Medicament delivery tray to treat dental disease and preserve dental implants

Abstract

The present disclosure provides an improved medicament delivery tray for treating dental disease and preserving dental implants in vivo, and methods of its use. The disclosure also provides methods for automated manufacturing of said medicament delivery tray. Furthermore, the disclosure contemplates various medicament gel compositions to be used in conjunction with the medicament delivery tray.

Description

81777-428087MEDICAMENT DELIVERY TRAY TO TREAT DENTAL DISEASE AND PRESERVE DENTAL IMPLANTSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 679,489, filed August 5, 2024; the entire content of that application is hereby incorporated by reference herein.BACKGROUND OF INVENTION

[0002] The dental implant market in the United States has experienced significant growth in recent decades with millions of implant procedures being performed annually. While dental implants offer several advantages, the high prevalence of peri-implant diseases may pose a challenge to their long-term effectiveness and overall prosthesis integrity. Specifically, meta-analyses estimate a weighted mean prevalence of 43% for peri-implant mucositis and 22% for peri- implantitis, respectively, which is primarily driven by oral microbiome changes commensurate with periodontal disease.

[0003] The predominant initial colonizers of the oral environment are predominantly grampositive facultative anaerobic cocci and rods, including Streptococcus and Actinomyces species. These initial colonizers provide a foundation for further development of dental biofilm. Streptococcus recognizes components in the pellicle, such as a specific interaction between a pilus protein of S. sanguinis and salivary a-amylase enabling these bacteria to attach to the tooth and oral surfaces.

[0004] The surface molecules of these early gram-positive colonizers allow for coaggregation of gram-negative bacteria possessing a lower level of adherence to the pellicle, including members of the genera Veillonella and Fusobacterium . Bacteria belonging to the genus Fusobacterium, such as Fusobacterium nucleatum, are able to co-aggregate with both initial and late colonizers, thus are called bridge species and known to promote successful development of dental biofilm. For bridging neighboring bacteria, F. nucleatum utilizes surface molecules such as RadD, an arginine-inhabitable adhesin, and the fusobacterial apoptosis protein Fap2.

[0005] It has been postulated that a shift occurs in the microbial concentrations as periodontal pockets are formed. The shift in the periodontal microbiome that accompanies an increase in gram-negative anaerobic species is now accepted as an indicator of periodontal disease. Uematsu81777-428087 et al report that approximately 90% of microorganisms isolated from periodontal pockets are strictly anaerobic and certain sets of bacteria have been frequently detected at elevated levels in periodontal lesions as compared with healthy tissues. Researchers have analyzed distribution of approximately 40 species in subgingival plaque using a DNA-DNA hybridization technique.

[0006] Their findings indicated that typical co-colonization of specific oral species, among which a cluster with the nomenclature “red complex” composed of the gram-negative anaerobic species Tannerella forsythia, P. gingivalis, and Treponema denticola, is associated with increased pocket depth and bleeding upon clinical pocket probing, while Sokransky et al report the other four clusters examined were not shown to be associated with clinical parameters indicating periodontal disease. The same bacteria associated with advanced periodontal disease, and periimplant diseases, are also reported to be associated with systemic diseases.

[0007] The possible correlations between oral disease and systemic ramifications is not new. W.D. Miller in 1891 and William Hunter in 1900 published articles regarding the possible correlations between oral disease and systemic illnesses. This helped develop Frank Billings “theory of focal infection” in 1914 leading to the extraction of endodontic and periodontic involved teeth; but these removals did not reduce the systemic problems.

[0008] Evidence supports the oral bacteria / systemic correlation and suggests that altering periodontal disease may have a positive effect on helping manage systemic diseases like cardiovascular disease. High risk periodontal pathogens are linked to the pathogenesis of atherosclerosis through lipoprotein production and binding to arterial intima. Three possible pathways of causal factors are offered: bacteria entering the bloodstream (bacteremia), the spread of bacterial toxins, and a spreading of the host derived immune system resulting in inflammatory response to the bacteria. Periodontitis is a probable cause of immune system response through shared risk factors, subgingival biofilms as reservoirs of gram-negative bacteria, and reservoirs of immune inflammatory products.

[0009] Periodontitis occurs when the subgingival gram-positive bacteria that predominate in healthy gingiva are surpassed with a greater number of bacteria, predominantly gram-negative bacteria. Periodontal healthy sites show a low number of bacteria (102-103) that are mostly grampositive microorganisms, that increase in number and are overtaken by a greater number (104- 105) of gram-negative anaerobic microorganisms. The increased incidence of gram-negative anaerobic bacteria induces systemic challenges.81777-428087

[0010] Gram-negative bacteria produce lipopolysaccharides (LPS) that induces inflammatory cell infiltrate in the blood vessel walls, causing vascular smooth muscle proliferation, vascular fatty degeneration and intravascular coagulations. LPS upregulates endothelial cell adhesion molecule expression and increase the secretion of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF- alpha) and thromboxane, which increases platelet aggregation and adhesion, causing the formation of lipid laden foam cells and deposits of cholesterol and cholesterol esters.

[0011] Periodontal disease can be managed through control of the pathogens causing local and systemic inflammation and infection. The prevention and treatment of dental biofilm infections through both supragingival and subgingival means has been evaluated for controlling and preventing dental disease. Scaling and root planning are effective in reducing the initial numbers of bacteria, but scaling and root planning leave all of the bacteria in place after treatment that were there before treatment. These bacteria are resistant to short-term periodontal therapy and can regrow in a matter of days, continuing the infectious process.

[0012] Critical wound colonization is a term utilized to express wound chronicity as it relates to the quantity and quality of the infectious agents as well as the host responses. An increased number of more virulent bacteria more commonly relates to an increase in the host inflammatory responses. This involves a framework where virulent immune provoking behaviors and enhanced immune resistance enables invading pathogens to overcome resident microorganisms. The pathogenic bacteria succeed by creating a novel immunologic challenge to which they are already adapted. Decreasing the qualitative form of pathogens reduces virulence, while a quantitative form of resistance generally selects for higher virulence. It appears that both the quantity and quality of bacteria must be part of a sufficient treatment scheme to control the etiology and inflammatory host responses.

[0013] Published research shows a direct medication delivery method resulted in statically significant improvements in modifying the gram-positive and gram-negative pathogens resulting in a less virulent population with decreased numbers of bacteria. These changes resulted in periodontal disease pocket probing depth and bleeding upon probing decreasing or were eliminated.

[0014] Patients treated with the direct medication delivery method demonstrated significant changes in systemic inflammatory markers, such as type 2 diabetes blood glucose markers patients with elevated C-reactive protein levels decreased during and after treatment, and patients81777-428087 with elevated LpPLA2 levels decreased with periodontal treatment with the direct medication delivery system. These results point to possible means where periodontal treatment improved patient’s systemic health and inflammatory markers as the patient’s periodontal disease is successfully treated.

