Subgingival medication delivery tray

Abstract

Oral appliance delivery trays are provided for use in maintaining or improving oral health, particularly the subgingival area. Methods of manufacturing personalized oral appliance delivery trays are provided. Prefabricated oral appliance trays are provided that include pre-deposited compounds. The compositions and methods may be used to maintain or improve oral, periodontal and systemic health, or to prevent or delay oral, periodontal or systemic health problems associated with the oral cavity.

Description

[Technical Field]

[0001] The present invention relates to the fields of oral health, therapeutic dental and systemic health applications and periodontal care. [Background technology]

[0002] More than half of all adults over the age of 30 and 70% of adults over the age of 65 have periodontal disease. Untreated periodontal disease can lead to chronic periodontitis, an oral infection that causes bone and tooth loss. Periodontal disease is associated with many other systemic conditions, including diabetes, cardiovascular disease, Alzheimer's disease, respiratory disease, digestive disease, autoimmune degenerative diseases, and rheumatic diseases. People with poorly controlled diabetes are more susceptible to gum disease and tooth loss. People with periodontal disease are more susceptible to the oral and systemic effects of diabetes and plaque buildup. Periodontal disease makes diabetes more difficult to control. Diabetics, including those with type 2 diabetes, are more susceptible to periodontal disease and have a reduced ability to fight infection. Diabetics tend to have increased glucose in their saliva, which provides a source of oral bacteria, making periodontal disease and its damaging effects much more widespread and prevalent over time. Periodontal disease worsens the prognosis of pre-existing heart conditions, which can lead to death, and increases the risk of stroke. Oral bacteria are found in arterial plaque. Periodontal disease is also a likely risk factor for Alzheimer's disease, which affects 5.7 million adults in the United States. People over 60 with chronic periodontal disease (10 years or more) were 70% more likely to develop dementia than those with healthy gums. Alzheimer's patients with periodontal disease decline more rapidly than those without periodontal disease. Harmful bacteria from periodontal disease can be inhaled into the lungs, causing bronchitis, emphysema, and pneumonia. This can lead to chronic obstructive pulmonary disease (COPD), which can cause irreversible damage to the respiratory system. Chronic inflammation caused by periodontal disease can worsen these respiratory conditions and potentially increase the risk of other emerging respiratory conditions, such as COVID-19 and SARS. Periodontal disease (gum disease) during pregnancy increases the risk of giving birth to a preterm and / or low birth weight baby. Moderate to advanced periodontal disease is common in people with rheumatoid arthritis. Rheumatoid arthritis patients with advanced periodontal disease are prone to increased chronic and painful relapses, along with increased permanent degenerative effects such as joint damage.Higher incidence and more severe periodontal disease occurs in patients with immune-related chronic inflammatory diseases, including lupus, Crohn's disease, colitis, inflammatory bowel disease, and colorectal cancer. These diseases can lead to ulcers and perforations, further worsening people's overall health and well-being and can even be fatal.

[0003] Biofilm accumulation in the supragingival and subgingival or subgingival sulci occurs continuously. Diet and dental visits may disrupt or temporarily slow biofilm accumulation, but this biofilm buildup occurs daily and becomes established. Thorough debridement by a specialized clinician in the dental setting temporarily destroys or removes much of the biofilm, but biofilm continues to accumulate. Biofilm adheres to tooth structure, reconstructed tooth structure, exposed dentin, or areas of bone loss, accumulating on cementum and dentin surfaces. Biofilm accumulation results in a decrease in pH, accelerating the disease process. The damaging and destructive consequences of periodontal disease are irreversible once destruction of soft tissue, periodontal ligament (PDL) attachment, and / or alveolar bone occurs. Bone resorption and degeneration may occur. Bone loss does not regrow and is permanent.

[0004] The pellicle is an acellular proteinaceous film that forms on tooth structures. Bacteria adhere to the pellicle and colonize the tooth surface. The first bacteria to colonize are oxygen-dependent bacteria. As oxygen-dependent bacterial colonies grow, plaque forms. Oxygen diffusion becomes limited, and anaerobic gram-negative bacteria colonize the plaque. Gram-negative bacteria form colonies containing bacteria using a fermentation pathway that produces lactic acid as a by-product. Over time, lactic acid can lower the pH below 5.5, leading to tooth demineralization. To avoid destruction of enamel rods and dentin surfaces and reduce the risk of dental caries, the mineralization rate in a subject's mouth must remain equal to the demineralization rate.

[0005] The accumulation of certain forms of gram-negative and gram-positive bacteria in periodontal pockets can lead to pocket involvement, which can become more generalized and result in multiple pockets. As pathogen levels increase, pH decreases, crevicular fluid flow increases, and oxygen levels decrease. The presence of pathogens contributes to attachment loss, further degenerative periodontal function, and future systemic risk for tooth loss and overall oral and systemic disease. Gingivitis, periodontal disease, or periodontitis may occur. Additional health risks include, but are not limited to, Alzheimer's disease / dementia, respiratory disease, cardiovascular / heart and stroke disease, type 2 diabetes, premature and low birth weight in newborns, colorectal disease and potential cancer, rheumatoid arthritis and autoimmune diseases that contribute to painful joint damage and erectile dysfunction.

[0006] In degenerative periodontal disease, oral structures surrounding the bony socket become inflamed around tissue attachment areas, including the gingival sulcus and the vicinity of the periodontal ligament (PDL). While not limited by mechanism, increased bleeding and edematous crevicular fluid flow lead to the proliferation of gram-negative bacteria and increased biofilm. Soft plaque accumulates and elevates to a hard, calculus-like substance. Cementum degenerates, and the disease process infects the periodontal ligament. The affected PDL damages healthy supporting alveolar bone structures necessary for tooth strength, stability, and support. Ultimately, one or more teeth may be lost. Patients may opt for complex and costly procedures, such as tooth structure removal, prosthetic and reconstructive dental procedures, soft or connective tissue grafts, bone grafts, surgically placed implants, removable or permanent dentures, or partial dental devices.

[0007] Dental implant care is further complicated because clinical debridement can damage titanium threads, and probing or scaling with dental probes or other instruments can increase the risk of implant infection and failure. Radiographs provide only two-dimensional information about implant health, and the absence of clinical soft tissue information can prolong the time to diagnose infection at or near the implant site. Because periapical radiographs can only provide a two-dimensional image of a three-dimensional object, many infected bone defects may be missed. The inability to determine buccolingual bone dimensions is a major drawback for implant procedures. Two-dimensional radiographs are insufficient to determine bone quantity and quality, identify critical structures, and depict the spatial relationships between structures within the proposed implant site. Therefore, periapical radiographs are usually limited to initial, intraoperative, and postoperative evaluations of the proposed implant site. Therefore, it is difficult to diagnose and monitor implant failure in a timely manner.

[0008]

[0009] Although brushing and flossing remove some biofilm and bacteria, they only penetrate pockets to a depth of 3-4 mm. There are many treatment protocols for gingivitis, periodontal disease, and attachment loss, which leads to the destruction of degenerated alveolar bone support structures. Treatment methods include, but are not limited to, general hygienic debridement, chemical topical solution rinses, antimicrobial injections, antibiotic injections such as minocycline, HCl, microspheres, scaling and root planing, gingivectomy, osteotomy surgical procedures, and bone grafting. However, many of these procedures must be performed by a dental professional and are expensive or ineffective.

[0010] Furthermore, no devices currently exist for maintaining fixed, surgically placed dental implants. Dental implants are subject to the same deteriorative forces as natural teeth. Although implant materials may be more resistant to degradation than natural teeth, implants can serve as sites for bacterial colonization and periodontal disease processes. Furthermore, the pocket surrounding the implant is vulnerable to infection and periodontal disease and no longer has the periodontal ligament for support. Routine dental care procedures, such as periodontal probing, clinical debridement, and scaling, are not appropriate for all implant types. Summary of the Invention

[0011] The present application provides oral appliance trays for delivering compounds to the gingival, supragingival, subgingival, or gingival and subgingival regions of at least one tooth of a subject, methods for manufacturing individualized oral appliance trays for delivering compounds to the gingival, supragingival, subgingival, or gingival and subgingival regions of a tooth, and methods for managing biofilm by managing the pH of a subject. The oral appliance trays include a gasket, the gasket including a supragingival portion, a gingival delivery region, and one or more delivery ports including an outlet within the gingival delivery region, the delivery port selected from the group including a delivery reservoir, and a delivery pore including an inlet located in the supragingival portion. In one aspect, the gasket includes a material suitable for oral use. In some aspects, the material suitable for oral use is selected from the group including a non-biodegradable polymer, a thermoformable plastic, and a thermoformable polymer. In some embodiments, when the tray is placed in the subject's mouth, the compound flows through one or more delivery pores to the gingival, subgingival, or gingival and subgingival region of at least one tooth. In some embodiments, when the tray is placed in the subject's mouth, the delivery reservoir maintains the outlet and the compound within a fixed reservoir in the subgingival region of at least one tooth.

[0012] In various embodiments, the oral appliance tray includes one or more delivery ports for delivering a compound to the gingival, subgingival, or gingival and subgingival regions of at least two teeth of a subject. In various embodiments, the gingival region includes one or more regions selected from the group including the supragingival region, the gingiva, the subgingival region, the sulcus, the periodontal ligament, the periodontal region, the root, the margins of natural and reconstructed dentition, the dental implant region, and the implant base. In some embodiments, the oral appliance tray is selected from the group including a mandibular arch oral appliance tray and a maxillary arch oral appliance tray.

[0013] In some embodiments, the compound is selected from the group including oxygenating agents, antimicrobial agents, antibiotic agents, desensitizing compounds, remineralizing compounds, therapeutic compounds, anti-plaque forming compounds, anti-caries compounds, whitening compounds, pH increasing compounds, pH maintaining compounds, biofilm managing compounds, cleansing compounds, and maintenance compounds.

[0014] In various embodiments, the diameter of the one or more delivery pores is within the range of 0.5 mm to 12 mm. In certain embodiments, the outlet height of the one or more delivery ports is within the range of 0.5 mm to 12 mm, and the outlet width of the one or more delivery ports is within the range of 0.5 mm to 12 mm. In some embodiments, the supragingival portion and gingival delivery area are shaped to conform to the subject's teeth and gingival tissue structure. In certain embodiments, the tray is a personalized oral appliance tray, and the at least one outlet location is determined by at least one periodontal measurement from the subject's teeth. In some embodiments, the outlet location is determined by at least six periodontal measurements from the subject's teeth.

[0015] The present application provides a method for reducing the amount of one or more bacteria in the gingival region of a subject at risk for periodontal disease, the method comprising the steps of: (a) providing an oral appliance tray of the present application; and (b) delivering a compound to the subject, wherein the compound is selected from the group including an oxygenating agent, an antimicrobial agent, an antibiotic agent, a remineralizing compound, a desensitizing compound, a whitening compound, an anti-caries compound, a mediator vesiculo-blistering compound, a cleansing compound, a stabilizing compound, and a pH-balancing compound, wherein the compound is provided in the oral appliance tray. In embodiments of the method, the bacterium is selected from the group consisting of Gram-negative bacteria, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Eubacterium nucleaturm, Fusobcterium nucleatum, Prevotella intermedia, Campylobacter rectus, and the like. rectus, Capnocytophaga species (gingivalis, ochracea, sputigena), oral anaerobes (Peptostreptococcus micros, and Eikenella corrodens species). The method may further comprise preparing the compound according to a delivery regimen comprising multiple delivery events.

[0016] There is provided a method for manufacturing a personalized oral appliance tray according to claim 1. The method may be used to treat a subject at risk of periodontal disease, a subject at risk of demineralization, a subject at risk of bleeding on probing, a subject at risk of inflammation or degeneration, a subject at risk of increased biofilm accumulation of actinomyces and aerobic cocci, a subject in need of pre-operative bacterial treatment, a subject in need of post-operative bacterial treatment, a subject at risk of pre-operative susceptibility, a subject at risk of post-operative susceptibility, a subject at risk of dental discomfort, a subject at risk of phagocytosis, a subject at risk of hyperresponsive phagocytosis, a subject at risk of overproduction of interleukins, prostaglandins and cytokines, a subject at risk of uncontrolled colonization of anaerobic gram-negative bacteria, or .... The method includes obtaining at least one periodontal measurement from a tooth of a subject selected from the group including subjects at risk, subjects at risk for endotoxins, subjects at risk for increased crevicular fluid, subjects at risk for increased acidic saliva production, subjects at risk for increased C-reactive protein (CRP) levels, subjects at risk for oral or systemic autoimmune responses, subjects at risk for peri-implantitis, subjects at risk for implant failure, subjects at risk for acute and chronic xerostomia, subjects at risk for halitosis, subjects at risk for reduced pH levels, subjects at risk for systemic disease, and subjects at risk for effects from medication from acute and chronic disease. The method further includes determining the morphology of the target dental arch using at least one periodontal measurement to determine the placement of an outlet for at least one port using at least one periodontal measurement, and forming a personalized oral appliance tray with a gasket complementary to the morphology of the target dental arch, the gasket including a supragingival portion, a gingival delivery region, and one or more delivery ports including an outlet within the gingival delivery region, the delivery port selected from the group including a delivery reservoir and a delivery pore including an inlet located in the supragingival portion. In an embodiment of the method, forming the oral appliance tray includes a process selected from the group including laser cutting, layer deposition, laser printing, laser deposition, molding, and casting. In various embodiments, the method further includes correlating at least one dimension of the outlet of the delivery port with the at least one periodontal measurement.

[0017] Methods for managing biofilm in a subject are provided. The methods include providing a compound in an oral appliance tray of the present application, placing the oral appliance tray containing the compound in the subject's mouth, and maintaining the oral appliance tray in the subject's mouth for a predetermined period of time and frequency, thereby altering the biofilm accumulation rate, pH, or biofilm accumulation rate and pH in the subject's mouth. In various aspects, the methods provide guided biofilm therapy. In some aspects, the methods further include determining the location of at least one port using at least one periodontal measurement. In various aspects, the methods further include correlating the dimensions of the outlet of the at least one port with the at least one periodontal measurement.

[0018] In one embodiment, the present application provides an oral appliance tray for delivery of a compound to reduce the risk of oral pathogens from mask wearing, respiratory infection or any respiratory disease.

[0019] 1. A prefabricated oral appliance tray for delivering a compound to the gingival, supragingival, subgingival, or gingival and subgingival regions of at least one tooth of a subject, comprising a gasket, the gasket comprising a supragingival portion, a gingival delivery region, and one or more delivery ports comprising an outlet within the gingival delivery region, the delivery port selected from the group comprising a delivery reservoir and a delivery pore comprising an inlet located within the supragingival region.

[0020] In one embodiment, a veterinary oral appliance tray is provided for delivering a compound to the gingival, supragingival, subgingival, or gingival and subgingival regions of at least one tooth of a non-human animal. The veterinary oral appliance tray includes a gasket, the gasket including (a) a supragingival portion, (b) a gingival delivery region, and (c) one or more delivery pores with an inlet and an outlet, the inlet being located in the supragingival portion and the outlet being in the gingival delivery region. In some aspects, the veterinary oral appliance tray further includes a toy element.

[0021] In one embodiment, the present application provides a non-transitory computer-readable medium comprising instructions that, when executed by a processor of a three-dimensional (3D) printer, instruct the processor to receive and process a digital 3D image model of a patient's maxillary arch, mandibular arch, or both the maxillary and mandibular arches to create a dental device; receive and process coordinates and dimensions of delivery ports configured in the dental device, the delivery port coordinates and dimensions being based on periodontal measurements performed on the patient's maxillary and mandibular arches; map the delivery port coordinates and dimensions to the digital 3D image model; and instruct the 3D printer to form a dental device having a delivery port according to the digital 3D image model and according to the coordinates and dimensions of the delivery port mapped thereto.

[0022] In one embodiment, a computer-implemented method is provided, operable in a three-dimensional (3D) printer, comprising receiving and processing a digital 3D image model of at least one dental arch selected from the group consisting of a maxillary arch and a mandibular arch of a subject to create a dental device, receiving and processing coordinates and dimensions of a delivery port configured in the dental device, the delivery port coordinates and dimensions being based on periodontal measurements performed on the subject dental arch, mapping the delivery port coordinates and dimensions to the digital 3D image model, and instructing the 3D printer to form the dental device having the delivery port according to the digital 3D image model and according to the coordinates and dimensions of the delivery port mapped thereto.

[0023] In one embodiment, a computer-implemented method operable on a CAD / CAM machine is provided, the method including receiving and processing coordinates and dimensions of a delivery port configured on a dental device, the delivery port coordinates and dimensions being based on periodontal measurements taken on at least one dental arch of a subject, mapping the delivery port coordinates and dimensions to the dental device, and instructing the CAD / CAM machine to form the delivery port on the dental device according to the delivery port coordinates and dimensions mapped thereto.

[0024] In one embodiment, a computer-implemented method operable on a CAD / CAM machine is provided, the method including the steps of receiving and processing coordinates and dimensions of a delivery port configured in a dental device, the delivery port coordinates and dimensions being based on periodontal measurements taken on at least one dental arch of a subject, mapping the delivery port coordinates and dimensions to a digital 3D image model of the subject's dental arch to create the dental device, the at least one dental arch being selected from the group consisting of the subject's maxillary arch and mandibular arch, and instructing the CAD / CAM machine to form the dental device including the delivery port according to the delivery port coordinates and dimensions and according to the digital 3D model.

[0025] Incorporation by Reference All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. [Brief explanation of the drawings]

[0026] [Figure 1A] Showing healthy teeth and grooves. [Figure 1B] Healthy teeth and grooves are shown, along with a brush placed next to the teeth.

[0027] [Figure 2] X-rays of teeth are provided using a periodontal dental probe to measure the sulcus. Figure 2A shows a healthy tooth and a periodontal dental probe measuring a healthy shallow sulcus, with the sulcus being less than 3 mm deep. Figure 2A shows a healthy attachment. Figure 2B shows a tooth with periodontal disease. The sulcus is measured over a depth of 5 mm using a dental probe. Bone loss and furcations are visible. Figure 2B shows an unhealthy example with attachment loss, bone loss, and furcation involvement, as well as periodontal disease.

[0028] [Figure 3]A tooth with an affected groove beyond the reach of the brush bristles is shown.

[0029] [Figure 4] A tooth with an affected sulcus and visible inflammation of the gums is shown.

[0030] [Figure 5] Shows the same tooth as in Figure 4 shown with a periodontal probe. The groove is more than 5 mm deep.

[0031] [Figure 6] 5 shows teeth as shown in FIG. 4 with an oral appliance tray placed over the teeth.

[0032] [Figure 7] Teeth are shown with oral appliance trays placed over the teeth to deliver compounds of interest supragingivally and subgingivally below the gum line.

[0033] [Figure 8] The teeth are shown after a completed treatment regimen that included reduced sulcus probing depth, decreased inflammation, and removal of hard calculus.

[0034] [Figure 9]This figure summarizes the results of oral DNA analysis in saliva samples obtained from patients before treatment with oral appliance trays. Bacterial counts in copies / ml (bacterial genome) are shown on the y-axis, and bacterial types are shown on the x-axis. High-risk pathogens, including A. actinomycetemcomitans (Aa), P. gingivalis (Pg), T. forsythia (Tf), and Treponema denticola (Td), are present at levels above the treatment threshold. Moderate-risk pathogens, including Eubacterium nucleaturm (En), Fusobacterium nucleatum (Fn), Prevotella intermedia (Pi), Campylobacter rectus (Cr), and oral anaerobe Peptostreptococcus micros (Pm), are present at levels above the treatment threshold. Low-risk pathogens, including Eikenella, are present at levels above the treatment threshold. LQ refers to the limit of quantitation that can be repeated. The line across each bar indicates the treatment threshold. Oral DNA testing was performed by OralDNA Labs, Access Genetics, Eden Prairie, MN.

