliance or product of claim 6, wherein the surface comprises a multilayer coating, said multilayer coating comprising:(a) a primary PDA layer; and(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent.

9. The device, appliance or product of claim 6, wherein the surface comprises a multilayer PDA coating, said multilayer PDA coating comprising:(a) a primary PDA layer;(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and(c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA.

10. The device, appliance or product of claim 8 or 9, wherein the antimicrobial agent comprises a plant-derived antimicrobial extract(s), green-synthesized metal nanoparticles, metal ion, non- metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, silver, silver nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

11. The device, appliance or product of any one of claims 6-10, wherein each PDA coating or PDA derivative coating independently has a thickness of between about 20 nanometers and about 100 nanometers.

12. The device, appliance or product of any one of claims 1-11. wherein 50% to 100% of the surface is PDA coated or PDA derivative coated.

13. A method for reducing the persistence of oral microorganisms in the oral cavity, preserving integrity of enamel on a tooth surface, providing a protective barrier against oral pathogens on an oralUCLA 2025-031 P-638957-PC surface, or any combination thereof, comprising using the oral hygiene device, appliance or product of any one of claims 1-12.

14. An antimicrobial toothbrush comprising a handle and a brush head attached thereto by a neck portion extending between the brush head and the handle, the brush head comprising a top surface and a bottom surface, the top surface comprising a bundle of polydopamine (PDA)- or PDA derivative- coated bristles embedded in or fused into the top surface of the brush head.

15. The antimicrobial toothbrush of claim 14, wherein the bristles comprise a coating of about 20 nanometers to about 1 mm PDA or PDA derivative.

16. The antimicrobial toothbrush of claim 14, wherein the PDA- or PDA derivative-coated bristles comprise at least one PDA coating.

17. The antimicrobial toothbrush of claim 14, wherein the PDA- or PDA derivative-coated bristles comprise two PDA coatings.

18. The antimicrobial toothbrush of claim 14, wherein the PDA- or PDA derivative -coated bristles comprise a multilayer coating, said multilayer coating comprising:(a) a primary PDA layer; and(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent.

19. The antimicrobial toothbrush of claim 14, wherein the PDA- or PDA derivative-coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising:(a) a primary PDA layer;(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and(c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA.UCLA 2025-031 P-638957-PC20. The antimicrobial toothbrush of claim 18 or 19, wherein the antimicrobial agent comprises a plant-derived antimicrobial extract(s), green-synthesized metal nanoparticles, metal ion, non- metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, silver, silver nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

21. The antimicrobial toothbrush of any one of claims 14-20, wherein each PDA or PDA derivative coating has a thickness of between about 20 nanometers and about 100 nanometers.

22. The antimicrobial toothbrush of claim 14, wherein 50% to 100% of the bristles are PDA or PDA derivative coated.

23. The antimicrobial toothbrush of claim 14, wherein the PDA or PDA derivative coating further comprises an additional agent, such as an antimicrobial agent, such as a plant-derived antimicrobial extract(s), green synthesized nanoparticles, green-synthesized metal nanoparticles, metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a remineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

24. The antimicrobial toothbrush of claim 23, wherein the PDA or PDA derivative is functionalized with an antimicrobial agent.

25. The antimicrobial toothbrush of claim 14, wherein the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to about 90 degrees from the perpendicular, or a combination thereof.

26. The antimicrobial toothbrush of claim 14, wherein the brush head is permanently attached to the toothbrush by the neck portion.UCLA 2025-031 P-638957-PC27. The antimicrobial toothbrush of claim 14, wherein the brush head is removably attached to the toothbrush by a removable neck portion.

28. The antimicrobial toothbrush of claim 14, wherein the toothbrush is a manual toothbrush.

29. The antimicrobial toothbrush of claim 14, wherein the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate.

30. A method for providing a protective barrier against oral pathogens on a tooth surface and / or a gum surface and / or a fixed or removable appliance surface in the oral cavity of a subject, the method comprising: brushing the tooth surface and / or the gum surface and / or the fixed or removable appliance surface at least once or twice per day with an antimicrobial tooth brush comprising a handle and a brush head attached thereto by a neck portion extending between the brush head and the handle, the brush head comprising a top surface and a bottom surface, the top surface comprising a bundle of polydopamine (PDA)- or PDA derivative-coated bristles embedded in or fused into the top surface of the brush head, wherein brushing the tooth surface and / or the gum surface and / or the fixed or removable appliance surface with the antimicrobial toothbrush generates reactive oxygen species thereby inducing oxidative stress in the oral pathogens.