[0015] Current modalities for treating peri-implant diseases depend on the extent of disease progression but include mechanical debridement to remove biofilm, plaque and calculus buildup, antiseptic or antibiotic treatment (typically performed in tandem with mechanical debridement), and in certain instances surgery. The success rate of these various treatments is questionable and typically multiple procedures and doctor visits are necessary which results in an unnecessary time and cost burden to patients and dental professionals alike. Furthermore, many of the cleaning tools used for mechanical debridement may damage the surface morphology of the implants leading to crevices and defects where bacteria can hide and proliferate. Lastly, the rise of antibiotic resistant microbes poses a threat to antibiotic therapy.

[0016] To address some of these limitations, various approaches have been used. U.S. Pat. application publication no. US 2016 / 0310525 discloses to a kit comprising various aqueous components that are mixed before use and applied to the treatment site using a syringe. In this disclosure, the two parts are necessary to keep separate until use due to the chemical incompatibility of the two components, making this disclosure potentially cumbersome and subject to user error risks.

[0017] U.S. Pat. application publication no. US 2024 / 0216418 relates to use of a chitosan-based gel for preventing and treating periodontal and peri-implant disease in conjunction with a brush that attempts to reach into the sulcus or perio-pocket. Although this type of brush has advantages compared to a typical toothbrush, it is still limited in its ability to reach deep into the perio- pocket, and it still requires an initial and subsequent office visits to a dental professional.

[0018] U.S. Pat. No. US 6,966,773 by Dr. Duane Keller discloses a periodontal medicament delivery tray for treating periodontal disease and a manual method of manufacturing said tray following typical dental laboratory procedures. However, Keller does not disclose an automated method of manufacturing that tray, nor the ability of a dental tray to specifically treat peri -implant diseases.81777-428087

[0019] Irrespective of prior developments, there exists a need for improved devices, methods and compositions for treating peri-implant diseases in vivo that are non-invasive, non-damaging to the implant, and conducive to at home administration and management by the patient.BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 shows the manufacturing flow chart for creating a medicament delivery tray. Optionally, various image processing and image analysis steps may be added within Step 3, prior to Step 3 a, to facilitate the processing of the 3D model by the artificial intelligence and machine learning algorithms within the proprietary software.

[0021] Figure 2 shows Step 2 from Figure 1 (i.e., a patient’s 3D model is opened within the proprietary software).

[0022] Figure 3 shows Step 3a through Step 3c from Figure 1 within the proprietary software (i.e., identifying the interface between the gum tissue and target treatment site, placement of the seal about 1mm or 2mm from the interface, and any customization for the seal).

[0023] Figure 4 shows Step 3d from Figure 1 (i.e., engraving of the seal into the 3D model).

[0024] Figure 5 shows Step 4 from Figure 1 (i.e., manipulated 3D model is printed on a 3D printer to create a 3D shell).

[0025] Figure 6 shows Step 5 from Figure 1 (i.e., an EVA sheet is thermoformed over the 3D shell).

[0026] Figure 7 shows Step 6 from Figure 1 (i.e., the EVA material is trimmed and cleaned up to remove burrs, points, etc.,).

[0027] Figure 8 shows the final medicament delivery tray separated from the 3D shell that is ready for use by the patient.

[0028] Figure 9 shows a patient with peri-implantitis displaying significant bone loss around the dental implant (seven threads are exposed), and a radiograph after daily application of a hydrogen peroxide medicament gel for one year using the disclosed medicament delivery tray showing a decrease in bone loss and reestablishment of osseointegration between the implant and surrounding bone tissue.

[0029] Figure 10 shows a straight seal variant of the medicament delivery tray where the proprietary software automatically adds a straight seal that does not follow the curvature of the gumline. While this is a software representation of the medicament delivery tray, this model can81777-428087 be 3D printed to obtain a physical shell for manufacturing of the disclosed medicament delivery tray via thermoforming.

[0030] Figure 11 shows a representative example of the disclosed medicament delivery tray (standard thickness, curved seal) mated to a TruJaw model.

[0031] Figure 12 shows a mass results of medicament (PerioGel) delivery to sulcus regions of the TruJaw model compared to various medicament delivery tray designs.

[0032] Figure 13 shows a representative medicament delivery tray with two different seal thicknesses. The left image shows a seal with a thickness of 1 mm, whereas the right image shows a seal with a thickness of 0.5 mm. While these are software representations of the medicament delivery tray, these models can be 3D printed to obtain a physical shell for manufacturing of the disclosed medicament delivery tray via thermoforming.

[0033] Figure 14 shows a representative medicament delivery tray where the seal is placed at three different displacement values proximal to the gumline. In the left image, the seal at placed 0 mm from the interface (i.e., at the same location). In the middle image, the seal is placed 2 mm from the interface. In the right image, the seal is placed 4 mm from the interface. While these are software representations of the medicament delivery tray, these models can be 3D printed to obtain a physical shell for manufacturing of the disclosed medicament delivery tray via thermoforming.

[0034] Figure 15 shows a depth of medicament (PerioGel) delivery to sulcus regions of the TruJaw model compared to various medicament delivery tray designs.DESCRIPTION OF THE INVENTION

[0035] The following paragraphs define in more detail the embodiments of the invention described herein. The following embodiments are not meant to limit the invention or narrow the scope thereof, as it will be readily apparent to one of ordinary skill in the art that suitable modifications and adaptations may be made without departing from the scope of the invention, embodiments, or specific aspects described herein.

[0036] The present disclosure provides an improved medicament delivery tray for treating dental disease and preserving dental implants in vivo, and methods of its use. The improved medicament delivery tray is effective at combating oral disease, is easy to use by patients, and does not damage implants, teeth or other dental restorations. The disclosure also provides methods for automated81777-428087 manufacturing of said medicament delivery tray, thereby increasing manufacturing throughput, decreasing manufacturing time and cost, and ultimately allowing for same day in office manufacturing (through in-office 3D printing or molding, for example) of the medicament delivery tray for patient and doctor convenience. Furthermore, the disclosure contemplates various medicament gel compositions to be used in conjunction with the medicament delivery tray. While specific details and examples are provided within the specification related to the invention’s use for preserving dental implants in vivo, the invention finds many uses for more general oral and dental applications, such as treating gingivitis, periodontitis, among other diseases, and helping facilitate wound healing.