[0035] [Figure 10]Figure 9 summarizes the results of oral DNA analysis of saliva samples obtained from the same patient (shown in Figure 9) after 30 days of twice-daily 15-minute treatment with the compounds of interest in an oral appliance tray. Bacterial counts, expressed as copies / ml (bacterial genome), are shown on the y-axis, and bacterial types are shown on the x-axis. High-risk pathogens, including A. actinomycetemcomitans (Aa), P. gingivalis (Pg), T. forsythia (Tf), and Treponema denticola (Td), were below the treatment threshold. A. actinomycetemcomitans (Aa), P. gingivalis (Pg), and Treponema denticola (Td) were below the limit of quantification. Moderate-risk pathogens, including Eubacterium nucleaturm (En), Fusobacterium nucleatum (Fn), Prevotella intermedia (Pi), Campylobacter rectus (Cr), and oral anaerobe Peptostreptococcus micros (Pm), were present at levels below the treatment threshold. Eubacterium nucleaturm (En), Prevotella intermedia (Pi), and Campylobacter rectus (Cr) were below the limit of quantification. Low-risk pathogens, including Eikenella, were present at levels below the treatment threshold. The change in pathogen prevalence after treatment using the oral appliance trays of the present application is significant and significant. The line across each bar indicates the treatment threshold. Oral DNA labs were performed by OralDNA Labs, Access Genetics, Eden Prairie, MN.

[0036] [Figure 11A]Provides a depiction of the progression from healthy tissue to unhealthy periodontal diseased tissue. [Figure 11B] Depiction of biofilm formation obtained from Johnson & Johnson Consumer Inc 2018.

[0037] [Figure 12] Intraoral photographs are provided from a subject with advanced periodontal disease (Case 1). Class IV subgingival and supragingival soft plaque and hard calculus are present. Note the exposed dentin and lower gingival level from a previous surgical pocket reduction procedure. The subject's daily home care routine consisted of brushing with a battery-operated toothbrush, flossing, flossing for implant and bridge restorations, medicated mouthwash, and fluoridated mouthrinse. Additionally, the subject underwent clinical debridement up to twice a month prior to treatment. Teeth have several problems such as: attachment loss, bone loss, edematous affected tissue, inflammation, bleeding, open margins on reconstructed crowns and bridgework, exposed dentin, fractures of demineralized incisor edges with exposed dentin, enamel wear from bruxism and acid erosion on the buccal, facial, occlusal and incisal surfaces, elongated raised crowns and natural dentition and structured bone sockets and attachment loss due to bone loss, malignant transformation due to bone loss and attachment stability, displacement, fractured dentition and unstable alignment and obliteration, loss of oxygenation and blood circulation in soft tissues due to split hard calculus deposits causing advanced irreversible periodontal disease with necrotic tissue and a potential increased risk of further systemic disease.

[0038] [Figure 13] 1 provides intraoral photographs from a subject with advanced periodontal disease after 10 days of use of an oral appliance delivery tray with a case-specific compound of interest applied (Case 1). Compared to FIG. 12, there is a substantial reduction in supragingival and subgingival calculus, as well as a substantial reduction in inflammatory and edematous soft tissue.

[0039] [Figure 14]1 provides intraoral photographs from a subject with advanced periodontal disease after 20 days of use of an oral appliance delivery tray with a case-specific compound of interest applied (Case 1). There is a substantial reduction in supragingival and subgingival calculus, as well as inflamed and edematous soft tissue, between the 20-day time point and both the 10-day time point (FIG. 13) and before treatment (FIG. 12).

[0040] [Figure 15] Intraoral photographs are provided from a subject (Case 1) after 30 days of use of an oral appliance delivery tray containing the case-specific compound of interest. No subgingival or supragingival calculus was observed, visual indicators such as edematous areas and redness had resolved, no bleeding occurred on probing, and the maximum probing depth was healthy at 3 mm or less.

[0041] [Figure 16] 1 shows periodontal charts from the subject of Case 1 at initial presentation, at the start of treatment, and after completing 30 days of treatment with oral appliance trays. Note the reduction in probing depth after treatment.

[0042] [Figure 17]Shown are full mouth series radiographs of a subject having an endodontic root canal procedure with a surgically placed titanium abutment core implant, a three-unit semi-precious metal fused to a porcelain titanium implant bridge, a semi-precious metal fused to a porcelain crown, a bonded composite restoration, and a semi-precious metal fused to a porcelain cantilever fused crown, and a semi-precious metal fused to a porcelain crown. The radiographic series shows the presence of implant-based reconstructive dental procedures, reconstructed crowns and bridgework and implant-abutment bridgework, the presence of natural dentition showing advanced attachment loss, bone loss, open margins on the reconstructed crowns and bridgework, exposed dentin, fractured incisal edges of demineralized incisors with exposed dentin, enamel wear from bruxism and acid erosion on the buccal, facial, occlusal, and incisal surfaces, elongated, elevated crowns and natural dentition and formed bone sockets and attachment loss due to bone loss, malignant transformation due to bone loss and attachment stability, displacement, fractured dentition, and unstable alignment, loss of oxygenation and blood circulation in the soft tissues due to split, hard calculus deposits causing necrotic tissue and advanced, irreversible periodontal disease. This photographic example demonstrates the effectiveness and capability of this oral device concept and the satisfactory results in improving the prognosis of patients susceptible to periodontal disease.

[0043] [Figure 18A] 1 is an image of an oral appliance delivery tray for the maxillary arch. The pore or channel inlets are located within the supragingival region. The outlets are positioned based on the subject's periodontal chart and periodontal measurements. The outlets allow delivery of the compound of interest to the subject's extended pocket depths. [Figure 18B]An image of the oral appliance delivery tray is provided, showing the ports. The dark areas on the distal buccal and lingual walls of the tray indicate pores or port channels designed to allow compound to flow into the open areas located all around the periodontal implant measurement. The tray reveals the large unprotected gaps available for tray preparation, which exist due to the patient no longer having bone loss from the periodontal ligament and previous subgingival infection. This device was designed to access the subgingival area, which is extremely difficult to cleanse and restore homeostasis and stability to the surrounding soft tissue structures. Measurements were obtained from a periodontal probe during the periodontal examination. The measurements were used to position the pore outlets to coincide with locations where the patient had evidence of attachment and bone loss, inflammation, bleeding, edematous tissue, exposed dentin and recessed gingiva, hard, mineralized calculus, and intrinsic and extrinsic staining, as well as where Class IV aggressive periodontal disease was present. Typically, a periodontal chart establishes accurate pocket depth measurements for a minimum of six teeth. Periodontal measurements may include information on bleeding, cavities, peri-implant cavities, furcation involvement, mobility, clinical attachment loss or (CAL), gingival margin, plaque load, bleeding on probing or (BOP), cemento-enamel junction or (CEJ), implant, healthy and unhealthy implant and peri-implant tissues, alveolar bone attachment, gingival hyperplasia, pseudo-pocket, peri-implant pocket, and esthetic zone. To ensure periodontal measurements with a minimum of six measurements per tooth, alginate impressions and digital scans were taken to fabricate dental appliance trays. The trays allowed for direct delivery of compounds to the sulci in the affected tissues by mirroring the findings on the periodontal chart.

[0044] [Figure 19]

[0023] Figure 19A provides images of an oral appliance delivery tray for the maxillary arch for compound delivery to a single affected pocket depth or compound delivery to a surgical implant pocket. Figure 19A is an image of a portion of the entire tray shown in Figure 19B. The delivery tray includes a delivery reservoir.

[0045] [Figure 20] 1 provides an image of a standard oral appliance delivery tray for the mandibular arch for delivering compounds to multiple pocket depths of each tooth pocket, the delivery tray including delivery slots.

[0046] [Figure 21]Images of teeth from three subjects are provided before treatment and after 30 days of twice-daily delivery of compounds at 15-minute intervals via an oral appliance delivery tray. After treatment, teeth and gums are improved. Plaque, tartar, and hard calculus buildup are reduced after treatment. The white mineralized line at the base of the margin where the tooth meets the pre-treatment tissue forms a defined white line across the margin. In the second post-treatment image, the hard calcified plaque and tartar line are gone. In the second example, the dark black stains are gone in addition to the hard calcified plaque. This demonstrates a substantial reduction in the pathogens, biofilm, and bacteria contained in the hard calcified plaque and its diseased formations. This is substantially reduced by the specific compounds placed inside the tray device in the specified cases. The patient wore the tray for 15 minutes in the morning and 15 minutes in the evening. Within 10 days of the test, pathogens were substantially reduced, and the patient's oral and general health was significantly improved by the present invention. The compound used in this patient's custom-made tray device was a combination of 1.7g of hydrogen peroxide oral debridement in a foam formulation described as an oral wound cleanser consisting of 3% ethyl alcohol, potassium sorbate, peppermint oil, xylitol, 1% povidone-iodine, and 1% chlorhexidine solution. This combination provided direct access to the port channel and acted as an antimicrobial and antiseptic oxygenated cleansing source, achieving and maintaining steady-state timed intervals on a daily basis to destroy colonizing pathogen formations. This resulted in the removal of degenerating pathogens and the debridement of existing parthenogenetic formations by disrupting further formation of biofilm, pellicle, and plaque calcification, as well as staining. This particular combination raises the pH level to homeostasis, reducing the formation of degenerative effects such as the breakdown of surrounding natural tooth structure, further periodontal infection, abscesses, periapical abscesses, further attachment and bone loss, halitosis, and reducing the spread of this difficult and devastating prognosis of advanced degenerative periodontal and systemic disease that claims the oral and overall health and well-being of so many patients.

[0047] [Figure 22]1 provides images of multiple teeth from a subject before treatment and after 30 days of delivery of compound via an oral appliance delivery tray twice daily at 15 minute intervals.

[0048] The white calcified line distinguishes the marking at the base of the margin where the tooth meets the tissue in the pre-treatment image, creating a defined white line across the margin. In the second post-treatment photograph, the line is gone. Pathogens, biofilm, and bacteria contained in hard, calcified plaque and its diseased formations are substantially reduced. This is achieved by specific compounds placed inside the tray device in a prescribed case. This was achieved by the patient wearing the tray for 15 minutes in the morning and 15 minutes in the evening for 10 days at the time of examination. Pathogens were reduced, and the patient's oral and general health were significantly improved by the present invention. The specific patient in this case used a custom-made tray device with a different compound combination due to the subject's sensitivity. The subject was experiencing exposed dentin and pitting from toothbrush abrasion, as well as sensitivity associated with overuse of commercial whitening products, which demineralize tooth minerals and dry out enamel rods and tubules on the dentin surface. The patient required a combination of debridement and oxygenation mechanisms designed to minimize further demineralization of natural tooth structure. While not limited by mechanism, demineralization can increase sensitivity, accelerate tooth degeneration, and lead to severe future caries. A combination of 3% potassium nitrate for sensitivity, ethyl alcohol-free demineralization of natural tooth structure, potassium sorbate, peppermint oil, xylitol, 1% povidone-iodine and 1% chlorhexidine solutions in a gel solution, and 1% sodium fluoride, which acts as an antimicrobial and antiseptic oxygenating cleansing source, was used. Delivery of this compound via direct access to the port channel maintains steady-state compound delivery at timed intervals on a daily basis to destroy colonizing pathogens. This combination provided a great source of comfort in reducing sensitivity to eating and drinking, and remineralized the dentinal tubules, not only reducing sensitivity but also reducing the potential risk of future caries by strengthening exposed, unprotected tooth structure. Without being limited by mechanism, this combination may disrupt further formation of biofilm, pellicle, and plaque mineralization.It may also be beneficial to remove degenerative pathogens and introduce debriding of existing pathogen formations. This specific combination raises the pH level to homeostasis and reduces the formation of degenerative effects. Degenerative effects may include, but are not limited to, the destruction of surrounding natural tooth structure, failure of reconstructed tooth structure, further periodontal infection, abscesses, periapical abscesses, further attachment and bone loss, dry mouth and halitosis.

[0049] [Figure 23] An image of a periodontal tray with wider ports for subjects with advanced periodontal classification is provided. This figure shows six buccal ports on two teeth. Lingual ports may also be present (not shown).

[0050] [Figure 24] 1 illustrates an exemplary process for forming a dental device having one or more delivery ports according to the coordinates and dimensions of the delivery ports mapped thereto, the port coordinates and dimensions being based on periodontal measurements performed on at least one dental arch of a subject.

[0051] [Figure 25] Illustrated is a computing system 200 in which a computer-readable medium 206 can provide instructions for performing any of the methods disclosed herein.

[0052] [Figure 26] 23 provides a post-treatment x-ray image (Eaglesoft) of an advanced periodontal case using an intraoral appliance delivery tray as shown in Figure 23. Bone regeneration occurred and the implant stabilized.

[0053] [Figure 27] 24 provides intraoral images of an advanced periodontal case after treatment using the oral appliance delivery tray shown in FIG. 23. The severity of multiple periodontal disease-related symptoms was reduced. The improvement in oral health is significant. DETAILED DESCRIPTION OF THE INVENTION

[0054] The following sections describe different aspects of the invention in more detail. Each aspect, embodiment, or feature of the invention can be combined with any other aspect, embodiment, or feature of the invention, unless expressly stated otherwise.

[0055] Unless otherwise defined, all technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which this invention belongs.

[0056] When a range of values ​​is provided, it is understood that each intervening value is encompassed within the invention. The upper and lower limits of smaller ranges may independently be included in the smaller ranges and are encompassed within the present application. Certain ranges are described herein by numerical values ​​preceded by the term "about." The term "about" is used to provide literal support for the exact number it precedes, as well as a number that is close to or approximately near the number it precedes. In determining whether a number is close to or approximately near a specifically recited number, the near or approximating unrecited number may be a number that, in the context in which it is presented, provides a substantial equivalent to the specifically recited number.

[0057] As used herein, "a," "an," and "the" can include multiple referents unless expressly and unambiguously limited to one referent.

[0058] Periodontal disease is a problem of global and national importance. Periodontal disease is believed to increase the risk or severity of numerous systemic diseases. Over 90 percent of adults in the United States have cavities, and one in four have untreated cavities. Prior to the present application, there were no effective treatments for sustained risk reduction of periodontal disease in patients, including but not limited to those with a genetic predisposition.

[0059] The present application provides oral appliance trays for delivering compounds to the gums and / or subgingival areas of patients at risk for periodontal disease. The oral appliance trays non-surgically deliver compounds of interest to the gums, supragingival, and / or subgingival areas of one or more teeth in a subject's oral cavity. Both standard and personalized oral appliance trays are provided. The oral appliance trays may be used in regimens including multiple daily uses, daily use, multiple intermittent daily uses, weekly use, or monthly use. As described below, the oral appliance trays may be used on the maxillary or mandibular arch of a subject's oral cavity. In some cases, the oral appliance trays are shaped to fit the subject's teeth. In some cases, one or more delivery ports in the oral appliance tray are positioned based on measurements obtained from the subject. In some cases, the one or more delivery ports are generally positioned to deliver compounds to all pocket depths. Use of the oral appliance trays has resulted in a significant reduction in periodontal pathogen levels and unexpectedly improved oral health.

[0060] Furthermore, the oral appliance delivery tray can be used to deliver compounds to treat, prevent, or slow the progression of periodontal disease. Use of the oral appliance tray and compound can result in a change in periodontal disease-related symptoms. It is recognized that the change in periodontal disease-related symptoms can be an improvement. It is further recognized that the second, third, fourth, or fifth periodontal disease-related symptoms may remain unchanged, may change negatively, or may improve to a different extent than the first periodontal disease-related symptom. The oral appliance delivery tray can be used to maintain oral homeostasis in the soft tissues surrounding one or more implants.

[0061] The oral delivery tray provides for delivery of compounds to gingiva, supragingival or subgingival areas including, but not limited to, sulci, pockets, pocket bases, dentinal tubule(s), structured walls, oral tissues, alveolar bone, periodontal ligament, periodontal ligament areas, tooth roots, furcations, implants and implant bases, abutments, fixed restoration crowns, bridge margins of restorations, laminates, veneers, composite and amalgam margin restorations, inlays, onlays, natural enamel, natural cementum surfaces, fibers, attached and unattached gingiva.

[0062] By supragingival region is meant the area of ​​a tooth that is exposed in a healthy tooth, such as the crown of the tooth. By gingival region is meant the area of ​​the tooth that includes one or more areas selected from the group including, but not limited to, the subgingival region, the sulcus, the periodontal ligament, the periodontal ligament area, the root, the dental implant area, and the implant base. By subgingival region is meant the area below the gum, particularly the area between the gum and the base of the crown of the tooth, including, but not limited to, the sulcus, the periodontal ligament, the periodontal ligament area, the root, and the implant base.

[0063] "Teeth" is intended to encompass naturally occurring hard bony appendages for the mastication of food and non-naturally occurring hard manufactured objects within the mouth. Teeth include, but are not limited to, primary teeth, permanent teeth, dental implants, dentures, bridges, caps, crowns, inlays and onlays, gold, composite and amalgam restorations, surgically implanted teeth, removable replacement abutments and teeth, fillings, and partial dentures. Healthy sulci are 0mm to 3mm deep without periodontal probing.

[0064] By delivery, it is meant dispensing, placing, exposing, depositing, incubating, conveying, transporting, or providing a compound to a designated area. Delivery may occur over a predetermined period of time, at predetermined intervals, or at predetermined intervals for a predetermined period of time. The tray delivers the compound to a predetermined location without significantly altering the concentration of the compound. The oral appliance tray can deliver the compound to the gingival, subgingival, or gingival and subgingival regions of at least one tooth, two teeth, three teeth, four teeth, five teeth, six teeth, seven teeth, eight teeth, nine teeth, ten teeth, eleven teeth, twelve teeth, thirteen teeth, fourteen teeth, fifteen teeth, sixteen teeth, or seventeen or more teeth. It is recognized that veterinary oral appliance delivery trays are adapted to the oral anatomy of the subject animal. Veterinary oral appliance delivery trays are understood to include standard oral appliance delivery trays for non-human mammalian species or strains and customized veterinary oral appliance delivery trays for specific subjects.

[0065] By "subject" is intended any living organism having an oral cavity containing one or more teeth. Subjects may include, but are not limited to, humans, domestic animals, livestock, pets, animal specimens, veterinary animals, and mammals, including, but not limited to, humans, domestic animals, livestock, pets, horses, cows, dogs, cats, sheep, camelids, pigs, goats, and primates.

[0066] In some embodiments, the oral appliance tray is an individualized oral appliance tray personalized to one or more measurements of the subject's teeth, including, but not limited to, a tray in which at least one exit location is determined by at least one periodontal measurement from the subject's teeth. The terms "individualized" and "case-specific" are used interchangeably herein. In some embodiments, the oral appliance delivery tray is a combination of an individualized tray, with the tray adapted according to one or more measurements of one or more of the subject's teeth and the placement or arrangement of a universal or standard exit port. In some embodiments, the oral appliance tray is a standard or generic tray that can be fitted to the patient's mouth or a commonly selected size, in either case with a universally positioned delivery port.