31. The method of claim 30, further comprising:(a) rinsing the oral cavity with water; and(b) rinsing the oral cavity with an antimicrobial mouthwash.

32. The method of claim 30, wherein the oral pathogens are bacteria, fungi and / or viruses.

33. The method of claim 30, wherein the bacteria are cariogenic and / or periodontopathic bacteria.

34. The method of claim 30, wherein the bristles comprise a coating of about 20 nanometers to about 1 mm PDA or PDA derivative.UCLA 2025-031 P-638957-PC35. The method of claim 30, wherein the PDA- or PDA derivative-coated bristles comprise a first layer of a PDA coating and optionally a second layer of PDA coating.

36. The method of claim 30, wherein the PDA- or PDA derivative-coated bristles comprise a multilayer coating, said multilayer coating comprising:(a) a primary PDA layer; and(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent.

37. The method of claim 30, wherein the PDA- or PDA derivative-coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising:(a) a primary PDA layer;(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and(c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA.

38. The method of claim 36 or 37, wherein the antimicrobial agent comprises a plant-derived antimicrobial extract(s), green synthesized nanoparticles, green-synthesized metal nanoparticles, metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, silver, silver nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

39. The method of any one of claims 30-38, wherein each PDA or PDA derivative coating has a thickness of between about 20 nanometers and about 100 nanometers.

40. The method of claim 30, wherein 50% to 100% of the bristles are PDA or PDA derivative coated.

41. The method of claim 30, wherein the PDA or PDA derivative coating further comprises an additional agent such as an antimicrobial agent, such as a plant-derived antimicrobial extract(s),UCLA 2025-031 P-638957-PC green synthesized nanoparticles, green-synthesized metal nanoparticles, metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a remineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

42. The method of claim 41, wherein the PDA or PDA derivative is functionalized with an antimicrobial agent.

43. The method of claim 30, wherein the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to about 90 degrees from the perpendicular, or a combination thereof.

44. The method of claim 30, wherein the brush head is permanently attached to the toothbrush by the neck portion.

45. The method of claim 30, wherein the brush head is removably attached to the toothbrush by a removable neck portion.

46. The method of claim 30, wherein the toothbrush is a manual toothbrush.

47. The method of claim 30, wherein the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate.

48. A method for preserving integrity of enamel of a tooth surface in the oral cavity of a subject, the method comprising: brushing the tooth surface at least twice per day with an antimicrobial tooth brash comprising a handle and a brash head attached thereto by a neck portion extending between the brash head and the handle, the brash head comprising a top surface and a bottom surface, the top surface comprising a bundle of polydopamine (PDA)- or PDA derivative- coated bristles embedded in or fused into the top surface of the brush head, whereinUCLA 2025-031 P-638957-PC brushing the tooth surface with the antimicrobial toothbrush creates a smooth hydrophilic interface with the tooth structure, thereby preserving the integrity of the enamel of the tooth surface.

49. The method of claim 48, further comprising:(a) rinsing the oral cavity with water; and(b) rinsing the oral cavity with an antimicrobial mouthwash.

50. The method of claim 48, wherein the bristles comprise a coating of about 20 nanometers to about 1 mm PDA or PDA derivative.

51. The method of claim 48, wherein the PDA- or PDA derivative -coated bristles comprise a first layer of a PDA coating and optionally a second layer of PDA coating.

52. The method of claim 48, wherein the wherein the PDA- or PDA derivative-coated bristles comprise a multilayer coating, said multilayer coating comprising:(a) a primary PDA layer;(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent.

53. The method of claim 48, wherein the wherein the PDA- or PDA derivative-coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising:(a) a primary PDA layer;(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and(c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA.

54. The method of claim 52 or 53, wherein the antimicrobial agent comprises a plant-derived antimicrobial extract(s), green synthesized nanoparticles, green-synthesized metal nanoparticles,UCLA 2025-031 P-638957-PC metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, silver, silver nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

55. The method of any one of claims 48-54, wherein each PDA or PDA derivative coating has a thickness of between 20 nanometers and 100 nanometers.

