WO2025147712A1

WO2025147712A1 - Xenogeneic oral repair compositions and implants thereof

Info

Publication number: WO2025147712A1
Application number: PCT/US2025/010459
Authority: WO
Inventors: Peter H. Gingras; Nicole FRAIFOGL; Hector Capella MONSONIS
Original assignee: Viscus Biologics LLC
Current assignee: Viscus Biologics LLC
Priority date: 2024-01-05
Filing date: 2025-01-06
Publication date: 2025-07-10
Anticipated expiration: 2026-07-05

Abstract

The present disclosure relates generally to oral tissue repair compositions and implants thereof; and, more particularly, to customized acellular extracellular matrix repair compositions and implants for patient-specific treatment of various oral tissue defects, such as periodontal recession.

Description

XENOGENEIC ORAL REPAIR COMPOSITIONS AND IMPLANTS THEREOF

TECHNICAL FIELD

[0001] The present disclosure relates generally to oral repair compositions and implants thereof; and, more particularly, to customized xenogeneic acellular oral tissue extracellular matrix repair compositions and associated implants for patientspecific treatment of various oral tissue defects, such as periodontal recession.

RELATED APPLICATION

[0002] This application claims priority from U.S. Provisional Application No. 63/618,235, filed on January 5, 2024, the subject matter of which is incorporated herein by reference in its entirety for all purposes.

BACKGROUND

[0003] Periodontitis is the loss of attachment to the underlying bone generally caused by gram-negative bacteria associated with inflammation of the gingiva and periodontium. The body responds to the pathogens by secreting proinflammatory mediators, which can lead to connective tissue destruction and bone loss. The loss of gingiva tissue can allow oral pathogens direct access to the connective tissue. Surgical intervention for gingival recession is used to reduce tooth root hypersensitivity, improve plaque control, and prevent further disease progression. [0004] Autologous connective tissue grafts are commonly used and require a second surgical site leading to greater morbidity, longer surgical procedures, and a more painful postoperative phase for the patient. Autografts are limited in size and are generally only used to correct defects over one or two teeth. Other options, such as dermal allografts have ethical concerns, pathogen-associated risks, and are generally less available.

SUMMARY

[0005] In view of the shortcomings of existing autologous connective tissue grafts (e.g., dermal allografts), the present disclosure provides oral repair compositions and implants thereof comprising xenogeneic, decellularized oral tissue extracellular matrix (ECM) that more closely approximate an oral tissue defect being repaired or regenerated. Advantageously, once administered to, or implanted in, a patient, the patient’s cells can populate the oral repair compositions and implants to create a dense fibrous tissue that more closely approximates an oral tissue defect being repaired by virtue of the highly keratinized nature of the oral repair compositions and implants. Additionally, oral repair compositions of the present disclosure can be customized to provide three-dimensional, patient-specific implants that physically conform to an oral tissue defect more completely, thereby improving contact with surrounding tissue and more accurately restoring oral anatomy with a lower risk of dislodgement and migration.

[0006] As such, one aspect of the present disclosure can include a biocompatible, xenogeneic oral repair composition comprising an acellular oral tissue extracellular matrix (ECM).

[0007] Another aspect of the present disclosure can include an oral repair implant comprising a composition attached to a barrier layer, wherein the composition comprises a biocompatible, xenogeneic oral repair composition including an acellular oral tissue ECM.

[0008] Another aspect of the present disclosure can include a method for producing a pre-formed oral repair implant or a pre-formed oral repair composition. The method can comprise the steps of: (a) obtaining, from an oral cavity of a subject, one or more images of a region of interest having, or suspected of having, an oral tissue defect; (b) processing the obtained one or more images to generate a three-dimensional (3D) model of the subject’s gum tissue and teeth; (c) selecting at least one oral tissue defect from the 3D model; (d) generating an oral repair model based on the selected at least one oral tissue defect; and (e) forming, based on the oral repair model, the pre-formed oral repair implant, or the pre-formed oral repair composition, which is sized and dimensioned to conform to all, or substantially all, of an oral tissue defect in a subject.

[0009] Another aspect of the present disclosure can include a method for repairing an oral tissue defect in a subject, the method comprising administering, to an oral cavity of the subject, a therapeutically effective amount of an oral repair composition comprising a biocompatible, xenogeneic oral repair composition comprising an acellular oral tissue ECM. [0010] Another aspect of the present disclosure can include a method for repairing an oral tissue defect in a subject, the method comprising administering, to an oral cavity of the subject, a therapeutically effective amount of an oral repair implant comprising a composition attached to a barrier layer, wherein the composition comprises a biocompatible, xenogeneic oral repair composition including an acellular oral tissue ECM.

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The foregoing and other features of the present disclosure will become apparent to those skilled in the art to which the present disclosure relates upon reading the following description with reference to the accompanying drawings, in which:

[0012] Fig. 1 is a series of photographs showing harvesting of porcine gingiva and hard palate tissue;

[0013] Fig. 2A is a schematic illustration showing an oral repair composition constructed in accordance with one aspect of the present disclosure and having a stratified structure;

[0014] Fig. 2B is a schematic illustration showing an exploded view of the oral repair composition in Fig. 2A;

[0015] Fig. 2C is a histology image showing the oral repair composition in Figs. 2A-B;

[0016] Fig. 2D is a magnified view of a vascular structure layer comprising the oral repair composition in Fig. 2C;

[0017] Fig. 3A is a schematic illustration showing a shaped or pre-formed oral repair composition constructed in accordance with another aspect of the present disclosure and having a trapezoidal cross-sectional geometry;

[0018] Fig. 3B is a schematic illustration showing the shaped or pre-formed oral repair composition of Fig. 3A implanted at an oral tissue defect;

[0019] Fig. 4 is a schematic showing one example of a method for preparing a patient specific oral repair composition or oral repair implant of the present disclosure;

[0020] Fig. 5 is a series of photographs showing harvesting of porcine gingiva tissue;

[0021] Fig. 6 is an image showing decellularized porcine gingiva tissue; [0022] Fig. 7 is a graph showing DNA content (ng/mg) of harvested cellularized porcine gingiva (black) and decellularized porcine gingiva (red);

[0023] Figs. 8A-B are a series of images showing hydrated decellularized porcine gingiva micronized powder;

[0024] Figs. 9-11 are a series of graphs showing hydrolytic (Fig. 9), enzymatic (Fig. 10), and microbial (Fig. 11 ) degradation characteristics for native decellularized gingiva, porcine peritoneum (BioGide), 3% micronized gingiva powder, 3% micronized gingiva powder with EDC crosslinking, 5% micronized gingiva powder, and 5% micronized gingiva powder with EDC crosslinking;

[0025] Fig. 12 is a graph showing compressive properties of oral repair compositions comprising 3% micronized gingiva powder, 3% micronized gingiva powder with EDC crosslinking, 5% micronized gingiva powder, and 5% micronized gingiva powder with EDC crosslinking;

[0026] Fig. 13 is an image showing bioprinting of an oral repair composition according to another aspect of the present disclosure;

[0027] Fig. 14 is a series of images showing preparation of an oral repair implant comprising decellularized porcine gingiva and peritoneal membrane according to another aspect of the present disclosure; and

[0028] Fig. 15 is an image showing the oral repair implant produced in Fig. 14.

DETAILED DESCRIPTION

[0029] Definitions

[0030] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which the present disclosure pertains.

[0031] Throughout the description and claims of this specification, the word “comprise” and variations of the word, such as “comprising” and “comprises,” means “including but not limited to,” and is not intended to exclude, for example, other additives, components, integers or steps. In particular, in methods stated as comprising one or more steps or operations it is specifically contemplated that each step comprises what is listed (unless that step includes a limiting term such as “consisting of”), meaning that each step is not intended to exclude, for example, other additives, components, integers or steps that are not listed in the step.

[0032] In the context of the present disclosure, the term “about”, when expressed as from “about” one particular value and/or “about” another particular value, also specifically contemplated and disclosed is the range from the one particular value and/or to the other particular value unless the context specifically indicates otherwise. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another, specifically contemplated embodiment that should be considered disclosed unless the context specifically indicates otherwise. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint unless the context specifically indicates otherwise. Finally, it should be understood that all of the individual values and subranges of values contained within an explicitly disclosed range are also specifically contemplated and should be considered disclosed unless the context specifically indicates otherwise. The foregoing applies regardless of whether in particular cases some or all of these aspects are explicitly disclosed.

[0033] Optionally, in some aspects, when values or characteristics are approximated by use of the antecedents “about,” “substantially,” or “generally,” it is contemplated that values within up to 15%, up to 10%, up to 5%, or up to 1 % (above or below) of the particularly stated value or characteristic can be included within the scope of those aspects.

[0034] As used herein, phrases such as “between X and Y” and “between about X and Y” can be interpreted to include X and Y.

[0035] As used herein, phrases such as “between about X and Y” can mean “between about X and about Y”.

[0036] As used herein, phrases such as “from about X to Y” can mean “from about X to about Y”.

[0037] As used herein, the term “attached” can refer to being fastened, fixed, joined, connected, bound, adhered to, or assembled with.

[0038] It will be understood that when an element is referred to as being “on”, “attached” to, “connected” to, “coupled” with, “contacting”, etc., another element, it can be directly on, attached to, connected to, coupled with or contacting the other element or intervening elements may also be present. In contrast, when an element is referred to as being, for example, “directly on”, “directly attached” to, “directly connected” to, “directly coupled” with or “directly contacting” another element, there are no intervening elements present. It will also be appreciated by those of skill in the art that references to a structure or feature that is disposed “adjacent” another feature may have portions that overlap or underlie the adjacent feature.

