Biomedical glasses and glass-ceramics

Abstract

The invention relates to glasses and glass-ceramics, and their use in therapeutic applications such as in dental applications and orthopaedic applications, as well as in 3D printing applications. The invention also relates to methods of making the glasses and glass-ceramics.

Description

[0001] P5523GB00-KN4KE

[0002] BIOMEDICAL GLASSES AND GLASS-CERAMICS

[0003] TECHNICAL FIELD

[0004] This invention relates to glasses and glass-ceramics, and their use in therapeutic applications such as in dental applications and orthopaedic applications, as well as in 3D printing applications. The invention also relates to methods of making the glasses and glass-ceramics.

[0005] BACKGROUND

[0006] All mammalian teeth have the same general structure and contain three layers: an outer layer of enamel, a middle layer of dentin, and an inner layer of pulp.

[0007] Disorders of dental enamel are well known in the art, including tooth wear. Tooth wear is a multifactorial disease characterised by the loss of dental hard tissues (enamel and dentin) by either erosion, attrition, abrasion or abfraction, or a combination of these factors. Erosive tooth wear is a major condition that affects teeth, particularly human teeth, in which the teeth lose a significant amount of structure over time. The estimated worldwide prevalence of erosive tooth wear in permanent human teeth is approximately 37%. In advanced tooth wear, dental enamel is lost completely, and it cannot regenerate itself, exposing the sensitive part of the tooth known as dentine. Exposure of dentine typically leads to dentin hypersensitivity. Hypersensitivity of a tooth occurs when the enamel is worn away or there is less gum around the tooth, causing the dentin layer to be exposed. Therefore, at this stage, dental restoration procedures become essential.

[0008] Dental glass-ceramics (DGCs) have been used to restore teeth in cases of tooth wear.

[0009] Glass-ceramics are developed by controlled crystallization of glasses and form an important group of biomaterials used in modern dentistry. However, commercially available dental glass-ceramics possess higher hardness and low long-term fatigue values compared to natural dental enamel leading to unfavourable outcomes, leading to progressive wear of the opposing natural teeth. In addition, these materials tend to be placed in thick sections, and the presence of cracks or faults within the structures can induce catastrophic failures of the restoration.

[0010] While dental restorations are used to treat tooth wear, they can also accelerate the wear of natural teeth opposed by the restoration. One reason that gold has traditionally been the restorative material of choice for posterior indirect restorations, is that it causes minimal wear to the opposing enamel. In contrast, glass-ceramics tend to be more abrasive to enamel. Studies comparing the wear behaviour of restorative materials have shown that higher strength, fracture, toughness and crack growth resistance, is associated with reduced antagonist wear.P5523GB00-KN4KE

[0011] There is therefore a need for a glasses and glass-ceramics for use in dental applications, having a combination of aesthetic and physical properties, including chemical durability, biocompatibility, wear properties, fracture toughness, biaxial flexural strength and / or microhardness similar to that of natural teeth. Such materials are also useful in orthopaedic applications, for example as bone substitute materials or for stimulating bone re-growth. It is desirable to mimic the natural structure of teeth and bone both at the surface level and in the bulk of the teeth and bone.

[0012] Dental enamel is predominantly made of crystals of a mineral called hydroxyapatite. Yeom, B. et al. Abiotic tooth enamel. Nature 543, 95-98 (2017) aimed to synthesise a human enamel-like structure, but was unable to mimic the real architectures and chemistry of the enamel. Elsharkawy, S. et al. Nat. Commun. 9, (2018) used a protein based approach to mimic the structure of human dental enamel. However, this approach was only able to produce a coating with micrometres' thick mineralisation.

[0013] Thus, one objective of the invention may be to provide a glass-ceramic which mimics the hierarchical structures of human dental enamel not just at the surface, but also within the bulk of the material.

[0014] Several research teams have endeavoured to explore the development of the fluorapatite glass-ceramic system. For example, Stanton, K. T. & Hill, R. G., Journal of Crystal Growth vol. 275 e2061-e2068 (2005) prepared fluorapatite-mullite glass-ceramics.

[0015] Thus, one objective of the invention may be to provide novel glass-ceramics which are capable of being used in dental and orthopaedic applications.

[0016] SUMMARY OF THE INVENTION

[0017] A first aspect of the invention relates to a glass comprising SiO2, AI2O3, P2O5, CaO and CaF2, wherein the molar ratio of Ca:F of the glass is from about 48:1 to 0.75: 1, and wherein the molar ratio of Ca:P of the glass is from about 0.5:1 to 3.3:1, with the proviso that when the glass comprises at least 98 mol% of said SiO2, AI2O3, P2O5, CaO and CaF2, the molar ratio of Ca:P of the glass is from about 0.5:1 to 1.5:1.

[0018] A second aspect of the invention relates to a method of preparing a glass of the first aspect comprising the steps of:

[0019] a) Providing a mixture comprising:

[0020] i. SiO2,

[0021] ii. AI2O3,

[0022] iii. P2O5or a source thereof,

[0023] iv. CaO or a source thereof,

[0024] v. CaF2,P5523GB00-KN4KE

[0025] wherein the molar ratio of Ca:F of the mixture is from about 48:1 to 0.75: 1, and wherein the molar ratio of Ca:P of the mixture is from about 0.5:1 to 3.3:1, with the proviso that when the mixture comprises at least 98 mol% of components i-v, the molar ratio of Ca:P in the mixture is from about 0.5:1 to 1.5:1; and

[0026] b) Melting the mixture to form a molten glass; and

[0027] c) annealing the molten glass.

[0028] A third aspect of the invention relates to a glass-ceramic comprising a combination of fluorapatite (Ca5(PO4)3F), aluminium phosphate (AIPO4) and silicone dioxide (SiO2).

[0029] A fourth aspect of the invention relates to a method of producing a glass-ceramic of the third aspect, the method comprising the steps of:

[0030] a. heating the glass of the first aspect at a first heating rate to a first temperature,

[0031] b. optionally holding the glass at said first temperature for a first holding time;

[0032] c. after steps a) and b), heating said glass at a second heating rate to a second temperature,

[0033] d. optionally holding the glass at said second temperature for a second holding time.

[0034] A fifth aspect of the invention relates to the glass of the first aspect or the glass-ceramic of the third aspect for use in therapy.

[0035] A sixth aspect of the invention relates to a method of treating a patient comprising applying the glass of the first aspect or the glass-ceramic of the third aspect to a patient in need thereof.

[0036] A seventh aspect of the invention relates to the glass of the first aspect or the glass-ceramic of the third aspect for use in dental applications, or as a dental glass or dental glassceramic, and for use in a method of preventing or treating a disorder in a tooth of a patient.

[0037] An eighth aspect of the invention relates to a method of cosmetic treatment of a tooth of a patient, said cosmetic method comprising applying the glass of the first aspect or the glass ceramic of the third aspect to said tooth, or replacing at least a part of said tooth with the glass of the first aspect or the glass-ceramic of the third aspect.

[0038] A ninth aspect of the invention relates to the glass of the first aspect or the glass-ceramics of the third aspect for use in orthopaedic applications or as a bone substitute or for bone regeneration, and to a method for regenerating or replacing bone, said method comprisingP5523GB00-KN4KE

[0039] applying said the glass of the first aspect or the glass-ceramics of the third aspect to a bone in need of regeneration or replacement in a patient in need thereof.

[0040] A tenth aspect of the invention relates to the glass of the first aspect or the glass-ceramics of the third aspect for use in 3D printing applications, including a 3D printing resin comprising the glass of the first aspect or the glass-ceramic of the third aspect.

[0041] Throughout the description and claims of this specification, the words "comprise" and "contain" and variations of the words, for example "comprising" and "comprises", mean "including but not limited to", and do not exclude other components, integers or steps. Moreover, the singular encompasses the plural unless the context otherwise requires: in particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

[0042] Preferred features of each aspect of the invention may be as described in connection with any of the other aspects. Within the scope of this application, it is expressly intended that the various aspects, embodiments, examples and alternatives set out in the preceding paragraphs, in the claims and / or in the following description and drawings, and in particular the individual features thereof, may be taken independently or in any combination. That is, all embodiments and / or features of any embodiment can be combined in any way and / or combination, unless such features are incompatible.

[0043] BRIEF DESCRIPTION OF THE DRAWINGS

[0044] One or more embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

[0045] Figure 1 shows SEM images of Example 1A compared to human dental enamel at different scales, namely 10pm, 5pm, 1pm and lOOnm.

[0046] Figure 2 shows XRD (Figure 2a) and MAS-NMR results using19F,27AI and31P probes (Figures 2b-d respectively).

[0047] Figure 3 shows SEM images at 5pm, 1pm and lOOnm scales of the surface and in the bulk of the material of Example 1A.

[0048] Figure 4 shows SEM images at a scale of 5pm for Examples 1A, 2A, 3A and 4A.

[0049] Figure 5 shows the composition of Examples 1A (FAF3), 2A (FAF6), 3A (FAF12) and 4A (FAF24).

[0050] Figure 6 shows SEM images at a scale of 5pm for Examples IB, 1A and IF (no hold, 30 min hold, and 60 min hold).P5523GB00-KN4KE

[0051] Figure 7 shows SEM images at a scale of 5|jm for Examples 1C, IF and 1G (10°C / min, 60°C / min, and 120°C / min).

[0052] Figure 8 shows photographs at a 2mm scale, SEM images at a scale of 5pm and pie charts showing the ratio of glass to ceramic (crystal) material for when the glass of Example 1 was subject to holding at different second temperatures, namely 779°C, 795°C, 808°C or 860°C.

[0053] Figure 9 shows the results of microhardness and fracture toughness tests for Example 1A (F), human dental enamel (E), E.max CAD (EC), Vita Mark II (V), E.max Ceram (ECM), and E.max Zirpress (ZP).

[0054] Figure 10 shows the results of wear testing in terms of step height (pm) for Example 1A (F), E.max CAD (EC), Vita Mark II (V) and E.max Ceram (ECM).

[0055] DETAILED DESCRIPTION

[0056] Glasses and glass-ceramics

[0057] Glass ceramics are of particular interest as biologically active materials. A biologically active (or bioactive) material is one which, when implanted into living tissue, induces formation of an interfacial bond between the material and the surrounding tissue. Bioactive glasses and bioactive glass-ceramics are a group of surface-reactive materials, which exhibit bioactivity. The bioactivity of these materials is the result of complex reactions which take place on the surface of the material under physiological conditions, and which result in the formation of hydroxycarbonated apatite (HCA) on the surface of the material. The glass and glassceramic described herein are preferably a biologically active material.

[0058] Because of the ability of bioactive glasses and glass-ceramics to bond with living tissue, and in particular bone, they are used in a number of medical applications, including dental applications and orthopaedics.

[0059] A glass-ceramic may be manufactured in two main steps. First, the raw materials may be converted to a glass, and then the glass may be converted into a glass-ceramic.