[0037] The disclosed medicament delivery tray exhibits significant advantages compared to products presently available on the market. In certain embodiments, the medicament delivery tray may be custom designed for the patient’s anatomy for use on a single tooth, on two or more teeth, on a full arch or full arches, on an implant screw or implant screws, on an implant post or implant posts, or on an implant abutment or implant abutments. For the avoidance of doubt, the term “tooth” or “teeth” may refer to natural or artificial teeth (e.g., an implant with a crown). In certain embodiments, two or more trays are manufactured for a patient for use during various stages of receiving a dental implant. For example, a first medicament delivery tray may be created to treat disease and promote healing and osseointegration of the implant before the crown is placed. A second medicament delivery tray may be created once the implant crown is placed, and the tooth anatomy is finalized. The second medicament delivery tray may then be used by the patient periodically to deliver medicaments to preserve the implant. For patients that have removable implant-supported dentures (also called implant-retained overdentures), a medicament delivery tray may be designed specifically for the implant abutments, implant bar, etc., such that the medicament delivery tray is used after the denture is removed from the implant supports so the medicament is delivered most effectively to the implants. The medicament delivery tray is designed to be easy to use for patient compliance and can be easily placed in the mouth and removed from the mouth.

[0038] Regardless of the specific medicament delivery tray design, the medicament delivery tray is made of a flexible elastomeric material that conforms to the specific dental anatomy within the patient’s mouth. Additionally, a seal is incorporated into the medicament delivery tray to create a barrier at the interface between the gum tissue and target treatment site (which may be a single81777-428087 tooth, two or more teeth, a full arch or full arches, an implant screw or implant screws, an implant post or implant posts, or an implant abutment or implant abutments). When a medicament is added to the medicament delivery tray and placed inside the mouth, the seal mechanism provides a physical barrier that inhibits the medicament from escaping into the mouth. Because the medicament delivery tray precisely conforms to the patient-specific dental anatomy, and the seal prevents the medicament from escaping out of the tray, the only location for the medicament to go is the treatment site (i.e., the sulcus between the tooth and the gums). In other words, the custom-fit medicament delivery tray forces the medicament into the sulcus purely by physical means and without the need of another device or propulsion agent. In this manner, the seal provides an efficacy benefit (by physically forcing medicament into the target treatment site), while also providing a safety benefit as medicaments are not unnecessarily exposed to non-target treatment sites. This is especially important for medicaments that may cause tissue irritation, for example, hydrogen peroxide which may irritate and chemically burn non-target treatment site tissue. The seal may be customized and modified accordingly if the tooth is natural or artificial (e.g., dental implant) and depending on the extent of disease. For example, a thicker or more robust seal may be advantageous around an implant to help force medicament more effectively to the implant screw. A thicker or more robust seal may also be necessary around teeth that have deeper perio-pocket or sulcus depth measurements. As is shown in the examples, and unknown previously in the field, the disclosed seal within the medicament delivery tray allows for significantly more medicament to be maintained within the tray and delivered subgingivally for treatment. In preferred embodiments, the seal exhibits a convex shape. In other preferred embodiments, the seal exhibits a shape that is not substantially concave.

[0039] The medicament delivery tray has several methods of use in vivo that are easy for patients to perform at home. In certain embodiments, the medicament delivery tray is used to treat oral disease, including peri-implant diseases such as peri-implantitis and peri-implant mucositis, and preserve dental implants by keeping peri-implant tissue and bone healthy. In particular situations, the medicament delivery tray is useful throughout the dental implant process including promoting osseointegration of the implant screw with the surrounding bone tissue, promoting tissue healing in teeth adjacent to a dental implant, maintaining and preserving tissue health at the dental implant and adjacent teeth, amongst others. The medicament delivery tray can be designed for use on one implant or more and can be useful for maintaining the health and preserving implant81777-428087 supported dentures. In other embodiments, the medicament delivery tray can be used to treat periodontitis or debride and promote healing around oral surgery sites (e.g., tooth extraction, bone grafts, periodontal surgery, gum grafts, amongst others).

[0040] The medicament delivery tray can deliver any medicament or material to the treatment site. Generally, medicaments may comprise antimicrobial agents (e.g., elemental iodine (I2), hypochlorous acid, sodium hypochlorite, chlorhexidine, hydrogen peroxide, sodium dichloroisocyanurate amongst others), antibiotics (e.g., doxycycline, amongst others), bone, tissue, or cell growth factors, remineralizing agents, prebiotics, probiotics, vitamins, proteins, antioxidants (e.g., ferulic acid, phloretin, amongst others), remineralizing agents, amino acids, salts, amongst other materials that may promote or enhance healing. Specifically related to dental implants, the inclusions of agents promoting osseointegration is preferred within certain compositions. For the avoidance of doubt, medicaments many include any material comprised of drugs, chemistry-based medical devices, cosmetics, dietary supplements, vitamins, as well as any other materials that may promote or enhance healing. The medicament delivery tray and medicament container therein does not damage teeth, implants, abutments, or other dental appliances. The medicament delivery tray, and medicaments contained therein, can be used once per day (or multiple times per day) for days, weeks, months, or years. In certain instances, the medicament delivery tray is used at a specific frequency (i.e., daily) for a period of time (i.e., four weeks) to treat the oral disease and then a different frequency and duration may be used for maintenance and preserving oral health. It may be possible for different medicaments to be used during different parts of the treatment process.

[0041] Suitable materials for manufacturing the medicament delivery tray can include, but are not limited to ethylene vinyl acetate (EVA), thermoplastic polyurethane (TPU), polyurethane (PU), polyethylene (PE), polyethylene terephthalate (PET), polyethylene terephthalate-glycol modified (PETG), polypropylene (PP), poly(methyl methacrylate) (PMMA), copyplast, isofolan, IBT flex resin, and copolymers thereof, amongst others. The hardness of the material is preferably soft and pliable (Shore A30 to A90), but in certain instances, it maybe be hard (Shore D10 to D50). The thickness of the tray is preferably between 0.1 mm and 5 mm, more preferably between 1mm and 4mm, and most preferably about 2 mm or about 3 mm. The material must be compatible with thermoforming temperatures (120°C to 370°C, but more preferably 180°C to 280°C) and pressures (50 psi to 150 psi, but more preferably 80 psi to 100 psi). The medicament81777-428087 delivery tray material must be chemically compatible with the various medicaments placed therein.