[0039] Spatially relative terms, such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature’s relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms can encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is inverted, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features.

[0040] As used herein, the terms “first,” “second,” etc. should not limit the elements being described by these terms. These terms are only used to distinguish one element from another. Thus, a “first” element discussed below could also be termed a “second” element without departing from the teachings of the present disclosure. The sequence of operations (or acts/steps) is not limited to the order presented in the claims or figures unless specifically indicated otherwise.

[0041] As used herein, the terms “optionally” and “optional” can mean that the subsequently described event, circumstance, or material may or may not occur or be present, and that the description includes instances where the event, circumstance, or material occurs or is present and instances where it does not occur or is not present.

[0042] As used herein, the term “administer” can mean to give or to apply (e.g., to a subject).

[0043] As used herein, the term “allogeneic” can refer to being genetically different although belonging to or obtained from the same species.

[0044] As used herein, the term “autologous” can mean derived from the same organism.

[0045] As used herein, the term “biocompatible” can refer to causing no clinically relevant tissue irritation, injury, toxic reaction, or immunological reaction to living tissue.

[0046] As used herein, the terms “acellular” and “decellularized” can be used interchangeably and refer to a biological tissue (e.g., an oral tissue, such as gingiva or palate) that has been treated by a process in which cells and cellular components (including DNA) are removed from the biological tissue, thereby leaving the extracellular matrix (ECM) thereof free, or essentially free, of such cells and cellular components.

[0047] As used herein, the term “extracellular matrix” or “ECM” can refer to a scaffold in a cell’s external environment with which the cell interacts via specific cell surface receptors. The ECM serves many functions, including, but not limited to, providing support and anchorage for cells, segregating one tissue from another tissue, and regulating intracellular communication. The ECM is composed of an interlocking mesh of fibrous proteins and glycosaminoglycans (GAGs). Examples of fibrous proteins found in the ECM include collagen, elastin, fibronectin, and laminin. Examples of GAGs found in the ECM include proteoglycans (e.g., heparin sulfate), chondroitin sulfate, keratin sulfate, and non-proteoglycan polysaccharide (e.g., hyaluronic acid).

[0048] As used herein, the term “improve” (or “improving”) can refer to bringing into a more desirable or excellent condition.

[0049] As used herein, the term “oral tissue defect” can refer to abnormal spaces, voids, or physical (tissue) damage/defects formed in oral keratinized tissue (or keratinized mucosa), such as the gums and hard palate as the result of injections, surgical incisions, tumor or tissue removal, acute or chronic tissue injuries, tissue recession (e.g., as the result of microbial infection, growth, and/or related pathological processes, such as tartar production), smoking, diseases (e.g., diabetes, AIDS), genetic predisposition, diet, teeth grinding, stress, improper oral hygiene, hormonal changes or imbalances (e.g., during pregnancy or menopause), abscess formation, medications, or any other similar cavity, tissue defect, space, or pocket formed by action of clinical assessment and/or treatment or physiologic response to disease or pathology, as non-limiting examples thereof.

[0050] As used herein, the terms “reduced” or “to reduce” can refer to a diminishing, a decrease in, an attenuation or abatement of the degree, intensity, extent, size, amount, density, or number.

[0051] As used herein, the terms “regeneration” and “regenerate” can refer to a process of recreation, reconstitution, renewal, revival, restoration, differentiation, and growth to form an oral tissue (e.g., keratinized tissue, such as the gums and hard palate) with characteristics that conform with a natural counterpart of the oral tissue. [0052] As used herein, the term “repair” (when used herein as a noun) can refer to any correction, reinforcement, reconditioning, remedy, making up for, making sound, renewal, mending, patching, or the like that restores biological function to an oral tissue (e.g., keratinized tissue, such as the gums and hard palate). When used as a verb, it can mean to correct, to reinforce, to recondition, to remedy, to make up for, to make sound, to renew, to mend, to patch or to otherwise restore biological function to an oral tissue (e.g., keratinized tissue, such as the gums and hard palate). The term can include full repair and partial repair.

[0053] As used herein, the term “substantially similar” can mean that a first value, aspect, trait, feature, number, or amount is of at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% of a second value, aspect, trait, feature, number, or amount.

[0054] As used herein, the terms “subject” and “patient” can be used interchangeably and refer to a vertebrate, such as a mammal (e.g., a human). Mammals can include, but are not limited to, humans, dogs, cats, horses, cows, and pigs.

[0055] As used herein, the phrase “subject in need thereof” can refer to a patient that: (i) will be administered an oral tissue repair composition, or implant thereof, of the present disclosure; (ii) is receiving an oral tissue repair composition, or implant thereof, of the present disclosure; or (iii) has received an oral tissue repair composition, or implant thereof, of the present disclosure; unless the context and usage of the phrase indicates otherwise.

[0056] As used herein, the term “xenogeneic” can refer to cells or tissues derived from individuals of different species, including, but not limited to, porcine, bovine, ovine, caprine, avian, equine, canine, lapine, feline, and/or other non-human mammals.

[0057] As used herein, the term “acellular oral tissue extracellular matrix” or “acellular oral tissue ECM” can refer to a tissue-derived structure that is made from an obtained oral tissue sample and which lacks, or is devoid of all, or substantially all, viable cells and all detectable subcellular components and/or debris generated by killing or lysing cells comprising the obtained oral tissue sample. In one example, an acellular oral tissue ECM is a tissue-derived structure that is not made or derived from a dermal tissue sample.

[0058] As used herein, the term “lacking substantially all viable cells” can mean that the concentration of viable cells in an acellular gingiva ECM is less than about 1% (e.g., 1 %; 0.9%; 0.8%; 0.7%; 0.6%; 0.5%; 0.4%; 0.3%; 0.2%; 0.1%; 0.01%; 0.001 %; 0.0001%; 0.00001%; 0.000001%, or any value between) of that in the oral tissue sample from which the acellular gingiva ECM was made. However, acellular gingiva ECM may be reseeded with autologous and/or allogeneic cells from other sources, e.g., after processing to support oral tissue regeneration or repair.

[0059] As used herein, an acellular oral tissue ECM lacking “substantially all DNA” can refer to an acellular oral tissue ECM in which the concentration of DNA is less than about 1% e.g., less than: 1%; 0.9%; 0.8%; 0.7%; 0.6%; 0.5%; 0.4%; 0.3%; 0.2%; 0.1%; 0.01%; 0.001%; 0.0001 %; 0.00001%; or 0.000001%) of that in the oral tissue sample from which the acellular oral tissue ECM was made. This includes all DNA (e.g., DNA within intact cells (alive or dead cells)) or residual DNA material left from the decellularization process.

[0060] As used herein, an acellular oral tissue ECM that “substantially lacks an epithelial basement membrane” can refer to an acellular gingiva ECM containing less than about 5% (e.g., less than: 4%; 3%; 2%; 1 %; 0.5%; 0.25%; 0.1%; 0.01%; 0.001 %; or even less than 0.001 %) of the epithelial basement membrane possessed by the corresponding unprocessed gingiva tissue sample from which the acellular oral tissue ECM matrix was derived or obtained.

[0061] As used herein, the term “therapeutically effective amount”, when referring to an oral repair composition or an oral repair implant of the present disclosure, can refer to an amount effective thereof, when administered to a patient, to provide a therapeutic effect, such as an amelioration of symptoms, reduced disease progression, and/or causing or increasing disease regression. A quantity of a specified oral repair composition or oral repair implant is sufficient to achieve a desired effect in a subject being treated, such as to reduce or inhibit gum disease (e.g., periodontal regression) and/or mitigate the effects of such disease and/or increase keratinized gingival tissue volume. A therapeutically effective amount can be administered orally, and can be administered in a single application, or in several applications over time. One skilled in the art will appreciate that the effective amount can be dependent on the preparation applied, the subject being treated, the severity and type of the affliction, and the manner of administration.

[0062] As used herein, the term “therapeutic effect” can refer to a consequence of treatment with an oral repair composition, or oral tissue repair implant, of the present application, the results of which are judged to be desirable and beneficial. A therapeutic effect may include, directly or indirectly, the arrest, reduction, or elimination of a disease manifestation. A therapeutic effect also may include, directly or indirectly, the arrest reduction or elimination of the progression of a disease manifestation.

[0063] Oral Repair Compositions

[0064] One aspect of the present disclosure can include a biocompatible, xenogeneic oral repair composition comprising an acellular oral tissue ECM. As discussed in more detail below, oral repair compositions of the present disclosure advantageously comprise a non-cytotoxic, homologous keratinized tissue ECM that possesses biological and mechanical cues that promote keratinized tissue repair and regeneration, which can optionally be combined with other components in specific configurations to provide improved handling and personalized design.

[0065] In one aspect, an oral repair composition of the present disclosure can comprise an acellular ECM derived from, made of, or obtained from a xenogeneic tissue source. In one example, the xenogeneic tissue source is a pig. The xenogeneic tissue source can comprise an oral tissue, such as a keratinized oral tissue. In one example, the xenogeneic tissue source can comprise a keratinized oral tissue selected from a gum tissue (gingiva), a palate tissue (e.g., hard palate), or a combination thereof. Methods for obtaining xenogeneic tissues are known in the art and include, for example, oral biopsies (e.g., using a scalpel or punch biopsy) and other surgical dissection techniques.

[0066] In one example, gum tissue (gingiva) is obtained from a pig as described in Example 1 below.