[0060] Glass

[0061] Aspects of the invention relate to a glass comprises SiO2, AI2O3, P2O5, CaO, and CaF2.

[0062] Thus, a first aspect of the invention relates to a glass comprising SiO2, AI2O3, P2O5, CaO and CaF2, wherein the molar ratio of Ca:F of the glass is from about 48:1 to 0.75: 1, and wherein the molar ratio of Ca:P of the glass is from about 0.5:1 to 3.3:1, with the proviso that when the glass comprises at least 98 mol% of said SiO2, AI2O3, P2O5, CaO and CaF2, the molar ratio of Ca:P of the glass is from about 0.5:1 to 1.5:1.P5523GB00-KN4KE

[0063] The SiO2may be present in the mixture in an amount of at least 5mol%, at least 10mol%, at least 15mol%, at least 20mol%, at least 25mol%, at least 30 mol% or at least 35 mol%.

[0064] The SiO2may be present in the mixture in an amount of up to 70mol%, up to 65mol%, up to 60mol%, up to 55mol%, up to 50mol%, up to 45 mol%, up to 40mol%, up to 35mol% or up to 30 mol%.

[0065] It will be appreciated that any of the lower limits and any of the upper limits of the amounts for the SiO2may be combined. For example, the SiO2may be present in the mixture in an amount of from 5 to 70mol%, 5 to 50 mol%, 10 to 45mol%, or 20 to 45 mol%.

[0066] The AI2O3may be present in the mixture in an amount of at least 5mol%, at least 10mol%, at least 15mol%, at least 20mol%, at least 25mol%, at least 30 mol% or at least 35 mol%.

[0067] The AI2O3may be present in the mixture in an amount of up to 70mol%, up to 65mol%, up to 60mol%, up to 55mol%, up to 50mol%, up to 45 mol%, up to 40mol%, up to 35mol% or up to 30 mol%.

[0068] It will be appreciated that any of the lower limits and any of the upper limits of the amounts for the AI2O3may be combined. For example, the AI2O3may be present in the mixture in an amount of from 5 to 70mol%, 5 to 50 mol%, 10 to 40mol%, or 10 to 30 mol%.

[0069] The P2O5or source thereof, preferably the P2O5, may be present in the mixture in an amount of at least 5mol%, at least 10mol%, at least 15mol%, at least 20mol%, at least 25mol%, at least 30 mol% or at least 35 mol%.

[0070] The P2O5or source thereof, preferably the P2O5, may be present in the mixture in an amount of up to 70mol%, up to 65mol%, up to 60mol%, up to 55mol%, up to 50mol%, up to 45 mol%, up to 40mol%, up to 35mol%, up to 30 mol%, up to 25mol% or up to 20 mol%.

[0071] It will be appreciated that any of the lower limits and any of the upper limits of the amounts for the P2O5or source thereof, preferably the P2O5, may be combined. For example, the P2O5or source thereof, preferably the P2O5, may be present in the mixture in an amount of from 5 to 70mol%, 5 to 50 mol%, 10 to 40mol%, or 10 to 25 mol%.

[0072] The CaO or source thereof, preferably the CaO, may be present in the mixture in an amount of at least 2mol%, at least 5mol%, at least 10mol%, at least 15mol%, at least 20mol%, at least 25mol%, at least 30 mol% or at least 35 mol%.

[0073] The CaO or source thereof, preferably the CaO, may be present in the mixture in an amount of up to 60mol%, up to 55mol%, up to 50mol%, up to 45 mol%, up to 40mol%, up to 35mol%, up to 30 mol%, up to 25mol% or up to 20 mol%.P5523GB00-KN4KE

[0074] It will be appreciated that any of the lower limits and any of the upper limits of the amounts for the CaO or source thereof, preferably the CaO, may be combined. For example, the CaO or source thereof, preferably the CaO, may be present in the mixture in an amount of from 2 to 60mol%, 2 to 50 mol%, 5 to 40mol%, or 5 to 35 mol%.

[0075] The CaF2may be present in the mixture in an amount of at least 0.5 mol%, at least 1 mol%, at least 2 mol%, at least 5 mol%, at least 10mol%, at least 15mol%, at least 20mol%, at least 25mol%, at least 30 mol% or at least 35 mol%.

[0076] The CaF2may be present in the mixture in an amount of up to 60mol%, up to 55mol%, up to 50mol%, up to 45 mol%, up to 40mol%, up to 35mol%, up to 30 mol%, up to 25mol% or up to 20 mol%.

[0077] It will be appreciated that any of the lower limits and any of the upper limits of the amounts for the CaF2may be combined. For example, the CaF2may be present in the mixture in an amount of from 0.5 to 60mol%, 1 to 45 mol%, 1 to 40mol%, or 2 to 35 mol%.

[0078] The glass may comprise at least about 75mol% of SiO2, AI2O3, P2O5, CaO and CaF2. For example, the glass may comprise at least about 80mol%, at least about 85mol%, at least about 90mol%, at least about 95mol% of SiO2, AI2O3, P2O5, CaO and CaF2, or at least 98 mol% of SiO2, AI2O3, P2O5, CaO and CaF2.

[0079] The glass may comprise up to about 99.5mol% of SiO2, AI2O3, P2O5, CaO and CaF2. For example, the glass may comprise up to 99 mol%, up to 98 mol%, up to 95mol% up to 90 mol% of SiO2, AI2O3, P2O5, CaO and CaF2. It will also be appreciated that the glass may consist essentially of or consists of SiO2, AI2O3, P2O5, CaO and CaF2.

[0080] It will be appreciated that any of the lower limits and any of the upper limits of the amounts of the SiO2, AI2O3, P2O5, CaO and CaF2may be combined. For example, the SiO2, AI2O3, P2O5, CaO and CaF2may be present in the glass in an amount of from 75 to 100 mol%, 80 to 99.5 mol% or 85 to 99 mol% of the SiO2, AI2O3, P2O5, CaO and CaF2.

[0081] The molar ratio of Ca:P in the glass is from about 0.5:1 to 3.3:1, with the proviso that when the glass comprises at least 98 mol% of the SiO2, AI2O3, P2O5, CaO and CaF2, the molar ratio of the Ca:P in the glass is from about 0.5:1 to 1.5:1. For example, the molar ratio of the Ca:P in the glass may be from 0.5:1 to 2:1.

[0082] The molar ratio of Ca:P in the glass is preferably from about 0.5:1 to 1.5:1. For example, the molar ratio of Ca:P in the glass may be from about 1:0.9 to 1:1, preferably from about 1:0.92 to 1:0.96. It will be appreciated that any of the values in the ranges may be combined. For example, the molar ratio of Ca:P in the glass may be from 0.5:1 to 1:1, or 0.5:1 to 1:0.94, or 1:0.9 to 1.5:1.P5523GB00-KN4KE

[0083] The molar ratio of Ca:F of the glass is from about 48:1 to 0.75: 1. For example, the molar ratio of Ca:F of the glass may be from about 18:1 to 1:1, preferably from about 12:1 to 1.5:1. It will be appreciated that any of the values in the ranges may be combined. For example, the molar ratio of Ca:F of the glass may be from 48:1 to 1:1, or 24:1 to 1.5:1, or 24:1 to 0.75:1 or 12:1 to 1.5:1.

[0084] The glass may additionally comprise a colourant. Colourants may be desirable to try and achieve the same or similar colour as natural dental enamel, such as human dental enamel.

[0085] Suitable colourants include iron oxide (Fe2O3), ceria (CeO2), vanadium pentoxide (V2O5), vanadium trioxide V2O3, Er2O3, Tb2O3, Pr2O3, TaO2, MnO2, or combinations thereof. For example, iron oxide (Fe2O3), ceria (CeO2), and / or vanadium pentoxide (V2O5) may be included to achieve a light yellow which is similar to the colour of dental enamel.

[0086] The colourant may be present in an amount of from about 0.1 to 5 mol% of the glass, for example from 0.1-3 mol% of the glass.

[0087] The glass may comprise one or more additives to adjust the physical and mechanical properties of the glass and the resulting glass-ceramic.

[0088] For example, titanium dioxide (TiO2) may be added to improve the biaxial flexural strength of the resulting glass-ceramic. The titanium dioxide may be present in the glass in an amount of from about 0.1 to 15mol%, for example from 0.5-12 mol%, such as from 0.5-5 mol%.

[0089] The glass may comprise one or more additional components, such as ZrO2, LiSi, Li2Si2Os, l_i2SiO3, LiSi2, K2O, Na2O, KAISi2O6, Y2O3, CeO2, MgO, Sc2O3, La2O3, B2O3, BaO, SrO, Cr2O3and combinations thereof. The additional components may be present in the glass in an amount of from about 0.5 to 10mol%, for example from 0.5 to 5 mol%.

[0090] The term "glass" describes a state of matter where the atoms / molecules are randomly arranged, in other words, glass materials may be amorphous or substantially amorphous. For example, the glass may comprise less than 1 mol% of crystalline phase.

[0091] Method of preparing the glass

[0092] A second aspect of the invention relates to a method of preparing a glass of the first aspect.

[0093] Thus, the second aspect relates to a method of preparing a glass of the first aspect comprising the steps of:

[0094] d) Providing a mixture comprising:

[0095] i. SiO2,

[0096] ii. AI2O3,P5523GB00-KN4KE

[0097] iii. P2O5or a source thereof,

[0098] iv. CaO or a source thereof,

[0099] v. CaF2,

[0100] wherein the molar ratio of Ca:F of the mixture is from about 48:1 to 0.75: 1, and wherein the molar ratio of Ca:P of the mixture is from about 0.5:1 to 3.3:1, with the proviso that when the mixture comprises at least 98 mol% of components i-v, the molar ratio of Ca:P in the mixture is from about 0.5:1 to 1.5:1; and

[0101] e) Melting the mixture to form a molten glass; and

[0102] f) annealing the molten glass.

[0103] The starting materials i-iv and any additional optional components may be measured and mixed to prepare the mixture.

[0104] It will be appreciated that any source of the starting materials may be used. For example, CaCO3, may be used instead of CaO and carbon dioxide (CO2) as a carbon (C) component of CaCO3may be discharged and removed as gas in a melting process of the glass. Thus, the term "CaO or a source thereof" encompasses CaO and CaCO3. It may be desirable to use a source of CaO instead of CaO due to its more favourable toxicity profile.

[0105] Similarly, ammonium phosphate monobasic, also known as mono-ammonium phosphate, having the formula NH4H2PO4may be used as a source of P2O5. Thus, the term "P2O5or a source thereof" encompasses P2O5and NH4H2PO4. It may be desirable to use a source of P2O5instead of P2O5due to its more favourable toxicity profile.

[0106] The mixing may be mixed by a dry mixing process. A milling process may be used as the dry mixing process. Milling may involve placing the materials in a milling machine and mechanically grinding the materials. The milling may be performed for 1 to 48 hours.