[0042] An automated manufacturing technique is additionally disclosed for manufacturing the improved medicament delivery tray. This manufacturing process comprises the following steps: 1) scan a patient’s dental anatomy to obtain a 3D model of the patient’ s dental anatomy (including the treatment site’s anatomy), 2) upload the 3D model into proprietary software, wherein the proprietary software automatically and independently manipulates the 3D model to 3a) identify the interface between the gum tissue and target treatment site, 3b) place a seal at a defined distance from the interface, 3c) customize the seal design based on anatomical features or other dental data (e.g., periodontal probe measurements), and 3d) engrave the seal into the 3D model,4) print the manipulated 3D model using a 3D printer to create a 3D shell, and5) thermoform a flexible elastomeric material over the 3D shell to create the medicament delivery tray. Depending on the size and design of the elastomeric material used, trimming of the formed medicament delivery tray may be required (step 6) to remove excess material for optimal fitment in the patient’s mouth. Various post-printing steps may be optionally undertaken on the 3D shell following 3D printing (for example, heating, curing, cleaning, amongst others). In certain embodiments, dental offices may purchase the proprietary software and elastomeric material (or alternative) for in office 3D printing of the medicament delivery tray (in this case step 5 would not be necessary since the 3D printed model will be the medicament delivery tray; however, an optional trimming and cleanup step may still be required prior to patient delivery and clinical use). In preferred embodiments, the proprietary software is cloud-based thereby allowing any internet connected device to access the proprietary software.

[0043] Additional details for the manufacturing steps are provided subsequently. Generally, the manufacturing technique for the medicament delivery tray starts with a dental professional obtaining a 3D scan (STL file, or equivalent) of the patient’s dental anatomy, and specifically the identified target treatment site, during a dental office visit, such as through use of a 3D scanning apparatus. Preferably, this 3D scan is obtained using commercially available intraoral scanners, such as iTero, 3 Shape, Cerec, Primescan, Medit, Planmeca, and Carestream, amongst others. In order to achieve the desired resolution of the identified target treatment site, scanning of the patient’s dental anatomy should be performed using an imaging rate of preferably at least 60 frames per second (fps), more preferably at least 200 fps, and most preferably at least 1000 fps.81777-428087The 3D scan is then automatically manipulated, modified, and / or transformed in proprietary software to precisely engineer and place the seal within the medicament delivery tray. Without being bound by the limitations of theory, the proprietary software can accomplish the seal placement task in several ways. One method may be to analyze the 3D scan and identify the interface between the gum tissue and target treatment site through the relative changes in model contouring from point to point as a type of feature extraction / feature identification. It may also be possible to co-register the STL file with the 3D color scan and identify the interface between the gum tissue and target treatment site through color differences between the gum tissue and target treatment site. Other methods to identify the interface between the gum tissue and target treatment site preferably include the use of a convolutional neural network (e.g., U-Net, ResNet, PointNet, PointNet++, transformer-based models, or similar), convolutional layers with filtering to identify edges, corners, and textures, other machine learning techniques (such as random forests, supervised machine learning models, and k-means clustering) amongst other image analysis techniques and other image processing techniques. Generally, any method of machine learning or artificial intelligence-based image analysis, in certain instances using human assisted examples, may be utilized for feature recognition within the 3D scan.

[0044] In certain preferred embodiments, the proprietary software first recognizes the interface between the gum tissue and target treatment site across the whole arch buccally, lingually, and distally. The proprietary software then smooths out any kinks, sharp transitions, or inconsistencies within the identified interface to ensure a smooth profile. While this is preferably achieved automatically by the proprietary software, it is possible for human operators to manipulate and override the software-identified interface, from which the proprietary software learns.

[0045] Once the interface between the gum tissue and target treatment site is identified, the medicament delivery tray seal is placed preferably 0.5 mm to 4 mm proximal to said interface. The displacement of the seal from the interface between the gum tissue and target treatment site may be user defined or automatically generated based on factors such as, but not limited to, patient diagnosis, the planned treatment regiment, amongst others. Additionally, to further optimize the placement of the seal, the proprietary software may also specifically identify certain dental features, and take specific measurements of said dental features, such as the interproximal height.81777-428087

[0046] In other methods, the medicament delivery tray seal is placed in the software by a human and then read by the software for machine learning purposes via semantic segmentation, pattern recognition, and other common deep learning algorithms for image processing of 3D models. In this fashion, the proprietary software uses a number of 3D model examples from a human to then learn from (i.e., artificial intelligence; the software is taught via human-provided examples) so the software can automatically and seamlessly identify the proper placement of the seal within the medicament delivery tray in future patients and future 3D models.

[0047] Once the medicament delivery tray seal placement is identified by the software, the seal design (thickness, height, curvature, etc.) is then customized automatically by the software or manually by a human. The seal may be customized and modified accordingly if the tooth is natural or artificial (e.g., dental implant) and depending on the extent of disease. For example, a thicker or more robust seal may be advantageous around an implant to help force medicament more effectively to the implant screw. A thicker or more robust seal may also be necessary around teeth that have deeper perio-pocket or sulcus depth measurements. Therefore, the software may link with dental record databases to automatically import periodontal probing measurements for sulcus depth. Artificial intelligence methods, similar to those previously disclosed, can be used for customizing the seal design. In certain instances, the medicament delivery tray seal may be a relatively straight line, while in other instances, the medicament delivery tray seal may exhibit various curves that may follow the natural curvature of the patient’s gumline. In certain embodiments, the seal thickness is preferably between 0.3 mm and 3.0 mm, more preferably between 0.3 mm and 2 mm, even more preferably between 0.65 mm and 1.25 mm, and most preferably about 1 mm.

[0048] After the seal design has been finalized by the software, the software then automatically engraves the seal design into the 3D model. The manipulated 3D model can then be 3D printed as a shell or directly as the medicament delivery tray (depending on the 3D printer’s capabilities and the 3D printer resin). 3D printing can be accomplished in a number of ways including fused deposition modeling (FDM), stereolithography (SLA) and selective laser sintering (SLS) amongst others. To achieve the unique geometry of the convex seal within the medicament delivery tray, the 3D printer has a resolution preferably less than 50 microns, more preferably less than 30 microns, and most preferably less than 10 microns. Additionally, the 3D printer layer thickness is preferably less than 40 microns, more preferably less than 25 microns, and most81777-428087 preferably less than 10 microns. If a shell is printed, then the medicament delivery tray is created by thermoforming a sheet of elastomeric material over the shell. In certain embodiments, the medicament delivery tray is thermoformed over the 3D shell using positive pressure, for example, using any number of commercially available machines such as a Biostar or Erkopress. The thermoforming process is performed between 120°C to 370°C (preferably between 180°C to 280°C), between 50 psi to 150 psi (preferably between 80 psi to 100 psi) and typically takes between 1 and 10 minutes (preferably between 2 and 6 minutes). Accordingly, 3D printed shell should be strong and does not exhibit significant deformation when subjected to the heat and pressure stresses of thermoforming. In preferred embodiments, the 3D printing resin exhibits a cured-state tensile strength preferably greater than 40 MPa, more preferably greater than 70 MPa, and most preferably greater than 100 MPa. In preferred embodiments, the 3D printing resin exhibits a cured-state flexural strength preferably greater than 60 MPa, more preferably greater than 100 MPa, and most preferably greater than 120 MPa. In preferred embodiments, the 3D printing resin exhibits a cured-state heat deflection temperature of preferably greater than 150°C, more preferably greater than 180°C, and most preferably greater than 210°C.DEFINITIONS

[0049] For purposes of interpreting this specification, the following abbreviations, terms and definitions will apply and whenever appropriate, terms used in the singular will also include the plural and vice versa. In the event that any definition set forth below conflicts with any document incorporated herein by reference, the definition set forth below shall control.