[0067] In another example, gum tissue (gingiva) and hard palate tissue from a pig can be obtained from the oral cavity as shown in Fig. 1 . From the back of the mandible, for example, an incision can be made to separate bone from gingival tissue, whereafter a strip can be mechanically peeled off with forceps from the back to the front lingual section. The hard palate can be mechanically peeled off the bone with forceps.

[0068] Within the varied shape of the stratified squamous gingival epithelium, there are distinct areas of morphology and function. As keratinocyte cells migrate through the gingiva tissue they differentiate, change shape, and lose their nucleus to form a tough outer layer that protects the underlying teeth and alveolar bone during mastication. The long dense fibrous types of keratins secreted by the keratinocytes that are present on the surface of gingiva are absent from dermis. The use of dermis-based grafts does not lead to the cell differentiation that produces a keratinized surface. A reduced height of keratinized tissue has been associated with implant instability, increased plaque accumulation, soft-tissue inflammation, greater patient discomfort, mucosal recession, bone loss, and tooth loss. As such, one aspect of the present disclosure includes an acellular oral tissue ECM that is not made or derived from dermis (e.g., a dermal tissue sample).

[0069] In another aspect, an acellular oral tissue ECM can be derived from, obtained by, or made by, chemical processing of xenogeneic tissue with acids, detergents, buffered salt solutions, and enzymatic digestion solutions. Examples of such methods can include those described by Gilbert, TW etal., Biomaterials, 27(19), 3675-3683 (2006) and Capella-Monsonfs, H. etal., Xenotransplantation, 28(4), e12683 (2021 ).

[0070] In another aspect, an oral repair composition of the present disclosure can be formulated from tissues comprised of type IV collagen, type VIII collagen, or a combination thereof.

[0071] In another aspect, an oral repair composition of the present disclosure can be formulated to include an effective amount of a bone graft matrix sufficient to repair or regenerate bone underlying an oral tissue defect as well as soft tissue loss (e.g., as a result of gum recession). In one example, the bone graft matrix can comprise demineralized bone matrix (DBM). DBM can refer to a bone-derived material that has osteoconductive and osteoinductive activity. DBM can be prepared by acid extraction of allograft bone, resulting in loss of most of the mineralized component but retention of collagen and non-collagenous proteins, including growth factors. Methods for preparing DBM from bone are known in the art, as disclosed, for example, in U.S. Pat. Nos. 5,073,373, 5,484,601 , and 5,284,655. DBM can be prepared from autologous bone, allogeneic (or “allograft”) bone, or xenogeneic bone. DBM can be prepared from cancellous bone, cortical bone, or combinations of cancellous and cortical bone. In some instances, demineralized bone can include bone matrix having a residual mineral content of 5% or less (w/w), 2% or less (w/w), 1 % or less (w/w), 0.5% or less (w/w), or consisting essentially of collagen, noncollagen proteins such as growth factors, and other non-mineral substances found in the original bone, although not necessarily in their original quantities.

[0072] The combination of an acellular oral tissue ECM and a bone graft matrix can provide an effective approach for restoring maxillofacial tissue at the bone and gum interface. This formulation leverages the regenerative properties of the ECM to promote soft tissue healing, while the bone graft matrix enhances structural support and facilitates osseointegration. The ECM serves as a biologically active scaffold that encourages cellular infiltration and tissue remodeling, promoting the regeneration of both soft and hard tissues. Meanwhile, the bone graft matrix provides the necessary mineral content to support new bone formation and maintain the integrity of the maxillofacial structure. This combination is particularly beneficial in procedures such as ridge augmentation, sinus lifts and periodontal defect repair, where the simultaneous regeneration of bone and soft tissue is critical for successful outcomes. By integrating acellular oral tissue ECM and bone graft matrix, clinicians can achieve enhanced healing and functional restoration at complex tissue interfaces.

[0073] In another aspect, an oral repair composition of the present disclosure can have a stratified structure as shown in Figs. 2A-D. Decellularized gingiva and palate are stratified tissue structures with different layers containing ECM. The decellularized gingiva is carefully processed to remove cellular content while preserving the intricate vascular structures within the ECM. The gingiva matrix provides a naturally-occurring scaffold with channels and pathways that facilitate nutrient and oxygen diffusion, promoting rapid revascularization and integration with host tissues. Advantageously, this vascular-rich ECM can significantly enhance the healing and regenerative potential, making it ideal for applications in soft tissue repair, augmentation, and periodontal regeneration. The presence of preserved vascular structures also supports cellular infiltration and angiogenesis, further improving the functional outcomes of the oral repair compositions of the present disclosure.

[0074] Referring again to Figs. 2A-D, an oral repair composition 10 can have a stratified structure comprising the following layers: a keratinized layer 12 having oppositely disposed first and second surfaces 14 and 16; a basement membrane layer 18 (e.g., an epithelium basement membrane layer that includes collagen types IV and VIII) having oppositely disposed first and second surfaces 20 and 22; a connective tissue layer 24 (including lamina propria with collagen types I and III) having oppositely disposed first and second surfaces 26 and 28; and a vascular structure layer 30 having oppositely disposed first and second surfaces 32 and 34 and comprising preserved vascular structures (e.g., channels) (indicated by “V” in Fig. 2D) that support cellular infiltration and angiogenesis therein upon implantation of the composition 10 in a subject.

[0075] As shown in Fig. 2B, the keratinized layer 12 can include a first surface 14 that functions as a gliding surface when the oral repair composition 10 is implanted in a subject, e.g., the first surface can contact the buccal mucosa or the tongue surface depending upon the implantation site. The second surface 16 of the keratinized layer 12 can be in contact with (e.g'., direct physical contact) the first surface 20 of the basement membrane layer 18. In situ, the keratinized layer 12 forms the outermost layer of the gingiva and palate, providing a tough protective barrier that resists mechanical forces and microbial invasion. When cellularized, this layer 12 is composed of stratified squamous epithelium, with varying degrees of keratinization depending on the location within the oral cavity.

[0076] The basement membrane layer 18 can include a first surface 20 that is in contact with (e.g., direct physical contact) with the second surface 16 of the keratinized layer 12, and a second surface 22 that is in contact with (e.g., direct physical contact) the first surface 26 of the connective tissue layer 24. The basement membrane layer 18, in situ, can serve as an anchoring interface between the epithelial cells and the underlying connective tissue. This layer 18 plays a crucial role in maintaining tissue integrity and regulating cell behavior through biochemical signaling.

[0077] The connective tissue layer 24 can include a first surface 26 that is in direct contact with (e.g., direct physical contact) the second surface 22 of the basement membrane layer 18, and a second surface 28 in direct contact with (e.g., direct physical contact) the first surface 32 of the vascular structure layer 30. The connective tissue layer 24, also known as the lamina propria, provides structural support and ECM components, such as collagen fibers. This layer 24 is essential for maintaining tissue resilience, repair, and nutrient exchange.

[0078] The vascular structure layer 30 can include a first surface 32 that is in contact with (e.g., direct physical contact) the second surface 28 of the connective tissue layer 24, and a second surface 34 that is adapted for contact (e.g., direct physical contact) with host tissue (e.g., gum, palate, bone) upon implantation of the oral repair composition 10. By virtue of its preserved vascular structures, the vascular structure layer 30 plays a critical role in wound healing by facilitating angiogenesis to the oral defect area(s). [0079] Such a stratified oral repair composition 10 is different than other stratified epithelia, like skin. A preserved (epithelium) basement membrane layer 18, for example, can serve as a substrate for host keratinocyte proliferation and organization after implantation. In addition, the vascular structure layer 30 can provide a native vascular network that promotes host angiogenesis during remodeling. Advantageously, this unique stratified structure of an oral repair composition 10 of the present application provides not only the biological cues but also structure to promote regeneration of keratinized tissue after following placement in the oral cavity, e.g., after oral surgery.

[0080] In another aspect, an oral repair composition of the present disclosure can be cross-linked, cross-linkable, or not cross-linked. In one example, an oral repair composition of the present disclosure can be cross-linked to a desired degree, e.g., to match tissue regeneration and provide longer mechanical support as required. More particularly, chemical cross-linking of acellular oral tissue ECMs can be done to create binding between free amines comprising the acellular oral tissue ECMs and thereby allow for a longer time of remodeling by slowing down the effect of hydrolysis and enzymatic degradation, while also increasing the mechanical resilience of materials. Oral repair compositions of the present disclosure can be cross-linked prior to administration to a subject in need thereof; or, such compositions may be cross-linked during or after administration. An oral repair composition of the present disclosure can be cross-linked using a chemical cross-linking agent including, but not limited to, glutaraldehyde, hexamethylene diisocyanate, EDC, CMC, NHS, and combinations thereof. In one example, the chemical cross-linking agent is EDC. [0081] In one aspect, a desired degree of cross-linking of an oral repair composition can refer to the percentage of functional groups (e.g., free amines) comprising the acellular oral tissue ECM thereof that are cross-linked with a crosslinking agent. In one example, the method may include crosslinking about 0.01% to about 90% of the functional groups comprising the acellular gingiva ECM with a cross-linking agent. In another example, about 0.1% to about 5%, about 5% to about 10%, about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to about 80%, about 80% to about 90%, or about 90% of the functional groups comprising the acellular oral tissue ECM can be cross-linked with a crosslinking agent. [0082] One skilled in the art will appreciate that the proportion of functional groups that are linked with the cross-linking agent is at least partially a function of the concentration of the cross-linking agent that is added to the acellular oral tissue ECM in the crosslinking reaction. In some instances, an acellular oral tissue ECM of the present disclosure can be chemically cross-linked using a desired concentration of EDC and a desired concentration of glutaraldehyde. For example, a desired concentration range for EDC can be about 0.01 mM to about 10 mM, e.g., about 0.01 mM to about 0.1 mM, or about 1 mM to about 2 mM or about 2 mM to about 3 mM, or about 3 mM to about 4 mM, or about 4 mM to about 5 mM, or about 5 mM to about 6 mM, or about 6 mM to about 7 mM, or about 7 mM to about 8 mM, or about 8 mM to about 9 mM, or about 9 mM to about 10 mM. A desired concentration of range for glutaraldehyde can be about 0.01% to about 0.5%, e.g., about 0.01% to about 0.1%, or about 0.1% to about 0.2%, or about 0.2% to about 0.3%, or about 0.3% to about 0.4%, or about 0.4% to about 0.5%.