[0067] The terms "oral appliance tray," "oral appliance delivery tray," and "dental device" are used interchangeably herein. An oral appliance tray 10 for delivering a compound to the gingival and / or subgingival region of at least one tooth comprises a gasket including a supragingival portion 20, a gingival delivery region 30, and one or more delivery ports 40, each including an outlet 45 within the gingival delivery region. The device is adapted to fit either the upper (maxillary) dental arch, the lower (mandibular) dental arch, or a portion of either arch. The gasket is generally U-shaped, with an inner surface shaped to fit the teeth of either the maxillary or mandibular arch. The oral appliance tray may be a mandibular arch oral appliance tray, a maxillary arch oral appliance tray, a partial mandibular arch oral appliance tray, or a partial maxillary arch oral appliance tray. The gasket includes a supragingival portion that fits the teeth, and the shaped inner surface provides a reservoir for delivery of the compound to the gingival or subgingival region. The gasket includes a gingival delivery area with port channels that conform to the gingival tissue structure. In personalized oral appliance trays, the supragingival portion conforms to the target teeth and the target gingival area. In standard oral appliance trays, the supragingival portion conforms to the standard tooth preparation for a particular dental arch, and the gingival delivery area conforms to the standard gingival area.

[0068] By "normal" tooth formation and "normal" gum area is intended the average tooth formation or gum area obtained from a population of subjects. It is recognized that normal formation in adult subjects may differ from normal formation in juvenile subjects, and it is also recognized that normal formation may vary by species.

[0069] The gasket includes one or more delivery ports 40 including an outlet 45 within the gingival delivery region. The terms "delivery port" and "port channel" are used interchangeably herein. The one or more outlets are located within the gingival delivery region and may be positioned on the gasket near the facial, buccal, labial, lingual, palatal, proximal, vestibular, or occlusal side of the tooth. In one aspect, the outlets deliver the compound to a region of the tooth selected from the group including the buccal gingival region, buccal subgingival region, buccal supragingival region, facial gingival region, facial subgingival region, facial supragingival region, proximal gingival region, proximal subgingival region, proximal supragingival region, occlusal gingival region, occlusal subgingival region, and occlusal supragingival region. The delivery port may be selected from the group including a delivery reservoir and a delivery pore 50 including an inlet 55 located within the supragingival region.

[0070] The exit location may be a universally positioned, universal exit location for delivering the compound to the gingival, subgingival, or gingival and subgingival areas. The exit may be positioned or placed at an individualized exit location. The individualized exit location may be determined by at least one periodontal measurement of a tooth from a subject. The location of the exit may be described by one or more coordinates. The individualized exit location may be determined by multiple periodontal measurements of a tooth from a subject. In some embodiments, the individualized exit location may be determined by periodontal measurements of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, and 20 teeth from a subject, and up to 198 teeth. In one embodiment, the exit location is determined by periodontal measurements of six sectors from the subject's teeth. If the periodontal measurements of a sector of a tooth indicate that the sector is at risk for periodontal disease, the delivery port exit is positioned within the delivery area of ​​the tray proximal to the sector at risk. If periodontal measurements of a tooth sector indicate that the sector is healthy, the oral appliance tray may not have an outlet proximal to that sector. If periodontal measurements of a tooth sector indicate that the sector is healthy but adjacent to an unhealthy sector, the oral appliance tray may have an outlet proximal to the healthy sector. It is recognized that different periodontal measurements can be used to determine the location of additional outlets for the same or different teeth. It is recognized that the number of periodontal measurements used to determine the outlet location can be different for different outlets on the same personalized oral appliance tray. The outlet is located, positioned, or placed within the gingival delivery area of ​​the tray to deliver the compound to the gingival, subgingival, or gingival and subgingival areas. It is understood that delivery of the compound to one or more dental areas surrounding the implant can include delivery of the compound to one or more additional dental areas surrounding the implant.

[0071] The dimensions of the outlet of at least one delivery port may vary. In standard delivery trays, the outlet dimensions may be predetermined to approximately correlate with the intended delivery area. Such approximation may be based on measurements from an average group or population of subjects. In personalized delivery trays, the outlet dimensions may be correlated with at least one periodontal measurement. The height of the exit is approximately 0.1 mm to approximately 60 mm, 0.1 mm to approximately 50 mm, approximately 0.25 mm to approximately 50 mm, approximately 0.25 mm to approximately 40 mm, approximately 0.3 mm to approximately 30 mm, approximately 0.3 mm to approximately 25 mm, approximately 0.4 mm to approximately 20 mm, approximately 0.5 mm to approximately 19 mm, Approximately 0.5mm to approximately 18mm, approximately 0.5mm to approximately 17mm, approximately 0.5mm to approximately 16mm, approximately 0.5mm to approximately 15mm, approximately 0.5mm to approximately 14mm, approximately 0.5mm to approximately 13mm, approximately 0.5mm to approximately 12mm, approximately 0.5mm to approximately 12mm, approximately 0.5mm to approximately 11mm, about 1mm to about 20mm, about 1mm to about 19mm, about 1mm to about 18mm, about 1mm to about 17mm, about 1mm to about 16mm, about 1mm to about 15mm, about 1mm to about 14mm, about 1mm to about 13mm, about 1mm to about 12mm, about 1mm to about 11 mm, about 2 mm to about 20 mm, about 3 mm to about 20 mm, about 4 mm to about 20 mm, about 2 mm to about 15 mm, about 3 mm to about 15 mm, about 4 mm to about 15 mm, about 2 mm to about 12 mm, about 3 mm to about 12 mm, and about 4 mm to about 12 mm. In some embodiments, the height can be in the range of 0.25mm, 0.5mm, 1mm, 1.5mm, 2mm, 2.5mm, 2.75mm, 3mm, 3.25mm, 3.5mm, 3.75mm, 4mm, 4.25mm, 4.5mm, 4.75mm, 5mm, 5.25mm, 5.5mm, 5.75mm, 6mm, 6.25mm, 6.5mm, 6.75mm, 7mm, 7.25mm, 7.5mm, 7.75mm, 8mm, 8.25mm, 8.5mm, 8.75mm, 9mm, 9.25mm, 9.5mm, 9.75mm, or 10mm.

[0072] The width of the exit is approximately 0.1 mm to approximately 60 mm, 0.1 mm to approximately 50 mm, approximately 0.25 mm to approximately 50 mm, approximately 0.25 mm to approximately 40 mm, approximately 0.3 mm to approximately 30 mm, approximately 0.3 mm to approximately 25 mm, approximately 0.4 mm to approximately 20 mm, approximately 0.5 mm to approximately 19 mm, Approximately 0.5mm to approximately 18mm, approximately 0.5mm to approximately 17mm, approximately 0.5mm to approximately 16mm, approximately 0.5mm to approximately 15mm, approximately 0.5mm to approximately 14mm, approximately 0.5mm to approximately 13mm, approximately 0.5mm to approximately 12mm, approximately 0.5mm to approximately 12mm, approximately 0.5mm to approximately 11mm, about 1mm to about 20mm, about 1mm to about 19mm, about 1mm to about 18mm, about 1mm to about 17mm, about 1mm to about 16mm, about 1mm to about 15mm, about 1mm to about 14mm, about 1mm to about 13mm, about 1mm to about 12mm, about 1mm to about 11 mm, about 2 mm to about 20 mm, about 3 mm to about 20 mm, about 4 mm to about 20 mm, about 2 mm to about 15 mm, about 3 mm to about 15 mm, about 4 mm to about 15 mm, about 2 mm to about 12 mm, about 3 mm to about 12 mm, and about 4 mm to about 12 mm. In some embodiments, the width can be in the range of 0.25mm, 0.5mm, 1mm, 1.5mm, 2mm, 2.5mm, 2.75mm, 3mm, 3.25mm, 3.5mm, 3.75mm, 4mm, 4.25mm, 4.5mm, 4.75mm, 5mm, 5.25mm, 5.5mm, 5.75mm, 6mm, 6.25mm, 6.5mm, 6.75mm, 7mm, 7.25mm, 7.5mm, 7.75mm, 8mm, 8.25mm, 8.5mm, 8.75mm, 9mm, 9.25mm, 9.5mm, 9.75mm, or 10mm.

[0073] Any outlet dimension may be correlated to a periodontal measurement. The correlation may be within the ranges of 1:1, 1:1.25, 1:1.5, 1:1.75, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5, 1:10, 10:1, 9.5:1, 9:1, 8.5:1, 8:1, 7.5:1, 7:1, 6.5:1, 6:1, 5.5:1, 5:1, 4.5:1, 4:1, 3.5:1, 3:1, 2.5:1, 2:1, 1.75:1, 1.5:1, and 1.25:1. In some embodiments, the dimensions of the outlet can correspond to the dimensions of the area of ​​the tooth at risk for periodontal disease. For example, without limitation, periodontal measurements can indicate a depth of 5 mm relative to the area at risk for periodontal disease, correlating with an outlet height of 5 mm. In some embodiments, the dimensions of the outlet can exceed the dimensions of the area of ​​the tooth at risk for periodontal disease. In some embodiments, the height and width of the outlet are each correlated with at least one periodontal measurement. The height and width of the outlet can be correlated with the same periodontal measurement or different periodontal measurements.

[0074] In one aspect, the gasket includes a delivery reservoir. A delivery reservoir refers to a portion of the oral delivery tray in which the compound is retained. The delivery reservoir can include, but is not limited to, a depression, void, groove, pocket, hollow, trough, indentation, slit, opening, or notch. The delivery reservoir may include an outlet, particularly an outlet that is proximate to the gingival, subgingival, or gingival and subgingival areas of a subject's teeth when the tray is placed in the subject's mouth. In personalized trays, the dimensions of the outlet correlate with the area of ​​the teeth at risk for periodontal disease as determined by one or more periodontal measurements. When the tray is placed in the subject's mouth, the delivery reservoir maintains the compound proximal to the gingival area of ​​one or more teeth.

[0075] In one aspect, the gasket includes one or more delivery pores including at least one inlet and at least one outlet. The terms "delivery pore" and "delivery channel" are used interchangeably herein. The one or more inlets are located in the supragingival portion of the formed inner surface. The compound enters the pores through the one or more inlets and flows through the delivery pores to one or more outlets in the gingival delivery area. It is recognized that the tray can deliver the compound to one or more regions of one or more teeth or dental implants. In various aspects, the formed inner surface of the gasket allows for the flow of the compound throughout the tray and across one or more supragingival surfaces. It is recognized that the compound is thus delivered to the supragingival surface.

[0076] A delivery pore or delivery channel is a continuous passageway within a gasket of sufficient diameter to allow a compound to flow through the delivery pore from at least one inlet to at least one outlet. The structure of the delivery pore may be any shape, including, but not limited to, circular, rectangular, oval, triangular, and polygonal. It is recognized that the structure of the delivery pore may vary along its length. In some embodiments, the pore is circular, and in such cases, the pore may be described in terms such as "diameter." In some embodiments, the pore may be described in terms such as height and width. Pore height refers to the dimension of the continuous passageway, and pore width refers to the second dimension of the continuous passageway offset by 90° from the pore height. Both the pore height and pore width are offset from the pore length. It is recognized that a delivery pore with a single inlet may have multiple outlets. It is recognized that a delivery pore may have multiple inlets and multiple outlets. It is recognized that a delivery pore with multiple inlets may have a single outlet. It is understood that placing the oral appliance tray in the subject's mouth may increase the flux of the compound through the delivery orifice or orifices.

[0077] Pore ​​length is the distance from the entrance to the exit. Pore lengths can range from 0.1 mm to the entire length of any tooth structure, including the root, gums, and underlying bone. Pore lengths can range from 0.1 mm to approximately 40 mm, 0.3 mm to approximately 35 mm, 0.5 mm to approximately 30 mm, 0.6 mm to approximately 30 mm, 0.7 mm to approximately 30 mm, 0.8 mm to approximately 30 mm, 0.9 mm to approximately 30 mm, 1 mm to approximately 28 mm, 1 mm to approximately 26 mm, 1 mm to approximately 25 mm, 0.7 mm to approximately 28 mm, 0.7 mm to approximately 26 mm, 0.7 mm to approximately 25 mm, 0.7 mm to approximately 24 mm, 0.7 mm to approximately 23 mm, 0.7 mm to approximately 22 mm, 0.7 mm to approximately 21 mm, 0.7 mm to approximately 20 mm. mm, 0.7 mm to about 19 mm, 0.7 mm to about 18 mm, 0.7 mm to about 17 mm, 0.7 mm to about 16 mm, 0.7 mm to about 15 mm, 0.7 mm to about 14 mm, 0.7 to about 13 mm, 0.7 mm to about 12 mm, 0.7 mm to about 11 mm, 0.7 mm to about 10 mm, 0.7 mm to about 9 mm, 0.7 mm to about 8 mm, 0.7 mm to about 7 mm, 0.7 mm to about 6 mm, 0.7 mm to about 5 mm, 0.7 mm to about 4 mm, 1 mm to about 3 mm, and 1 mm to about 2 mm. The pores may be bent, rotated, curved, angled, or split.

[0078] Pore ​​diameters are approximately 0.1 mm to approximately 60 mm, 0.1 mm to approximately 50 mm, approximately 0.25 mm to approximately 50 mm, approximately 0.25 mm to approximately 40 mm, approximately 0.3 mm to approximately 30 mm, approximately 0.3 mm to approximately 25 mm, approximately 0.4 mm to approximately 20 mm, approximately 0.5 mm to approximately 19 mm, Approximately 0.5mm to approximately 18mm, approximately 0.5mm to approximately 17mm, approximately 0.5mm to approximately 16mm, approximately 0.5mm to approximately 15mm, approximately 0.5mm to approximately 14mm, approximately 0.5mm to approximately 13mm, approximately 0.5mm to approximately 12mm, approximately 0.5mm to approximately 12mm, approximately 0.5mm to approximately 11mm, about 1mm to about 20mm, about 1mm to about 19mm, about 1mm to about 18mm, about 1mm to about 17mm, about 1mm to about 16mm, about 1mm to about 15mm, about 1mm to about 14mm, about 1mm to about 13mm, about 1mm to about 12mm, about 1mm to about 11 mm, about 2 mm to about 20 mm, about 3 mm to about 20 mm, about 4 mm to about 20 mm, about 2 mm to about 15 mm, about 3 mm to about 15 mm, about 4 mm to about 15 mm, about 2 mm to about 12 mm, about 3 mm to about 12 mm, and about 4 mm to about 12 mm.

[0079] It is understood that the dimensions of each delivery port on an oral appliance tray can be different from one another or the same. It is recognized that two or more delivery ports can have the same dimensions.

[0080] The thickness of the gasket varies. The gasket may range from 0.03 inches to approximately 0.75 inches thick, preferably 0.03 inches to approximately 0.5 inches thick. The gasket, including the supragingival portion and gingival delivery area, is shaped to fit the teeth. Universal oral appliance trays may be shaped for a typical or average dental arch.

[0081] The shaped inner surface of the gasket of the personalized oral appliance tray may be shaped to fit one or more oral structures selected from the group including the subject's teeth, internal contours, oral cavity, pocket depths, sulci, connective tissue, fibers, tunica interna, attached gingiva, and unattached gingiva. Methods for shaping a gasket to fit one or more oral structures are known in the art and may include impressions, molds, manual molds, digital molds, manual impressions, physical model impressions, physical model manual impressions, digital impressions, CT scans, X-ray scans, and clinical periodontal charts. Methods for fabricating oral appliance trays are known in the art. Methods for fabricating oral appliance trays may include, but are not limited to, laser cutting, layer deposition, laser printing, laser deposition, molding, casting and creating manual impressions, casting and creating digitized impressions, Itero digital scanning, CT scans, and MRI techniques. The length, depth, and width of the tooth pockets on the shaped inner surface complement the length, depth, and width of the tooth structures in the subject's mouth. Any method for determining the morphology of a subject's dental arch known in the art can be used in the present method. Methods for determining the morphology of a subject's dental arch may include, but are not limited to, impressions, molds, manual molds, digital molds, manual impressions, physical model impressions, physical model manual impressions, digital impressions, CT scans, X-ray scans, and clinical periodontal charts.

[0082] The exit location can be determined by at least one periodontal measurement from at least one tooth. Periodontal measurements include, but are not limited to, periprobe measurements, x-ray measurements, and CT scan measurements. Periodontal measurements include, but are not limited to, measurements of the gingival margin, pocket depth, plaque measurement, bleeding on probing, furcation, mobility, peri-implant probing depth, peri-implant mucosa, mucosal margin, reconstructive defect, structural defect, clinical attachment, recess, peri-implant recess, alveolar bone loss, secondary bone loss, attachment loss, cemento-enamel junction, gingival hyperplasia, gingival overgrowth, pseudo-pocket depth, esthetic zone margin, residual pocket depth, and peri-implantitis. It is recognized that any number of periodontal measurements can be obtained per tooth or implant. In one embodiment, six periodontal measurements per tooth or implant are used to determine the exit location. An example of six suitable periodontal measurements is shown in FIG. 17. The exit location can correspond to an area at risk for periodontal disease based on one or more periodontal measurements. A periodontal site may be considered healthy if the periodontal probe measurement is between 1 and 3 mm and there are no visual indicators of infection or disease at the site. A site may be considered at risk for periodontal disease if the site has indicators of infection or disease or if the periodontal probe measurement is greater than 3 mm. In personalized oral appliance trays, port outlets may be positioned on the tray so that when the tray is placed in the oral cavity, the outlets are proximal to sites at risk for periodontal disease. Thus, oral appliance trays may have port outlets proximal to each periodontal section of a tooth, or proximal to fewer periodontal sections than each periodontal section of a tooth.

[0083] It is recognized that teeth may be divided into multiple sections when viewed from the occlusal plane. Periodontal measurements may be obtained from each section. Teeth may be divided into sections including, but not limited to, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, It is recognized that the probe may be divided into many sections, including 105, 110, 115, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, or more sections. In some embodiments, the preferred number of sections is in the range of 1 to 50, 1 to 25, 1 to 12, 2 to 10, 3 to 9, 4 to 9, 4 to 8, 5 to 8, or 5 to 7. In some cases, measurements around the probe are obtained from one or more sections.

[0084] A preferred embodiment uses periodontal measurements from six sites per tooth or implant. Perio Probe Charting: The selection of six sites per tooth or implant for both periodontal pocket and attachment level measurements is important. Each tooth or implant is divided into six sections when viewed from the occlusal surface. The site with the deepest periodontal or peri-implant probing depth should be recorded for each section when probing with the peripheral probe. Various embodiments of manufacturing an oral appliance tray may include recording periodontal measurements at the deepest point of each of the six sites per tooth with other measured contributing factors, including, but not limited to, the angle of the periodontal probe, and fabricating an oral appliance tray with one or more delivery port outlets positioned so that, when the oral appliance tray is placed in the oral cavity, one or more delivery port outlets are proximal to each segment at risk for periodontal disease. The periodontal probe is inserted along the root surface to measure the periodontal probing depth. The instrument should be angled mesial-distal while remaining parallel to the long axis of the tooth (avoiding buccolingual angulation). Peripheral probing measurements include documentation of gingival margin, pocket depth, plaque measurements, bleeding on probing, furcation, mobility, peri-implant probing depth, peri-implant mucosa, mucosal margin, reconstruction defect, structural defect, clinical attachment, recess, peri-implant recess, alveolar bone loss, secondary bone loss, attachment loss, cemento-enamel junction, gingival hyperplasia, gingival overgrowth, pseudo-pocket depth, esthetic zone margin, residual pocket depth, and measurements contributing to peri-implantitis.

[0085] With this device, we use standard periodontal probing measurements and digital scans to determine the exact depth and involvement of each periodontal category required for each probing tooth and up to the entire dentition. A complete periodontal examination and evaluation using all terms and descriptions includes details of each specified tooth with a minimum of six periodontal probing measurements across the entire dentition, including the oral mucosa and oral cavity. It is recognized that periodontal measurements from fewer than a complete periodontal examination may be used to fabricate the oral appliance delivery tray.