56. The method of claim 48, wherein 50% to 100% of the bristles are PDA or PDA derivative coated.

57. The method of claim 48, wherein the PDA or PDA derivative coating further comprises an additional agent such as an antimicrobial agent, such as a plant-derived antimicrobial extract(s), green synthesized nanoparticles, green-synthesized metal nanoparticles, metal ion, non-metal ion, zinc oxide, chlorhexidine. a mineral, an antiseptic, a remineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

58. The method of claim 57, wherein the PDA or PDA derivative is functionalized with an antimicrobial agent.

59. The method of claim 48, wherein the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to 90 degrees from the perpendicular, or a combination thereof.

60. The method of claim 48, wherein the brush head is permanently attached to the toothbrush by the neck portion.

61. The method of claim 48, wherein the brush head is removably attached to the toothbrush by a removable neck portion.

62. The method of claim 48, wherein the toothbrush is a manual toothbrush.UCLA 2025-031 P-638957-PC63. The method of claim 48, wherein the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate.

64. A method for reducing the persistence of oral microorganisms on a tooth brush post-brushing of teeth in an oral cavity of a subject and reducing re-contamination risk of the oral cavity, the method comprising: a. brushing the teeth with a toothbrush comprising bristles coated with at least one layer of poiydopamine (PDA) or PDA derivative; and b. rinsing the toothbrush with water and / or an antimicrobial mouthwash.

65. The method of claim 64, further comprising sanitizing the toothbrush by exposing the PDA- or PDA derivative-coated bristles to ultraviolet light.

66. The method of claim 64, wherein the oral microorganisms are bacteria, fungi and / or viruses.

67. The method of claim 64, wherein the bacteria are cariogenic and / or periodontopathic bacteria.

68. The method of claim 64, wherein the bristles comprise a coating of about 20 nanometers to about 1 mm PDA.

69. The method of claim 64, wherein the PDA coated-bristles comprise a first layer of a PDA or PDA derivative coating and optionally a second layer of PDA or PDA derivative coating.

70. The method of claim 64, wherein the PDA- or PDA derivative-coated bristles comprise a first layer of a PDA coating and optionally a second layer of PDA coating.

71. The method of claim 64, wherein the wherein the PDA- or PDA derivative-coated bristles comprise a multilayer coating, said multilayer coating comprising:(a) a primary PDA layer; and(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent.UCLA 2025-031 P-638957-PC72. The method of claim 64, wherein the wherein the PDA- or PDA derivative-coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising:(a) a primary PDA layer;(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and(c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA.

73. The method of claim 64, wherein the antimicrobial agent comprises a plant-derived antimicrobial extract(s), green synthesized nanoparticles, green-synthesized metal nanoparticles, metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, silver, silver nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

74. The method of any one of claims 64-73, wherein each PDA or PDA derivative coating has a thickness of between 20 nanometers and 100 nanometers.

75. The method of claim 64, wherein 50% to 100% of the bristles are PDA or PDA derivative coated.

76. The method of claim 64, wherein the PDA or PDA derivative coating further comprises an additional agent such as an antimicrobial agent, such as a plant-derived antimicrobial extract(s), green synthesized nanoparticles, green-synthesized metal nanoparticles, metal ion, non-metal ion, zinc oxide, chlorhexidine. a mineral, an antiseptic, a remineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

77. The method of claim 76, wherein the PDA or PDA derivative is functionalized with an antimicrobial agent.UCLA 2025-031 P-638957-PC78. The method of claim 64, wherein the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to 90 degrees from the perpendicular, or a combination thereof.

79. The method of claim 64, wherein the brush head is permanently attached to the toothbrush by the neck portion.

80. The method of claim 64, wherein the brush head is removably attached to the toothbrush by a removable neck portion.

81. The method of claim 64, wherein the toothbrush is a manual toothbrush.

82. The method of claim 64, wherein the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate.

83. A method for reducing the risk of physical wear and tear of a toothbrush, the method comprising:(a) coating bristles of the toothbrush with a first layer of polydopamine (PDA) or PDA derivative; and(b) optionally coating the PDA- or PDA derivative-coated bristles of step (a) with a second layer of PDA or PDA derivative.

84. The method of claim 83, wherein the bristles comprise a coating of about 20 nanometers to about 1 mm PDA or PDA derivative.