[0083] In one example, an acellular oral tissue ECM of the present disclosure can be chemically cross-linked using about 3 mM and about 6 mM carbodiimide EDC + NHS and about 0.25 % glutaraldehyde.

[0084] In another aspect, an oral repair composition of the present disclosure can be formulated as a photo-crosslinkable composition. As such, in one example, an oral repair composition can be methacrylated and include a photoinitiator. A methacrylated oral repair composition of the present disclosure can comprise an acellular oral tissue ECM including at least one protein or peptide in which one or more amino acids of the protein or peptide are functionalized and/or modified to include a methacryl moiety. The methacryloylation of the protein or peptide involves placing the methacryl moiety on an amino acid side chain capable of receiving it. Of the twenty naturally occurring amino acids, lysine, tyrosine, cysteine, threonine, and serine are capable of receiving the methacryl moiety on their side chain. The degree of methacryloylation can be determined via a chemical assay (e.g., a TNBS assay) or mass spectrometry, as known in the art. Briefly, the degree of methacryloylation is calculated by determining the percentage of sites on a protein or peptide that have a methacryl moiety in relation to the number of sites on the protein or peptide that could receive the methacryl moiety. A degree of methacryloylation of 100% means that there is a methacryl moity on all of the sites that could receive a methacryl moiety. A degree of methacryloylation of 90%, for example, means that for every 100 sites on the protein or peptide that could receive the methacryl moiety, 90 of the sites actually have a bound methacryl moiety.

[0085] In one example, a desired amount of an acellular oral tissue ECM of the present disclosure (e.g., about 10% w/v) can be formulated with a desired amount of gelatin methacryloyl (GelMA) (e.g., about 10% w/v) to form a methacrylated oral repair composition of the present disclosure.

[0086] The photoinitiator used in the preparation of a photo-crosslinkable composition of the present disclosure is not particularly limited and can include, for example, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), 2-hydroxy-4’-(2- hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959), or ascorbic acid. When ultraviolet light is used to activate the photoinitiator, it may be provided in an intensity of between about 1 to about 500 mW/cm², e.g., about 1 -100 mW/cm², about 100-200 mW/cm², about 200-300 mW/cm², about 300-400 mW/cm², such about 300 mW/cm² (e.g., 300 mW/cm²), or about 400-500 mW/cm².

[0087] In one example, a photo-crosslinkable composition of the present disclosure can comprise a desired amount of an acellular oral tissue ECM of the present disclosure (e.g., about 10% w/v), a desired amount of gelatin methacryloyl (GelMA) (e.g., about 10% w/v), and a desired amount of a photoinitiator (e.g., about 1 % w/v Irgacure).

[0088] In another aspect, an oral repair composition of the present disclosure can be substantially free of native DNA and/or native cellular components. In one example, the concentration of native DNA in an oral repair composition of the present disclosure can be less than about 2000 ng/mg, less than about 1500 ng/mg, less than about 1000 ng/mg, less than about 500 ng/mg, or less than about 50 ng/mg.

[0089] In another aspect, an oral repair composition of the present disclosure can have a total protein content of about 50 pg/mg to about 200 pg/mg, e.g., more than about 50 pg/mg, more than about 100 pg/mg, more than about 150 pg/mg, or more than about 200 pg/mg. Total protein content can be measured by bicinchoninic Acid (BCA) protein assay, for example.

[0090] In another aspect, an oral repair composition of the present disclosure can, but need not necessarily, lack, or substantially lack, an epithelial basement membrane. [0091] In another aspect, an oral repair composition of the present disclosure can be in particulate form, e.g., as micronized particles or microspheres. Decellularized tissue can be converted into micronized material through cryomilling or other milling methods to facilitate its use in various methods and applications described herein. Cryomilling involves subjecting the decellularized tissue to extremely low temperatures, which makes the ECM brittle and more easily reduced to fine particles. The frozen tissue is then processed in a specialized milling apparatus to achieve a consistent micronized form. Alternatively, mechanical milling methods, such as ball milling, cut milling, or jet milling, can be used to achieve similar results. Micronized ECM particles can be incorporated into injectable formulations, scaffolds, or coatings to enhance the versatility of oral repair compositions and oral repair implants of the present disclosure. These processes allow for the production of ECM materials with optimized particle size and surface area, which can improve cellular adhesion, proliferation, and tissue integration.

[0092] Micronized ECM material can be further processed into microspheres using specialized fabrication techniques, such as emulsion-based methods, spray drying, microfluidics, or electrostatic encapsulation. The microspheres offer a versatile form factor for delivering ECM material to repair oral tissue and fill oral defects in a minimally invasive manner. The spherical shape and controlled size of the microspheres enable easy handling, injectability, and precise placement at a target site (e.g., an oral tissue defect). Additionally, the porous structure of the microspheres promotes cellular infiltration and tissue regeneration. Microspheres can be used as standalone fillers or combined with other biomaterials to create composite scaffolds, enhancing their mechanical properties and regenerative potential. This conversion process broadens the applicability of oral tissue repair compositions and oral tissue repair implants of the present disclosure, providing customizable solutions for diverse clinical needs.

[0093] In another aspect, an oral repair composition of the present disclosure can be formulated as an oral gel. In one example, an oral repair composition of the present disclosure can be formulated as an oral gel using one or combination of polymers (e.g., polysaccharide gums, e.g., gellan gum, gum tragacanth, gum Arabic, sulfated carrageenan gums, alginic acid), modified celluloses (e.g., methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose), chitosans, dextrans, hyaluronic acid, hyaluronic acid salts,), an orally acceptable base comprising ingredients selected from one or more of abrasives, buffering agents, humectants, surfactants, thickeners, gum strips or fragments, breath fresheners, flavoring, fragrance, coloring, antibacterial agents, whitening agents, agents that interfere with or prevents bacterial attachment, calcium sources, phosphate sources, orally acceptable potassium salts, and anionic polymers, and/or an aqueous carrier comprising water, ethanol, glycerol, propylene glycol, sorbitol, and xylitol, or mixtures thereof.

[0094] In one example, micronized ECM can be formulated into liquid or gelbased products designed to reduce gingival inflammation and promote overall gingival health. These formulations leverage the bioactive components of ECM to modulate the inflammatory response, enhance tissue hydration, and support the natural healing processes of the gingival tissues. When applied to affected areas, the liquid or gel forms create a protective barrier, facilitating wound healing and reducing bacterial colonization. Additionally, such formulations can promote fibroblast proliferation and extracellular matrix deposition, further enhancing tissue regeneration and long-term gingival health. This versatile delivery method offers a non-invasive option for managing periodontal inflammation and improving patient outcomes.

[0095] In another aspect, an oral repair composition of the present disclosure can be formulated as an oral rinse or mouthwash. In one example, an oral rinse or mouthwash can include an effective amount of an acellular oral tissue ECM (e.g., in micronized form) in combination with one or more ingredients including, but not limited to, water, surfactants, solvents, vitamins, minerals, polymers, enzymes, humectants, thickeners, additional antimicrobial agents, additional preservatives, flavorings, colorings and/or combinations thereof. Effective amounts for the acellular oral tissue ECM in the oral rinse or mouthwash can include, for example, as follows, by percent weight: about 0.01 % to about 10%, e.g., about 0.01% to about 1 %, about 1% to about 2%, about 2% to about 3%, about 3% to about 4%, about 4% to about 5%, about 5% to about 6%, about 6% to about 7%, about 7% to about 8%, about 8% to about 9%, or about 9% to about 10%.

[0096] In another aspect, an oral repair composition of the present disclosure can be formulated as a moldable putty or paste. Effective amounts for the acellular oral tissue ECM in the moldable putty or paste can include, for example, as follows, by percent weight, about 5% to about 95%, e.g., about 5% to about 10%, about 10% to about 20%, about 20% to about 30%, about 30% to about 40%, about 40% to about 50%, about 50% to about 60%, about 60% to about 70%, about 70% to about 80%, about 80% to about 90%, or about 90% to about 95%, when mixed with water, saline, or other buffer solutions.

[0097] In another aspect, an oral repair composition of the present disclosure can further comprise at least one exogenous growth-inductive substance. In one example, an exogenous growth-inductive substance can include any agent, molecule, compound, or moiety that promotes or increases repair or regeneration of damaged or diseased keratinized gingiva tissue. Non-limiting examples of growth- inductive substances include keratinocyte growth factor, epidermal growth factor, transforming growth factor-0, insulin-like growth factor-1 , and platelet-rich plasma. [0098] In one example, a growth-inductive substance is platelet-rich plasma (PRP). PRP is a concentrated source of autologous growth factors and cytokines that promote wound healing, angiogenesis, and tissue regeneration. When combined with acellular oral tissue ECM of the present disclosure, PRP can accelerate the healing process by enhancing cell migration, proliferation, and differentiation at the site of tissue damage. The synergistic effect of oral tissue ECM and PRP creates an environment conducive to soft tissue and bone repair, making the resultant composition particularly beneficial in treating periodontal defects, gingival recession, and other oral tissue injuries. The liquid form of PRP facilitates easy application to targeted areas, providing localized delivery of bioactive molecules that stimulate natural regenerative processes and improve clinical outcomes.