[0086] Periodontal probe charts are known in the art. Typically, a minimum of six sites per tooth or implant is used. In some embodiments, the six periodontal measurements per tooth are mesio-buccal, direct buccal, distal buccal, mesio-lingual, direct lingual, and distal lingual. It is recognized that periodontal measurements such as mesio-buccal, direct buccal, distal buccal, mesio-lingual, direct lingual, and distal lingual measurements can affect multiple aspects. For example, if a direct lingual measurement indicates a section is at risk for periodontal disease, a delivery port outlet can be placed in the direct lingual section. The probing depth of the direct lingual measurement can be correlated with the dimensions of the delivery port outlet. If the measurement indicates a section is not at risk for periodontal disease, it can be determined that no outlet is desirable in that section. Periodontal probe charting can include assessment of furcation involvement, tooth mobility, gingival margin, probing depth, and attachment level. See, for example, Periodontal Chart - Department of Periodontology School of Dental Medicine University of Bern - Switzerland - copyright by www.perio-tools.com. Figures 1A, 1B and 3-8 are based on figures taken from www.perio-tools.com.

[0087] The selection of six sites per tooth or implant for both periodontal pocket and attachment level measurements is important. Each tooth or implant is divided into six sections when viewed from the occlusal surface. The site with the deepest periodontal or peri-implant probing depth is recorded for each section. The periodontal probe is inserted along the root surface to measure periodontal probing depth. The instrument should be angled in the mesial-distal direction A or B, respectively, while remaining parallel to the long axis of the tooth (avoiding buccolingual angulation). The furcations of all maxillary molars and first premolars should be evaluated with a furcation probe. Furcation lesions are the most difficult aspect for patients to reach and access, and therefore are extremely difficult to care for and keep clean. Many periodontal pathogens colonize these areas daily and, although not limited by mechanism, contribute to the progression of bone and attachment loss. The horizontal component of probing is graded according to the following criteria (0-3): Grade 0 = Full cation not detected Grade 1 = detectable full cation, horizontal component of probing ≤ 3 mm Grade 2 = detectable full cation, horizontal component of probing >3 mm Grade 3 = Open furcation Tooth mobility should be determined using two single-ended instruments and assessed according to criteria. Grade 0 = normal (physiological) tooth mobility Grade 1 = detectable mobility (up to 1 mm horizontally) Grade 2 = detectable mobility (>1 mm horizontally) Grade 3 = detectable vertical tooth mobility

[0088] The goal of a clinical periodontal chart is to record gingival recession, probing depth, and attachment level in mm at six sites per tooth or implant. It is common to combine all readings taken with the periodontal probe.

[0089] For all sites, the "gingival margin" value is first determined, followed by a periodontal measurement "probe depth." The "gingival margin" is the distance from the clinical gingival margin to any given reference, most often the cementoenamel junction. The crown margin and restoration margin should be selected as references if they are at least 3 mm apical to the cementoenamel junction (CEJ); otherwise, a virtual reference line should be selected at the location of the original cementoenamel junction. The "probe depth" is the distance between the gingival margin and the bottom of the gingival sulcus or periodontal pocket, respectively. The "attachment level" for each site is calculated based on the following formula: Probe depth (mm) - gingival margin (mm) = attachment level (mm)

[0090] In healthy periodontium, the cement-enamel junction is located below the gingival margin and just above the attachment level. There is no attachment loss in sites with healthy periodontium. In this case, the values ​​of both the gingival margin and the probing depth are identical, and the attachment level is 0 mm. In healthy peri-implant sites, the edge of the upper structure is located somewhat below the edge of the peri-implant mucosa. There is no alveolar bone loss in healthy peri-implant sites. In such cases, the attachment level or alveolar bone level can be calculated based on the following formula: attachment level = probing depth - mucosal margin.

[0091] In cases of gingival overgrowth or gingival hyperplasia, the cement-enamel junction may be located far below the gingival margin but just above the attachment level. In such cases, the gingival margin and probing depth values ​​may be the same, and the attachment level is 0 mm. A pseudopocket is a pocket 4 mm or larger with no attachment loss.

[0092] In healthy peri-implant sites, the margin of the superstructure is located further below the margin of the peri-implant mucosa in the esthetic zone. In healthy peri-implant sites in the esthetic zone, there is little or no alveolar bone loss. In such cases, the attachment level or alveolar bone level can be calculated based on the following formula: attachment level = probing depth - mucosal margin. In some diseased sites, the cement-enamel junction may be located somewhat below or above the gingival margin. The distance between the gingival margin and the bottom of the periodontal pocket is then recorded as the periodontal probing depth. In such cases, the attachment level can be calculated based on the following formula: attachment level = probing depth - gingival margin. Periodontal pockets greater than 4 mm after active periodontal treatment are also known as residual pockets.

[0093] In sites with peri-implantitis, the edge of the superstructure may be located somewhat below or above the peri-implant mucosal edge. The distance between the mucosal edge and the bottom of the peri-implant pocket is then recorded as the peri-implant probing depth. The attachment level can be calculated based on the following formula: attachment level = probing depth - mucosal edge.

[0094] Gingival recession is a condition observed when the gingival margin is located apical to the cemento-enamel junction. The value noted for gingival margin should be recorded as a negative value. Attachment level can be calculated based on the following formula: Attachment level = probing depth - gingival margin.

[0095] Peri-implant recession occurs when the mucosal margin is located apical to the margin of the superstructure. The value indicated for the mucosal margin is recorded as a negative value. In such cases, the alveolar bone (attachment) level can be calculated based on the following formula: alveolar bone (attachment) level = probing depth - mucosal margin.

[0096] A method for manufacturing a personalized oral appliance tray is provided, comprising the steps of obtaining at least one periodontal measurement from a subject's teeth, determining the subject's dental arch morphology, correlating the location of an outlet for at least one port with the at least one periodontal measurement, and forming a personalized oral appliance tray with a gasket complementary to the subject's dental arch morphology, the gasket including: a) a supragingival portion, (b) a gingival delivery region, and (c) one or more delivery ports including an outlet within the gingival delivery region, the delivery ports selected from the group consisting of delivery ports including a delivery reservoir and an inlet located in the supragingival portion. "Complementary to" contemplates a structurally inverse, opposite, or reversed morphology, e.g., a mold being complementary to a casting thereof.

[0097] "Biofilm" and "evening biofilm" are used interchangeably herein. Biofilm formation occurs continuously throughout the day and night. The biofilms were composed of Gram-negative bacteria, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Eubacterium nucleaturm, Fusobcterium nucleatum, Prevotella intermedia, Campylobacter rectus, oral anaerobes (Peptostreptococcus micros), Capnocytophaga species, Capnocytophaga gingivalis, and other oral bacteria. The biofilm may comprise one or more bacteria from the group including: Capnocytophaga gingivalis, Capnocytophaga ochracea, Capnocytophaga sputigena, Eikenella species, Lactobacillis species, Streptococcus mutans, Streptococcus sobrinus, and Streptococcus species. The biofilm may contribute to the formation of solid biofilm compounds, soft plaque, hard mineralized plaque, tartar, calculus, intrinsic staining, extrinsic staining, increased crevicular fluid, changes in pH levels contributing to disease, acidic salivary compounds, lipopolysaccharides or (LPD), fermentable carbohydrates, or collagenases.

[0098] Subjects at risk for periodontal disease include, but are not limited to, subjects with a high degree of dental caries, subjects in the early stages of periodontal disease, subjects with dental implants, subjects over 30 years of age, subjects with a history of poor home dental hygiene, subjects with a medical history of periodontal disease, subjects with a family history of periodontal disease, subjects with a predisposing IL-1 polymorphism, subjects with a predisposing IL-2 polymorphism, subjects with a predisposing IL-6 polymorphism, the presence of thymine bases at positions 4845 of ILIA and 3954 of ILIB, a high dietary intake of fermentable carbohydrates, diabetes, smoking, chewing tobacco, and use of snuff-like products, subjects with biological markers of disease, subjects with a history of a debilitating condition, subjects at risk of demineralization, subjects at risk of caries, subjects at risk of bleeding on probing, subjects at risk of inflammation or degeneration, subjects at risk of increased actinomycete and aerobic cocci biofilm accumulation, subjects requiring pre-operative bacterial treatment, subjects requiring post-operative bacterial treatment, subjects at risk of pre-operative sensitivity, subjects at risk of post-operative sensitivity, subjects at risk of dental discomfort, subjects at risk of phagocytosis, subjects at risk of hyperresponsive phagocytosis, subjects at risk of overproduction of interleukins, prostaglandins and cytokines, subjects at risk of uncontrolled colonization of anaerobic gram-negative bacteria, subjects at risk of endotoxins, subjects at risk of increased crevicular fluid, subjects at risk of increased acidic saliva production, increased C-reactive protein (CRP) levels, negative autoimmune response, increased degenerative biofilm markers, increased liposaccharides, hyporesponsive phagocytes, interleukin overproduction, increased levels of prostaglandins, increased cytokines, increased systemic levels of acute phase proteins, plasma antibody levels increased clotting factors, increased total white blood cell count, increased neutrophils, increased INF-γ, increased TNF-α, increased IL-1β, increased IL-2, increased IL-6, osteoclastic activity, bone loss, basal bone loss, structural bone loss, destruction of oral tissues, exposure to roots and dentin, thinning or abrasion of enamel or dentin, bruxism, increased thick mucus, increased biofilm formation, decreased saliva production and subjects at risk for hypersensitivity, subjects at risk for oral or systemic autoimmune response, subjects at risk for peri-implantitis, subjects at risk for implant(s) failure,This includes subjects at risk for chronic dry mouth, subjects at risk for halitosis, subjects at risk for systemic disease, and subjects at risk for effects from medications for chronic disease.

[0099] A subject exhibiting biological markers of disease is a subject exhibiting at least one biological marker of disease, including, but not limited to, increased lipopolysaccharide, hyporesponsive phagocytes, overproduction of interleukins, increased levels of prostaglandins, increased cytokines, increased systemic levels of acute phase proteins, increased plasma antibody levels, increased clotting factors, increased total white blood cell count, increased neutrophils, increased INF-γ, increased TNF-α, increased IL-1β, increased IL-2, increased IL-6, increased C-reactive protein, and decreased pH levels.

[0100] Dental implants are not protected from food debris, soft plaque, hard mineralized plaque, debris accumulation, tartar formation, and biofilm formation. Dental implants may experience electrochemical degradation, corrosion, release of biotoxins or biotoxic ions into the oral cavity, and changes in pH levels. Therefore, dental implants are at risk of periodontal disease.

[0101] Periodontal disease can be classified into different stages based on various physical characteristics and clinical criteria. Some clinical criteria and stages of periodontal disease are listed in Table 1. Clinical criteria include, but are not limited to, bleeding on probing (BOP) and a probing depth greater than 3 mm. A probing depth greater than approximately 3 mm indicates some type of periodontal disease. The progression from healthy to unhealthy stages is shown in Figure 11A. As periodontal disease progresses, the pH level of the gingival, subgingival, and / or supragingival regions may decrease. While not being limited by mechanism, the lower pH levels, increased crevicular fluid flow, and reduced redux present during the progression of periodontal disease may result in oxidative reduction and lower oxygen concentrations favorable for the growth of Gram-negative bacteria. Again, without being limited by mechanism, restoring pH levels to healthy levels may reduce the risk of periodontal disease-related symptoms. [Table 1]

[0102] Periodontal diseases include, but are not limited to, peri-implantitis, implant failure, root decay, periodontal abscess, gum infection, pyorrhea, halitosis, xerostomia, gingivitis, inflammation, destruction of oral tissues, dental caries, and dental caries.

[0103] Periodontal disease can lead to complications such as furcation lesions, furcation invasion, bleeding on probing, bleeding, altered bone formation, basal bone loss, and structural bone loss.

[0104] By "furcation lesion" and "furcation involvement" is intended an area of ​​bone loss at the bifurcation of a tooth root. Furcation lesions can lead to tooth loss.

[0105] Peri-implantitis is an infection of the area surrounding a dental implant. Peri-implantitis can lead to implant failure and even implant removal.

[0106] Symptoms associated with periodontal disease are known in the art and include, but are not limited to, furcation involvement, demineralization, furcation invasion, redness, bleeding on probing, severe pain, increased pain and inflammation, increased probing depth, sensitivity, temperature sensitivity, calculus deposition, plaque formation, soft plaque formation, increased biofilm formation, soft tissue loss, alveolar bone loss, periodontal abscess, pellicle formation, inflammation, localized inflammation, systemic inflammation, colonization with anaerobic gram-negative bacteria, increased endotoxin levels, decreased saliva production, acidic salivary formulation, increased crevicular fluid, increased C-reactive protein levels (CRP), negative autoimmune response, increased degenerative biofilm markers, phagocytosis, These include increased lipopolysaccharides, hyporesponsive phagocytes, overproduction of interleukins, increased levels of prostaglandins, increased cytokines, increased systemic levels of acute-phase proteins, increased plasma antibody levels, increased clotting factors, increased total white blood cell count, increased neutrophils, increased INF-γ, increased TNF-α, increased IL-1β, increased IL-2, increased IL-6, osteoclast activity, bone loss, basal bone loss, structural bone loss, destruction of oral tissues, exposed roots, thinning of enamel, enamel wear from teeth grinding, dentin wear, increased thick mucus, increased biofilm formation, decreased saliva production, and hypersensitivity. A segment of a tooth is at risk for periodontal disease if one or more periodontal disease-related symptoms are present in that segment of the tooth, or if one or more periodontal disease-related symptoms are present in adjacent or nearby segments. The terms "segment," "section," "part," and "division" may be used interchangeably herein.

[0107] Improvement in periodontal disease-related symptoms may include, but is not limited to, remineralization, increased barrier to dentinal tubules, decreased sensitivity, decreased temperature sensitivity, decreased probing depth, reduced bleeding on probing, reduced crevicular fluid, increased pH levels and reduced biofilm formation, and the presence of altered pathogens and biological markers that contribute to the disease and disease process.

[0108] Improving periodontal health can reduce the risk of one or more conditions associated with periodontitis or poor periodontal health, including, but not limited to, cardiovascular disease, stroke, arteriosclerosis, respiratory infections, lung diseases, ear, nose and throat infections, dementia, brain diseases, Alzheimer's disease, premature birth, preterm birth rate, pregnancy complications, oral cancer, cancer, diabetes, autoimmune disorders, bone and joint diseases, arthritis, rheumatoid arthritis, gastrointestinal diseases, erectile dysfunction, obesity, gut biome disruption, gut barrier dysfunction, altered gut immune profile, non-alcoholic fatty liver disease (NAFLD), fibrosis, endotoxemia, low-grade inflammation, medium-grade inflammation, high-grade inflammation, bacteremia inflammatory mediators, dysbiosis, severe osteopenia, osteoporosis, candidiasis, viral diseases, Sjogren's disease, and men's and women's health issues.

[0109] Compound can be any compound suitable for use in dental care.The compound suitable for use in dental care includes but is not limited to the compound for controlling caries risk, controlling plaque, controlling biofilm, maintaining oral pH level, correcting oral pH level, stabilizing oral pH level, preventing periodontal disease, inhibiting the progression of periodontal disease, dental implant maintenance, reconstructive dental maintenance, fixed prosthesis maintenance, osteotomy surgery maintenance, scaling and root flattening maintenance, pocket depth reduction surgery maintenance, bone graft maintenance, connective tissue lattice maintenance, free tissue graft maintenance, connective tissue and pedal tissue graft maintenance, bleaching, whitening or intrinsic and extrinsic stain maintenance.

[0110] Compounds suitable for use in dental care include, but are not limited to, fluorinated pharmaceuticals, ACP, amorphous calcium phosphate, oxygenated pharmaceuticals, fluorinated gels, remineralizing compounds, analgesics, hydrogen peroxide base oxidizing gel, doxycycline / vibromycin liquid solution, antimicrobial agents, chlorhexidine gel, amorphous calcium phosphate / soluble phosphate, pH adjusted calcium salts, calcium hydroxide paste, doxycycline gel, osteoblast promoters, minocycline, HCl, antibiotics, desensitizing compounds, oxygenating agents, antiplaque agents, essential oils, hydrogen peroxide, baking soda, xylitol, oral therapeutic agents, and anti-anxiety agents.

[0111] Oxygenating agents include, but are not limited to, hydrogen peroxide liquid, oxidizing gel solution, oxidizing gel paste, hydrogen peroxide liquid paste, and pastes for oxidizing supragingival and subgingival accumulations of bacteria and pathogens, including all destructive and degenerative gram-negative and even some gram-positive bacteria and pathogens that contribute to gingivitis, periodontal disease, bleeding, inflammation, and the presence of gram-negative and gram-positive pathogens and bacteria that destructively destroy oral tissues compromised by oral flora, oral pathology, and surrounding tissues and tooth structures, including all tooth structures, and all structures surrounding single or multiple dental implants, as well as reconstructive fixed and removable dental crown and bridge prostheses, surgical stainless steel, titanium, ceramic, zirconia, and gold structures, with or without implant abutments and natural tooth structure abutments. They also contribute to increased osteoblast activity, which causes a breakdown in osteoclast activity, resulting in altered bone formation and irreversible basal and structural bone loss.

[0112] Antimicrobial agents include, but are not limited to, chlorhexidine solution, locally delivered antimicrobial agents (LDA), LDA with minocycline monospheres, doxycycline hydrochloride in an absorbable polymer, chlorhexidine in a gelatin matrix, soluble phosphates, calcium salts, metal salts, Sn-11, Zn-11, oxide salts, iodine, povidone-iodine, baking soda, vitamin C, charcoal, glyoxide, essential oils, tea tree oil, arnica, hydrated silica, xylitol, calcium carbonate, zinc citrate, sodium cocoyl, erthirto, peppermint oil, coconut oil, tea tree oil, and modified biofilms, antimicrobial agents that reduce the presence of gram-negative or gram-positive pathogens.

[0113] Anti-plaque agents may include, but are not limited to, bleach, fluoride, dichloride, sodium monofluorophosphate, sanquinilia, antiseptic cleanser, antiseptic rinse, hydrochloride, hydrogen peroxide, sodium chlorite, oxygen, and xylitol.

[0114] Antibiotic preparations include, but are not limited to, doxycycline, minocycline microspheres, doxycycline hydrochloride in absorbable polymers, vibromycin, tetracycline, tetracycline hydrochloride, minocycline, clindamycin, amoxicillin, ciprofloxacin, digoxin, floxacillin, levofloxacin, clarithromycin, prebiotics, probiotics, and antibiotic solutions that reduce the presence of gram-negative and / or gram-positive pathogens.

[0115] Desensitizing and remineralizing agents include, but are not limited to, ACP, amorphous calcium phosphate, sodium fluoride, sodium fluoride gel, fluoride ions, stannous fluoride, hydroxide ions, calcium carbonate, glycerin, potassium phosphate, potassium and sodium nitrate, sodium saccharin, tincture mill, hydrated silica, calcium ions, phosphate ions, insoluble calcium compounds, amino acids, arginine bicarbonate, fluoridating agents, and mineralizing agents. Amorphous calcium phosphate (ACP) can be used for therapeutic purposes in the treatment of remineralization, insulation, and sensitivity, demineralization, root exposure, dentinal tubules, enamel thinning, enamel and dentin wear from bruxism, erosion, gingival recesses, gingivectomy, osteotomy surgery, surgical removal of infected tissue, surgical removal of infected bone, effects from bleaching / whitening of tooth structure, scaling and root planing, effects of surgical procedures, hypersensitivity, and normal wear and tear and surface destruction of fragile tooth structure on one or more teeth. It has been recognized that minerals, including but not limited to fluoride, can be incorporated into hydroxyapatite crystals in teeth, forming the mineral hydroxyapatite. Without being limited by mechanism, hydroxyapatite crystals and the mineral hydroxyapatite can increase tooth resistance to acid attack, occlude dentinal tubules to reduce sensitivity, and strengthen dentin structure. A mineralizer for manipulating pH to healthy levels, designed to control the pH conditions of the sulcus base and / or surrounding oral tissues to increase, manage or improve healthy sustainable levels and homeostasis.