[0107] Once the mixture has been provided, it is then melted to form a molten glass. To achieve the melting, the mixture may be placed in a furnace and then heated.

[0108] The melting may be performed for 1 to 12 hours. The melting may be performed at atmospheric pressure. The melting temperature of the mixture depends on the amounts and identity of the starting materials.

[0109] Typically, the mixture may be heated to a temperature of at least 1400°C. For example, the mixture may be heated to a temperature of at least 1450°C, at least 1500°C, at least 1550°C, at least 1600°C, at least 1650°C or at least 1700°C.P5523GB00-KN4KE

[0110] The mixture may be heated to a temperature of up to about 2200°C. For example, the mixture may be heated to a temperature of up to about 2150°C, up to 2100°C, up to 2050°C, up to 2000°C, up to 1950°C, or up to 1900°C.

[0111] It will be appreciated that any of the lower limits and any of the upper limits of the temperatures may be combined. For example, the mixture may be heated to a temperature of from 1400°C to 2200°C, from 1450°C to 2100°C or from 1450 to 1900°C.

[0112] When the temperature is less than 1400 °C, the mixture may not be completely melted. When the temperature is more than 2200 °C, the process may be less economic due to excessive energy consumption. Thus, it is preferred that the mixture is heated within the above temperatures.

[0113] The mixture may be heated at a rate of at least l°C / min. For example, the mixture may be heated at a rate of at least 5°C / min, at least 10°C / min, at least 15°C / min or at least 20°C / min.

[0114] The mixture may be heated at a rate of up to 50°C / min. For example, the mixture may be heated at a rate of up to 40°C / min, up to 30°C / min, up to 25°C / min or up to 20°C / min.

[0115] It will be appreciated that any of the lower limits and any of the upper limits of the heating rates may be combined. For example, the mixture may be heated at a rate of from 1 to 50°C / min, from 5 to 30°C / min or from 5 to 20°C / min. An exemplary heating rate is 10°C / min.

[0116] Optionally, once the mixture has been heated to form a molten glass, the molten glass may be maintained as said molten glass (e.g. at the above temperature) for at least 15 minutes. For example, the molten glass may be maintained as said molten glass for at least 30 minutes, at least 45 minutes, at least 60 minutes or at least 75 minutes.

[0117] The molten glass may be maintained as said molten glass for up to 120 minutes. For example, the molten glass may be maintained for up to 105 minutes or for up to 90 minutes.

[0118] It will be appreciated that any of the lower limits and any of the upper limits of the holding times may be combined. For example, the molten glass may be maintained at the temperature for 15 to 120 minutes, for 30 to 90 minutes, or for 45 to 75 minutes.

[0119] The molten glass may be cast into a mould. The mould may be of any shape or size. The mould may suitably be made from graphite or carbon.P5523GB00-KN4KE

[0120] Prior to casting, the mould may desirably be preheated to prevent thermal shock. For example, prior to casting, the mould may be preheated to a temperature from 200°C to 650°C, from 250°C to 600°C, or from 300°C to 550°C.

[0121] The molten glass is annealed. The annealing may involve holding the glass at an annealing temperature and then cooling of the glass.

[0122] The glass may be held at the annealing temperature. The annealing temperature may be at least 200°C, at least 250°C, at least 350°C or at least 400°C. The annealing temperature may be up to 650°C, up to 600°C or up to 550°C.

[0123] It will be appreciated that any of the lower limits and any of the upper limits of the annealing temperature may be combined. For example, the annealing temperature may be from 200°C to 650°C, from 250°C to 600°C, or from 300°C to 550°C.

[0124] The glass may be held at the annealing temperature for at least 15 minutes, at least 30 minutes, at least 45 minutes, at least 60 minutes or at least 75 minutes. The glass may be held at the annealing temperature for up to 120 minutes, up to 105 minutes or for up to 90 minutes.

[0125] It will be appreciated that any of the lower limits and any of the upper limits of the holding times at the annealing temperature may be combined. For example, the glass may be held at the annealing temperature for 15 to 120 minutes, for 30 to 90 minutes, or for 45 to 75 minutes.

[0126] The annealing may involve cooling the molten glass at a rate of at least l°C / min. For example, the molten glass may be cooled at a rate of at least 5°C / min, at least 10°C / min, at least 15°C / min or at least 20°C / min.

[0127] The molten glass may be cooled at a rate of up to 50°C / min. For example, the molten glass may be cooled at a rate of up to 40°C / min, up to 30°C / min, up to 25°C / min or up to 20°C / min.

[0128] It will be appreciated that any of the lower limits and any of the upper limits of the cooling rates may be combined. For example, the molten glass may be cooled at a rate of from 1 to 50°C / min, from 5 to 30°C / min or from 5 to 20°C / min.

[0129] The glass may desirably be cooled to room temperature (e.g. 20°C).

[0130] All features in relation to the glass as described in the first aspect apply equally to the second aspect, including in relation to the amounts and molar ratios of the components.P5523GB00-KN4KE

[0131] It will be appreciated that the invention provides a glass obtainable by the method of the second aspect.

[0132] Glass-ceramic

[0133] Aspects of the invention relate to a glass-ceramic. Glass-ceramics are materials in which at least one crystalline phase is present in a glass matrix. Thus, glass-ceramics contain both glass (amorphous) and ceramic (crystalline) phases.

[0134] The third aspect of the invention relates to a glass-ceramic comprising a combination of fluorapatite (Ca5(PO4)3F), aluminium phosphate (AIPO4) and silicone dioxide (SiO2).

[0135] The glass-ceramic may comprise at least 85 mol% of the combination of fluorapatite, aluminium phosphate and silicone dioxide. For example, the glass-ceramic may comprise at least 90 mol%, at least 95 mol%, or at least 98 mol% of the combination. It will also be appreciated that the glass-ceramic may consist essentially of or consist of said combination of fluorapatite, aluminium phosphate and silicone dioxide.

[0136] The glass-ceramic may comprise up to 99 mol%, up to 98 mol%, up to 97 mol%, up to 96 mol%, up to 95 mol%, or up to 90 mol% of said combination.

[0137] It will be appreciated that any of the lower limits and any of the upper limits of the combination may be combined. For example, the glass-ceramic may comprise 85-99 mol%, 85-98 mol%, 85-95 mol%, 90-99 mol%, 90-98 mol%, 90-95 mol%, 95-99 mol%, or 95-98 mol% of said combination.

[0138] The fluorapatite may be present in an amount of at least 3 mol% of the glass-ceramic. For example, the fluorapatite may be present in an amount of at least 5 mol%, at least 10 mol%, at least 15 mol%, or at least 20 mol% of the glass-ceramic.

[0139] The fluorapatite may be present in an amount of up to 98 mol% of the glass ceramic. For example, the fluorapatite may be present in an amount of up to 95 mol%, up to 90 mol%, up to 85 mol%, up to 80 mol% up to 75 mol%, or up to 70 mol% of the glass-ceramic.

[0140] It will be appreciated that any of the lower limits and any of the upper limits of the fluorapatite may be combined. For example, the glass-ceramic may comprise 3 to 98 mol%, 5-95 mol%, 10-90 mol% 15-85 mol%, 20-80 mol% or 20-75 mol% fluorapatite.

[0141] The aluminium phosphate may be present in an amount of at least 0.1 mol% of the glassceramic. For example, the aluminium phosphate may be present in an amount of at least about 0.3 mol%, at least 0.5 mol%, at least 0.7 mol% or at least 1 mol% of the glassceramic.P5523GB00-KN4KE

[0142] The aluminium phosphate may be present in an amount of up to 60 mol% of the glassceramic. For example, the aluminium phosphate may be present in an amount of up to 55 mol%, up to 50 mol%, up to 45 mol% or up to 40 mol% of the glass ceramic.

[0143] It will be appreciated that any of the lower limits and any of the upper limits of the aluminium phosphate may be combined. For example, the glass-ceramic may comprise 0.1-60 mol%, 0.3-55 mol%, 0.5-50 mol%, 0.7-45 mol% or 1-45 mol% aluminium phosphate.

[0144] The silicone dioxide may be present in an amount of at least 1 mol% of the glass-ceramic. For example, the silicone dioxide may be present in an amount of at least about 2 mol%, at least 3 mol%, at least 4 mol%, at least 5 mol % or at least 7 mol% of the glass-ceramic.

[0145] The silicone dioxide may be present in an amount of up to 70 mol% of the glass-ceramic. For example, the silicone dioxide may be present in an amount of up to 65 mol%, up to 60 mol%, up to 55 mol%, up to 50 mol%, or up to 45 mol% of the glass ceramic.

[0146] It will be appreciated that any of the lower limits and any of the upper limits of the silicone dioxide may be combined. For example, the glass-ceramic may comprise 1-70 mol%, 2-65 mol%, 3-60 mol%, 3-50 mol%, or 5-50 mol% of silicone dioxide.

[0147] The glass-ceramic may comprise colourants, additional components and / or TiO2as defined in the first aspect. For example, the glass-ceramic may comprise up to 15 mol% of colourants, additional components and / or TiO2.

[0148] The glass-ceramic may comprise TiO2. For example, the glass-ceramic may comprise up to 15 mol% of titanium dioxide. It will be appreciated that the titanium dioxide may be present in the glass-ceramic in an amount of from about 0.1 to 15mol%, for example from 0.5-12 mol%, such as from 0.5-5 mol%.

[0149] It will also be appreciated that the glass ceramic may comprise a colourant as defined in the first aspect. The colourant may be present in an amount of from about 0.1 to 5 mol% of the glass, for example from 0.1-3 mol% of the glass-ceramic.

[0150] The glass ceramic may comprise the one or more additional components as defined in the first aspect in an amount of from about 0.5 to 10mol%, for example from 0.5 to 5 mol% of the glass ceramic.

[0151] The glass ceramic preferably comprises less than 1 mol% of mullite. Mullite, also known as porcelainite, may have two stoichiometric forms: 3AI2O32SiO2or 2AI2O3SiO2. Preferably, the glass-ceramic does not comprise mullite.

[0152] In the glass-ceramic, the molar ratio of crystalline (ceramic) to amorphous (glass) phases may be from 3:97 to 97:3. For example, the molar ratio of crystalline to amorphous phasesP5523GB00-KN4KE

[0153] may be from 5:95 to 95:5, from 10:90 to 90:10, from 20:80 to 80:20, or from 30:70 to 70:30.

[0154] The molar ratio of Ca:F of the glass-ceramic may be from about 48:1 to 0.75: 1. For example, the molar ratio of Ca:F of the glass-ceramic may be from about 18:1 to 1:1, preferably from about 12:1 to 1.5:1. It will be appreciated that any of the values in the ranges may be combined. For example, the molar ratio of Ca:F of the glass-ceramic may be from 48: 1 to 1: 1, or 24: 1 to 1.5:1, or 24: 1 to 0.75: 1 or 12:1 to 1.5:1.