[0099] In another aspect, an oral repair composition of the present disclosure can have a definite shape (e.g., one that maintains a consistent or fixed recognizable form) or an indefinite shape (e.g., one that is adaptable to its environment). As such, an oral repair composition of the present disclosure can have a definite or indefinite shape and be sized and dimensioned so that the oral repair composition can conform to all, or substantially all, of an oral tissue defect in a subject. For example, an oral repair composition of the present disclosure can have a definite or indefinite shape and be sized and dimensioned so that one or more areas of the oral repair composition conform to one or more areas beyond the area comprising the oral tissue defect; in other words, the oral repair composition can be sized and dimensioned such that it extends beyond the area comprising the oral tissue defect in at least one dimension of the oral tissue repair implant, e.g., length and/or width. [00100] As discussed in more detail below, oral repair compositions having a definite shape can be formed by one or more of the processes of molding, machining, three-dimensional (3D) printing, laminating, and other technologies known for use in shaping 3D objects from soft or flowable materials. In some instances, shaped oral repair compositions may be provided in a lyophilized, cryopreserved, or frozen form.

[00101] In one example, the oral repair composition can be in the form of a sheet. In another example, the oral repair composition can be injectable. In another example, the oral repair composition can be in a dried, preformed shape. In another example, the oral repair composition can be in a porous form. In another example, the oral repair composition can be in a fibrous form.

[00102] In another aspect, shaped oral repair compositions can include 3D-shaped structures formed by a process in which acellular oral tissue ECMs are broken into smaller components (e.g., by milling or homogenization), then reformed into a 3D structure that is different from the source material. In one example, an acellular oral tissue ECM can be mechanically or chemically manipulated into a particulate form, which can be resuspended in a liquid (e.g., water or a buffer solution) to form a flowable mass, such as a slurry. The flowable mass may be poured into a mold of a desired shape, in which it may form a porous or sponge-like shaped composition. In some instances, the liquid and the acellular oral tissue ECM particles can be manipulated to form a putty or paste, which can then be molded into a desired shape. In some instances, a hydrogel material (e.g., chitosan, collagen, etc.) and acellular oral tissue ECM particles can be manipulated to form a gel. In some instances, the porosity of a shaped, acellular oral tissue ECM can be controlled by selecting the amount of a diluent (e.g., a liquid) relative to the amount of particulate acellular oral tissue ECM particles. In some instances, a porous or sponge-like shaped acellular oral tissue ECM can be a solid piece that conforms to the shape of a mold after being dried. In some instances, shaped oral repair compositions have porosities and/or a pH customized for their intended use.

[00103] In another aspect, a shaped oral repair composition can have a variety of shapes including, but not limited to, simple shapes, complex shapes, symmetrical shapes, asymmetrical shapes, shapes similar to the shapes of anatomical structures, and combinations thereof. In other aspects, shaped oral repair compositions can be provided for in vivo use (/.e., for injection or implantation).

[00104] In one example, a shaped or pre-formed oral repair composition 40 can include a defined cross-sectional geometry, such as a trapezoidal geometry as shown in Figs. 3A-B. Advantageously, the geometry facilitates implantation and improves healing due to conformability and contact with surrounding tissue. The shaped or pre-formed oral repair composition 40 can have dimensions (a length L, height H, and width W) such that the shaped or pre-formed oral repair composition is sized and dimensioned to conform to all, or substantially all, of an oral tissue defect in a subject (Fig. 3B). In some instances, the shaped or pre-formed oral repair composition 40 can have a length L of about 10 mm to about 60 mm, e.g., about 10- 55 mm, about 10-50 mm, about 10-45 mm, about 10-40 mm, about 10-35 mm, about 10-30 mm, about 10-25 mm, about 10-20 mm, or about 10-15 mm. In some instances, the shaped or pre-formed oral repair composition 40 can have a height H of about 0.5 mm to about 5 mm, e.g., about 0.5-4.5 mm, about 0.5-4 mm, about 0.5- 3.5 mm, about 0.5-3 mm, about 0.5-2.5 mm, about 0.5-2 mm, about 0.5-1 .5 mm, or about 0.5-1 mm. In some instances, the shaped or pre-formed oral repair composition 40 can have a width W of about 1 mm to about 20 mm, e.g., about 1 -15 mm, about 1 -10 mm, or about 1 -5 mm.

[00105] In one example, as shown in Fig. 3B, the shaped or pre-formed oral repair composition 40 can have a length L of 45 mm, a width W of about 5-9 mm (e.g., 5-9 mm), and a height H of about 1-2 mm (e.g., 1 -2 mm).

[00106] In one example, a shaped or pre-formed oral repair composition can include one or more tunnels or channels (e.g., the vascular structures V shown in Fig. 2D) extending partially or completely therethrough. Blood supply to gingiva tissue is unique and surgical technique impacts the degree of vascularization. In a split flap or tunnel technique, vascularization must form through the depth of a graft to connect arterioles of the alveolar bone to loop capillaries in the papillary epithelium. Current dermal-based grafts have most vascular structures running through the length of the graft — not the depth. Additionally, if a graft is too dense or sutured too tightly, blood flow will be limited and poor revascularization will occur. Further, if a graft is too porous or sutured too loosely, it can collapse, migrate, and lose blood flow resulting in necrotic tissue, thereby negating any proposed benefits of the surgery. As such, a shaped or pre-formed oral repair composition of the present disclosure can include one or more tunnels or channels extending partially or completely through the depth of the shaped composition, and be configured (e.g., formulated) with controlled stiffness, so that the shaped composition does not collapse. Such a configuration advantageously connects arterioles of the alveolar bone to loop capillaries in the papillary epithelium to promote vascularization.

[00107] Oral Repair Implants

[00108] Another aspect of the present disclosure can include an oral repair implant that is sized and dimensioned to conform to all, or substantially all, of an oral tissue defect in a subject. In one example, an oral repair implant can be sized and dimensioned to conform to one or more areas beyond the area comprising the oral tissue defect; in other words, the oral repair implant can be sized and dimensioned such that it extends beyond the area comprising the oral tissue defect in at least one dimension of the oral tissue repair implant, e.g., length and/or width.

[00109] An oral repair implant of the present disclosure can comprise an oral repair composition, as described above, as well as a barrier layer attached to (e.g., in physical contact with) the oral repair composition. Advantageously, oral repair implants of the present disclosure provide improved mechanical properties (e.g., suture retention, tensile strength, and tear resistance) while promoting host cell invasion to generate denser keratinized oral tissue for increased repair or regeneration of damaged or diseased gingiva as well as long-term stability of dental implants, for example. Additionally, the presence of a barrier layer advantageously aids in placement and tensioning of the oral repair implants as sutures can be located far outside a particular oral tissue defect.

[00110] In one example, the barrier layer can comprise a peritoneal membrane. [00111] Peritoneal tissue can be derived from a segment of an abdominal wall of a warm-blooded vertebrate, and may comprise a peritoneal membrane, muscle, adipose tissue, and two fascia layers. Peritoneal tissue can be derived or obtained from a xenogeneic source (e.g., a bovine or porcine membrane) or an autologous or allogeneic human source. As discussed below, the peritoneal membrane can be decellularized and lyophilized.

[00112] In some instances, the peritoneal membrane can be non-crosslinked, or partially crosslinked, or fully crosslinked.

[00113] Obtained peritoneal tissue can be processed after harvesting from the abdominal wall of, e.g., a warm-blooded vertebrate. The processing can include removing the muscle and adipose tissue from the peritoneal tissue, screening the peritoneal tissue for viruses such as Hepatitis B, and cleaning the peritoneal tissue to remove viruses, bacteria, and the adipose tissue. After processing of the peritoneal tissue, the two fascia layers thereof can merge into a single fascia layer. The single fascia layer can enhance the mechanical strength of the peritoneal membrane in both axes.

[00114] In one example, the peritoneal membrane can be formed into a predefined shape to suit the area of application and/or the shape of the associated oral repair composition.

[00115] In another example, the peritoneal membrane can comprise a peritoneal membrane as described in U.S. Patent No. 8,709,096 to Gingras etal., and may further be prepared according to methods described therein.

[00116] In another aspect, the barrier layer can be attached to (e.g., directly attached) to the oral repair composition by any chemical and/or biological bonding material or technique leading to a monolithic multilayer structure. Non-limiting examples of such materials and techniques can include partial acid solubilization, a gluing agent, cross-linking, or mechanical compaction and freeze drying.

[00117] In another aspect, an oral repair implant of the present disclosure can have a definite shape (e.g., one that maintains a consistent or fixed recognizable form) or an indefinite shape (e.g'., one that is adaptable to its environment). As discussed in more detail below, oral repair implants having a definite shape can be formed by one or more of the processes of molding, machining, using three- dimensional printing, laminating, and other technologies known for use in shaping three-dimensional objects from soft or flowable materials.

[00118] In one example, the oral repair implant can be in the form of a sheet. In another example, the oral repair implant can be in a dried, preformed shape. In another example, the oral repair implant can be in a porous form. In another example, the oral repair implant can be in a fibrous form.