[0116] Oral remedies for opening nasal passages and relieving nasal congestion include, but are not limited to, camphor, menthol, eucalyptus oil, cedarwood oil, cedar leaf oil, nutmeg, thymol, and peppermint oil. Oral remedies for opening nasal passages and relieving nasal congestion can be in a formulation selected from the group including liquid, gel, and paste forms. Nasal congestion may be due to wearing a mask or other respiratory illnesses. Oral remedies for anxiety or stress are also included.

[0117] Anxiety or stress can be present for any reason, including, but not limited to, oral sensitivity, acute pain, chronic pain and muscle spasms due to temporomandibular joint (TMJ) disorders, discomfort due to any of the above dental procedures and dental problems, lack of restorative dentistry, lack of availability of necessary restorative work, hygiene procedures, and restorative dentistry, dental phobia, dental fear, and previous adverse experiences with dental visits that result in the need for therapeutic delivery of anti-anxiety medications and therapeutics from natural, holistic, and organic sources. Anti-anxiety agents can include, but are not limited to, hemp oil, hemp seed oil, tetrahydrocannabinol (THC), cannabidiol, cannabinol, tetrahydrocannabivarin, and the flowers and / or fruits of Cannabis sativa, Cannabis indica, and Cannabis ruderalis. Hemp oil can contain a 3:1 ratio of omega-6 to omega-3 essential fatty acids. Hemp seed oil may contain approximately 76% polyunsaturated fat, approximately 5% to 11% monounsaturated fat, and approximately 5% to 7% saturated fat. Hemp seed oil may contain omega-6 fatty acids such as linoleic acid and gamma-linolenic acid, as well as omega-3 fatty acids such as alpha-linolenic acid (ALA) and stearidonic acid. Both LA and ALA are essential fatty acids. Additionally, hemp seed oil contains 5% to 11% monounsaturated fat and 5% to 7% saturated fat. In common with other oils and fats, hemp seed oil provides 9 kcal / g and can be used in liquid form to soothe and comfort oral sensitivity, pain, and discomfort. Hemp seed oil may reduce dental anxiety, dental phobia, and dental fear through application to the oral mucosa.

[0118] The compounds relieve, ameliorate, eliminate, reduce, prevent, or alleviate at least one of periodontal disease-related symptoms, discomfort due to oral sensitivity, acute pain, chronic pain, muscle spasm due to temporomandibular joint (TMJ) disorders, discomfort or sensitivity associated with dental work, open nasal passages, and reduce nasal congestion.

[0119] By "maintenance compound" is meant a compound that reduces the risk of implant failure or periodontal disease. Maintenance compounds may include, but are not limited to, antiplaque agents, oxygenators, disinfectants, antimicrobial agents, antibiotics, and desensitizing agents. Dental implant failure can occur at any time during the life of the implant. Clinical indicators of dental implant failure include, but are not limited to, (1+) mobility, inflammation, redness, bleeding, peri-implantitis (infection or abscess suppuration around the implant), bone loss greater than 1.0 mm in the first year, or bone loss greater than 0.2 mm in the first year after implantation.

[0120] The compounds may be present in a variety of formulations, including, but not limited to, aqueous solutions, gels, foams, ointments, oils, pastes, polymers, powders suspended in solutions, gels, foams, oils, polymers, or pastes, powders, and other formulations known in the dental art. It is recognized that the viscosity of the formulation may affect the appropriate diameter of the delivery pores in the oral appliance delivery tray. It is recognized that the viscosity of the formulation may affect the flow rate of the compound through the pores in the oral appliance tray. It is also recognized that it may be preferable to use a medium or high viscosity formulation in an oral appliance tray for delivering the compound to the gingival or subgingival areas of the teeth on the mandibular arch.

[0121] The flow rate of the compound can affect the preferred delivery period. Suitable delivery periods may include, but are not limited to, about 15 seconds, 30 seconds, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 60 minutes, 65 minutes, 70 minutes, 75 minutes, 80 minutes, 85 minutes, 90 minutes, 2 hours, 2.5 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 15 hours, 18 hours, 21 hours, 24 hours, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, or longer. It is further recognized that treatment duration can change during the course of treatment.For example, early treatment can be longer than later treatment.Or later treatment can be longer than early treatment.Suitable delivery frequency can include, but is not limited to, every hour, 6 times a day, 5 times a day, 4 times a day, 3 times a day, 2 times a day, once a day, every other day, 3 times a week, every week, every month and yearly.It is further recognized that frequency can change during the course of treatment.For example, early treatment can be more frequent, while later treatment can be less frequent.

[0122] It is recognized that the compound may be placed, disposed, deposited, loaded, deployed, provided, applied, or preloaded onto the oral appliance tray. An individual, a dental professional, or a manufacturer may place the compound into the oral appliance delivery tray. A prefabricated tray includes an oral appliance delivery tray and a compound of interest preloaded onto the oral appliance tray by the manufacturer. The prefabricated tray may contain a predetermined dose of the compound of interest. The prefabricated tray may deliver a compound for use in altering oral pH levels, restoring oral homeostasis, altering caries risk, desensitization, remineralization, altering gum sensitivity, halitosis, dry mouth, induced biofilm therapy, antimicrobial, disinfecting, antiplaque, pain, discomfort, oral therapy, TMJ relief, or periodontal disease. The oral appliance delivery tray and the prefabricated tray containing the compound of interest may be a disposable tray. Providing a compound into the oral appliance tray is understood to encompass placing, placing, depositing, loading, applying, or preloading the compound into the tray.

[0123] Dental care procedures include, but are not limited to, gingival recession, gingivectomy, osteotomy, surgical removal of infected tissue, surgical removal of infected bone, bleaching / whitening procedures, scaling, root planing, and reconstructive and restorative dental procedures. Reconstructive and restorative dental procedures include, but are not limited to, surgically placed titanium abutment core implants, three-unit semi-precious metal fused to porcelain titanium implant bridges, semi-precious metal fused to porcelain crowns, bonded composite restorations, semi-precious metal fused to porcelain cantilever fused crowns, semi-precious metal fused to porcelain crowns, endodontic root canal procedures, and fixed and removable dental crown and bridge prostheses, implants with or without abutments and natural tooth structure abutments. Dental materials may include, but are not limited to, stainless steel, surgical stainless steel, titanium, ceramic, zirconia, silver or amalgam, art glass, composite, porcelain, and gold. Dental implants increase the risk of periodontal disease. Dental implants lack the periodontal ligament. Without being limited by mechanism, the absence of a periodontal ligament (PDL) may be a factor in the increased risk of periodontal disease occurring in patients with dental implants.

[0124] The gasket comprises a material suitable for oral use. Materials suitable for oral use are known in the art. Materials suitable for oral use include, but are not limited to, biocompatible, non-toxic polymers, polyacrylates, polyamideimides, phenols, nylons, nitrile resins, petroleum resins, fluoropolymers, copolyvidone (copovidone), epoxies, melamine-formaldehyde, diallyl phthalates, acetals, coumarone-indenes, acrylics, acrylonitrile-butadiene-styrene, alkyds, celluloses, polybutylenes, polycarbonates, polycaprolactones, polyethylenes, polyimides, polyphenylene oxides, polypropylenes, polystyrenes, polyurethanes, polyvinyl acetates, polyvinyl chlorides, poly(vinyl alcohol-co-ethylene), styrene-acrylonitriles, sulfone polymers, saturated or unsaturated polyesters, urea-formaldehyde, ethylene vinyl acetates, poly(meth)acrylic acids, polyamides, copolymers, and combinations or mixtures thereof. Preferred polymers may have low melting points. The thermoformable plastic or polymer may be modified with a plasticizer or optional durometer adjusting agent as needed. A plasticizer may be added to adjust the softness, flexibility, or compressibility of the gasket. In various aspects, the gasket material is a compressible, non-porous material. In some aspects, the gasket comprises a non-biodegradable material. In some embodiments, the oral appliance further comprises an outer layer. In various embodiments, the outer layer may be more resistant to compression, stiffness, hardness, or a combination thereof.

[0125] A method for reducing the amount of one or more bacteria in the gingival region of a subject at risk for periodontal disease is provided, comprising delivering to the subject a compound selected from the group consisting of an oxygenating agent, an antifungal agent, an antibiotic agent, a caries prevention agent, a maintenance agent, and a remineralization compound using an oral appliance tray of the present application. Bacteria include gram-negative bacteria, Aggregatibacter actinoycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Eubacterium nucleaturm, Fusobacterium species, Fusobacterium nucleatum, Prevotella species, Prevotella intermedia, Campylobacter species, Campylobacter rectus, and oral anaerobes (Peptostreptococcus Micros, Streptococcus species, Streptococcus mutans, Streptococcus sobrinus, Lactobacillus species, and Eikenella species are examples of bacteria that can be effectively treated with oral appliance trays. A method for reducing the amount of one or more bacteria in the gingival region of a subject can include preparing a compound according to a delivery regimen including one delivery event or multiple delivery events. The delivery event can have a predetermined duration. The multiple delivery events can have a predetermined frequency or a predetermined frequency and duration. It is recognized that the predetermined frequency and predetermined duration can vary over the multiple delivery events. The oral appliance tray of the present application can provide the compound at a predetermined frequency and duration to provide induced biofilm therapy.

[0126] Methods for analyzing the amount of one or more bacteria in the gingival area of ​​a subject are known in the art. Any method for analyzing the amount of one or more bacteria in the gingival area of ​​a subject can be used in this method. Methods for analyzing the amount of one or more bacteria in the gingival area of ​​a subject can include, but are not limited to, saliva collection and culture, saliva staining, PCR, NGS, antibody staining, immunological methods, antibody screening, antibody testing, culture growth, and labeled primer binding.

[0127] 1. A dental implant retention device comprising an oral appliance tray for delivering retention compound to a dental implant base region, wherein the oral appliance tray comprises a gasket comprising a supragingival portion, a gingival delivery region, and one or more delivery ports comprising an outlet within the gingival delivery region, the delivery ports being selected from the group comprising delivery reservoirs, and wherein a delivery pore is provided comprising an inlet located in the supragingival portion.

[0128] A method for managing biofilm in a subject is provided. The method includes providing a compound in an oral appliance tray, placing the oral appliance tray containing the compound in the subject's mouth, and maintaining the oral appliance tray in place in the subject's mouth for a predetermined period of time and frequency. "Managing biofilm" refers to altering the rate of biofilm accumulation. Altering the rate of biofilm accumulation includes reducing, eliminating, preventing, eliminating, or diminishing the amount of biofilm, or slowing, slowing, eliminating, or diminishing the rate of biofilm formation. Methods for determining biofilm accumulation rate are known in the art and include, but are not limited to, plaque index measurements, biomolecular staining, staining, image analysis, polymerase chain reaction (PCR) testing, biofilm diagnostics, quantitative PCR (Q-PCR), and Gram stain analysis.

[0129] Methods for identifying bacteria present in the oral cavity are known in the art and will be described herein below.Any method for identifying bacteria present in the oral cavity known in the art can be used in this method.It is recognized that some assays are preferred for specific applications, and those skilled in the art will select an appropriate assay.Biofilm Diagnostics Q-PCR (quantitative polymerase chain reaction) technology identifies bacteria present in the oral cavity.Q-PCR is a specific, sensitive, and quantitative method that accurately measures the number of target species in individual oral biofilms, as this method can detect even single bacterial cells.

[0130] Q-PCR technology is used to analyze biofilm samples collected with swabs or specific diagnostic tools, and the Biofilm DNA test provides highly accurate DNA analysis of saliva, subgingival and tongue / throat samples collected via paper points and wipes.

[0131] The Biofilm GS test, a site-specific Gram stain analysis, provides six individual site-specific Gram stain analyses that provide information on biofilms on the tongue base, tongue dorsum, and four oral quadrants, helping to see pathogens moving within the secondary saliva and oral mucosa. Unlike swish and rinse tests, OraVital's Biofilm DNA test provides a full-mouth picture of a patient's oral health. Testing the throat and tongue is critical because these reservoirs contribute to reinfection after gum care / implant placement. This comprehensive test identifies the following bacteria: Treponema denticola, Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, oral anaerobes (Pepto streptococcus micros, Fusobacteria nucleatum, Streptococcus mutans), and the fungus: Candida albicans.

[0132] Treponema denticola, Porphyromonas gingivalis, and Tannerella forsythia are some of the most harmful opportunistic pathogens. Aggregatibacter actinomycetemcomitans, an invasive bacterium, is involved in destructive periodontitis and contributes to many systemic diseases, including CVD. Oral anaerobes Pepto streptococcus micros and Fusobacteria nucleatum are important components of pathogenic biofilms. Streptococcus mutans is a bacterial species that may be involved in the initiation of caries lesions.

[0133] Candida albicans is frequently found in association with severe periodontal infections caused by S. mutans in plaque biofilms and is also responsible for severe childhood caries. This creates an oral reservoir that allows periodontal pathogens to easily invade tissues through these wounds, leading to candidiasis and other lesions in soft tissues. This species is also found in peri-implantitis sites co-colonized with other pathogens.

[0134] MyPerioPath® is a widely used test for the detection of oral pathogens that cause periodontal disease and threaten oral and systemic health. MyPerioPath® provides early warning of oral pathogens to enable individualized periodontal treatment. Pathogens tested with MyPerioPath® can help determine whether patients are at increased risk for cardiovascular disease, diabetes, stroke, and birth complications. The MyPerioPath® test identifies high-risk pathogens, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Eubacterium nodatum, Fusobacterium nucleatum / periodonticum, Prevotella intermedia, and Campylobacter rectus. Oral bacteria are identified, including medium-risk pathogens including Eikenella corrodens and Capnocytophaga species (gingivalis, ochracea, sputigena), oral anaerobes (Peptostreptococcus (Micromonas) micros), and high-risk pathogens including Eikenella corrodens and Capnocytophaga species (gingivalis, ochracea, sputigena).

[0135] The MyPerioID® IL-6 (Interleukin-6) test identifies an individual's genetic susceptibility to periodontal disease. This information allows clinicians to establish which patients are at higher risk for more severe periodontal infections due to an exaggerated immune response, allowing for personalized therapy and treatment. The MyPerio Saliva Diagnostic Test can be administered as a simple mouthwash, using a specific rinse designed to indicate increased genetic predisposition to oral and systemic disease risk.

[0136] OraRisk® Caries is a simple saliva screening test that identifies three harmful bacteria known to cause cavities: Streptococcus mutans, Streptococcus sobrinus, and Lactobacillus casei. Celsus One™ helps you understand how genetics affect your health. Celsus One™ evaluates eight genetic markers related to the inflammatory response: interleukin-1 complex genotype, interleukin-6, interleukin-17A, beta-defensin 1, CD14, tumor necrosis factor-alpha, Toll-like receptor 4 complex genotype, and matrix metalloproteinase-3. OraRisk® Candida identifies all common species of yeast, Candida, which are known to cause thrush in patients with normal or compromised immune systems. Because some species of Candida are resistant to standard antifungal treatments, identification of the Candida species is key to treatment selection. Candida species identified by this assay include C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, C. rugosa, C. guilliermondii / C. zeylanoides, C. kefyr, and C. lusitaniae (up to three species may be reported).

[0137] The MyPerioID® IL-1 (Interleukin-1) test identifies an individual's genetic susceptibility to periodontal disease. This information allows clinicians to establish which patients are at higher risk for more severe periodontal infections due to an excessive immune response, allowing for the personalized treatment and therapy provided by the claimed devices and methods.

[0138] The OraRisk® HSV test is an accurate, sensitive, and simple method for diagnosing herpes simplex virus outbreaks involving the oropharynx. HSV infection is very common but can often be mistaken for other causes of oral vesicles, ulcers, and other forms of painful oral and pharyngeal lesions. OraRisk® HSV will identify HSV1 or HSV2 by detecting the "shed virus" specific to an active infection or outbreak.

[0139] OraRisk® CT / NG is the most sensitive method to test for one of the oropharyngeal STD manifestations, Chlamydia trachomatis (CT) and / or Neisseria gonorrhea (NG). While these conditions may be asymptomatic or involve only mild sore throat, the consequences of undetected infection can be severe and contagious to partners and others with whom they share close contact.

[0140] OraRisk® CT / NG provides highly sensitive detection of either Chlamydia trachomatis or Neisseria gonorrhea, or both, and the report includes interpretive comments with specific recommendations for treatment. SARS-CoV-2 is a virus that infects respiratory epithelia: cells lining the nose, oral cavity, trachea, and bronchi. Specifically, the virus binds to a cell surface receptor called ACE2. Infection involves the virus being taken up by a host cell, where the viral genome, consisting of RNA, is replicated and packaged to produce new virions.

[0141] To diagnose COVID-19, a sample of nasal or oral secretions is taken to look for viral RNA, evidence of the presence of SARS-CoV-2 in the person. The RNA is extracted, and then the polymerase chain reaction (or PCR) is used to amplify sequences specific to SARS-CoV-2. The results of these tests are either "detected" - positive for the virus, "not detected" - no or barely detectable virus, or "indeterminate" - the sample has degraded or there is insufficient material to perform the test. COVID-19 RT-PCR tests can be applied.

[0142] An oral appliance tray for delivering a compound to reduce the risk of oral pathogens from mask wearing and from SARS-CoV-2 or respiratory epithelia: any virus that infects cells lining the nose, oral cavity, trachea, and bronchi. Specifically, the virus binds to a cell surface receptor called ACE2. Infection involves the virus being taken up by the host cell, where the viral genome, consisting of RNA, is replicated and packaged to produce new virions. The oral appliance tray comprises a gasket including a supragingival portion, a gingival delivery region, and one or more delivery ports including an exit port within the gingival delivery region, the delivery port selected from the group including a delivery reservoir, and a delivery pore including an entrance located in the supragingival portion is provided.

[0143] The placement of an entrance or exit port for a veterinary oral appliance delivery tray may be standard for the target species or strain, or may be determined by one or more periodontal measurements from a non-human animal subject. It is understood that appropriate periodontal measurements will vary by species. It is further recognized that the veterinary oral delivery tray may further include a toy element. By "toy element" is intended a structural component with which the animal can play while the veterinary oral appliance delivery tray is maintained in place. In some embodiments, the toy element distracts the non-human animal subject from the unfamiliarity of having the veterinary oral appliance delivery tray placed in its oral cavity.