[0155] The molar ratio of Ca:P in the glass-ceramic may be from about 0.5:1 to 3.3:1. For example, the molar ratio of the Ca:P in the glass-ceramic may be from 0.5:1 to 2:1.

[0156] The molar ratio of Ca:P in the glass-ceramic is preferably from about 0.5:1 to 1.5:1. For example, the molar ratio of Ca:P in the glass-ceramic may be from about 1:0.9 to 1:1, preferably from about 1:0.92 to 1:0.96. It will be appreciated that any of the values in the ranges may be combined. For example, the molar ratio of Ca:P in the glass-ceramic may be from 0.5:1 to 1:1, or 0.5:1 to 1:0.94, or 1:0.9 to 1.5:1.

[0157] The mechanical properties of the glass-ceramic are designed to match or closely approximate those of a natural tooth (e.g. a human tooth) or natural bone (e.g. natural bone).

[0158] The mol% of the components in the glass-ceramic may be determined by XRD analysis followed by Rietveld refinement of the XRD spectrum produced by the XRD analysis.

[0159] XRD measurements may be carried out on a CubiX3 X-ray powder diffractometer (Malver PANalytical, UK) and copper target operating in subtractive transmission mode at 45kV and 40mA. X-rays may be pure monochromatic Cu Koi with A = 1.540598A. PDF card 00-015-0776 may be used to identify mullite and 00-015-0876 for fluorapatite. The 2-theta scan measurements may be carried out in standard reflection mode, using Cu K alpha radiation, with sample holders spinning on the stage during the scan.

[0160] The Rietveld refinement may be carried out using Match! 3 analysis software, version 4.1 Build 309 by Crystal Impact GbR.

[0161] The glass of the first aspect may be subjected to a heat treatment process to produce the glass-ceramic.

[0162] Manufacture of the glass-ceramic

[0163] The fourth aspect of the invention relates to a method of producing a glass-ceramic of the third aspect.P5523GB00-KN4KE

[0164] Therefore, the fourth aspect of the invention relates to a method of producing a glassceramic of the third aspect, the method comprising the steps of:

[0165] e. heating the glass of the first aspect at a first heating rate to a first temperature,

[0166] f. optionally holding the glass at said first temperature for a first holding time;

[0167] g. after steps a) and b), heating said glass at a second heating rate to a second temperature,

[0168] h. optionally holding the glass at said second temperature for a second holding time.

[0169] The first heating rate may at least l°C / min. For example, the first heating rate may be at least 3°C / min, at least 5°C / min, at least 6°C / min, at least 10°C / min, at least 15°C / min or at least 20°C / min.

[0170] The first heating rate may be up to 60°C / min. For example, the first heating rate may be up to 50°C / min, up to 40°C / min, up to 30°C / min, up to 25°C / min, up to 20°C / min or up to 15°C / min.

[0171] It will be appreciated that any of the lower limits and any of the upper limits of the first heating rate may be combined. For example, the first heating rate may be from 1 to 60°C / min, from 3 to 40°C / min or from 6 to 20°C / min. Exemplary first heating rates include 10°C / min and 60°C / min.

[0172] The second heating rate may at least l°C / min. For example, the second heating rate may be at least 3°C / min, at least 5°C / min, at least 6°C / min, at least 10°C / min, at least 15°C / min or at least 20°C / min.

[0173] The second heating rate may be up to 60°C / min. For example, the second heating rate may be up to 50°C / min, up to 40°C / min, up to 30°C / min, up to 25°C / min, up to 20°C / min or up to 15°C / min.

[0174] It will be appreciated that any of the lower limits and any of the upper limits of the second heating rate may be combined. For example, the second heating rate may be from 1 to 60°C / min, from 3 to 40°C / min or from 6 to 20°C / min. Exemplary second heating rates include 10°C / min and 60°C / min.

[0175] It will be appreciated that the first heating rate and said second heating rate may be the same or different, preferably the first heating rate and said second heating rate are the same.

[0176] The first temperature may be at least 450°C. For example, the first temperature may be at least 500°C, at least 550°C, or at least 600°C.P5523GB00-KN4KE

[0177] The first temperature may be up to 850°C. For example, the first temperature may be up to 800°C, up to 750°C, or up to 700°C.

[0178] It will be appreciated that any of the lower limits and any of the upper limits of the first temperature may be combined. For example, the first temperature may be from 450°C to 850°C, from 500°C to 800°C, from 550°C to 750°C, or from 600°C to 700°C.

[0179] The first temperature may be within ±150°C of the glass transition temperature (Tg) of the glass, within ±100°C of the glass transition temperature (Tg) of the glass, or within ±50°C of the glass transition temperature (Tg) of the glass. It will also be appreciated that the first temperature may be at or above the glass transition temperature (Tg) of the glass, preferably at the glass transition temperature (Tg) of the glass.

[0180] The second temperature may be at least 700°C. For example, the second temperature may be at least 750°C, at least 800°C, or at least 850°C.

[0181] The second temperature may be up to 1250°C. For example, the second temperature may be up to 1200°C, up to 1150°C, or up to 1100°C.

[0182] It will be appreciated that any of the lower limits and any of the upper limits of the second temperature may be combined. For example, the second temperature may be from 700°C to 1250°C, from 750°C to 1200°C, from 800°C to 1150°C, or from 850°C to 1100°C.

[0183] The second temperature may be within ±150°C of the peak crystallisation temperature (Tp) of the glass, within ±100°C of the peak crystallisation temperature (Tp) of the glass, or within ±50°C of the peak crystallisation temperature (Tp) of the glass. It will also be appreciated that the second temperature may be at or above the peak crystallisation temperature (Tp) of the glass, preferably at the peak crystallisation temperature (Tp) of the glass.

[0184] The first holding time may be a time sufficient to induce nucleation. For example, the first holding time may be at least 5 minutes, at least 15 minutes, at least 20 minutes or at least 30 minutes.

[0185] The first holding time may be up to 120 minutes. For example, the first holding time may be up to 90 minutes, up to 75 minutes, or up to 60 minutes.

[0186] It will be appreciated that any of the lower limits and any of the upper limits of the first holding time may be combined. For example, the first holding time may be from 5 minutes to 120 minutes, from 15 minutes to 90 minutes, or from 20 minutes to 75 minutes.P5523GB00-KN4KE

[0187] The second holding time may be a time sufficient to induce crystallisation. For example, the second holding time may be at least 5 minutes, at least 15 minutes, at least 20 minutes or at least 30 minutes.

[0188] The second holding time may be up to 120 minutes. For example, the second holding time may be up to 90 minutes, up to 75 minutes, or up to 60 minutes.

[0189] It will be appreciated that any of the lower limits and any of the upper limits of the second holding time may be combined. For example, the second holding time may be from 5 minutes to 120 minutes, from 15 minutes to 90 minutes, or from 20 minutes to 75 minutes.

[0190] Preferably, step b) is conducted, or step d) is conducted, or steps b) and c) are conducted. Preferably both steps b) and d) are conducted.

[0191] It will be appreciated that the first holding time and the second holding time may be the same or different, preferably the first holding time and the second holding time are the same.

[0192] It will also be appreciated that varying the first and second holding times, first and second heating rates and first and second holding temperatures may impact the structure of the resultant glass-ceramic.

[0193] For example, when the first heating rate is relatively slow, for example up to 40°C / min or less, such as from 3 to 40°C / min, more preferably from 6 to 20°C / min then the first holding time may be reduced (e.g. up to 30 minutes) or omitted, as the crystals may be capable of sufficient nucleation at the lower heating rate.

[0194] Similarly, when the second heating rate is relatively slow, for example up to 40°C / min or less, such as from 3 to 40°C / min, more preferably from 6 to 20°C / min, then the second holding time may be reduced (e.g. up to 30 minutes) or omitted, as the crystals may be capable of sufficient crystal growth at the lower heating rate. At a lower second heating rate, for example up to 40°C / min or less, or when the second holding time is not omitted, at least a portion of the crystals, particularly the fluorapatite crystals, may be capable of forming spherulites. It is preferred for the glass-ceramic to comprise spherulites because spherulites are also present in dental enamel, meaning that the glass-ceramic may closely mimic the structure of natural dental enamel.

[0195] It will also be appreciated that both steps b) and d) may be conducted and a relatively slow first and second heating rate, for example up to 40°C / min or less, such as from 3 to 40°C / min, more preferably from 6 to 20°C / min, may be used. An exemplary first and second heating rate in this embodiment is 10°C / min. The first and second holding times are preferably up to 30 minutes in this embodiment.P5523GB00-KN4KE

[0196] After steps a)-d) have been conducted, the glass-ceramic may be cooled. For example, the glass-ceramic may be cooled at a rate of at least l°C / min. For example, the glass-ceramic may be cooled at a rate of at least 5°C / min, at least 10°C / min, at least 15°C / min or at least 20°C / min.

[0197] The glass-ceramic may be cooled at a rate of up to 50°C / min. For example, the glassceramic may be cooled at a rate of up to 40°C / min, up to 30°C / min, up to 25°C / min or up to 20°C / min.

[0198] It will be appreciated that any of the lower limits and any of the upper limits of the cooling rates may be combined. For example, the glass-ceramic may be cooled at a rate of from 1 to 50°C / min, from 5 to 30°C / min or from 5 to 20°C / min.

[0199] The glass transition temperature (Tg) and the peak crystallisation temperature (Tp) may be determined by DSC. The DSC analysis may be carried out using a Stanton Redcroft DSC 1500 instrument (Rheometric Scientific, Epsom, UK). The sample may be placed in a crucible made of platinum-rhodium alloy. Testing cycles may be conducted at a heating rate of 10°C / min under a continuous flow of dry nitrogen, with reagent-grade alumina serving as a reference, from 25°C to 1200°C.

[0200] If the glass comprises more than one peak crystallisation temperature (Tp), then the highest peak crystallisation temperature (Tp) is used. Thus, the reference to the peak crystallisation temperature (Tp) is interchangeable with the term "the highest peak crystallisation temperature (Tp)".

[0201] It will be appreciated that the invention also relates to a glass-ceramic obtainable by the process of the fourth aspect.

[0202] Therapeutic applications

[0203] A fifth aspect of the invention relates to the glass of the first aspect or the glass-ceramics of the third aspect for use in therapy. The glass of the first aspect or the glass-ceramics of the third aspect may be for use in a patient in need thereof.

[0204] A sixth aspect of the invention relates to a method of treating a patient comprising applying the glass of the first aspect or the glass-ceramic of the third aspect to a patient in need thereof.

[0205] Preferably the patient is a human.

[0206] The glass of the first aspect or the glass-ceramic of the third aspect may be used in a variety of therapeutic applications, which are outlined below.

[0207] Dental applicationsP5523GB00-KN4KE

[0208] The glass of the first aspect or the glass-ceramic of the third aspect may be used in dental applications. In other words, they may be a dental glass or a dental-glass ceramic.