[00119] In another aspect, shaped oral repair implants can include threedimensional-shaped structures formed by a process in which acellular oral tissue ECMs are broken into smaller components (e.g., by milling or homogenization), reformed into a three-dimensional structure that is different from the source material, and then attached to a barrier layer as described herein. In one example, an acellular oral tissue ECM can be mechanically or chemically manipulated into a particulate form, which can be resuspended in a liquid (e.g., water or a buffer solution) to form a flowable mass, such as a slurry. The flowable mass may be poured into a mold of a desired shape, in which it may form a porous or sponge-like shaped composition, whereafter the composition is attached to a barrier layer. In some instances, the liquid and the acellular oral tissue ECM particles can be manipulated to form a putty or paste, which can then be molded into a desired shape and then attached to a barrier layer. In some instances, a porous or sponge-like shaped acellular oral tissue ECM can be a solid piece that conforms to the shape of a mold after being dried, whereafter the solid piece is attached to a barrier layer. In some instances, shaped oral repair implants have porosities and/or a pH customized for their intended use.

[00120] In another aspect, a shaped oral repair implant can have a variety of shapes including, but not limited to, simple shapes, complex shapes, symmetrical shapes, asymmetrical shapes, shapes similar to the shapes of anatomical structures, and combinations thereof. In other aspects, shaped oral repair implants can be provided for in vivo use (/.e., for implantation).

[00121] In one example, a shaped or pre-formed oral repair implant can include a defined cross-sectional geometry, such as a trapezoidal geometry as shown in Figs. 3A-B and described above.

[00122] In another aspect, an oral repair implant of the present disclosure can have a stratified structure, as described above.

[00123] In one example, a shaped or pre-formed oral repair implant can include one or more tunnels (not shown) extending partially or completely therethrough. Blood supply to gingiva tissue is unique and surgical technique impacts the degree of vascularization. In a split flap or tunnel technique, vascularization must form through the depth of a graft to connect arterioles of the alveolar bone to loop capillaries in the papillary epithelium. Current dermal-based grafts have most vascular structures running through the length of the graft - not the depth.

Additionally, if a graft is too dense or sutured too tightly, blood flow will be limited and poor revascularization will occur. Further, if a graft is too porous or sutured too loosely, it can collapse, migrate, and lose blood flow resulting in necrotic tissue, thereby negating any proposed benefits of the surgery. As such, a shaped or preformed oral repair implant can include one or more tunnels extending partially or completely through the depth of the shaped implant, and be configured (e.g., formulated) with controlled stiffness, so that the shaped implant does not collapse. Such a configuration advantageously connects arterioles of the alveolar bone to loop capillaries in the papillary epithelium to promote vascularization.

[00124] Methods of Production

[00125] In clinically normal humans, the depth and height of the gingiva differs between the incisor and molar regions, between the maxilla and mandible, with age, and with the eruption of teeth or implants. Facial gingiva can have a pyramidal shape with a concave area where papilla meet. Commercially available rectangular grafts, however, do not account for the unique shape of the gingival tissue.

[00126] One aspect of the present disclosure can include a method for producing a pre-formed oral repair implant, or a pre-formed oral repair composition, that is sized and dimensioned to conform to all, or substantially all, of an oral tissue defect of a subject. Advantageously, the method of the present disclosure utilizes patientspecific imaging scans and certain manufacturing techniques (e.g., additive and subtractive manufacturing) to produce oral tissue repair compositions and implants that account for the complex structure of the oral maxillofacial region. The methods of the present disclosure thereby provide patient-matched grafts to allow for extra depth of tissue (where needed) and increased implant size to accommodate the unique oral tissue defects of patients.

[00127] In one aspect, the method can include forming a shaped oral repair implant or composition, as described herein, that includes a step of scanning or imaging at least a portion of a patient’s oral cavity having, or suspected of having, an oral tissue defect, then making a shaped oral repair implant or composition to repair or regenerate the oral tissue defect(s) identified during the scanning or imaging step. In some instances, a shaped oral repair implant or composition is made to restore the shape of an oral tissue defect (e.g., an anatomical structure). In other instances, a shaped oral repair implant or composition is made to provide a substitute for a missing anatomical structure. As discussed in more detail below, patient scans can advantageously be used to determine the extent of tissue recession, for example, so that the oral repair implants and compositions of the present disclosure provide added tissue depth and height where it is needed most to maintain the natural function and aesthetic of the gums. This can allow for complete coverage of the oral tissue defect area in one surgery with ease of placement and suturing (if needed). [00128] In one aspect, the method can include the following steps: (a) obtaining, from an oral cavity of the subject, one or more images of a region of interest having, or suspected of having, an oral tissue defect; (b) processing the obtained one or more images to generate a 3D model of the subject’s gum tissue and teeth; (c) selecting at least one oral tissue defect from the 3D model; (d) generating an oral repair implant model based on the selected at least one oral tissue defect; and (e) forming, based on the oral repair implant model, an oral repair implant or composition.

[00129] At Step (a), one or more images of a region of interest that has, or is suspected of having, an oral tissue defect can be obtained from an oral cavity of the subject using one or combination of imaging modalities. Such imaging modalities are known in the art and can include, for example, digital, CT (e.g., CBCT), MRI, ultrasound, PET-CT, and PET-MRI.

[00130] At Step (b), the image(s) obtained in Step (a) can be used to generate a 3D model of the subject’s gum tissue and teeth. In one example, generating the 3D model can be done by segmenting the obtained images to generate the 3D model; selecting, by a user, a plurality of locations within the 3D model; and selecting, by the user, one or more regions of interest (e.g., a region or area of gum tissue recession). [00131] At Step (c), at least one oral tissue defect (e.g., a region or area of gum tissue recession) can be selected from the 3D model.

[00132] In some instances, Step (d) can further comprise the steps of: generating an initial oral regeneration implant model; editing, by a user, the initial oral regeneration implant model; and providing a final oral regeneration implant model based on the user edits.

[00133] At Step (e), an oral repair implant model can be formed based on the selected at least one oral tissue defect. In one aspect, the oral repair implant can be formed using a molding process, an additive manufacturing process, a subtractive manufacturing process, or a combination thereof. In one example, an additive manufacturing process can include any process involving an additive build platform (e.g., printer) that creates physical objects from 3D digital models by layering materials on top of each other. Non-limiting types of such devices can include stereolithography (SLA) printers, selective laser sintering (SLS) printers, fused deposition modeling (FDM) printers, digital light process (DLP) printers, multi jet fusion (MJF) printers, PolyJet printers, direct metal laser sintering (DMLS) printers, and electron beam melting (EBM) lasers.

[00134] One example of a method for producing a patient-specific oral repair composition or oral repair implant is illustrated in Fig. 4.

[00135] Methods of Use

[00136] Another aspect of the present disclosure can include a method for repairing or regenerating an oral tissue defect in a subject. In some instances, the method can comprise administering, to an oral cavity of the subject, a therapeutically effective amount of an oral repair composition, as described herein. In other instances, the method can comprise administering, to an oral cavity of the subject, a therapeutically effective amount of an oral repair implant, as described herein. [00137] In procedures with a small oral defect, an implant (autograft, allograft or xenograft) is commonly used with a tunnel or flap technique. The graft is cut so that it covers the oral defect and surrounding healthy tissue and is then encased within the gums. This allows for blood flow to the graft from both sides, since vascularization is important to the success and longevity of the graft. Where there is not enough healthy tissue, a free graft technique can be used. The graft is then stitched directly to the outside margins of the defect. However, this has a higher rate of failure due to the drying out and separation of the graft from defect site, which interrupts the flow of blood and healing process.

[00138] Advantageously, the oral repair compositions and implants of the present disclosure comprise an acellular ECM with intact keratinized structure that promotes rapid and complete healing following contact with an oral defect. In certain aspects, oral repair compositions and implants of the present disclosure can be cross-linked and patient-specific to provide improved fit and greater stability while allowing angiogenesis from one side of the composition or implant; while providing barrier properties from the other side to protect the tissue, provide suture retention, and a gliding surface. The degree of crosslinking improves the duration and stability of the oral repair composition or implant, which is important for the outcome of the procedure. Additionally, the structure of the oral repair composition or implant provides the patient with adequate thickness and degree of crosslinking, which results in less shrinkage and recession of the oral repair composition or implant as it heals in vivo. [00139] One skilled in the art will appreciate that the determination of whether an oral repair composition, or an oral repair implant, is administered to a patient will depend upon the particular oral tissue defect(s) being repaired or regenerated. As such, the skilled artisan will appreciate when application of a shaped composition or implant is appropriate. Where introduction of a surgical site to the patient is needed to treat an oral tissue defect, for example, the method of present disclosure advantageously requires that only a single surgical site be made since the compositions and implants herein are not autologous, i.e., they are formed from xenogeneic tissue sources. The ability to repair an oral tissue defect using only a single surgical site is advantageous because autologous connective tissue grafts are commonly used and require a second surgical site leading to greater morbidity, longer surgical procedures, and a more painful postoperative phase for the patient. [00140] In another aspect, methods of the present disclosure can be used to repair or regenerate an area of gum damage associated with an artificial tooth (e.g., an artificial tooth comprising a screw, an abutment, and a crown).

[00141] In another aspect, methods of the present disclosure can be used to repair or regenerate damaged keratinized tissue (e.g., damaged gum and/or palate tissue) caused by periodontal recession.

[00142] In another aspect, methods of the present disclosure can be used to repair or regenerate damaged keratinized tissue (e.g., damaged gum and/or palate tissue) caused by trauma, periodontitis, a mucous ulcer, mucositis, and/or combinations thereof.

[00143] In another aspect, administering a therapeutically effective amount of an oral repair composition or an oral repair implant of the present disclosure can be performed by the subject having an oral tissue defect. Additionally, or alternatively, administering a therapeutically effective amount of an oral repair composition or an oral repair implant of the present disclosure to the subject can be performed by a person other than the subject, e.g., a medical professional, a dental professional, a dental technician, etc.