[0144] FIG. 1 illustrates an exemplary process 100 for forming a dental appliance. The process 100 forms an intraoral delivery tray having one or more delivery ports according to a digital 3D image model and according to coordinates and dimensions of the delivery ports mapped thereto. In block 102, a digital 3D image model of a subject arch may be received by one or more processors of a computing device. The digital 3D image model may be generated by a digital scan of the subject arch, by a digital scan of an impression of the subject's arch, or by a digital scan of a cast of the subject dental arch. The digital 3D image model may be of the subject maxillary arch, the subject mandibular arch, or both the subject maxillary arch and mandibular arch. In block 104, the presence of a feature to be included in the dental appliance is determined. The feature may be a delivery port (block 106) or another feature. If another feature is configured using the dental appliance, coordinates and dimensions of at least one feature may be received and processed (block 114). Similarly, if additional features are configured using the dental device, coordinates and dimensions of the additional features may be received and processed in block 116. In block 118, coordinates and dimensions of one or more features can be mapped to the digital 3D image model. In block 108, coordinates and dimensions of a delivery port configured in the dental device, the delivery port coordinates and dimensions being based on periodontal measurements performed on the target dental arch. In block 110, the delivery port coordinates and dimensions are mapped to the digital 3D image model. In block 112, a 3D printer can be instructed to form a dental device having a delivery port or other features according to the 3D digital image model and according to the delivery port coordinates and dimensions mapped thereto. Other features can include, but are not limited to, toy elements, placement elements, loading elements, and any other desired structures or components.

[0145] Any of the above embodiments herein may be reconfigured and / or combined with other embodiments. Accordingly, the concepts herein are not limited to any particular embodiment disclosed herein. Furthermore, the embodiments may take the form entirely of hardware or may include both hardware and software elements. Portions of the embodiments may be implemented in software, including, but not limited to, firmware, resident software, microcode, etc. FIG. 25 illustrates a computing system 200 in which a computer-readable medium 206 may provide instructions for performing any of the methods disclosed herein.

[0146] Furthermore, embodiments may take the form of a computer program product that provides program code for use by or in connection with a computer or any instruction execution system, accessible from computer-readable medium 206. For purposes of this description, computer-readable medium 206 may be any apparatus that can tangibly store a program for use by or in connection with an instruction execution system, apparatus, or device, including computer system 200.

[0147] The medium 206 can be any tangible electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system (or apparatus or device). Examples of the computer-readable medium 206 include a semiconductor or solid-state memory, magnetic tape, a removable computer diskette, a random access memory (RAM), a NAND flash memory, a read-only memory (ROM), a rigid magnetic disk, and an optical disk. Some examples of optical disks include a compact disk-read-only memory (CD-ROM), a compact disk-read / write (CD-R / W), and a digital versatile disk (DVD).

[0148] A computing system 200 suitable for storing and / or executing program code may include one or more processors 202 coupled directly or indirectly to memory 208 via a system bus 210. The memory 208 may include local memory used during the actual execution of the program code, mass storage devices, and cache memory that provides temporary storage of at least some of the program code to reduce the number of times code is retrieved from mass storage devices during execution. Input / output or I / O devices 204 (including, but not limited to, keyboards, displays, pointing devices, etc.) may be connected to the system directly or through intervening I / O controllers. Network adapters may also be connected to the system to enable the computing system 200 to connect to other data processing systems, such as through a host system interface 212 or through remote printers or storage devices over intervening private or public networks. Modems, cable modems, and Ethernet cards are just a few of the currently available types of network adapters.

[0149] Three-dimensional (3-D) printing systems, including computer-aided drafting (CAD), are known in the art. 3-D printing systems include, but are not limited to, FDM-based systems, PolyJet-based systems, Stratasys F123 series, F770, F900, Fortus, uPrint SE and SE Plus, Dimension Elite, Dimension BST / SST 1200 es, J8 series, J7 series, J5 series, J4100, Connex3, Objet30, Objet 30 V3, Objet 30 V5, dental Objet1000 Plus, etc. 3-D printing systems that can be used with materials suitable for oral use are preferred.

[0150] Computer-aided design (CAD) and computer-aided manufacturing (CAM) are known in the art. CAD / CAM systems are known in the art. CAD / CAM systems include, but are not limited to, Solid Edge CAM Pro, Gibbs CAM, Fusion 360, Solidworks CAM, and SolidCAM. CAD / CAM systems can include milling, drilling, tapping, boring, turning, machining, or vacuum forming of dental devices. CAD / CAM machines can include, but are not limited to, CAD / CAM milling machines, CAD / CAM mills, CEREC PrimeMill, Dentsply Sirona CEREC, Planmeca Planmill, and Ivoclar PrograMill One, wet milling machines, dry milling machines, vacuum forming machines, CNC machining, and thermoforming machines. Vacuum forming machines include, but are not limited to, TrayVac, Formech 508FS, and Precision Dental Vacuum Former II. Systems that can be used with materials suitable for oral use are preferred.

[0151] It will be understood that references to the following examples are for illustrative purposes only and do not limit the scope of the claims.

[0152] [Example]

[0153] Example 1. Analysis of pathogens before and after treatment

[0154] Saliva was obtained from subjects exhibiting periodontal disease and subjected to analysis by MyPerioPath™. Levels of A. actinomycetemcomitans, P. gingivalis, T. forsythia, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Eubacterium nucleaturm, Fusobacterium nucleatum, Prevotella intermedia, Campylobacter rectus, oral anaerobes (Peptostreptococcus micros), and Eikenella were determined.

[0155] A periodontal measurement of the mouth was performed. An oral appliance tray was fabricated, including a gasket, supragingival area, gingival delivery area, and delivery pores. A predetermined compound was placed in the supragingival area of ​​the device. The oral appliance tray and compound were placed in the subject's mouth, allowing the compound to enter the inlet in the supragingival area, flow through the pores, and exit the outlet in the subject's gingival area. The appliance tray and compound remained in the subject's mouth for 15 minutes. The 15-minute treatment was performed twice daily (morning and evening) for 30 days.

[0156] Thirty days later, subjects collected saliva samples, which were then analyzed by MyPerioPath™. A. actinomycetemcomitans, P. gingivalis, T. forsythia, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Eubacterium nucleaturm, Fusobacterium nucleatum, Prevotella intermedia, Campylobacter rectus, oral anaerobes (Peptostreptococcus micros, Peptostreptococcus micros, and Fusobacteria The levels of E. nucleatum, pathogenic biofilm, and key components of Eikenella were determined. The results of one such experiment are shown in Figures 9 and 10. A thin layer equivalent to a 1 mm x 1 mm thick paste gel and / or foam concentration was placed in a tray. The concentration of the compound in Example 1 was a combination of 1.7% hydrogen peroxide oral debridement in a foam formulation described as an oral wound cleanser composed of 3% ethyl alcohol, potassium sorbate, peppermint oil, xylitol, 1% povidone-iodine, and 1% chlorhexidine solution. Steady-state timed intervals were achieved and maintained routinely to destroy colonizing pathogen formation. Trays were digitally fabricated to reflect accurate measurements of the entire circumference of the oral mucosa, alveolar bone, PDL, sulci, and tooth surface size and shape for the maxillary and mandibular arches from complete and thorough periodontal probing during clinical periodontal examination and a complete periodontal chart.

[0157] The trays were formed by a licensed laboratory technician using a subject's case alginate impression, pouring over the model to create cast stone test image models of the maxillary and mandibular arches, and casting the fabricated oral device tray casing from a melting machine that melted silicone plastic and other materials to reflect the accurate measurements from the periodontal exam. The trays contained one or more delivery pores, each containing at least one inlet in the supragingival region and at least one outlet in the gingival delivery region. Figure 18A is an image of an oral appliance delivery tray for the maxillary arch. The pore inlet channel is located in the supragingival region. The outlets are positioned based on the subject's periodontal chart and periodontal measurements so that when the tray is placed in the oral cavity, the outlets are proximal to the section of the tooth or implant at risk for periodontal disease or healing and restoration. The outlets allow for delivery of the compound of interest to the subject's extended pocket depths. Figure 18B provides an image of the oral appliance delivery tray with the pores visible.

[0158] The oral appliances were made from non-biodegradable polymers, including ethylene vinyl acetate, poly(meth)acrylic acid, polyamides, copolymers, and mixtures thereof. The characteristics or properties of these thermoformable plastics or polymers were modified as needed through the use of plasticizers and optional durometer-adjusting substances. Plasticizers are added to better tailor the final properties and characteristics of the plastic or polymer, such as making it softer or more flexible. The oral appliances comprise non-porous materials and are disposable.

[0159] The patient in Example 1 underwent implant replacement at #15. The intraoral photograph of Example 1 (FIG. 12) shows improved tissue tone, as well as removal of calcified plaque and hard tartar from the hard gums, and disappearance of intrinsic and extrinsic staining. FIGS. 13-15 show the patient returning to increased homeostatic levels orally. While not limited by mechanism, the subject's overall systemic improvement may be related to the patient no longer needing to fight infections with an immune response and no longer swallowing and ingesting these pathogens.

[0160] Example 2: Case Study 1

[0161] A subject (Case 1) taking several medications for heart disease and advanced periodontal disease was evaluated. The subject's home dental care regimen included daily brushing with a battery-operated toothbrush, flossing, flossing for implant and bridge restorations, use of medicated mouthrinses, and use of fluoride mouthrinses. Additionally, the subject underwent clinical dental debridement up to twice a month prior to treatment with the appliance. The subject exhibited Class IV subgingival and supragingival soft plaque and hard calculus. There was exposed dentin from a previous periodontal pocket reduction procedure. Intraoral photographs of Case 1's teeth were obtained (see Figure 12). The subject had lost several teeth and was at risk for the high financial cost and investment of implants.

[0162] Periodontal measurements were taken, and an intraoral delivery tray was created, including a supragingival portion, gingival and subgingival delivery areas, and a gasket containing delivery pores. The compound was placed in the supragingival portion of the oral appliance tray. The oral appliance tray and compound were placed in the subject's mouth, allowing the compound to enter the inlet in the supragingival region, flow through the pores, and exit the outlet in the subject's gingival and subgingival regions. The appliance tray and compound were placed in the subject's mouth. Treatment was performed daily for 30 days. Intraoral photographs of Case 1's teeth after 10, 20, and 30 days of daily treatment are shown in Figures 13, 14, and 15, respectively. Periodontal measurements were taken before, during, and after the treatment course, and the periodontal measurements are shown in Figure 16. A thin layer of 1 mm x 1 mm thick corresponding to the paste gel and / or foam concentration was used in the tray. This compound included a combination of 3% potassium nitrate for sensitivity, no ethyl alcohol for demineralizing natural tooth structure, potassium sorbate, peppermint oil, xylitol, 1% povidone-iodine and 1% chlorhexidine solution in the gel solution, and 1.7% hydrogen peroxide oral debridement in a gel formulation described as an oral wound cleanser, which acts as an antimicrobial and antiseptic oxygenating cleansing agent. The compound was directly accessible to the port channel to achieve and maintain a timed interval of time in the subject's mouth each day to destroy colonizing pathogen formation. This combination provided a significant source of comfort, reducing sensitivity to eating and drinking, and remineralized dentinal tubules, not only reducing sensitivity but also reducing the potential risk of future caries by strengthening exposed, unprotected tooth structure. Without being limited by the mechanism, it may be beneficial to disrupt further formation of biofilm, pellicle, and plaque mineralization to remove degenerative pathogens and establish debridement of current parthenogenetic formations. This particular combination raised the pH level to homeostasis, reducing the formation of degenerative effects such as the breakdown of surrounding natural tooth structure, further periodontal infection, abscesses, periapical abscesses, further attachment and bone loss, halitosis, and reduced the spread of this difficult and devastating prognosis of advanced degenerative periodontal and systemic disease that claims the oral and overall health and well-being of so many patients.The trays were used twice daily for 15 minutes / am and 15 minutes / pm. This was done at home by the patient who had been wearing the trays for 10 days at the time of testing, and pathogens were substantially reduced, and the patient's oral and general health was significantly improved by the present invention.

[0163] Trays were digitally fabricated to reflect precise measurements of the oral mucosa, alveolar bone, PDL, sulci, and all tooth surfaces, as well as the entire circumference of the maxillary and mandibular arches, as determined by a complete and thorough periodontal probing and complete periodontal chart during clinical periodontal / examination. The trays were formed by a licensed laboratory technician using a case alginate impression of the subject, pouring over the model to create cast stone test image models of the maxillary and mandibular arches, and casting the casing of the fabricated oral device tray from a melting machine that melted silicone plastic and listed materials to reflect the precise measurements from the periodontal examination. The intraoral appliances were fabricated from non-biodegradable polymers, including ethylene vinyl acetate, poly(meth)acrylic acid, polyamides, copolymers, and blends thereof. The characteristics or properties of these thermoformable plastics or polymers were modified as needed through the use of plasticizers and optional durometer-adjusting substances. Plasticizers are added to better tailor the final properties and characteristics, such as making the plastic or polymer softer or more flexible. The oral appliance comprises a non-porous material and is disposable.

[0164] Example 3. Periodontal measurement

[0165] Each tooth or implant was divided into six sections when viewed from the occlusal surface. Periodontal probes were inserted along the root surface to measure periodontal probing depth. The instrument was angled mesial-distal while maintaining parallelism to the long axis of the tooth. Buccal-lingual angles were avoided. The deepest periodontal or peri-implant probing depth was recorded for each section when probing with the peripheral probe. See herein above for specifications and explanations of the periodontal probing chart. Dental impressions, digital diagnostics, and oral scans and screenings determine precise periodontal probing staining to reflect the precise specifications and measurements of each and every individual pocket depth and space surrounding the dentition, alveolar mucosa, sulcus, alveolar bone, and periodontal ligament, or the complete natural dentition or all individual reconstructed teeth (PDL), or implant or multiple implant locations.

[0166] Example 4 Oral appliance tray for advanced periodontal disease

[0167] Individualized oral appliance trays were fabricated with wider ports. In this example, the mesial buccal delivery port is 2.5 mm x 6.5 mm (Port 1) and the direct buccal port is 3 mm x 5 mm (Port 2). The distal buccal delivery port is 2.5 mm x 6.5 mm (Port 3). The mesial buccal delivery port is 2 mm x 5.5 mm (Port 4); the direct buccal delivery port is 2 mm x 4 mm (Port 5); and the distal buccal port is 3 mm x 5.8 mm long (Port 6). A portion of the oral appliance tray showing the mesial buccal, direct buccal, and distal buccal ports is shown in Figure 23; the lingual delivery port is not visible in the image.

[0168] Example 5. Case Study 2

[0169] A subject with advanced periodontal disease and implants was identified. The subject was at risk of losing expensive dental implants and reconstructive dental implants. The subject was treated with the oral appliance delivery tray described herein above. A post-treatment x-ray image is shown in FIG. 26, and a post-treatment intraoral image is shown in FIG. 27. Bone has regenerated and stabilized the implant, and the implant is integrated. The subject's prognosis is stable, and the severity of multiple periodontal disease-related symptoms has significantly decreased. The improvement is remarkable.

[0170] Exemplary Embodiments

[0171] It will be understood that references to embodiments below are for illustrative purposes only and do not limit the scope of the claims.

[0172] Embodiment 1

[0173] An oral appliance tray for delivering a compound to the gingival region of at least one tooth of a subject, the oral appliance tray comprising a gasket device, the gasket comprising: (a) a supragingival portion; (b) a gingival and subgingival delivery region; and (c) one or more delivery pocket pores comprising an inlet and an outlet, the inlet being located in the supragingival portion and the outlet being within the gingival and subgingival delivery region.

[0174] Embodiment 2

[0175] The above oral appliance tray, wherein the gasket construction and inner wall impair the force of the pressurized material that brings the compound directly into the periodontal measurement port and pocket formation depth and surrounding tissue, and holds the compound in place for a selected time interval or an unlimited length of measurement time.

[0176] Embodiment 3

[0177] The method is used to facilitate guided biofilm therapy (GBT) and saliva diagnostics for therapeutic, medical, oral and systemic maintenance and oral and systemic healing.

[0178] The gasket seal device is designed to securely hold compounds in place in the buccal, facial, proximal, occlusal, supragingival, and subgingival regions, and structurally hold compounds in place for an indefinite period of time without diluting or altering the concentration of the compound into the port channel as a way to manipulate the pH of the target area to control and correct the progression of perioral pathogens and biofilms that contribute to localized and systemic inflammation of affected oral tissues causing degeneration and failure of surrounding tooth structures, from uncontrolled colonization of anaerobic gram-negative bacteria, endotoxins, decreased saliva production, acidic saliva formulations, increased crevicular exudates, and increased C-reactive protein (CRP) levels that cause negative autoimmune responses (as C-reactive protein (CRP) is the most clear, quantifiable, and easily accessible marker of oral-systemic connectivity).

[0179] Periodontal disease also contains degenerative biofilm markers, such as the interleukin-1 (IL-1), interleukin-2 (IL-2), and IL-6 (IL-6) gene polymorphisms, and patients with these polymorphisms produce greater amounts of IL-1 and IL-6. This dramatically increases the risk of not only acute but also the much more troublesome and degenerative "chronic" periodontitis. Furthermore, in addition to inflammatory biomarkers, the combined ILIA and ILIB genotype, containing a "T" nucleotide at both the ILIA (+4845) and ILIB (+3954) positions, now increases the risk of periodontitis, with an odds ratio of 1:51, associated with the presence of high levels of interleukin-1 and interleukin-6, and uncontrolled colonization by pathogens and gram-negative bacteria.

[0180] The presence of phagocytic or hyporesponsive phagocytes, overproduction of interleukins, prostaglandins, and cytokines, and lipopolysaccharide (LPS) are also present. Furthermore, the present invention utilizes one to six or more measurements from periodontal examinations and clinical records to reveal disease or alterations, compromised conditions, and deviations from homeostasis in a subject. The present invention provides therapeutic, medicinal, antimicrobial, and antibiotic compound applications, as well as mineralizing and desensitizing compounds, to improve diseased oral tissues, compromised, vulnerable, exposed, or damaged tooth structures, surrounding fixed prostheses, or attached oral structures. It is also designed to maintain single or multiple implants, fixed prostheses, and surrounding structured walls, sulci, oral tissues, and alveolar bone.

[0181] Chronic periodontitis disease affects the supporting structures of the teeth, resulting in progressive loss of the attachment apparatus and surrounding bone. It is characterized by gingival pocket formation and / or gingival recession. The disease is initiated by bacteria and their lipopolysaccharide-like components, triggering an intense host inflammatory response. This cascade of inflammatory responses ultimately leads to increased osteoclast activity and bone loss. Individuals with periodontitis have elevated acute-phase proteins, plasma antibody levels, clotting factors, total white blood cell count, neutrophils, C-reactive protein (CRP), and systemic levels of cytokines such as INF-gamma (interferon gamma), TNF-α (tumor necrosis factor-alpha), IL-1β (interleukin-1β), IL-2, and IL-6. The same chronic inflammatory model seen in systemic disease has well-documented peer-reviewed evidence correlating the bidirectional link between the two.

[0182] an oral tray comprising said compounds for reducing the deleterious systemic risk of cardiovascular disease and stroke, arteriosclerosis, respiratory infections, lung diseases, ear, nose and throat infections, dementia and brain diseases, prematurity, preterm birth rates, pregnancy complications, oral and other cancers, diabetes, autoimmune disorders, bone and joint diseases, arthritis, rheumatoid arthritis, gastrointestinal diseases, erectile dysfunction, obesity, gut biome disruption and gut barrier dysfunction, altered gut immune profile, non-alcoholic fatty liver disease (NAFLED), fibrosis, endotoxemia, low, medium and high grade systemic inflammation, bacteremia inflammatory mediators, dysbiosis and severe osteopenia and osteoporosis, candidiasis, viral diseases and women's health issues.