[0050] The term “room temperature” or ambient temperature as used herein refers to common ambient temperatures ranging from about 18°C to about 27°C.

[0051] The term “treating” refers to administering a therapy in an amount, manner, or mode effective to improve a condition, symptom, or parameter associated with a disorder. In some aspects, treating refers to the treatment of a dental ailment such as an infected tooth.

[0052] The term “substantially” as used herein means to a great or significant extent, but not completely.

[0053] As used herein, “a”, “an”, “the”, “at least one”, and “one or more” are used interchangeably.81777-428087

[0054] The terms “comprises”, “comprising”, and variations thereof do not have a limiting meaning where these terms appear in the description and claims.

[0055] The term “patient” or “subject” refers to mammals and humans. Thus, in one aspect, the subject is a mammal, or a mammal in need thereof. In one aspect, the subject is a human, or human in need thereof. In one aspect, the human or human in need thereof is a medical patient. The subject can be from ~0 years of age to 99 years of age or older.

[0056] The term “in vivo” generally means in a living subject.

[0057] The term “composition” generally refers to the chemical makeup of certain embodiments of the disclosed invention and is synonymous with “formula”.

[0058] The term “gel” generally refers to the material consistency, where a thickener, or rheology modifier, has been added, such that the material is appreciably thicker than a liquid form. A gel may provide the ability of a material to better cling to surrounding surfaces. The term “gel” may be understood to be synonymous to “cream”, “lotion”, “paste”, “balm”, “ointment”, “salve”, “grease”, and the like.

[0059] The term “dentin” generally refers to a type of calcified tissue that is a major component of teeth. Hydroxyapatite is the main inorganic constituent of dentin and is a naturally occurring mineral from of calcium apatite with the formula CasfPOATOH).

[0060] The term “dental implant” generally refers to a dental prosthesis that interfaces with the maxilla bone or mandible bone and is synonymous with “endosseous implant”. Within this embodiment, dental implant is sometimes more generally referred to as “implant”. A dental implant typically consists of three parts: the implant screw, the abutment (also referred to as the post), and the crown.

[0061] The term “peri-implantitis” generally refers to an inflammatory disease that impacts the soft and hard tissues surrounding a dental implant. As peri-implantitis progresses, the soft tissue becomes increasingly inflamed and the hard tissue (bone) is lost over time, resulting in decreased retention and integrity of the dental implant.

[0062] The term “peri-mucositis” generally refers to an inflammatory lesion of the soft tissue surrounding a dental implant, that has not yet progressed to impact the surrounding hard tissue (bone).

[0063] The term “sulcus” generally refers to the natural space between the tooth and surrounding gum tissue, and is synonymous with “gingival sulcus”, “perio-pockef ’, and “periodontal pocket”.81777-428087

[0064] The term “arch” generally refers to the curved structure of teeth in each jaw, including the gum and alveolar bone of the maxilla (superior arch, or upper jaw) or mandible (inferior arch, or lower jaw; also called the jawbone).

[0065] The term “tooth” or “teeth” may be used interchangeably. For the avoidance of doubt, the term “tooth” or “teeth” may refer to natural or artificial teeth (e.g., an implant comprising a crown).

[0066] The term “treatment site” generally refers to the area within a patient’ s mouth that requires treatment. The treatment site may be a single tooth, two or more teeth, a full arch or full arches, an implant screw or implant screws, an implant post or implant posts, a sulcus or multiple sulcus areas in the oral cavity, or an implant abutment or implant abutments.

[0067] The term “proprietary software” generally refers to computer software that performs the tasks listed within the specification to create the medicament delivery tray. Specifically, the proprietary software: automatically and independently manipulates the 3D model to a) identify the interface between the gum tissue and target treatment site, b) place a seal at a defined distance from the interface, c) customize the seal design based on anatomical features or other dental data (e.g., periodontal probe measurements), and d) engrave the seal into the 3D model. While commercially available software might be able to import a 3D model and allow for manual manipulation by a human, this commercially available software does not satisfactorily achieve the aforementioned tasks. However, this commercially available software might be used in combination with, or modified to support, the automated model manipulation features disclosed herein. In preferred embodiments, the proprietary software is cloud-based while in other embodiments the proprietary software must be installed locally at the dental professional’ s office.

[0068] The term “seal” generally refers to the critical feature incorporated within the disclosed medical delivery tray that creates a barrier at a defined distance from the interface between the gum tissue and the target treatment site. When a medicament is added to the medicament delivery tray, and placed inside the mouth, the seal mechanism provides a physical barrier that inhibits the medicament from escaping into the mouth. Because the medicament delivery tray precisely conforms to the patient-specific dental anatomy, and the seal prevents the medicament from escaping out of the tray, the only location for the medicament to go is the treatment site (i.e., the sulcus between the tooth and the gums).81777-428087

[0069] The term “shell” generally refers to the 3D printed replica of the 3D model. In other words, the word “shell” is analogous to a physical 3D printed version of the 3D model. Said in yet another way, the “shell” is analogous to a physical 3D printed model of the 3D model within the software.

[0070] The above summary of the present invention is not intended to describe each disclosed embodiment or every implementation of the present invention. The description that follows more particularly exemplifies illustrative embodiments. In several places throughout the description, guidance is provided through lists of examples, which examples can be used in various combinations. In each instance, the recited list serves only as a representative group and should not be interpreted as an exclusive list.EXAMPLES

[0071] Figure 1 shows the manufacturing flow chart for creating the medicament delivery tray. Optionally, various image processing and image analysis steps may be added within Step 3, prior to Step 3 a, to facilitate the processing of the 3D model by the artificial intelligence and machine learning algorithms within the proprietary software.

[0072] Figure 2 shows Step 2 from Figure 1 (i.e., a patient’s 3D model is opened within the proprietary software). Figure 3 shows Step 3a through Step 3c from Figure 1 within the proprietary software (i.e., identifying the interface between the gum tissue and target treatment site, placement of the seal about 1 mm or 2 mm from the interface, and any customization for the seal). Figure 4 shows Step 3d from Figure 1 (i.e., engraving of the seal into the 3D model). Figure 5 shows Step 4 from Figure 1 (i.e., manipulated 3D model is printed on a 3D printer to create a 3D shell). Figure 6 shows Step 5 from Figure 1 (i.e., an EVA sheet is thermoformed over the 3D shell). Figure 7 shows Step 6 from Figure 1 (i.e., the EVA material is trimmed and cleaned up to remove burrs, points, etc.). Figure 8 shows the final medicament delivery tray separated from the 3D shell that is ready for use by the patient.