85. The method of claim 83, wherein the PDA- or PDA derivative-coated bristles comprise a first layer of a PDA or PDA derivative coating and optionally a second layer of PDA or PDA derivative coating.

86. The method of claim 83, wherein the wherein the PDA- or PDA derivative -coated bristles comprise a multilayer coating, said multilayer coating comprising:(a) a primary PDA layer; andUCLA 2025-031 P-638957-PC(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent.

87. The method of claim 83, wherein the wherein the PDA- or PDA derivative-coated bristles comprise a multilayer PDA coating, said multilayer PDA coating comprising:(a) a primary PDA layer;(b) a bioactive reservoir layer immobilized on the primary PDA layer, said bioactive reservoir layer comprising an antimicrobial agent; and(c) a second PDA layer, wherein said second PDA layer encapsulates the bioactive reservoir layer between the primary PDA layer and the second PDA.

88. The method of claim 86 or 87, wherein the antimicrobial agent comprises a plant-derived antimicrobial extract(s), green synthesized nanoparticles, green-synthesized metal nanoparticles, metal ion, non-metal ion, zinc oxide, chlorhexidine, a mineral, an antiseptic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, silver, silver nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.

89. The method of any one of claims 83-88, wherein each PDA or PDA derivative coating has a thickness of between 20 nanometers and 100 nanometers.

90. The method of claim 83, wherein 50% to 100% of the bristles are PDA or PDA derivative coated.

91. The method of claim 83, wherein the PDA or PDA derivative coating further comprises an additional agent such as an antimicrobial agent, such as a plant-derived antimicrobial extract(s), green synthesized nanoparticles, green-synthesized metal nanoparticles, metal ion, non-metal ion, zinc oxide, chlorhexidine. a mineral, an antiseptic, a remineralizing agent such as fluoride, bioglass and calcium phosphate, a sugar alcohol, a sugar alcohol derivative such as xylitol and erythritol, neem, essential oil, probiotic, a natural or synthetic antifungal such as chitosan, nystatin, and amphotericin B, an antifouling agent such as a zwitterionic polymer, a flavoring agent, silver, silver nanoparticles, curcumin, an antibiotic, or any combination thereof, or an extended release form thereof.UCLA 2025-031 P-638957-PC92. The method of claim 91 , wherein the PDA or PDA derivative is functionalized with an antimicrobial agent.

93. The method of claim 83, wherein the bristles are perpendicularly embedded in or fused into the top surface of the brush head, are embedded in or fused into the top surface of the brush head at an angle of from 0 degrees to 90 degrees from the perpendicular, or a combination thereof.

94. The method of claim 83, wherein the brush head is permanently attached to the toothbrush by the neck portion.

95. The method of claim 83, wherein the brush head is removably attached to the toothbrush by a removable neck portion.

96. The method of claim 83, wherein the toothbrush is a manual toothbrush.

97. The method of claim 83, wherein the toothbrush is an electric toothbrush and the bristles are configured to vibrate and / or rotate.

98. The device, appliance or product of any one of claims 1-12, wherein the device, appliance or product is or comprises a toothbrush, toothbrush bristles, toothbrush heads, toothbrush handles, protective caps, tongue cleaners, interdental sticks, toothpicks, denture fitting surfaces, retainers, aligners, night guards, appliance storage cases, sutures such as oral sutures, endoscope tubing, endoscope housings, CPAP ventilation tubing, reusable or non-reusable shaver heads, surgical robotic parts not autoclavable, toilet seat components, bidet components, coffee machine water contact parts, infant teething toys, high-touch consumer grips such as used in a gym or transit vehicles, or door handles.

99. A method for reducing microorganisms or providing a protective barrier against microorganisms on a device, appliance or product such as a toothbrush, toothbrush bristles, toothbrush heads, toothbrush handles, protective caps, tongue cleaners, interdental sticks, toothpicks, denture fitting surfaces, retainers, aligners, night guards, appliance storage cases, sutures such as oral sutures, endoscope tubing, endoscope housings, CPAP ventilation tubing, reusable or non-reusable shaver heads, surgical robotic parts not autoclavable, toilet seat components, bidet components, coffee machine water contact parts, infant teething toys, high-UCLA 2025-031 P-638957-PC touch consumer grips such as used in a gym or transit vehicles, or door handles, comprising providing the device, appliance or product of any one of claims 1-12.

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