[0183] The oral appliance tray as described herein above, comprising a prefabricated, preloaded, and pre-administered oral tray device available over the counter for purchase by a subject for self-application and comfortable use outside the supervision of a licensed dental or medical professional, chemically loaded with the compounds listed above, and prefabricated, preloaded, and pre-administered medications to the oral tray device, without the need for a prescription to purchase the prefabricated, preloaded, and pre-administered oral tray device, wherein the compounds include oxygenators, antimicrobials, anti-plaque agents, general health compounds such as essential oils, hydrogen peroxide, baking soda, xylitol, and remineralizing and desensitizing compounds. The pre-fabricated trays can contain any of the above-listed compounds from Embodiment 1 and Embodiment 4 in commercially legal amounts approved by each individual state law requirement by FDA, or any other state option requirement for maintenance of caries control for subjects at moderate to high caries risk, where streptococcal colonization on tooth structure reduces the risk of caries, corrects, improves and manipulates oral pH levels to restore the subject to homeostasis and reduced caries risk, as well as desensitizing compounds, remineralizing compounds for tooth and gum sensitivity, halitosis, xerostomia, antimicrobial, antiseptic, antiplaque, induced biofilm therapy (GBT), pain, discomfort, sensitivity, and therapeutic and medical properties.

[0184] The oral appliance tray as described herein above, wherein the compound is selected from the group including oxygenating agents, antimicrobial agents, antiplaque agents, antibiotic agents, and remineralizing and desensitizing compounds and additional therapeutic uses.

[0185] Embodiment 3

[0186] 10. The oral appliance tray as described herein above, wherein when the tray is placed in the oral cavity of the subject, a compound flows through the one or more delivery ports and the measured pocket depth to the gingival and subgingival region of at least one tooth.

[0187] Embodiment 4

[0188] An oral appliance tray as described herein, comprising delivery ports and individual pocket formation depths for delivery of compounds into the gingival region of at least two teeth of the subject, as well as the subject's complete / entire natural oral structure and dentition, or up to surgically or cosmetically reconstructed oral dentition.

[0189] Embodiment 5

[0190] The oral appliance tray as described herein above, wherein at least one tooth is an implant(s).

[0191] Embodiment 6

[0192] 1. A dental implant retention device comprising an oral appliance tray for delivery of retention compounds to the dental implant, an abutment, a surrounding base region, a surrounding ligament, and an alveolar bone structure, the surrounding inner and outer walls of which comprise a gasket device providing a port channel access opening, the gasket facilitating cleansing and daily hygienic maintenance processes for a more successful prognosis of the implant or implants over a prolonged period of time.

[0193] An oxygenated compound applied as a preventative solution for implant maintenance and maintaining fixed implant prostheses to increase the success rate of implant placement, where upon extraction of the subject's tooth structure and open port area, the subject has lost the surrounding support structure of the periodontal ligament and there is no barrier of protection from food debris, soft plaque, hard mineralized plaque, calculus and any other debris that accumulates within the area around the implant pocket, leaving the implant and surrounding structures unprotected from food debris, soft plaque, hard mineralized plaque, calculus and other debris that cause pH levels or colonization of gram-negative pathogens, endotoxins and infection and pathology that can contribute to implant failure and periodontitis.

[0194] Additionally, electrochemical degradation, corrosion, and biotoxicity due to ions released into the oral cavity. Implants made of synthetic materials are naturally coated by biofilms produced by the body, which act as a favorable medium for bacterial growth, degenerating biofilms, anaerobic gram-negative bacteria, and further increase the risk of destructive pathogens that may be harmful to the implant(s) as well as the surrounding tissue and underlying bone structure, increasing the risk of implant failure.

[0195] A dental implant is considered to be failed upon clinical examination when it is found to be mobile (1+) or shows any of the following signs: inflammation, redness, bleeding, peri-implantitis (infection or abscess around the implant), bone loss greater than 1.0 mm in the first year and greater than 0.2 mm after one year. Implant failure due to bacterial infection of the implant can occur at any time during the life of the implant.

[0196] Surgically placed single and multiple implants must be maintained daily, but this is often not done because it is extremely difficult, if not impossible, to reach deeper than 1-3 mm of pocket depth using floss, interdental flossing mechanisms, interdental proxy brushes and floss picks, bridge floss, water picks, toothbrushes, electric or sonic toothbrushes, and mouth rinses. Bacteria and biofilms may already be present on the implant or may be introduced daily during or immediately after implant placement. Lack of maintenance due to a lack of accessible areas surrounding the implant structure can lead to the failure and peri-implantitis listed above, and thus implant failure due to uninterrupted biofilm colonization and gram-negative colonization of bacterial pathogens, as well as constant and overlapping accumulation. Typical failure mechanisms include tissue damage, gram-negative pathogen colonization, and implant delamination due to bacteria and biofilms that are not addressed by daily oral hygiene due to the inaccessible access areas that the trays are designed to maintain daily, ensuring a healthy and appropriate pH level and reducing the risk of these degenerative bacterial pathogens.

[0197] Embodiment 7

[0198] 1. An oral appliance tray, wherein the gingival area comprises one or more areas selected from the group including subgingival area, sulcus, periodontal ligament, periodontal ligament area, tooth root, furcation, implants and implant bases, abutments, alveolar bone, fixed restorations and bridge margins of restorations, laminates, veneers, composite and amalgam margin restorations, gold, porcelain, art glass, inlays, onlays, composite and hybrid composites, natural tooth structure with full enamel, dentin, cementum surface, fibers, attached gingiva and unattached gingiva.

[0199] Embodiment 8 An oral appliance tray selected from the group consisting of a mandibular arch oral appliance tray and a maxillary arch oral appliance tray.

[0200] Embodiment 9

[0201] An oral appliance tray, wherein the compound is selected from the group that settles and incorporates on enamel, dentin, cementum to impair high, medium to low risk caries subjects who are prone to caries and maintenance from degenerative biofilms and anaerobic gram-negative bacteria and pathogens that cause tooth decay, acid erosion and destruction of the tooth structure. Demineralization, increased crevicular fluid, negative changes in the pH level of oral and surrounding dental structures and tissues, mineral degradation of enamel, dentin, and cementum resulting from lesions, acid deposits, xerostomia (dry mouth), ingestion of simple and synthetic sugars in food consumption, high dietary intake of fermentable carbohydrates, fermentable sugars to acid, sucrose, fructose, glucose, acidosis, diabetes mellitus, presence of oral Candida "thrush-like" microorganisms, Sjögren's disease, cariogenic biofilms, viral diseases, antihistamines and antidepressants, prescription and over-the-counter medications, poor hygiene, smoking, chewing tobacco and snuff-like products, and fatigue. These conditions listed above contribute to decreased saliva production, xerostomia, increased biofilm pellicle adhesion, and an increase in thick mucus-containing pathogens and gram-negative bacteria, which contribute to poor oral and general health. The most common bacteria associated with the oral cavity are Streptococci mutans, most notably but not limited to Streptococcus mutans and Streptococcus sobrinus, and lactobacilli.

[0202] Embodiment 10

[0203] 1. An oral appliance tray constructed to deliver a caries control and maintenance device for low, moderate to high caries risk to subjects at risk for all forms of degenerative gram-negative bacterial colonization and accumulation and all forms of streptococcal colonization on tooth structure, to reduce caries risk, correct, improve and manipulate oral pH levels to homeostasis, restore the subject to overall oral health and homeostasis, and reduce the risk of caries progression over the subject's lifetime.

[0204] Embodiment 11

[0205] An oral appliance tray, wherein the diameter and pocket depth of the one or more delivery holes range from 0.1 mm to 12 mm, or up to the entire length of any tooth structure, surrounding pocket depth and the surrounding structure to the limit of the infected and diseased areas for single to unlimited areas. Each port size section of the oral appliance gasket device system has a depth of 0.5 mm to approximately 7 mm. The port sizes of the oral appliance gasket device system have a width of 0.5 mm to approximately 12 mm. The oral appliance gasket device system has a thickness of 0.03 to approximately 0.5 inches.

[0206] The port size is a defined pocket formation length, depth, and width not limited by the volume of the diseased or abscessed area, requiring a measurably sized gasket reservoir. This port reservoir is fabricated by a large structure sized according to the location of the infected and compromised tissue. The pocket depth length, depth, and width of the tray measurements approximate the length, depth, and width of the infected circumferential sulcus and oral tissue structures, which correspond to clinical periodontal charts of probe circumferential measurements and X-rays or CT scans, or digital and clinical findings that reveal the full spectrum of measured diseased tissue and tooth structures consumed by the infected area. The port corresponds to a precisely measured percentage of the infected diseased area, and manual and digital impressions are calculated and correspond to accessible delivery to a single localized infection site or multiple sites, reaching up to 100% accessibility with this engineered port system for effective, reliable, and measurable effective results.

[0207] Embodiment 12

[0208] An oral appliance tray, the supragingival and subgingival portions of which are formed with precise precision to conform to the subject's teeth, their internal contours, oral cavity, pocket depths, sulci, connective tissue, fibers, interdental membranes, attached and unattached gingiva, and the inner surface defines a contour that allows continuous flow cushioning to extend over facial, buccal, lingual, interdental, occlusal, and surrounding gingival tissue structures, allowing material compound flow to secure and hold in place for a scheduled activated placement or unlimited period of time for the subject.

[0209] Embodiment 13

[0210] An oral appliance tray, the oral appliance tray being a personalized oral appliance tray, wherein at least one outlet is positioned according to at least one clinical periodontal measurement from the subject's tooth.

[0211] Embodiment 14

[0212] 1. An individualized oral appliance tray, wherein exit placement is determined by six periodontal measurements per tooth from a single tooth to multiple teeth of the subject, the periodontal measurements from the teeth being selected from the group including:

[0213] Embodiment 15. A personalized oral appliance tray, wherein periodontal measurements from teeth are selected from the group of 6 sites per tooth or implant: Impaired Perio Probe Charting.

[0214] The selection of six sites per tooth or implant for both periodontal pocket and attachment level measurements is important. Each tooth or implant is divided into six sections when viewed from the occlusal surface. The site of deepest periodontal or peri-implant probing depth should be recorded for each section when probing with the peripheral probe. An oral appliance tray is fabricated to the deepest depth at each of the six sites per tooth where periodontal measurements are recorded, along with other measured contributing factors listed below: angle of periodontal probe.

[0215] Peripheral probing measurements include documentation of gingival margin, pocket depth, plaque measurements, bleeding on probing, furcation, mobility, peri-implant probing depth, peri-implant mucosa, mucosal margin, reconstruction defect, structural defect, clinical attachment, recess, peri-implant recess, alveolar bone loss, secondary bone loss, attachment loss, cemento-enamel junction, gingival hyperplasia, gingival overgrowth, pseudo-pocket depth, esthetic zone margin, residual pocket depth, and measurements contributing to peri-implantitis.

[0216] Embodiment 16

[0217] 1. A method for reducing the amount of one or more bacteria in the gingival region of a subject at risk for periodontal disease, comprising the step of delivering a compound to the subject, wherein the compound is selected from the group consisting of an oxygenating agent, an antimicrobial agent, an antibiotic agent, and a remineralizing compound, and wherein the compound is provided in an oral appliance tray of the present application.

[0218] Embodiment 17

[0219] A method for reducing the amount of one or more bacteria, wherein the bacteria are selected from the group consisting of solid biofilm compounds, soft plaque, hard mineralized plaque, tartar, calculus, intrinsic staining, extrinsic staining, increased crevicular fluid, changes in pH levels contributing to disease, acidic salivary compounds, fermented carbohydrates, and gram-negative bacteria that contribute to the formation of biofilms and the increase in collagenases that attract biofilms. Periodontal disease markers include interleukin-1 (IL-1) and interleukin-6 (IL-6) gene polymorphisms, where patients with these polymorphisms produce more IL-1 and IL-6. This dramatically increases the risk of not only acute but also the much more troublesome and degenerative "chronic" periodontitis. In addition to inflammatory biological markers, the combined genotype of the ILIA and ILIB genes containing a "T" nucleotide at both the ILIA (+4845) and ILIB (+3954) positions is currently associated with an increased risk of periodontitis, with an odds ratio of (1:51). This modified biofilm is composed of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Eubacterium nucleaturm, Fusobcterium nucleatum, Prevotella intermedia, Campylobacter rectus, and oral anaerobes such as Peptostreptococcus difficile. micros), Capnocytophaga species (gingivalis, ochracea, sputigena), and Eikenella species.In addition to contributing to an increased risk of dental caries, Streptococcus mutans, Streptococcus sobrinus and lactobacilli are also included.

[0220] Embodiment 18

[0221] The method of the present application further comprises providing the compound according to a delivery regimen comprising multiple delivery events including caries risk control maintenance, plaque and biofilm control maintenance, correcting and stabilizing proper oral pH levels, periodontal disease classification maintenance, implant maintenance, reconstructive dentistry maintenance, fixed prosthesis maintenance, osteotomy surgery maintenance, scaling and root planing maintenance, pocket depth reduction surgery maintenance, bone graft maintenance, connective tissue lattice maintenance, free tissue graft maintenance, pedal tissue graft maintenance, bleaching, whitening, intrinsic and extrinsic staining maintenance to any subject who wishes to be proactive in the overall health and well-being of their oral cavity and whole body, and who wishes to maintain homeostasis and proper pH levels to reduce the risk of oral disease and oral health degeneration of organic and inorganic oral structures.

[0222] Embodiment 19

[0223] A method of manufacturing a personalized oral appliance tray of the present application, the method comprising the steps of obtaining at least one periodontal measurement from a tooth of a subject at risk for periodontal disease, determining the dental arch morphology of the subject at risk for periodontal disease, using the at least one periodontal measurement to determine the placement of an outlet for at least one port, and forming a personalized oral appliance tray comprising a pressurized compound gasket device having a surrounding fixed covering and barrier, the tray comprising: a) supragingival and subgingival portions complementary to the subject's dental arch morphology, (b) a gingival delivery region, and (c) one or more delivery ports comprising an outlet and clinically determined periodontal pocket measurements within the subgingival delivery region. When the delivery port comprises a delivery pore, the inlet is located in the supragingival portion.

[0224] Embodiment 20 1. A method for manufacturing a personalized oral appliance tray, wherein forming the oral appliance tray comprises a process selected from the group including laser cutting, layer deposition, laser printing, laser deposition, molding, and casting and fabrication manual and digitized impressions, Itero digital scanning, CT scanning, and MRI techniques.

[0225] Embodiment 21

[0226] The method for fabricating the intraoral tray device comprises receiving an initial digital computer-implemented method or physical model manual impression set representing at least said portion of the teeth and soft tissue regions within the oral cavity. This initial impression or data set of an initial database of internal oral cavity and tissue measurements imparts internal dividing surfaces and fitted gaskets for compressing a compound into said region of the extended buccal surfaces of the teeth and surrounding soft and gingival tissue, covering the occlusal surfaces of the teeth, the lingual sides of the teeth, the interdental spaces, the respective adjacent gingival tissues, and corresponding groove and pocket regions, the porous fabrication having an increasing width and thickness beginning at 0.05 mm and extending transversely to the length of the porous material. This section from the gasket is propelled and driven forward by a forward force that keeps the compound stationary and holds in place the formulation necessary for the use of medicinal and therapeutic drugs.

[0227] Embodiment 22

[0228] An oral appliance tray, wherein the gasket fabrication and inner wall comprise materials suitable for oral use. Methods for forming porous materials suitable for non-toxic biocompatible compounding processes of plastics and plastic combination polymers that are safe, effective, sustainable for oral use, and suitable and non-toxic for oral use include the following: Suitable polymers for making oral appliances can have low melting points. The melting point (or, rarely, the liquefaction point) of a substance is the temperature at which a substance changes state from solid to liquid. Because the melting points of the solid and liquid phases exist in equilibrium, they are generally non-toxic or biocompatible, allowing for easy incorporation of porous materials during the compounding process. Plastics and plastic combinations are suitable for making oral appliances.

[0229] These plastics include polyacrylates, polyamideimides, phenolics, nylons, nitrile resins, petroleum resins, fluoropolymers, copolyvidone (copovidone), epoxies, melamine-formaldehyde, diallyl phthalates, acetals, coumarone-indene, acrylics, acrylonitrile-butadiene-styrene, alkyds, celluloses, polybutylenes, polycarbonates, polycaprolactones, polyethylenes, polyimides, polyphenylene oxides, polypropylenes, polystyrenes, polyurethanes, polyvinyl acetates, polyvinyl chlorides, poly(vinyl alcohol-co-ethylene), styrene-acrylonitriles, sulfone polymers, saturated or unsaturated polyesters, urea-formaldehyde, or any similar plastic combinations thereof. Oral appliances may also be made from non-biodegradable polymers, including ethylene vinyl acetate, poly(meth)acrylic acid, polyamides, copolymers, and mixtures thereof. The characteristics or properties of these thermoformable plastics or polymers may be modified as needed through the use of plasticizers and optional durometer-adjusting substances. Plasticizers may be added to better tailor the final properties and characteristics of the plastic or polymer, such as making it softer or more flexible. Typically, oral appliances comprise non-porous materials and are disposable.

[0230] Embodiment 23

[0231] Any oral tray device for reducing the risk of adventitious disease mutations, pathogens and microorganisms associated with either SARS or COVID respiratory illnesses. Any oral tray device used to reduce the barrier of lack of oxygen to the oral and nasal passages that colonize from mask wearing and contribute to the spread of any SARS or COVID or any other pandemic or respiratory disease, oral contagion via air waves, and any surfaces with increased mobile droplets of air wave-bound bacterial load, oral contagion transmitted from person-to-person contact, person-to-animal contact, masks or face coverings, and cross-contaminated surfaces that harbor and carry infectious, mobile, investible, ingestible and injectable bacterial load.

[0232] Embodiment 24

[0233] Any intraoral tray device / apparatus bearing pre-fabricated compounds or compounds that can be manually placed or pre-fabricated, pre-loaded or pre-administered with measured benefits to reduce antimicrobial, antibiotic, disinfectant, desensitizing, remineralizing, oxygenating, implant retention, whitening / bleaching retention, stabilize oral, coronal pH and bridge and fixed prosthesis maintenance, reduce caries risk from gram-negative bacterial colonization, biofilm, endotoxin and other harmful ion release and pathogenic buildup threatening oral structures, said compounds reach supragingivally and subgingivally to surrounding tooth structures, tissue structures, organic and inorganic surrounding structures, maintaining sustainably increased benefits and increasing local and systemic adverse risks for maintaining oral health and therapeutically and medically improved oral and systemic homeostasis every day.

[0234] Embodiment 25

[0235] Oral tray devices / apparatus, foams, gels or compounds or rinses or oral toys, case-specific or broad-species bearing animal foods or snacks, or individually manufactured or pre-fabricated compounds or compounds that can be manually placed or pre-fabricated, pre-loaded or pre-administered with a measured benefit, contributing to oral bacteria known to cause degenerative and / or periodontal disease and systemic illness in dogs and animal species. Any oral tray device / augmenter, foam, gel or compound or rinse or oral toy, animal food or snack used to lower the antimicrobial, antibiotic, antiseptic, desensitizing, remineralizing, oxygenating, oral health maintenance stabilizes the pH of the animal's oral cavity, bacterial colonization of gram-negative bacteria, biofilm, reducing caries risk from the release of endotoxins and other harmful ions and pathogenic buildup that threatens oral structures, allowing said compounds to reach the supragingival and surrounding tooth structures, tissue structures, organic and inorganic surrounding structures subgingivally and sustainably increase benefits for maintaining oral health and therapeutically and medically improved oral and systemic homeostasis of any animal species daily that contribute to worsening local and systemic adverse risks.