[0209] Thus, a seventh aspect of the invention relates to the glass of the first aspect or the glassceramic of the third aspect for use in dental applications, or as a dental glass or dental glass-ceramic.

[0210] The glass of the first aspect or the glass-ceramics of the third aspect may be used for various dental applications including promoting remineralisation of teeth, preventing caries, blocking dentinal tubules, treating dentine hypersensitivity and treating periodontal disease.

[0211] Thus, the invention also relates to the glass of the first aspect or the glass-ceramics of the third aspect for use in a method of preventing or treating a disorder in a tooth of a patient.

[0212] The invention also provides a method of preventing or treating a disorder in a tooth of a patient, the method comprising applying the glass of the first aspect or the glass-ceramic of the third aspect to said tooth or replacing at least a part of said tooth with the glass of the first aspect or the glass-ceramic of the third aspect.

[0213] Preferably the disorder is dentin hypersensitivity, tooth wear, or wherein the disorder is dental caries. It will be appreciated that the treatment of "tooth wear" encompasses the prevention, retardation or reduction of the wear of said tooth, or a second tooth opposing said tooth in said patient.

[0214] It will also be appreciated that said treating may involve restoring enamel and / or dentin parts of said tooth or said second tooth.

[0215] The glass of the first aspect or the glass-ceramic of the third aspect may be provided as a dental appliance or prosthesis, such as an inlay, onlay, crown, bridge, or veneer. It will also be appreciated that the glass of the first aspect or the glass-ceramic of the third aspect may be provided as at least a part of an artificial tooth.

[0216] It will be appreciated that when the glass of the first aspect or the glass-ceramic of the third aspect is used to replace or restore at least a part of a tooth, or when the glass of the first aspect or the glass-ceramic of the third aspect is provided as at least a part of an artificial tooth, the tooth may be a whole tooth or a part of a tooth.

[0217] Preferably the tooth is a human tooth. Preferably the patient is a human.

[0218] The glass-ceramics of the third aspect may be milled to form a dental restoration material. This is particularly advantageous because many existing dental ceramics are too hard to be milled once they are in the glass-ceramic form, meaning that they are typically cast in their desired shape in glass form prior to being transformed into a glass ceramic. The glass-P5523GB00-KN4KE

[0219] ceramics of the invention provide a benefit over the prior art materials in that they may be milled into any desired shape, even in the glass-ceramic form, providing increased flexibility and ease of use for dental professionals.

[0220] The term dental restoration material encompasses at least a part of an artificial tooth, as well as any dental appliance or prosthesis, such as an inlay, onlay, crown, bridge, or veneer.

[0221] It is also possible to adjust the translucency / opacity of the glass-ceramics of the invention. This is particularly desirable in the dental field because when the dental restoration material is to be provided in a thin layer, it may be desirable for the material to be translucent, whereas when the dental restoration material is to be provided as at least a part of an artificial tooth, it may be desirable for the material to be opaque. Thus, the tunability of the glass-ceramics of the invention allows them to be used flexibly in a variety of dental restoration materials.

[0222] In other words, the aesthetics of the glass-ceramics of the invention are flexible.

[0223] The dental glass or dental glass-ceramic of the seventh aspect may be for the application to, or replacement of at least a part of, a tooth.

[0224] The dental glass-ceramic of the seventh aspect may have physical properties which are similar to those of natural dental enamel. For example, the dental glass-ceramic of the seventh aspect may have a fracture toughness, a biaxial flexural strength (BFS) and / or a microhardness which is similar to natural dental enamel, e.g. of the natural dental enamel of the tooth to which the dental glass-ceramic is for application to, or replacement of at least a part of.

[0225] For example, the dental glass-ceramic may have a fracture toughness of at least 50% of enamel of said tooth, such as at least 70%, at least 80%, or at least 90% of said enamel.

[0226] The dental glass-ceramic may have a fracture toughness of up to 200% of enamel of said tooth, such as up to 150%, up to 120%, or up to 110% of said enamel.

[0227] It will be appreciated that any of the lower limits and any of the upper limits of the fracture toughness may be combined. For example, the glass-ceramic may have a fracture toughness of from 50% to 200%, from 70% to 150%, from 80% to 120% or from 90% to 110% of enamel of said tooth.

[0228] The fracture toughness may be measured in accordance with ASTM C 1421-99 (1999).

[0229] The dental glass-ceramic may have a biaxial flexural strength (BFS) of at least 50% of enamel of said tooth, such as at least 70%, at least 80%, or at least 90% of said enamel.P5523GB00-KN4KE

[0230] The dental glass-ceramic may have a biaxial flexural strength (BFS) of up to 200% of enamel of said tooth, such as up to 150%, up to 120%, or up to 110% of said enamel.

[0231] It will be appreciated that any of the lower limits and any of the upper limits of the biaxial flexural strength (BFS) may be combined. For example, the glass-ceramic may have a biaxial flexural strength (BFS) of from 50% to 200%, from 70% to 150%, from 80% to 120% or from 90% to 110% of enamel of said tooth.

[0232] The biaxial flexural strength (BFS) may be measured in accordance with ASTM F394-78 (1991).

[0233] The dental glass-ceramic may have a microhardness of at least 50% of enamel of said tooth, such as at least 70%, at least 80%, or at least 90% of said enamel.

[0234] The dental glass-ceramic may have a microhardness of up to 200% of enamel of said tooth, such as up to 150%, up to 120%, or up to 110% of said enamel.

[0235] It will be appreciated that any of the lower limits and any of the upper limits of the microhardness may be combined. For example, the glass-ceramic may have a microhardness of from 50% to 200%, from 70% to 150%, from 80% to 120% or from 90% to 110% of enamel of said tooth.

[0236] The microhardness may be measured in accordance with ASTM standard C1327-0816 (2008).

[0237] Cosmetic applications

[0238] An eighth aspect of the invention relates to a method of cosmetic treatment of a tooth of a patient, said cosmetic method comprising applying the glass of the first aspect or the glass ceramic of the third aspect to said tooth, or replacing at least a part of said tooth with the glass of the first aspect or the glass-ceramic of the third aspect.

[0239] Preferably, the cosmetic treatment is the prevention, retardation or reduction of tooth discoloration, or the restoration of at least a part of the physical shape of said tooth.

[0240] Preferably the tooth is a human tooth. Preferably the patient is a human.

[0241] The glass of the first aspect or the glass-ceramic of the third aspect may be provided as a dental appliance or prosthesis, such as an inlay, onlay, crown, bridge, or veneer. It will also be appreciated that the glass of the first aspect or the glass-ceramic of the third aspect may be provided as at least a part of an artificial tooth.

[0242] Orthopaedic applicationsP5523GB00-KN4KE

[0243] A ninth aspect of the invention relates to the glass of the first aspect or the glass-ceramics of the third aspect for use in orthopaedic applications or as a bone substitute or for bone regeneration.

[0244] Thus, the invention relates to a method for regenerating or replacing bone, said method comprising applying said the glass of the first aspect or the glass-ceramics of the third aspect to a bone in need of regeneration or replacement in a patient in need thereof.

[0245] The glass of the first aspect or the glass-ceramics of the third aspect may be used as an implant or prothesis.

[0246] The invention also relates to a method for stimulating osteoblasts in a patient in need thereof, said method comprising applying the glass of the first aspect or the glass-ceramics of the third aspect to a bone in said patient.

[0247] Preferably the patient is human. Preferably the bone is a human bone.

[0248] 3D Printing

[0249] A tenth aspect of the invention relates to the glass of the first aspect or the glass-ceramics of the third aspect for use in 3D printing applications.

[0250] In particular, the tenth aspect provides a 3D printing resin comprising the glass of the first aspect or the glass-ceramics of the third aspect.

[0251] The glass of the first aspect or the glass-ceramics of the third aspect may be present in an amount of at least about lwt% of the 3D printing resin, also referred to as the doped resin. For example, the glass of the first aspect or the glass-ceramics of the third aspect may be present in an amount of at least about 5wt%, at least about 10wt%, at least about 15wt%, at least about 20wt%, at least about 25wt% or at least about 30wt% of the 3D printing resin.

[0252] The glass of the first aspect or the glass-ceramics of the third aspect may be present in an amount of up to 90wt%, up to 80 wt%, up to 70 wt%, up to 60 mol%, up to 50 mol%, or up to 40 mol% of the 3D printing resin.

[0253] It will be appreciated that any of the lower limits and any of the upper limits of the amounts may be combined. For example, the glass of the first aspect or the glass-ceramics of the third aspect may be present in an amount of from about 1 to 90wt%, 5 to 80wt%, 15 to 70wt%, 15 to 60wt% or 20 to 50wt% of the 3D printing resin.

[0254] The tenth aspect also provides a method of 3D printing a product comprising the glass of the first aspect or the glass-ceramics of the third aspect, the method comprising the steps of:P5523GB00-KN4KE

[0255] The glass of the first aspect or the glass-ceramics of the third aspect may be provided as a powder in the 3D printing resin.

[0256] The powder may have an average particle diameter of at least about 0.5 nm, at least about 1 nm, at least about 2 nm, at least about 3 nm, at least about 4 nm, or at least about 5 nm.

[0257] The powder may have an average particle diameter of up to about 100 nm, up to about 80 nm, up to about 60 nm, up to about 40 nm, up to about 20 nm, or up to about 10 nm.

[0258] It will be appreciated that any of the lower limits and any of the upper limits of the average particle diameter may be combined. For example, the powder may have an average particle diameter in the range of from about 0.5 to lOOnm, in the range of about 1 to 80 nm, in the range of about 2 to 60 nm, in the range of about 3 to 40 nm, or in the range of about 4 to 20nm.

[0259] The average particle diameter may be measured using dynamic light scattering (DLS), such as according to ISO 13321.

[0260] Thus, the method may additionally comprise the step of grinding the glass of the first aspect or the glass-ceramics of the third aspect prior to being added to the resin.

[0261] The product may be a product for use in orthopaedic applications or as a bone substitute or for bone regeneration according to the ninth aspect or a product for use in dental applications, or as a dental glass or dental glass-ceramic according to the seventh aspect. EXAMPLES

[0262] Materials

[0263] High-purity raw materials (SiO2, AI2O3, P2O5, CaO, and CaF2) with a purity greater than 99%, (Sigma-Aldrich, England), were utilized. These components were accurately weighed using a precision electronic balance (±0.0002g) (XS105 Dual Range, Mettler Toledo, Switzerland).

[0264] Analysis Methods

[0265] Differential Scanning Calorimetry (DSC) was carried out using a Stanton Redcroft DSC 1500 instrument (Rheometric Scientific, Epsom, UK). The relevant sample was placed in a crucible made of platinum-rhodium alloy. All testing cycles were conducted at a heating rate of 10°C / min under a continuous flow of dry nitrogen, and reagent-grade alumina served as a reference, from 25°C to 1200°C.