[00144] In another aspect, administering a therapeutically effective amount of an oral repair composition or an oral repair implant of the present disclosure to an oral cavity of a subject in need thereof can include placing the composition or the implant on or about an oral tissue defect so that the composition or the implant physically conforms to all, or substantially all, of the oral tissue defect. In some instances, an oral repair implant can be sized and dimensioned prior to placement. To treat an area of gum recession associated with at least one tooth, e.g., four teeth (e.g., four to six teeth), an oral repair implant can be sized and dimensioned, prior to placement about the area of gum recession, so that the oral repair implant physically conforms to all, or substantially all, of the area of gum recession - including at least one tooth associated therewith (e.g., at least four teeth associated therewith) - upon application to the area. If deemed appropriate (e.g., by a medical or dental professional), the oral repair implant can then be secured, e.g., using sutures on or about the area of gum recession.

[00145] In one example, treatment of an oral tissue defect may entail a surgical approach that requires incision and mobilization at the mucogingival junction. In such instances, the dimensions of the recipient periosteal bed can be designed according to the dimensions of an oral tissue repair implant of the present disclosure. The customized oral tissue repair implant can be rehydrated in saline before being positioned below the lingual flap edge. Immobilization and complete contact of the oral tissue repair implant with the periosteum can then be accomplished with deep sutures.

[00146] In another example, a method for repairing or regenerating an oral tissue defect (e.g., damaged keratinized gingiva tissue) of a subject can comprise formulating an oral repair composition, or an oral repair implant thereof, as a methacrylated composition or an implant thereof, that includes a photoinitiator (discussed above). Next, the methacrylated composition, or the implant thereof, can be administered on or about all, or substantially all, of the oral tissue defect. Light (e.g., UV light) can then be applied to the methacrylated composition, or the implant thereof, for a time sufficient to obtain a desired degree of cross-linking of the methacrylated composition, or the implant thereof.

[00147] Exemplary Aspects

[00148] In view of the described compositions, devices, and methods and variations thereof, herein below are certain more particularly described aspects of the present disclosure. These particularly recited aspects should not, however, be interpreted to have any limiting effect on any different claims containing different or more general teachings described herein, or that the “particular” aspects are somehow limited in some way other than the inherent meanings of the language literally used therein. [00149] Aspect 1 : A biocompatible, xenogeneic oral repair composition comprising an acellular oral tissue extracellular matrix (ECM).

[00150] Aspect 2: The oral repair composition of Aspect 1 , wherein the acellular oral tissue ECM is gingiva ECM or palate ECM.

[00151] Aspect 3: The oral repair composition of any one of Aspects 1 -2, wherein the acellular oral tissue ECM is porcine gingiva ECM or porcine palate ECM.

[00152] Aspect 4: The oral repair composition of any one of Aspects 1 -3, being cross-linked.

[00153] Aspect 5: The oral repair composition of any one of Aspects 1 -4, being cross-linked by 1 -ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC).

[00154] Aspect 6: The oral repair composition of any one of Aspects 1 -5, being methacrylated and further including a photoinitiator.

[00155] Aspect 7: The oral repair composition of any one of Aspects 1 -6, being substantially free of native DNA and/or native cellular components.

[00156] Aspect 8: The oral repair composition of any one of Aspects 1 -7, being formulated as micronized particles or microspheres.

[00157] Aspect 9: The oral repair composition of any one of Aspects 1 -8, being formulated as an oral gel or rinse.

[00158] Aspect 10: The oral repair composition of any one of Aspects 1 -9, being formulated as a moldable putty or paste.

[00159] Aspect 11 : The oral repair composition of any one of Aspects 1 -10, further comprising at least one exogenous growth-inductive substance.

[00160] Aspect 12: The oral repair composition of any one of Aspects 1 -11 , wherein the at least one exogenous growth-inductive substance is platelet-rich plasma.

[00161] Aspect 13: The oral repair composition of any one of Aspects 1 -12, having a stratified structure and comprising the following layers: a keratinized layer; a basement membrane layer; a connective tissue layer; and a vascular structure layer comprising preserved vascular structures that support cellular infiltration and angiogenesis therein upon implantation of the composition in a subject.

[00162] Aspect 14: The oral repair composition of any one of Aspects 1 -13, further comprising type IV collagen, type VIII collagen, or a combination thereof.

[00163] Aspect 15: The oral repair composition of any one of Aspects 1 -14, further comprising a bone graft matrix for hard tissue repair. [00164] Aspect 16: The oral repair composition of any one of Aspects 1 -15, having a pre-formed configuration and including a defined cross-sectional geometry, wherein the defined cross-sectional geometry is trapezoidal.

[00165] Aspect 17: An oral repair implant comprising the composition of any one of Aspects 1 -16 attached to a barrier layer.

[00166] Aspect 18: The oral repair implant of Aspect 17, wherein the barrier layer is in physical contact with the acellular oral tissue ECM by virtue of one or a combination of partial acid solubilization, a gluing agent, cross-linking, or mechanical compaction and freeze drying.

[00167] Aspect 19: The oral repair implant of any one of Aspects 17-18, wherein the barrier layer comprises a peritoneal membrane.

[00168] Aspect 20: The oral repair implant of any one of Aspects 17-19, being sized and dimensioned to conform to all, or substantially all, of an oral tissue defect in a subject.

[00169] Aspect 21 : A method for producing a pre-formed oral repair implant or a pre-formed oral repair composition, the method comprising the steps of: (a) obtaining, from an oral cavity of a subject, one or more images of a region of interest having, or suspected of having, an oral tissue defect; (b) processing the obtained one or more images to generate a three-dimensional (3D) model of the subject’s gum tissue and teeth; (c) selecting at least one oral tissue defect from the 3D model; (d) generating an oral repair model based on the selected at least one oral tissue defect; and (e) forming, based on the oral repair model, the pre-formed oral repair implant, or the pre-formed oral repair composition, which is sized and dimensioned to conform to all, or substantially all, of an oral tissue defect in a subject.

[00170] Aspect 22: The method of Aspect 21 , wherein step (e) is performed using a molding process, an additive manufacturing process, a subtractive manufacturing process, or a combination thereof.

[00171] Aspect 23: The method of any one of Aspects 21-22, wherein step (b) further comprises: segmenting one or more of the obtained images to generate the 3D model; selecting, by a user, a plurality of locations within the 3D model; and selecting, by the user, one or more regions of interest.

[00172] Aspect 24: The method of any one of Aspects 21-23, wherein the selected one or more regions of interest exhibit(s) gum tissue recession. [00173] Aspect 25: The method of any one of Aspects 21 -24, wherein step (d) further comprises: generating an initial oral repair model; editing, by a user, the initial oral repair model; and providing a final oral repair model based on the user edits.

[00174] Aspect 26: A method for repairing an oral tissue defect in a subject, the method comprising administering, to an oral cavity of the subject, a therapeutically effective amount of the oral repair composition of any one of Aspects 1 -16 or the oral repair implant of any one of Aspects 17-20.

[00175] Aspect 27: The method of Aspect 26, wherein the oral repair composition or the oral repair implant promotes repair of keratinized tissue comprising the oral tissue defect.

[00176] Aspect 28: The method of any one of Aspects 26-27, wherein administering is performed by the subject.

[00177] Aspect 29: The method of any one of Aspects 26-28, wherein administering is performed by a person other than the subject.

[00178] Aspect 30: The method of any one of Aspects 26-29, wherein the oral tissue defect is gum damage caused by periodontal recession.

[00179] Aspect 31 : The method of any one of Aspects 26-30, wherein the oral tissue defect is an area of gum damage associated with an artificial tooth.

[00180] Aspect 32: The method of any one of Aspects 26-31 , wherein the oral tissue defect is gum and/or palate damage caused by trauma, periodontitis, a mucous ulcer, mucositis, or a combination thereof.

[00181] Aspect 33: The method of any one of Aspects 26-32, further comprising placing the oral repair composition or the oral repair implant on or about the oral tissue defect so that the oral repair composition or the oral repair implant physically conforms to all, or substantially all, of the oral tissue defect.

[00182] Aspect 34: The method of any one of Aspects 26-33, wherein the oral tissue defect comprises an area of gum recession associated with at least one tooth, and wherein the oral repair implant is sized and dimensioned, prior to placement, to physically conform to all, or substantially all, of the area of gum recession.

[00183] Aspect 35: The method of any one of Aspects 26-34, further comprising the steps of: formulating the oral repair composition as a methacrylated oral tissue repair composition, or an oral repair implant thereof, that includes a photoinitiator; placing the methacrylated oral repair composition, or the oral repair implant thereof, on or about all, or substantially all, of the oral tissue defect; and applying light to the methacrylated oral repair composition, or the oral repair implant thereof, for a time sufficient to obtain a desired degree of cross-linking in the methacrylated oral repair composition or the oral repair implant thereof.

[00184] The following Examples are for the purpose of illustration only and are not intended to limit the scope of the claims, which are appended hereto.

Example 1

[00185] An oral repair composition comprised of porcine gingiva ECM was produced. Porcine gingiva tissue was harvested. The mandible was sawn in half longitudinally and the surrounding muscle tissue was removed. From the back of the mandible, an incision was made to separate bone from gingival tissue and a strip of gingiva was mechanically peeled off with forceps (Fig. 5). The gingiva tissue was decellularized (Fig. 6). The decellularization methods employed were based on chemical and enzymatic processes. The chemical process used comprised a peracetic acid de-contamination step, rinses in purified water, and subsequent treatments with salt-buffered solutions and non-ionic detergents. In the enzymatic process, an additional DNA-lytic enzyme incubation was applied after the chemical process to remove residual DNA. Both processes included a final decontamination with ethanol and rinses in purified water. DNA quantification (ng/mg) showed non- decellularized tissue at 1800, decellularized tissue at 900, and decellularized tissue with enzymatic process at under 5 (Fig. 7).