[0073] Figure 2 illustrates a patient’s 3D model is opened within the proprietary software.

[0074] Figure 3 illustrates that the proprietary software identifies the interface between the gum tissue and target treatment site, places the seal about 1 mm or 2 mm from the interface, and customizes the seal based on any patient-specific anatomy. Left, center, and right images are different rotational views of the same model in the proprietary software. In this specific81777-428087 example, the seal follows the natural curvature of the patient’s gumline; however, a straight seal may also be utilized.

[0075] Figure 4 illustrates that the seal is engraved into the 3D model within the proprietary software. The left and right images are different rotational views of the same model in the proprietary software.

[0076] Figure 5 illustrates that he manipulated 3D model from the proprietary software is 3D printed to create a 3D shell. The engraved seal is readily visible under the tooth / gum interface on both the buccal and lingual sides of the arch. The left and right images are different rotational views of the printed 3D shell.

[0077] Figure 6 illustrates that a flexible elastomeric material is thermoformed over the 3D shell; here, the material is EVA. The left and right images are different rotational views of the same 3D shell with the EVA thermoformed thereover.

[0078] Figure 7 illustrates that excess EVA material is trimmed away from the 3D shell. The left and right images are different rotational views of the same 3D shell with the EVA thermoformed thereover showing trimming on both sides of the arch.

[0079] Figure 8 illustrates that the final medicament delivery tray is ready for use by the patient. The top and bottom images are different rotational views of the same 3D shell and medicament delivery tray.

[0080] As a representative example, a medicament delivery tray was created for a patient suffering from peri -impl anti tis and experiencing significant bone loss. A hydrogen peroxide medicament gel was applied daily using the medicament delivery tray. Throughout the course of the year, the patient’s peri-implantitis was successfully treated and osseointegration of the implant with the bone was reestablished. In other words, treating the inflammation associated with peri-implantitis utilizing the disclosed medicament delivery tray, and medicament contained therein, resulted in preservation of the dental implant in vivo. (See Figure 9.) Figure 9 at left illustrates a patient with peri-implantitis displaying significant bone loss around the dental implant (seven threads are exposed). Figure 9 at right illustrates a radiograph after daily application of a hydrogen peroxide medicament gel for one year using the disclosed medicament delivery tray showing a decrease in bone loss and reestablishment of osseointegration between the implant and surrounding bone tissue.81777-428087

[0081] Figure 10 shows a straight seal variant of the medicament delivery tray where the proprietary software automatically adds a straight seal that does not follow the curvature of the gumline.

[0082] Test #1 - Delivery of a 1.7% hydrogen peroxide gel (PerioGel, PerioProtect, St. Louis, MO) using the disclosed medicament delivery tray with a TrueJaw model (PlanB Dental, Santa Barbara, C A). An experiment was conducted using multiple variants of the disclosed medicament delivery tray and a commercially available competitive tray (Gum Hero, Arklign, San Jose, CA). The Gum Hero medicament delivery tray exhibits a reservoir indent which is constructed in an inverse fashion of the disclosed curved seal. In other words, while the curved seal of the disclosed medicament delivery tray protrudes outward from the tray (i.e., in a convex fashion), the reservoir indent of the Gum Hero tray curves inward (i.e., in a concave fashion). The multiple variants of the disclosed medicament delivery tray include two different tray thicknesses (standard (3.18 mm) and thin (2.0 mm)) and two different seal design (straight, as depicted in Fig. 10, versus curved, as depicted in Figs. 2-8) along with a control medicament delivery tray that does not exhibit a seal but is otherwise identical in all facets to the other disclosed medicament delivery trays. By setting up the testing in this manner, the critical nature of the medicament delivery tray seal is observed by comparing the concave seal construction to an identical tray without a seal. All medicament delivery trays were custom manufactured to fit the TruJaw model to ensure standardization across all test groups. The TruJaw is an excellent substrate for this test as the TruJaw contains 3D printed teeth embedded in a 3D printed jaw that exhibits sulcus regions (i.e., potential treatment sites for periodontal disease) and other complex oral anatomies. Initially, the masses of the various trays and TruJaw were recorded. PerioGel was added to the various trays in accordance with the product’s instructions for use, then the medicament delivery trays were mated to the TruJaw (Fig. 11 shows a representative example of a medicament delivery tray mated to a TruJaw). Excess PerioGel that extruded out of the tray was wiped away. The mass of the TruJaw, medicament delivery tray, and PerioGel was then recorded to quantify how much PerioGel was delivered to the target treatment areas (i.e., sulcus regions) of the TruJaw. Testing was repeated five times per medicament delivery tray. Results are shown in Fig. 12. The disclosed medicament delivery tray resulted in statistically significantly more medicament (i.e., PerioGel) delivered to the sulcus region, regardless of design (i.e., standard vs thin thickness, and straight81777-428087 vs curved seal), compared to the identical medicament delivery tray without a seal and compared to the competitive Gum Hero tray on the market that exhibits an inferior and less effective concave seal. While difficult to photograph, deeper penetration of the PerioGel into the sulcus regions was readily apparent with the disclosed medicament delivery trays compared to the medicament delivery tray without a seal and compared to the competitive Gum Hero tray.

[0083] In preferred embodiments, the medicament delivery tray contains a curved convex seal or a straight convex seal. In certain embodiments of the invention, the incorporation of a convex seal within medicament delivery tray is designed to deliver at least 1.5 g of medicament to treatment sites (e.g., sulcus regions) of a full arch. In certain embodiments of the invention, the incorporation of a convex seal within the medicament delivery tray preferably results in at least 1.5x more medicament delivery than an identical medicament delivery tray without a seal, more preferably results in at least 1.75x more medicament delivery than an identical medicament delivery tray without a seal, and most preferably results in about 2x more medicament delivery than an identical medicament delivery tray without a seal. In certain embodiments of the invention, the incorporation of a convex seal within the medicament delivery tray preferably results in at least 1. lx more medicament delivery than an identical medicament delivery tray with a concave seal, more preferably results in at least 1.25x more medicament delivery than an identical medicament delivery tray with a concave seal, and most preferably results in about 1 ,5x more medicament delivery than an identical medicament delivery tray with a concave seal.

[0084] Figure 13 shows a representative medicament delivery tray with two different seal thicknesses (1 mm and 0.5 mm). Figure 14 shows a representative medicament delivery tray where the seal is placed at three different displacements (0 mm, 2 mm and 4 mm) proximal to the interface between the gum tissue (i.e., gumline) and target tissue.