[0266] Scanning Electron Microscopy (SEM) was carried out using a JEOL Prime (Japan) instrument. The sample was embedded in acrylic and then polished using the Struers laboforce-1000; Struers A / S, Dentmarek under continued water cooling. First, the surface and base of acrylics discs were polished with a P1200 grit silicon carbide foil for 90 seconds, ensuring any areas with acrylic unintentionally covering the surface of the glass ceramicP5523GB00-KN4KE

[0267] were removed. This was followed by P2000 grit foil for two minutes and P4000 grit foil for 5 minutes. The settings were 15N, 1000RPM for the main plate and 50 RMP for the holder. The polished samples excess acrylic was cut using the diamond watering blade on a low speed cutting saw (IsoMet 1000 Precision Saw, Buelhler Ltd., USA). The sample was etched for 20 seconds with Pulpdent Porcelain Etch Gel, 9.6% hydrofluoric acid etch, rinsed and then placed in an ultrasonic bath for 5 minutes in distilled water to remove any smear layer. It was mounted and then sputter-coated in a Leica ACE600 Coater to improve the conductivity prior to observation.

[0268] Xray Diffraction (XRD) measurements were collected on a CubiX3 X-ray powder diffractometer (Malver PANalytical, UK) and copper target operating in subtractive transmission mode at 45kV and 40mA. X-rays were pure monochromatic Cu Koi with A = 1.540598A. PDF card 00-015-0776 was used to identify mullite and 00-015-0876 for fluorapatite. The 2-theta scan measurements were carried out in standard reflection mode, using Cu K alpha radiation, with sample holders spinning on the stage during the scan. The samples were prepared onto the sample holders using the standard powder sample preparation technique. This involved using a mortar and pestle to grind up the powder with some ethanol to create a slurry. The slurry was then dropped onto the holder using a pipette and the ethanol left to evaporate, leaving a powder layer for scanning.

[0269] Production of glasses

[0270] 4 glasses were produced. In the first step, reagents were combined in specific ratios following the formula 4.5(SiO2)-3(Al2O3)-2.4(P2O5)-(4.5-y)CaO-yCaF2, with variations in y as shown in Table 1 below. In each of the glasses, the Ca:P ratio is 1:0.94.

[0271] Table 1: Composition of raw materials

[0272]

[0273] P5523GB00-KN4KE

[0274] Each mixture (Examples 1-4) was placed in a platinum crucible and then heated in an electric furnace (1700°C BLF, Carbolite Gero, UK) starting from room temperature (c.

[0275] 25°C), with a heating rate of 10°C / min, until it reached the melting temperature of 1450°C in air, where it was held for 60 minutes. Each molten glass was then poured into a graphite mould preheated to 500°C, and annealed at 500°C for 2 hours before being allowed to cool to room temperature overnight in the furnace.

[0276] Characterisation of the glasses

[0277] The characterization of the produced powdered glass samples as well as as-casted samples (approximately 50mg each) was carried out using DSC. The obtained results allowed for the identification of the glass transition temperature (Tg) and crystallization peak temperatures (Tp). The Tgwas determined by drawing two tangent lines at the first step of the curve, with the intersection of these lines indicating the Tg. The Tpwas identified as the peak point on the curve.

[0278] The Tgand Tpof the Examples were determined to be:

[0279] Example 1: Tg= 629°C and Tp= 860°C

[0280] - Example 2: Tg= 675°C and Tp= 971°C

[0281] Example 3: Tg= 675°C and Tp= 957°C

[0282] - Example 4: Tg= 681°C and Tp= 992°C

[0283] XRD analysis of Example 1 reveals an amorphous structure, with no crystalline phase detected and a broad amorphous peak observed in the approximate range of 17-36° (20).

[0284] Production of glass ceramic

[0285] A two-step heat treatment process was applied to the glass using the Programat Furnace (Programat furnace P510, Ivoclar Vivadent, Liechtenstein).

[0286] The glass was placed in a graphite mould and then placed in a furnace which was preheated to 500°C. The glass was then heated at a first heating rate to a first temperature and then held at this first temperature for a first holding time, after which the glass was heated at a second heating rate to a second temperature and then held at this second temperature for a second holding time. This process transformed the glass into a glass-ceramic.

[0287] Effect of fluoride contentP5523GB00-KN4KE

[0288] Glass ceramics were produced using the above two-step heat treatment process, using the glasses produced in Examples 1-4. The resulting glass-ceramics are referred to as 1A, 2A, 3 A and 4A.

[0289] For all Examples 1A, 2A, 3A and 4A, the first heating rate was 10 °C / min and the second heating rate was 10 °C / min, and the first holding time was 30 minutes and the second holding time was 30 minutes.

[0290] The first and second temperatures used were as follows:

[0291] Example 1A: 1sttemp. = 629°C, 2ndtemp. = 860°C

[0292] Example 2A: 1sttemp. = 675°C, 2ndtemp. = 971°C

[0293] Example 3A: 1sttemp. = 675°C, 2ndtemp. = 957°C

[0294] Example 4A: 1sttemp. = 681°C, 2ndtemp. = 992°C

[0295] The bulk of Example 1A was analysed using SEM at various scales, namely 10pm, 5pm, 1pm and lOOnm. The bulk of human dental enamel was also analysed using SEM at the same scales and compared to Example 1A. The results are shown in Figure 1.

[0296] Figure 1 shows that the glass-ceramic material of Example 1A closely resembles human dental enamel across various length scales, making it structurally unique with hundreds of nanocrystals hierarchically organized in a branching architecture, displaying an intricate, prismatic configuration that extends outward in a structured spherulitic manner.

[0297] Example 1A was also analysed using XRD which confirmed that crystallisation occurred during the heat treatment. The results are shown in Figure 2a which clearly indicates that the observed peaks correspond to fluorapatite crystals, along with some peaks indicating the presence of aluminium phosphate crystals in a cristobalite form.

[0298] The type of the crystals was further confirmed by solid-state MAS-NMR using19F,27AI and31P probes, the results of which are shown in Figures 2b-d. Fluorapatite (FAp) formation was proven by a sharp peak at -103ppm in the19F spectrum, which is characteristic of fluorapatite, as well as the peak at 3ppm in the31P spectrum. The presence of aluminium phosphate (AIPO4) was confirmed by a definite peak at 40ppm in the27AI spectrum, and a broad peak in the range of -25 to -32ppm in the31P spectrum.

[0299] SEM was used to analyse the structure of Example 1A both at the surface and in the bulk of the material. The results of this analysis are shown in Figure 3.

[0300] Figure 3 shows a dense crystalline structure containing large numbers of branches, well-organized elongated nanocrystals at both the surface (Figure 3a-c) and within the bulkP5523GB00-KN4KE

[0301] (Figure 3d-f), with minimal or nearly no glassy phase. The condensed nanocrystals were seen to assemble in highly ordered spherulitic structures at the microscale (3.3±0.5pm in the surface and 4.3±0.6pm in the bulk). The bulk of the material exhibited a higher density of smaller nanocrystals and larger spherulitic structures compared to its surface. These spherulites were then grouped to populate the whole surface and occupy the bulk of the glass as well.

[0302] Next, SEM was used to compare the glass-ceramics of Examples 1A, 2A, 3A and 4A both at the surface and in the bulk of the material at a scale of 5pm. The images of the bulk material are shown in Figure 4. Similar observations were seen for the surface images.

[0303] It was observed from Figure 4 that increasing fluoride content resulted in a denser and more organized crystalline phase with a reduced glassy phase.

[0304] Examples 1A, 2A, 3A and 4A were analysed to determine the composition of the glassceramics. In all Examples, three main components were consistently present: fluorapatite, aluminium phosphate, and silicon dioxide. However, the percentages of these components differed between the four variants as seen in the pie charts of Figure 5 (FAF3 = Example 1A, FAF6 = Example 2A, FAF12 = Example 3A, FAF24 = Example 4A). The variant with the highest fluoride content displayed the greatest concentration of fluorapatite, indicating a strong correlation between fluoride levels and fluorapatite formation during the crystallization process.

[0305] Effect of heating rate, hold temperature and hold stages

[0306] Glass ceramics were produced by varying the two-step heat treatment process to determine the effects of these steps on the resulting glass-ceramic. The glass of Example 1 was subjected to the following conditions:

[0307] Table 2: Conditions used to prepare the glass-ceramic materials

[0308]

[0309] P5523GB00-KN4KE

[0310]

[0311] In order to compare the effect of the holding time on the glass-ceramic, SEM images of both the bulk and surface were taken at a scale of 5 pm to compare Examples IB, 1A and IF (no hold, 30 min hold, and 60 min hold). The images of the bulk material are shown in Figure 6.

[0312] Figure 6 shows that longer holding times facilitated enhanced compaction of the crystals within the glass ceramic. Similar results were seen for the surface images.

[0313] To compare the effect of the heating rate on the glass ceramic, SEM images of both the bulk and surface were taken at a scale of 5 pm to compare Examples 1C, IF and 1G (10°C / min, 60°C / min, and 120°C / min). The images of the bulk materials are shown in Figure 7.

[0314] Figure 7 shows that the heating rate significantly influenced crystallization, with slower rates resulting in denser crystal formations. Similar results were seen for the surface images.

[0315] To assess whether the same trends were seen when the fluoride content was varied, additional experiments were conducted to vary the heat treatment process using different glasses, namely the glasses produced above in Examples 2, 3 and 4. These experiments are set out in Table 3 below:

[0316] Table 3: Conditions used to prepare the glass-ceramic materials

[0317]

[0318] P5523GB00-KN4KE

[0319]

[0320] The effect on fluorine content, heating rate, holding time, and holding temperature on both bulk and surface crystallization, as well as spherulitic growth was analysed. The results are shown in Table 4 below.

[0321] Table 4: effect on fluorine content, heating rate, holding time, and holding temperature on both bulk and surface crystallization, as well as spherulitic growth.

[0322] ""

[0323] ""

[0324]

[0325] P5523GB00-KN4KE

[0326] ""

[0327] ""

[0328] ""

[0329]

[0330] Surface crystallization

[0331]

[0332] Bulk crystallization Spherulitic growth

[0333]

[0334] HR = heating rate

[0335] EG = Example

[0336] The glass-ceramic produced from glass 1 exhibited the most pronounced crystallization behaviour and spherulitic growth across all variable conditions. Additionally, holding at the 1stand 2ndtemperatures for 30 minutes each, with a heating rate of 10°C / min, resulted in optimal crystallization response and spherulitic growth across all groups.

[0337] Variation of opacity

[0338] Glass ceramics were produced by varying the two-step heat treatment process to determine the effects of these steps on the opacity of the resulting glass-ceramic. Four separate tests were conducted. In the tests, the glass of Example 1 was used, the first heating rate was 10°C / min, the first temperature was 629°C, the first holding time was 30 minutes, the second heating rate was 10°C / min, the second holding time was 30 minutes, and the second temperature was 779°C, 795°C, 808°C or 860°C.