[0236] Embodiment 26

[0237] One embodiment provides an oral appliance delivery tray including a pre-fabricated, pre-loaded, pre-ordered, pre-dosed oral tray device for over-the-counter availability and production by said subject, which may or may not require a prescription for purchase and may or may not be purchased outside the supervision of a licensed medical or dental professional, that addresses moderate to high caries risk, improves and manages pH levels and conditions, oxygenating, holistic compounds, desensitizing minerals and compounds, remineralizing compounds, addresses halitosis, xerostomia, antimicrobial, anti-plaque, induced biofilm therapy and management, pain, discomfort, sensitivity, therapeutic, medical, oral, and systemic properties to reduce disease and enhance wellness. The present disclosure includes the following preferred embodiments. (1) 1. An oral appliance tray for delivering a compound to the gingival, supragingival, subgingival, or gingival and subgingival regions of at least one tooth of a subject, comprising a gasket, the gasket comprising: (a) a supragingival portion; (b) a gingival delivery region; and (c) one or more delivery ports comprising an outlet within the gingival delivery region, the delivery port selected from the group comprising a delivery reservoir and a delivery pore comprising an inlet located within the supragingival region. (2) The oral appliance tray of (1), wherein the gasket comprises a material suitable for oral use. (3) The oral appliance tray of (1), wherein the material suitable for oral use is selected from the group consisting of non-biodegradable polymers, thermoformable plastics, and thermoformable polymers. (4) 10. The oral appliance tray of claim 1, wherein when the tray is placed in a subject's mouth, the compound flows through one or more delivery pores to the gingival, subgingival, or gingival and subgingival regions of at least one tooth. (5) 10. The oral appliance tray of (1), wherein the delivery reservoir maintains the compound and the outlet within the subgingival region of at least one tooth when the tray is placed in the subject's mouth. (6) 10. The oral appliance tray of claim 1, comprising one or more delivery ports for delivering a compound to the gingival, subgingival, or gingival and subgingival regions of at least two teeth of the subject. (7) The oral appliance tray according to (1), wherein at least one tooth is an implant or multiple implants. (8) The oral appliance tray of (1), wherein the gingival area includes one or more areas selected from the group including the gingiva, subgingival area, sulcus, periodontal ligament, periodontal ligament area, tooth root, margins of natural and reconstructed dentition, dental implant area, and implant base. (9) The oral appliance tray according to (1), which is selected from the group consisting of mandibular arch oral appliance trays and maxillary arch oral appliance trays. (10) 10. The oral appliance tray of claim 1, wherein the compound is selected from the group consisting of oxygenating agents, antimicrobial agents, antibiotic agents, desensitizing agents, remineralizing compounds, therapeutic compounds, pharmaceutical compounds, anti-plaque compounds, anti-caries compounds, whitening compounds, compounds that increase pH, compounds that maintain oral pH, compounds that manage biofilm, cleansing compounds, and maintenance compounds. (11) The oral appliance tray of (4), wherein the diameter of the one or more delivery pores is within the range of 0.5 mm to 12 mm. (12) The oral appliance tray of (1), wherein the height of the outlet of one or more delivery ports is within the range of 0.5 mm to 12 mm, and the width of the outlet of one or more delivery ports is within the range of 0.5 mm to 12 mm. (13) The oral appliance tray of (1), wherein the supragingival portion and gingival delivery area are configured to conform to the target tooth and gingival tissue structure. (14) 10. The oral appliance tray of claim 1, wherein the oral appliance tray is an individualized oral appliance tray, and the location of at least one exit port is determined by at least one periodontal measurement from a target tooth. (15) The oral appliance tray of (12), wherein the location of the exit is determined by six periodontal measurements from the target teeth. (16) 1. A method for reducing the amount of one or more bacteria in the gingival region of a subject at risk for periodontal disease, oral discomfort, oral degenerative characteristics, or systemic disease symptoms, comprising: (a) providing an oral appliance tray as described in (1); and (b) delivering a compound to the subject, wherein the compound is selected from the group consisting of an oxygenating agent, an antimicrobial agent, an antibiotic agent, a remineralizing compound, a desensitizing compound, a whitening compound, a cleansing compound, a pH-raising compound, and a pH-stabilizing compound, wherein the compound is provided in the oral appliance tray. (17) The bacteria include gram-negative bacteria, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Eubacterium nucleaturm, Fusobcterium nucleatum, Prevotella intermedia, Campylobacter rectus, and the like. rectus), Capnocytophaga species (gingivalis, ochracea, sputigena), oral anaerobes (Peptostreptococcus micros), Streptococcus sobrinus, Streptococcus mutans, Lactobacillis species, Eikenella corrodens, and Eikenella species. (18) 17. The method of (16), further comprising preparing the compound according to a delivery regimen comprising multiple delivery events. (19) (a) obtaining at least one periodontal measurement from a tooth of a subject selected from the group including subjects at risk for periodontal disease and subjects exhibiting biological markers of the disease; (b) determining the morphology of the subject's dental arch; (c) determining the placement of an outlet of at least one delivery port using at least one periodontal measurement; (d) forming an individualized oral appliance tray with a gasket complementary to the morphology of the target dental arch, the gasket comprising: a) a supragingival portion; (b) a gingival delivery region; and (c) one or more delivery ports comprising an outlet within the gingival delivery region, the delivery port selected from the group comprising a delivery reservoir and a delivery pore comprising an inlet located within the supragingival region; A method for manufacturing the personalized oral appliance tray described in (1), comprising: (20) 20. The method of claim 19, wherein the step of forming the oral appliance tray comprises a process selected from the group including laser cutting, layer deposition, laser printing, laser deposition, molding, and casting. (21) (15) The method of (15), further comprising managing a biofilm in a subject, the method comprising: (a) providing a compound in an oral appliance tray; (b) placing the oral appliance tray with the compound in the subject's mouth; and (c) maintaining the oral appliance tray in the subject's mouth for a predetermined period of time and frequency, wherein a biofilm accumulation rate, pH, or a biofilm accumulation rate and pH in the subject's mouth is altered. (22) (21) A method according to (21) that results in an induced biofilm therapy. (23) 20. The method of (19), further comprising correlating at least one dimension of the outlet of the at least one delivery port with at least one periodontal measurement. (24) 10. An oral appliance tray as described in (1) for delivery of a compound to reduce the risk of oral pathogens due to mask wearing or any respiratory disease. (25) 1. A pre-fabricated oral appliance tray for delivering a compound to the gingival, supragingival, subgingival, or gingival and subgingival regions of at least one tooth of a subject, the tray comprising a gasket, the gasket comprising: (a) a supragingival portion; (b) a gingival delivery region; and (c) one or more delivery ports comprising an outlet within the gingival delivery region, the delivery port(s) selected from the group comprising a delivery reservoir and a delivery pore comprising an inlet located within the supragingival region; and a compound pre-loaded on the tray, the compound selected from the group comprising an oxygenator, an antimicrobial, an antibiotic, a desensitizing compound, a remineralizing compound, a therapeutic compound, a pharmaceutical compound, an anti-plaque compound, an anti-caries compound, a whitening compound, a compound that increases pH, a compound that maintains oral pH, a compound that manages biofilm, a cleansing compound, and a maintenance compound. (26) A veterinary oral appliance tray for delivering a compound to the gingival, supragingival, subgingival, or gingival and subgingival regions of at least one tooth of a non-human animal, comprising a gasket, the gasket comprising: (a) a supragingival portion; (b) a gingival delivery region; and (c) one or more delivery ports comprising an outlet within the gingival delivery region, the delivery port selected from the group comprising a delivery reservoir and a delivery pore comprising an inlet located within the supragingival region. (27) A non-transitory computer-readable medium that, when executed by a processor of a three-dimensional (3D) printer, receiving and processing a digital 3D image model of at least one dental arch of a subject selected from the group consisting of a maxillary arch and a mandibular arch to create a dental device; receiving and processing coordinates and dimensions of a delivery port configured in an oral appliance tray based on periodontal measurements performed on at least one dental arch selected from the group consisting of the subject's maxillary arch and mandibular arch, and creating a dental device; Mapping the coordinates and dimensions of the delivery port onto a digital 3D image model; and Directing a 3D printing machine to form a dental device having a delivery port according to the digital 3D image model and according to the coordinates and dimensions of the delivery port mapped to the digital 3D image model. a non-transitory computer-readable medium containing instructions that direct a processor to: (28) 1. A computer-implemented method operable in a three-dimensional (3D) printing machine, comprising: receiving and processing a digital 3D image model of at least one dental arch selected from the group consisting of a subject's maxillary arch and a subject's mandibular arch to create a dental device; receiving and processing coordinates and dimensions of a delivery port configured in a dental device, the coordinates and dimensions of the delivery port being based on periodontal measurements performed on the subject's dental arch; mapping the coordinates and dimensions of the delivery port onto a digital 3D image model; directing a 3D printing machine to form a dental device having a delivery port according to the digital 3D image model and according to coordinates and dimensions of the delivery port mapped to the digital 3D image model; 10. A computer-implemented method comprising: (29) 1. A computer-implemented method operable on a CAD / CAM machine, comprising: receiving and processing coordinates and dimensions of a delivery port configured in a dental device, the coordinates and dimensions of the delivery port being based on periodontal measurements taken on at least one dental arch of the subject; Mapping the coordinates and dimensions of the delivery port onto the dental device; instructing the CAD / CAM machine to form a delivery port on the dental device according to the coordinates and dimensions of the delivery port mapped to the dental device; 10. A computer-implemented method comprising: (30) 1. A computer-implemented method operable on a CAD / CAM machine, comprising: receiving and processing coordinates and dimensions of a delivery port configured in a dental device, the coordinates and dimensions of the delivery port being based on periodontal measurements taken on at least one dental arch of the subject; mapping the coordinates and dimensions of the delivery port onto a digital 3D image model; instructing a CAD / CAM machine to create a dental device including the delivery port according to the coordinates and dimensions of the delivery port and according to the digital 3D model; A method comprising:

Claims

1. An oral appliance tray (10) for delivering a compound to the gingival, supragingival, subgingival, or gingival and subgingival regions of at least one tooth of a subject, the tray comprising: (a) supragingival portion (20); (b) gingival delivery region (30); (c) lingual region; (d) the buccal region; and (e) a first plurality of delivery ports (40) extending along the buccal side and having an open entrance (55); a first plurality of delivery ports (40) for delivering a compound to the subgingival region, the open inlet (55) extending from inside the supragingival portion (20) to an open outlet (45) extending inside the gingival region; and (f) a second plurality of delivery ports (40) extending along the lingual side and having an open entrance (55); a second plurality of delivery ports (40) for delivering a compound to the subgingival region, the open inlet (55) extending from inside the supragingival portion (20) to an open outlet (45) extending inside the gingival region; Including, An oral appliance tray (10).

2. An oral appliance tray as described in claim 1, wherein the oral appliance tray (10) comprises a material suitable for oral use.

3. The oral appliance tray of claim 1 , wherein the material suitable for oral use is selected from the group consisting of non-biodegradable polymers, thermoformable plastics, and thermoformable polymers.

4. 10. The oral appliance tray of claim 1, wherein the tray maintains the compound and the outlet within the subgingival region of at least one tooth when the tray is placed in the subject's mouth.

5. 10. The oral appliance tray of claim 1, comprising a plurality of delivery ports (40) for delivering compounds to the gingival, subgingival, or gingival and subgingival regions of at least two teeth of the subject.

6. The oral appliance tray of claim 1 , wherein the at least one tooth is an implant or multiple implants.

7. 10. The oral appliance tray of claim 1, wherein the gingival region comprises a plurality of regions selected from the group including the gingiva, the subgingival region, the sulcus, the periodontal ligament, the periodontal ligament region, the tooth root, the margins of natural and reconstructed dentition, the dental implant region, and the implant base.

8. 10. The oral appliance tray of claim 1, selected from the group consisting of a mandibular arch oral appliance tray and a maxillary arch oral appliance tray.

9. 10. The oral appliance tray of claim 1, wherein the compound is selected from the group comprising oxygenating agents, antimicrobial agents, antibiotic agents, desensitizing agents, remineralizing compounds, therapeutic compounds, pharmaceutical compounds, anti-plaque compounds, anti-caries compounds, whitening compounds, compounds that increase pH, compounds that maintain oral pH, compounds that manage biofilm, cleansing compounds, and maintenance compounds.

10. An oral appliance tray as described in claim 1, wherein the diameters of the multiple delivery ports (40) are within the range of 0.5 mm to 12 mm.

11. An oral device tray as described in claim 1, wherein the height of the outlets (45) of the multiple delivery ports is within the range of 0.5 mm to 12 mm, and the width of the outlets (45) of the multiple delivery ports (40) is within the range of 0.5 mm to 12 mm.

12. The oral appliance tray of claim 1 , wherein the supragingival portion (20) and the gingival delivery portion (30) are shaped to conform to the subject's teeth and gingival tissue structure.

13. 10. The oral appliance tray of claim 1, wherein the oral appliance tray is a personalized oral appliance tray, and the location of the at least one outlet is determined by at least one periodontal measurement from a target tooth.

14. An oral appliance tray as described in claim 11, wherein the position of at least one outlet (45) is determined by six periodontal measurements from the target teeth.

15. (a) obtaining at least one periodontal measurement from a tooth of a subject selected from the group including subjects at risk for periodontal disease and subjects exhibiting biological markers of the disease; (b) determining the morphology of the subject's dental arch; (c) determining the placement of the outlet of the at least one delivery port using the at least one periodontal measurement; (d) forming a personalized oral appliance tray with a gasket complementary to the morphology of the target dental arch; The gasket is (a) supragingival portion (20); (b) gingival delivery region (30); (c) lingual region; (d) the buccal region; and (e) a plurality of delivery ports (40) extending along the buccal side and having open inlets (55) extending from inside the supragingival portion (20) to open outlets (45) extending inside the gingival region for delivering compounds to the subgingival region; 10. A method for manufacturing the personalized oral appliance tray of claim 1, comprising:

16. 16. The method of claim 15, wherein forming the oral appliance tray comprises a process selected from the group including laser cutting, layer deposition, laser printing, laser deposition, molding, and casting.

17. 16. The method of claim 15, further comprising managing a biofilm in a subject, the method comprising: (a) providing a compound in an oral appliance tray; (b) placing the oral appliance tray with the compound in the subject's mouth; and (c) maintaining the oral appliance tray in the subject's mouth for a predetermined period of time and frequency, wherein a biofilm accumulation rate, pH, or a biofilm accumulation rate and pH in the subject's mouth is altered.

18. 20. The method of claim 17, which results in induced biofilm therapy.

19. 16. The method of claim 15, further comprising correlating at least one dimension of the outlet of the at least one delivery port with at least one periodontal measurement.

20. 10. The oral appliance tray of claim 1 for delivery of a compound to reduce the risk of oral pathogens due to mask wearing or any respiratory illness.

21. 1. A prefabricated oral appliance tray for delivering a compound to the gingival, supragingival, subgingival, or gingival and subgingival region of at least one tooth of a subject, the tray comprising: a gasket; (a) supragingival portion (20); (b) gingival delivery region (30); (c) lingual region; (d) the buccal region; and (e) a plurality of delivery ports (40) extending along the buccal side and having open inlets (55) extending from inside the supragingival portion (20) to open outlets (45) extending inside the gingival region for delivering a compound to the subgingival region; 1. A prefabricated oral appliance tray, wherein the compound is selected from the group including oxygenators, antimicrobials, antibiotics, desensitizing compounds, remineralizing compounds, therapeutic compounds, pharmaceutical compounds, anti-plaque compounds, anti-caries compounds, whitening compounds, compounds that increase pH, compounds that maintain oral pH, compounds that manage biofilm, cleansing compounds, and maintenance compounds.

22. 1. A veterinary oral appliance tray for delivering a compound to the gingival, supragingival, subgingival, or gingival and subgingival region of at least one tooth of a non-human animal, the tray comprising: a gasket; (a) supragingival portion (20); (b) gingival delivery region (30); (c) lingual region; (d) the buccal region; and (e) including a plurality of delivery ports (40) extending along the buccal side and having open inlets (55) extending from inside the supragingival portion (20) to open outlets (45) extending inside the gingival region for delivering a compound to the subgingival region; Veterinary oral appliance trays.

23. A non-transitory computer-readable medium that, when executed by a processor of a three-dimensional (3D) printer, receiving and processing a digital 3D image model of at least one dental arch of a subject selected from the group consisting of a maxillary arch and a mandibular arch to create a dental device; The dental device comprises: (a) supragingival portion (20); (b) gingival delivery region (30); (c) lingual region; (d) the buccal region; and (e) a plurality of delivery ports (40) extending along the buccal side and having open inlets (55) extending from inside the supragingival portion (20) to open outlets (45) extending inside the gingival region for delivering a compound to the subgingival region; receiving and processing coordinates and dimensions of a delivery port configured in an oral appliance tray based on periodontal measurements performed on at least one dental arch selected from the group consisting of the subject's maxillary arch and mandibular arch, and creating a dental device; Mapping the coordinates and dimensions of the delivery port onto the digital 3D image model; and Instructing a 3D printer to form a dental device having a delivery port according to the digital 3D image model and according to the coordinates and dimensions of the delivery port mapped to the digital 3D image model. a non-transitory computer-readable medium containing instructions that direct a processor to:

24. 1. A computer-implemented method operable in a three-dimensional (3D) printing machine, comprising: receiving and processing a digital 3D image model of at least one dental arch selected from the group consisting of a subject's maxillary arch and a subject's mandibular arch to create a dental device; The dental device comprises: (a) supragingival portion (20); (b) gingival delivery region (30); (c) lingual region; (d) the buccal region; and (e) a plurality of delivery ports (40) extending along the buccal side and having open inlets (55) extending from inside the supragingival portion (20) to open outlets (45) extending inside the gingival region for delivering compounds to the subgingival region; Process including and, receiving and processing coordinates and dimensions of a delivery port configured in a dental device, the coordinates and dimensions of the delivery port being based on periodontal measurements performed on the subject's dental arch; mapping the coordinates and dimensions of the delivery port onto a digital 3D image model; instructing a 3D printer to form a dental device having a delivery port according to the digital 3D image model and according to the coordinates and dimensions of the delivery port mapped to the digital 3D image model; 10. A computer-implemented method comprising:

25. 1. A computer-implemented method operable on a CAD / CAM machine, comprising: receiving and processing coordinates and dimensions of a delivery port configured in a dental device, the dental device comprising: (a) supragingival portion (20); (b) gingival delivery region (30); (c) lingual region; (d) the buccal region; and (e) a plurality of delivery ports (40) extending along the buccal side and having open inlets (55) extending from inside the supragingival portion (20) to open outlets (45) extending inside the gingival region for delivering compounds to the subgingival region; wherein the coordinates and dimensions of the delivery port are based on periodontal measurements taken on at least one dental arch of the subject; Mapping the coordinates and dimensions of the delivery port onto the dental device; instructing the CAD / CAM machine to form a delivery port on the dental device according to the coordinates and dimensions of the delivery port mapped to the dental device; 10. A computer-implemented method comprising:

26. 1. A computer-implemented method operable on a CAD / CAM machine, comprising: receiving and processing coordinates and dimensions of a delivery port configured in a dental device, the dental device comprising: (a) supragingival portion (20); (b) gingival delivery region (30); (c) lingual region; (d) the buccal region; and (e) a plurality of delivery ports (40) extending along the buccal side and having open inlets (55) extending from inside the supragingival portion (20) to open outlets (45) extending inside the gingival region for delivering compounds to the subgingival region; wherein the coordinates and dimensions of the delivery port are based on periodontal measurements taken on at least one dental arch of the subject; mapping the coordinates and dimensions of the delivery port onto a digital 3D image model; instructing a CAD / CAM machine to create a dental device including the delivery port according to the coordinates and dimensions of the delivery port and according to the digital 3D model; A method comprising:

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