[0085] Test #2 - Depth of PerioGel sulcus delivery using the disclosed medicament delivery tray with a TrueJaw model. A peroxide sensitive strip was mounted onto teeth of the TrueJaw model and the gumline was marked using a Sharpie marker. The peroxide sensitive strip changes color (from white to blue) when exposed to peroxide. Commensurate with clinical use, a ribbon of PerioGel was added to the medicament delivery tray which was then mounted to the TrueJaw model. After 15 seconds of application, the medicament delivery tray was removed from the TrueJaw along with excess PerioGel. This test was replicated with the disclosed medicament delivery tray without a seal and the competitive tray (GumHero) containing a concave seal. The81777-428087 depth of PerioGel penetration into the sulcus region of the TrueJaw was quantified by measuring the extent of peroxide measurement (i.e., blue peroxide indication) on the peroxide sensitive strip. Results are shown in Figure 15. Overall, the disclosed medicament delivery tray with a convex seal resulted in considerably greater sulcus delivery and penetration of the PerioGel material than the tray without a seal or the competitive tray. Specifically, the disclosed medicament delivery tray resulted in greater than 50% greater sulcus delivery and penetration of the PerioGel material than the tray without a seal or the competitive tray.

[0086] In certain embodiments of the invention, the incorporation of a convex seal within the medicament delivery tray results in delivery of a medicament preferably at least 1mm into the sulcus, more preferably at least 3 mm into the sulcus, even more preferably at least 5 mm into the sulcus, and most preferably at least 7 mm into the sulcus. Compared to a medicament delivery tray without a seal or a medicament delivery tray with a concave seal, the incorporation of a convex seal within the medicament delivery tray results in delivery of a medicament preferably at least 20% deeper into the sulcus, more preferably at least 35% deeper into the sulcus, and most preferably at least 50% deeper into the sulcus.

[0087] Figure 12 illustrates results of medicament (PerioGel) delivery to sulcus regions of the TruJaw model compared to various medicament delivery tray designs. Figure 13 illustrates a medicament delivery tray with two different seal thicknesses. The left image shows a seal with a thickness of 1mm, whereas the right image shows a seal with a thickness of 0.5 mm.

[0088] Figure 14 illustrates a medicament delivery tray where the seal is placed at three different displacement values proximal to the gumline. In the left image, the seal at placed 0 mm from the interface (i.e., at the same location). In the middle image, the seal is placed 2 mm from the interface. In the right image, the seal is placed 4 mm from the interface.

[0089] Figure 15 illustrates a depth of medicament (PerioGel) delivery to sulcus regions of the TruJaw model compared to various medicament delivery tray designs.

[0090] As is known in the data processing and communications arts, a general -purpose computer typically comprises a central processor or other processing device, an internal communication bus, various types of memory or storage media (RAM, ROM, EEPROM, cache memory, disk drives etc.) for code and data storage, and one or more network interface cards or ports for communication purposes. The software functionalities involve programming, including executable code as well as associated stored data. The software code is executable by the general-81777-428087 purpose computer. In operation, the code is stored within the general -purpose computer platform. At other times, however, the software may be stored at other locations and / or transported for loading into the appropriate general-purpose computer system.

[0091] A server, for example, includes a data communication interface for packet data communication. The server also includes a central processing unit (CPU), in the form of one or more processors, for executing program instructions. The server platform typically includes an internal communication bus, program storage and data storage for various data files to be processed and / or communicated by the server, although the server often receives programming and data via network communications. The hardware elements, operating systems and programming languages of such servers are conventional in nature, and it is presumed that those skilled in the art are adequately familiar therewith. The server functions may be implemented in a distributed fashion on a number of similar platforms, to distribute the processing load.

[0092] Hence, aspects of the disclosed methods and systems outlined above may be embodied in programming. Program aspects of the technology may be thought of as “products” or “articles of manufacture” typically in the form of executable code and / or associated data that is carried on or embodied in a type of machine-readable medium. “Storage” type media includes any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, which may provide non- transitory storage at any time for the software programming. All or portions of the software may at times be communicated through the Internet or various other telecommunication networks. Thus, another type of media that may bear the software elements includes optical, electrical, and electromagnetic waves, such as used across physical interfaces between local devices, through wired and optical landline networks and over various air-links. The physical elements that carry such waves, such as wired or wireless links, optical links, or the like, also may be considered as media bearing the software. As used herein, unless restricted to non-transitory, tangible “storage” media, terms such as computer or machine “readable medium” refer to any medium that participates in providing instructions to a processor for execution.

[0093] A machine-readable medium may take many forms, including but not limited to, a tangible storage medium, a carrier wave medium or physical transmission medium. Non-volatile storage media include, for example, optical or magnetic disks, such as any of the storage devices in any computer(s) or the like, such as may be used to implement the disclosed methods and systems.81777-428087Volatile storage media include dynamic memory, such as main memory of such a computer platform. Tangible transmission media include coaxial cables, copper wire and fiber optics, including the wires that comprise a bus within a computer system. Carrier-wave transmission media can take the form of electric or electromagnetic signals, or acoustic or light waves such as those generated during radio frequency (RF) and infrared (IR) data communications. Common forms of computer-readable media therefore include for example: a floppy disk, a flexible disk, hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD or DVD-ROM, any other optical medium, punch cards, paper tape, any other physical storage medium with patterns of holes, a RAM, a PROM and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, cables or links transporting such a carrier wave, or any other medium from which a computer can read programming code and / or data. Many of these forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.STATEMENTS