[0339] To analyse the results of these tests, photographs were taken (2mm scale) and SEM analysis of the bulk and surface was conducted at 5pm for each sample. The images of the bulk materials are shown in Figure 8. Similar trends were observed for the surface images. In addition, the samples were analysed to determine the proportion of crystalline phase and the glassy phase. These results are also shown in Figure 8.

[0340] The results demonstrate that wen the second temperature is below that of the crystallization peak temperatures (Tp), the material has lower opacity and higher translucency. Bringing the second temperature closer to the Tpled to an increased formation of the crystalline phase and a reduction of the glassy phase. This change resulted in an increase in opacity.

[0341] Mechanical PropertiesP5523GB00-KN4KE

[0342] To demonstrate the excellent mechanical properties of the glass-ceramics, tests were conducted to compare the subject glass-ceramics to human dental enamel, as well as a number of widely-used glass-ceramics.

[0343] Materials

[0344] The following materials were tested for their mechanical properties:

[0345] - Example 1A ("F")

[0346] Human dental enamel ("E")

[0347] E.max CAD, the most widely used glass-ceramic ("EC")

[0348] - Vita Mark II, representing a feldspathic ceramic system ("V")

[0349] E.max Ceram, a commercially available fluorapatite system in powder / liquid form used for veneering ("ECM"), and

[0350] E.max Zirpress, a commercially available glass-ceramic system in a pressed form ("ZP").

[0351] E.max CAD, Vita Mark II, E.max Ceram and E.max Zirpress were all purchased from Henry Schein (UK).

[0352] Methods

[0353] Vicker's microhardness (HV) testing was carried out in accordance with the ASTM standard C1327-0816 (2008). A DuraScan 20 G5 micro indenter (Struers Ltd, UK) equipped with an optical microscope was utilized to measure the HV of the samples, 30 indents were made for each sample of the test and control groups by applying a load of HV1 for 15 seconds. Prior to testing, the specimen surfaces were meticulously polished with 1000, 1200, 2000, and 4000-grit silicon carbide discs to achieve a mirror-like finish. These indents were then observed under a digital microscope (Keyence Microscope, UK), and two diagonals of each indentation were measured and averaged. The calculated value was then used to determine the hardness number, which represents the average force per actual unit area of the indenter surface in contact with the test surface as set out in equation 1 as per ISO 4049:2019 (2019):

[0354] Hv = (1.854) x (P / D2) equation 1

[0355] where Hv represents the Vicker's hardness number in Kg / mm2, P is the applied load in Kg, and D is the average diagonal length in mm. Subsequently, the hardness values were converted to GPa using Hv (GPa) = 9.811 (1000 x Hv)2.P5523GB00-KN4KE

[0356] Fracture toughness was measured using the indentation method following the Vicker's hardness indention. This technique aims to create a crack in the diagonals of the indented surface. The length of the cracks of the single indent were measured from the center of the indent and the mean crack lengths (total 60 cracks per group) were calculated. The indented surface was observed under digital microscope (Keyence Microscope, UK) to measure the crack length. The indentation fracture toughness, KIc, was determined according to ASTM C 1421-99 (1999) using the equation 2:

[0357] KIc = q / h (P / Co15) equation 2

[0358] where i b = 1 / (nl.5*tamp) with ip being the half angle of the Vickers indenter (68°), resulting in ipb = 0.072558; P represents the indentation load in MN, and Codenotes the crack length in meters.

[0359] Biaxial Flexural Strength (BFS) was determined using a piston on three-ball geometry as set out in ASTM F394-78 (1991). The method involves placing the test specimen on a support circle with a diameter of 10mm, supported by three hardened steel balls positioned 120° apart. The load is applied at the center of the specimen using a flat punch with a diameter of 1.2mm to 1.6mm. 20 samples per group having a thickness of 1.2±0.2mm and a diameter of 12±2mm were prepared and the same finishing and polishing protocol were conducted.

[0360] Biaxial cyclic fatigue strength was evaluated using the staircase method, involving 105cycles at 10 Hz. Testing was conducted with a piston-on-three-balls setup in water, using Bose machine following ISO 6872, 2008 (2008). The staircase method, originally outlined by Collins (Collins, J. Staircase or up-and-down methods: failure of materials in mechanical design, John Wiley & Sons, Inc, 1993) has been widely adopted. In this approach, the number of cycles was predetermined at 105cycles. The first specimen was tested at a stress level lower than the maximum stress identified in a corresponding static test (60% of the mean monotonic load-to-failure test, conducted with the same setup as the fatigue test, in MPa). This specimen was subjected to the predetermined cycles until it either failed or survived. If it passed, the step size increment was added to the applied load, and testing proceeded to the next sample. In the event of failure, the step size increment was reduced, and testing continued accordingly for all 20 samples per group. The staircase method generates a stepped graph reflecting the success or failure of each specimen.

[0361] For the wear testing process, each sample was secured in a dental wear simulator (Electroforce® Series II 3330, TA Instruments, USA) and exposed to 105 testing cycles. Tests were performed under continuous irrigation with deionized water at a temperature of 37°C. A vertical load of 80N was applied, accompanied by a horizontal sliding movement ofP5523GB00-KN4KE

[0362] 0.7mm, a vertical displacement of 1mm, a vertical speed of 40 mm / s, a lateral speed of 0.7 mm / s, and a frequency of 0.8 Hz. After the wear simulation, the sample was analyzed using a red-light confocal laser profilometer (Taicaan, XYRIS 2000, UK) with a 2pm spot size, lOnm vertical resolution, and 10pm grid spacing. The maximum 3D step height in pm was determined using surface metrology software (Mountains9, DigitalSurf, France).

[0363] Results

[0364] The microhardness and fracture toughness of each of the materials was tested according to the above methods. The results of these tests are shown in Figure 9.

[0365] Fracture toughness can be defined as a material's ability to absorb energy from elastic deformation in relation to the level of tensile stress that can be achieved near the crack tip before the initiation of catastrophic fracture. More simply, it is the ease of crack propagation from an initiating flaw. Dental glass-ceramics tend to be brittle and susceptible to catastrophic failure in service due to crack propagation from existing defects, which may be introduced during their fabrication process. Fracture is the most frequently reported cause of failure for dental all ceramic crowns and occurs at a higher rate in posterior teeth versus anterior teeth.

[0366] A comparison with the control groups revealed that the microhardness and fracture toughness of the glass-ceramic of the invention are the closest to human dental enamel compared to the other control groups with Example 1A recording 4.3Mpa and 1.3MN / m3 / 2for hardness and fracture toughness respectively while enamel recorded 2.6Mpa for hardness and 1.2 MN / m3 / 2for fracture toughness values.

[0367] The BFS of Example 1A, E.max CAD, Vita Mark II and E.max Ceram was also tested and compared.

[0368] Although Example 1A had a lower BFS than that of E.max CAD (186.1±46.1MPa and 466.8±71.1MPa respectively), Example 1A closely approximates the BFS of the enameldentine complex reported in the literature (141.27±29.94 MPa, Ghavamnasiri, M. et al., J. Contemp. Dent. Pract. (2007), 8, 1-6). This alignment with the enamel-dentine complex is the primary objective of this glass-ceramic system, aiming to closely resemble dental enamel.

[0369] For biaxial cyclic fatigue strength, the staircase fatigue method was used using the BFS results. Example 1A demonstrated superior performance compared to the other comparative examples (E.max CAD, Vita Mark II and E.max Ceram).P5523GB00-KN4KE

[0370] For the wear testing, Example 1A (F), E.max CAD (EC), Vita Mark II (V) and E.max Ceram (ECM) were tested according to the above method to determine the step height in pm. The results are shown in Figure 10.

[0371] Figure 10 demonstrates that Example 1A (F) showed the lowest level of wear, shown by the lowest step height, among all of the samples tested.

[0372] Addition of TiO?

[0373] Experiments were conducted to analyse the impact of additional components on the glassceramics of the invention.

[0374] A mixture (Example 5) was prepared which contained 90 mol% of the blend of starting materials of Example 1, and 10 mol% of TiO2. Thus, the ratio of Ca:P and Ca:F for Example 5 are the same as for Example 1.

[0375] A further mixture (Example 6) was prepared which contained 92.5 mol% of the blend of starting materials of Example 1, and 7.5 mol% of TiO2. Thus, the ratio of Ca:P and Ca:F for Example 6 are the same as for Example 1.

[0376] Examples 5 and 6 were then separately placed in a platinum crucible and heated in an electric furnace (1700°C BLF, Carbolite Gero, UK) starting from room temperature (c.

[0377] 25°C), with a heating rate of 10°C / min, until they reached the melting temperature of 1450°C in air, where they were held for 60 minutes. The molten glasses were then poured into a graphite mould preheated to 500°C, and annealed at 500°C for 2 hours before being allowed to cool to room temperature overnight in the furnace.

[0378] The Tgof the glass of Example 5 was determined to be 671°C. The glass of Example 5 had three peak crystallisation temperatures (Tp), Tpl, Tp2 and Tp3. Tpl was 825°C, Tp2 was 882°C and Tp3 was 1102°C.

[0379] The glasses of Examples 5 and 6 were then transformed into glass-ceramics in which the first and second heating rates were 10 °C / min, the first and second holding times were 30 minutes, the first temperature was 671°C and the second temperature was 1102°C. The resulting glass-ceramics (Example 5A and 6A) were then analysed.

[0380] The microhardness of Examples 5A and 6A were measured and compared to Example 1A. using the same method as Example 1A. The microhardness of Example 5A was measured as being 5.204 GPa ± 0.325, and the microhardness of Example 6A was measured as being 4.8 GPa ± 0.5.

[0381] The BFS of Example 5A was also analysed and compared to Example 1. Example 5A showed an increase of 30% of its BFS compared to Example 1A, and Example 6A showed an increase of 29% of its BFS compared to Example 1A.P5523GB00-KN4KE

[0382] Finally, the fracture toughness of Example 5A was measured and compared to Example 1A. Example 5A showed an increase of 37% of its fracture toughness compared to Example 1A.

[0383] Titanium oxide successfully acted as a nucleating agent in Examples 5A and 6A, and appeared to increase the crystalline microstructure compared to glass-ceramic of Example 1A when viewed under SEM.

[0384] In natural enamel, cracks tend to propagate between and parallel to the prisms resulting in cracks extending towards the centre of the tooth which can put pulp vitality at risk.

[0385] However, there are a number of mechanisms in the microstructure of enamel which reduce the damage potential of a crack. Travelling along the prisms prevents chipping as cracks do not tend to travel back towards the tooths surface. Furthermore, the enamel prisms start to cross over (decussate) which reduces the crack potential and causes cracks to bifurcate, ultimately promoting crack retardation and arrest.