Example 2

[00186] The oral repair composition produced in Example 1 was further form factored after freeze drying. The decellularized porcine gingiva was micronized into a powder using cryomilling. The micronized gingiva had a particle size ranging from 5 to 100 microns.

Example 3

[00187] The oral repair composition produced in Example 2 was further form factored after micronization (Figs. 8A-B). A high viscosity gel was produced by mixing decellularized porcine gingiva powder with the appropriate buffer proportions. The samples produced included 1 xPBS with 200-300 mg/ml of gingiva powder, which gave positive preliminary results in injectability and mechanical properties. In addition, the mixture of micronized gingiva powder was compounded into a moldable paste that effectively retained its shape after freeze drying and rehydration, showing remarkable mechanical properties similar to those observed in native gingiva.

Example 4

[00188] Chemical crosslinking of the oral repair composition produced in Example 2 creates bindings between the free amines in the material and allows for a longer time of remodeling by slowing down the effect of hydrolytic, enzymatic, and microbial degradation, while also increasing the mechanical resilience of materials. The oral repair composition produced in Example 2 was chemically crosslinked using 3 and 6 mM carbodiimide EDC + NHS. Modeling of degradation characteristics in vitro was performed on native decellularized gingiva, porcine peritoneum (BioGide), 3% micronized gingiva powder, 3% micronized gingiva powder with EDC crosslinking, 5% micronized gingiva powder, and 5% micronized gingiva powder with EDC crosslinking. The native decellularized gingiva and micronized gingiva powder with EDC crosslinking showed favorable degradation characteristics (Figs. 9-11 ). Fig. 12 shows improved compression characteristics of oral repair compositions comprising 3% micronized gingiva powder, 3% micronized gingiva powder with EDC crosslinking, 5% micronized gingiva powder, and 5% micronized gingiva powder with EDC crosslinking.

Example 5

[00189] Chemical crosslinking of the oral repair composition produced in Example 2 creates bindings between the free amines in the material and allows for a longer time of remodeling by slowing down the effect of hydrolytic, enzymatic, and microbial degradation, while also increasing the mechanical resilience of materials. The oral repair composition was photocrosslinked after combination with gelMA (10% porcine gingiva powder / 10% gelMA / 1% Irgacure photoinitiator). These conditions were tested and showed improvements in the material properties.

Example 6

[00190] The oral repair composition produced in Example 2 was form factored into an additive manufacturing printing ink alone, and in combination with other bioinks, for direct 3D printing of patient-matched implants with custom infill patterns. Printing inks with 20-30% porcine gingiva material in PBS demonstrated printability (Fig. 13). In addition, the combination of fibrillar collagen type I ink (3%) + porcine gingiva powder 2% in pF showed excellent printability features.

Example 7 [00191] An oral repair implant comprising the oral repair composition produced in Example 2 in combination with a peritoneal membrane component is produced (Figs. 14-15). In this configuration, the porcine gingiva powder is patient-specific shaped or present in a pre-determined desired shape. Gingiva powder scaffolds act as porous materials for host cell repopulation and angiogenesis that remodels into keratinized tissue, while the peritoneal membrane acts as a barrier and anchoring point for sutures as it remodels into a mucosal surface. Both components are attached to each other with simple partial acid solubilization (e.g., using acetic acid), using a gluing agent (e.g., using gelatin), crosslinking (e.g., using EDO), or mechanical compaction and freeze drying. Additionally or alternatively, the oral repair implant is molded with bone graft material as a multilayer device to treat large oral defects that include bone.

[00192] From the above description of the present disclosure, those skilled in the art will perceive improvements, changes, and modifications. Such improvements, changes, and modifications are within the skill of those in the art and are intended to be covered by the appended claims. All patents, patent applications, and publications cited herein are incorporated by reference in their entirety.

Claims

CLAIMS The following is claimed:

1 . A biocompatible, xenogeneic oral repair composition comprising an acellular oral tissue extracellular matrix (ECM).

2. The oral repair composition of claim 1 , wherein the acellular oral tissue ECM is gingiva ECM or palate ECM.

3. The oral repair composition of claim 2, wherein the acellular oral tissue ECM is porcine gingiva ECM or porcine palate ECM.

4. The oral repair composition of claim 1 , being cross-linked.

5. The oral repair composition of claim 4, being cross-linked by 1 -ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC).

6. The oral repair composition of any one of claims 1 -5, being methacrylated and further including a photoinitiator.

7. The oral repair composition of claim 1 , being substantially free of native DNA and/or native cellular components.

8. The oral repair composition of claim 1 , being formulated as micronized particles or microspheres.

9. The oral repair composition of claim 1 , being formulated as an oral gel or rinse.

10. The oral repair composition of claim 1 , being formulated as a moldable putty or paste.

11 . The oral repair composition of claim 1 , further comprising at least one exogenous growth-inductive substance.

12. The oral repair composition of claim 1 1 , wherein the at least one exogenous growth-inductive substance is platelet-rich plasma.

13. The oral repair composition of claim 1 , having a stratified structure and comprising the following layers: a keratinized layer; a basement membrane layer; a connective tissue layer; and a vascular structure layer comprising preserved vascular structures that support cellular infiltration and angiogenesis therein upon implantation of the composition in a subject.

14. The oral repair composition of claim 1 , further comprising type IV collagen, type VIII collagen, or a combination thereof.

15. The oral repair composition of claim 1 , further comprising a bone graft matrix for hard tissue repair.

16. The oral repair composition of claim 1 , having a pre-formed configuration and including a defined cross-sectional geometry, wherein the defined cross-sectional geometry is trapezoidal.

17. An oral repair implant comprising the composition of any one of claims 1 -16 attached to a barrier layer.

18. The oral repair implant of claim 17, wherein the barrier layer is in physical contact with the acellular oral tissue ECM by virtue of one or a combination of partial acid solubilization, a gluing agent, cross-linking, or mechanical compaction and freeze drying.

19. The oral repair implant of claim 17, wherein the barrier layer comprises a peritoneal membrane.

20. The oral repair implant of claim 17, being sized and dimensioned to conform to all, or substantially all, of an oral tissue defect in a subject.

21 . A method for producing a pre-formed oral repair implant or a preformed oral repair composition, the method comprising the steps of:

(a) obtaining, from an oral cavity of a subject, one or more images of a region of interest having, or suspected of having, an oral tissue defect;

(b) processing the obtained one or more images to generate a three- dimensional (3D) model of the subject's gum tissue and teeth;

(c) selecting at least one oral tissue defect from the 3D model;

(d) generating an oral repair model based on the selected at least one oral tissue defect; and

(e) forming, based on the oral repair model, the pre-formed oral repair implant, or the pre-formed oral repair composition, which is sized and dimensioned to conform to all, or substantially all, of an oral tissue defect in a subject.

22. The method of claim 21 , wherein step (e) is performed using a molding process, an additive manufacturing process, a subtractive manufacturing process, or a combination thereof.

23. The method of claim 21 , wherein step (b) further comprises: segmenting one or more of the obtained images to generate the 3D model; selecting, by a user, a plurality of locations within the 3D model; and selecting, by the user, one or more regions of interest.

24. The method of claim 23, wherein the selected one or more regions of interest exhibit(s) gum tissue recession.

25. The method of claim 21 , wherein step (d) further comprises: generating an initial oral repair model; editing, by a user, the initial oral repair model; and providing a final oral repair model based on the user edits.

26. A method for repairing an oral tissue defect in a subject, the method comprising administering, to an oral cavity of the subject, a therapeutically effective amount of the oral repair composition of any one of claims 1 -16 or the oral repair implant of any one of claims 17-20.

27. The method of claim 26, wherein the oral repair composition or the oral repair implant promotes repair of keratinized tissue comprising the oral tissue defect.

28. The method of claim 26, wherein administering is performed by the subject.

29. The method of claim 26, wherein administering is performed by a person other than the subject.

30. The method of claim 26, wherein the oral tissue defect is gum damage caused by periodontal recession.

31 . The method of claim 26, wherein the oral tissue defect is an area of gum damage associated with an artificial tooth.

32. The method of claim 26, wherein the oral tissue defect is gum and/or palate damage caused by trauma, periodontitis, a mucous ulcer, mucositis, or a combination thereof.

33. The method of claim 26, further comprising placing the oral repair composition or the oral repair implant on or about the oral tissue defect so that the oral repair composition or the oral repair implant physically conforms to all, or substantially all, of the oral tissue defect.

34. The method of claim 33, wherein the oral tissue defect comprises an area of gum recession associated with at least one tooth, and wherein the oral repair implant is sized and dimensioned, prior to placement, to physically conform to all, or substantially all, of the area of gum recession.

35. The method of claim 26, further comprising the steps of: formulating the oral repair composition as a methacrylated oral tissue repair composition, or an oral repair implant thereof, that includes a photoinitiator; placing the methacrylated oral repair composition, or the oral repair implant thereof, on or about all, or substantially all, of the oral tissue defect; and applying light to the methacrylated oral repair composition, or the oral repair implant thereof, for a time sufficient to obtain a desired degree of cross-linking in the methacrylated oral repair composition or the oral repair implant thereof.