[0094] The following statements are illustrative and within the scope of the embodiments of the invention described herein.1. A medicament delivery tray for the application of at least one medicament to at least one oral treatment site in vivo, wherein, the medicament delivery tray is manufactured from an elastomeric material prepared to substantially conform to the at least one treatment site’s anatomy, wherein, a seal is incorporated into the medicament delivery tray to create a barrier at the interface between the gum tissue and at least one target treatment site, wherein, the barrier physically pushes the at least one medicament contained within the medicament delivery tray at least 3 mm into the sulcus areas of the at least one treatment site, and wherein, the use of a propulsion agent is not necessary.2. The tray of statement 1, wherein the seal exhibits a convex shape.3. The tray of statement 1, wherein the seal is curved to generally follow the gumline.4. The tray of statement 1, wherein the seal is curved to generally follow the gumline and exhibits a convex shape.81777-428087 The tray of any one of statements 1-4, wherein the elastomeric material is selected from ethylene vinyl acetate (EVA), thermoaplstic polyurethane (TPU), polyurethane (PU), polyethylene (PE), polyethylene terephthalate (PET), polyethylene terephthalate - glycol modified (PETG), polypropylene (PP), poly(methyl methacrylate) (PMMA), copyplast, isofolan, and copolymers thereof, amongst others. The tray of statement 1, wherein the elastomeric material is ethylene vinyl acetate (EVA). The tray of any one of statements 1-6, wherein the elastomeric material is about 2 mm to 3 mm thick. The tray of any one of statements 1-7, wherein the seal is customized to the at least one treatment site’s anatomy by modifying the seal’s thickness. The tray of any one of statements 1-8, wherein the at least one treatment site is a dental implant or a set of dental implants. The tray of any one of statements 1-8, wherein the at least one treatment site is a dental arch. The tray of any one of statements 1-10, wherein the at least one medicament is used to treat periodontal disease. The tray of any one of statements 1-11, wherein the at least one medicament is used to treat peri-implantitis or peri-implant mucositis. The tray of any one of statements 1-12, wherein the at least one medicament comprises an antimicrobial agent. The tray of any one of statements 1-13, wherein the at least one medicament comprises a remineralizing agent. The tray of any one of statements 1-14, wherein the at least one medicament comprises an agent promoting osseointegration. The tray of any one of statements 1-15, wherein the at least one medicament comprises at least one antioxidant. The tray of any one of statements 1-16, wherein the tray exhibits a hardness of Shore A30 to A90. The tray of any one of statements 1-17, wherein the tray delivers at least 1.5 g of medicament to the treatment sites.81777-428087 The tray of statement 1, wherein the tray is constructed as a full arch, and wherein the tray delivers at least 1.5 g of medicament to the sulcus areas. The tray of any one of statements 1-19, wherein, the barrier physically pushes the at least one medicament contained within the medicament delivery tray at least 5 mm into the sulcus areas of the at least one treatment site. A computer-controlled method of manufacturing a medicament delivery tray, the method comprising: receiving, by a computer-based manufacturing system, a scan of a target treatment site of a patient’s dental anatomy; determining, by the computer-based manufacturing system, a three-dimensional (3D) model the target treatment site; identifying, by the computer-based manufacturing system and based on the 3D model, an interface between the patient’s gum tissue and the target treatment site; defining, by the computer-based manufacturing system and based on the 3D model, a convex seal at a predetermined distance from the identified interface; and modifying, by the computer-based manufacturing system, the 3D model to include the defined convex seal. The method of statement 21, further comprising controlling, by the computer-based manufacturing system and based on the modified 3D model, formation of a medicament delivery tray comprising the convex seal. The method of any one of statements 21-22, further comprising at least one of: trimming the medicament delivery tray to promote oral fitment prior to clinical use, or cleaning up the medicament delivery tray to promote oral fitment prior to clinical use. The method of any one of statements 21-23, wherein identifying, by the computer-based manufacturing system and based on the 3D model, an interface between the patient’s gum tissue and the target treatment site further comprises applying a convolutional neural network of a machine learning artificial intelligence computer system. The method of statement 24, wherein the convolutional neural network comprises a U- Net.81777-428087 The method of statement 24, wherein the convolutional neural network is trained based on human-provided example training data sets. The method of any one of statements 21-26, wherein the convex seal is curved to generally follow the gumline. The method of any one of statements 21-27, wherein the convex seal is placed 0.5 mm to 4 mm proximal to the interface. The method of any one of statements 21-28, wherein the computer-based manufacturing system is a cloud-based computer-based manufacturing system. The method of any one of statements 21-29, wherein the convex seal exhibits a thickness of about 1mm.

Claims

81777-428087CLAIMSWhat is claimed is:

1. A medicament delivery tray for the application of at least one medicament to at least one oral treatment site in vivo, wherein, the medicament delivery tray is manufactured from an elastomeric material prepared to substantially conform to the at least one treatment site’s anatomy, wherein, a seal is incorporated into the medicament delivery tray to create a barrier at the interface between the gum tissue and at least one target treatment site, wherein, the barrier physically pushes the at least one medicament contained within the medicament delivery tray at least 3 mm into the sulcus areas of the at least one treatment site, and wherein, the use of a propulsion agent is not necessary.

2. The tray of claim 1, wherein the seal exhibits a convex shape.

3. The tray of claim 1, wherein the seal is curved to generally follow the gumline.

4. The tray of claim 1, wherein the seal is curved to generally follow the gumline and exhibits a convex shape.

5. The tray of claim 1, wherein the elastomeric material is selected from ethylene vinyl acetate (EVA), thermoaplstic polyurethane (TPU), polyurethane (PU), polyethylene (PE), polyethylene terephthalate (PET), polyethylene terephthalate-glycol modified (PETG), polypropylene (PP), poly(methyl methacrylate) (PMMA), copyplast, isofolan, and copolymers thereof.

6. The tray of claim 1, wherein the elastomeric material is ethylene vinyl acetate (EVA).

7. The tray of claim 1, wherein the elastomeric material is about 2 mm to 3 mm thick.

8. The tray of claim 1, wherein the seal is customized to the at least one treatment site’s anatomy by modifying the seal’s thickness.

9. The tray of claim 1, wherein the at least one treatment site is a dental implant or a set of dental implants.

10. The tray of claim 1, wherein the at least one treatment site is a dental arch.81777-42808711 . A method of treating periodontal disease, comprising, providing the tray of claim 1, wherein the at least one medicament is used to treat periodontal disease.

12. A method of treating peri-implantitis or peri-implant mucositis, comprising providing the tray of claim 1, wherein the at least one medicament is used to treat peri-implantitis or peri -implant mucositis.

13. The tray of claim 1, wherein the at least one medicament comprises an antimicrobial agent.

14. The tray of claim 1, wherein the at least one medicament comprises a remineralizing agent.

15. The tray of claim 1, wherein the at least one medicament comprises an agent promoting osseointegration.

16. A computer-controlled method of manufacturing a medicament delivery tray, the method comprising: receiving, by a computer-based manufacturing system, a scan of a target treatment site of a patient’s dental anatomy; determining, by the computer-based manufacturing system, a three-dimensional (3D) model the target treatment site; identifying, by the computer-based manufacturing system and based on the 3D model, an interface between the patient’s gum tissue and the target treatment site; defining, by the computer-based manufacturing system and based on the 3D model, a convex seal at a predetermined distance from the identified interface; and modifying, by the computer-based manufacturing system, the 3D model to include the defined convex seal.

17. The method of claim 16, further comprising controlling, by the computer-based manufacturing system and based on the modified 3D model, formation of a medicament delivery tray comprising the convex seal.

18. The method of claim 17, further comprising trimming the medicament delivery tray to promote oral fitment prior to clinical use.

19. The method of claim 16, wherein identifying, by the computer-based manufacturing system and based on the 3D model, an interface between the patient’s gum tissue and the81777-428087 target treatment site further comprises applying a convolutional neural network of a machine learning artificial intelligence computer system.

20. The method of claim 16, wherein the seal is placed 0.5 mm to 4 mm proximal to the interface.

21. The method of claim 16, wherein the thickness of the seal is about 1 mm.

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