[0386] In the glass-ceramic of Example 5A, long, elongated crystals present in a disorderly arrangement which, while not wishing to be bound by theory, may prevent crack propagation in a similar manner to natural dental enamel.

[0387] SEM analysis confirmed the formation of a new phase microstructure in the glass-ceramics of Examples 5A and 6A, corresponding to TiO2-based phases. These bead-like crystals were more prominent in the bulk than on the surface. This microstructural variation indicates that TiO2not only acts as a nucleating agent but also enhances the complexity and density of the crystalline network, which influences the overall mechanical response. Overall, the inclusion of TiO2resulted in reasonable improvements in hardness and flexural strength, accompanied by clear microstructural changes.

[0388] Preparation of crowns and veneers

[0389] Single crowns and veneers were milled from the glass-ceramic of Example 1A. A suitable crown and a suitable veneer were produced, with no issues.

[0390] These tests prove the machinability of the glass-ceramics of the invention, and that they can be milled in the fully crystalline form without damaging milling burs.

[0391] Powder / Liguid (P / L) formulation

[0392] The powder-liquid (P / L) technique is a traditional, manual method widely used to produce natural looking dental restorations. In this approach, a dental technician mixes ceramic powder with a liquid binder to create a paste called slurry. This slurry is carefully layered by hand onto a ceramic core, often made of materials like zirconia, lithium disilicate, or leucite-reinforced ceramics. Each layer is shaped and smoothed to build up the dental restoration's final form, allowing precise control over thickness and contour. Once the layering is complete, the restoration is allowed to dry and for the excess binder to evaporate then firedP5523GB00-KN4KE

[0393] in a ceramic oven. This sintering process fuses the particles into a dense, durable structure. The P / L technique is commonly used for crowns, bridges, and especially veneers, as it can mimic the natural tooth's colour and translucency. By layering different ceramic shades, technicians can achieve a seamless blend with adjacent teeth.

[0394] Despite being time-consuming, the P / L technique is still valued for its natural-looking, durable, and minimally invasive results making it a go-to choice in many high-end dental restorations. Therefore, a P / L version of the glass-ceramic materials of the invention was produced to demonstrate its' wide applicability in dentistry.

[0395] Sample preparation

[0396] The glass-ceramic of Example 1A was ground using a Pulverisette 2 mortar grinder (Fritsch, Germany) and then passed through a stainless-steel test sieve with a woven wire mesh (200 mm diameter, 45 pm aperture, Fisherbrand, UK). The sieved powder was weighed to 1.25 g using an electronic balance (± 0.0002 g). The powder was then mixed with IPS Build-Up Liquid binder (Ivoclar Vivadent, Liechtenstein) at a ratio of 1.25 g powder to 0.5 ml liquid, forming a slurry. The prepared slurry was then compacted at room temperature into a 15 mm pellet using a cylindrical rod mould (Pellet Press Die Set, UK). A hydraulic pressure machine (Reco-Hydromatic Dental Press, Reco Dental, Germany) was used to apply 1000 Kp (10 Bar) of pressure for one minute to form a compacted pellet. The compacted pellet was sintered using a Programat P510 furnace (Ivoclar Vivadent, Liechtenstein), employing a sintering temperature of 1200 °C, a HR of 60 °C / min, and a holding time of 10 mins.

[0397] Vacuum was applied during the heating phase, from 403 °C to 1199 °C.

[0398] Results and conclusion

[0399] The P / L product demonstrated a hardness of 4.3 ± 0.5 GPa, which was not significantly different from the CAD / CAM version 4.3 ± 0.2 GPa. These results indicate that, regardless of manufacturing technique, the glass-ceramics of the invention offer a more balanced mechanical profile, potentially reducing the risk of abrasion to opposing structures while having hardness values close to the human dental enamel.

[0400] 3D Printed Resins

[0401] 3D-printing has rapidly transformed dentistry by enabling the precise, efficient, and customisable fabrication of dental devices and restorations. Unlike traditional manufacturing methods, 3D-printing allows for the direct creation of complex dental models, crowns, bridges, surgical guides, orthodontic appliances, and even maxillofacial prostheses from digital scans, significantly reducing production time and cost while improving accuracy and patient outcomes.P5523GB00-KN4KE

[0402] Advances in digital imaging, including intraoral scanning and cone beam computed tomography, have further integrated 3D printing into clinical workflows, making chairside production increasingly feasible.

[0403] Incorporating glass-ceramic fillers into 3D-printed dental resins has emerged as a promising strategy to enhance the mechanical properties of dental restorations. Overall, the integration of glass ceramic fillers into 3D-printed dental resins holds significant potential for producing durable, biocompatible, and highly customizable dental restorations and scaffolds.

[0404] Methods

[0405] 1. Powder preparation

[0406] To prepare the glass-ceramic powder fillers for resin integration, a multi-stage micronisation process was carried out on the glass ceramic of Example 1A using a spiral jet mill (SSM44, Scheido, Switzerland) equipped with a 44 mm diameter milling chamber. The process was conducted using nitrogen as the milling gas and pharmaceutical-grade white PTFE internals (venturi, milling ring, upper plate) to minimise contamination and preserve material purity. The lower plate was made of stainless steel 316L.

[0407] The initial milling pass was performed at a feed rate of 300 g / h and a grinding pressure of 8 bar. The resulting powder was then re-processed in subsequent passes, including a second pass at an increased pressure of 10 bar, to further reduce particle size. Notably, the material volume expanded approximately threefold following micronisation.

[0408] To achieve a target D99 value of below 1 pm, repeated milling (five passes) of the glassceramic of Example 1A (=FAF3) was carried out. Particle size distribution was analysed using a LS 13 320 XR particle size analyser system (wet module, Beckman Coulter. USA), confirming progressive refinement of the powder with each pass.

[0409] 2. Resin composite preparation

[0410] To ensure uniform dispersion of the glass-ceramic fillers within the resin matrix, a multi-step mixing protocol was employed. The process began with manual mixing using a spatula for 10 mins to initiate the blending of the glass-ceramic powder with the resin and break up visible clumps. This was followed by mechanical stirring using a magnetic stirrer set at 35 °C for 30 mins. Finally, the mixture was subjected to ultrasonic bath sonication combined with high-speed mixing for 20 mins.

[0411] 3. Testing methodsP5523GB00-KN4KE

[0412] For hardness, BFS and fatigue testing, disc-shaped samples with a diameter of 10 mm and a thickness of 1 mm were prepared, following ASTM F394-78 and EN ISO 6872. For the three-point bending test, rectangular bars measuring 25 mm in length, 2 mm in width, and 2 mm in height were fabricated to evaluate flexural strength and modulus according to ISO 4049.

[0413] 4. Manufacturing and printing process

[0414] Manufacturing of the test specimens was performed using a SprintRay Pro S55 DLP 3D printer (SprintRay, Los Angeles, CA, USA / Weiterstadt, Germany). Post-printing, all specimens underwent a standardised cleaning and curing protocol. Initially, they were washed in isopropyl alcohol, IPA (Propan-2-ol, >99.8%, ThermoFisher Scientific, Loughborough, UK) for 11 mins using the wash / dry device (ProWash S, Weiterstadt, Germany), followed by a second rinse in 91% IPA to ensure the removal of residual resin. The samples were then post-cured under ultraviolet light (405 nm) at 60 °C for 3 mins using the post cure unit (ProCure 2, Weiterstadt, Germany).

[0415] Three resin groups were tested; each printed with a 50 pm layer thickness and consistent support configurations and orientations to standardise the manufacturing conditions. The first group employed SprintRay Temporary Crown resin (SR 0%). The second group used SprintRay Crown resin (SR Crown), with optimised support structures to enhance marginal adaptation and accuracy. The third group which is the test group was SprintRay Temporary Crown resin with 35wt% FAF3 powder (SR 35% FAF3) printed with SprintRay Model Gray (BR) resin program, as it was slightly darker in colour.

[0416] Results

[0417] The microhardness of SR 35% FAF3, SR 0%, and SR Crown were tested, using the same method as Example 1A.

[0418] The SR 0% group exhibited the highest mean hardness value at 27.1 ± 0.6 MPa, followed closely by the SR Crown group with a slightly reduced value of 25.5 ± 1.3 MPa. In contrast, the SR Crown resin modified with 35% FAF3 showed a significantly lower mean hardness of 15.3 ± 4.1 MPa. These findings suggest that FAF3 modification introduces novel functionalities of being less abrasive to the opposing natural human enamel.

[0419] Due to the inherently resilient nature of the resin matrix, indentation fracture toughness could not be measured reliably. The material's elasticity and ability to absorb stress prevented the formation and propagation of cracks around the indentations, which are essential for calculating fracture toughness using indentation-based methods. As a result, no measurable crack lengths developed.P5523GB00-KN4KE

[0420] Three-point bending test and the corresponding flexural modulus for three groups were tested. In the three-point bending test, all groups showed similar performance in terms of flexural strength, with SR 35% FAF3 recording a mean value of at 80.3 ± 8.9 MPa, SR 0% at 76.7 ± 11.4 MPa, and SR Crown at 76.9 ± 6.7 MPa. The differences between the groups were minimal and statistically insignificant, indicating that the incorporation of FAF3 filler at 35 wt% did not adversely affect the overall flexural strength of the printed composite. In contrast, the flexural modulus results demonstrated a marked difference among the groups. SR 0% and SR Crown exhibited comparable modulus values of 2458.9 ± 291.6 MPa and 2239.3 ± 242.2 MPa, respectively, while the SR 35% FAF3 showed a substantial increase, reaching a mean value of 3753.6 ± 500.8 MPa. This significant enhancement in stiffness suggests that the addition of the glass-ceramic filler contributed to a more rigid structure, improving the material's resistance to elastic deformation under load. Collectively, these findings indicate that while the filler had minimal effect on bending strength, it significantly reinforced the structural stiffness of the composite.

[0421] BFS values for three groups were tested using the same method as Example 1A. The SR 0% group exhibited the lowest mean BFS value at 202 ± 22.6 MPa, whereas the SR Crown and SR 35% FAF3 groups showed higher mean values of 249.5 ± 40.7 MPa and 259.1 ± 55.7 MPa, respectively. These results indicate that both the SR Crown resin formulation and the incorporation of FAF3 enhance resistance to biaxial loading, potentially through improved internal structure and filler reinforcement.

[0422] Conclusion

[0423] Incorporating powders of the inventive glass-ceramics into 3D-printed resins reflected the rapid rise of additive manufacturing in dentistry. The findings demonstrated that incorporating 35 wt% FAF3 reduced surface hardness of the resin compared with controls, as well as significant improvements in stiffness, evidenced by the marked increase in flexural modulus. This stiffer structure provided greater resistance to elastic deformation without compromising flexural strength, which remained statistically comparable across groups.

[0424] NUMBERED EMBODIMENTS

[0425] 1. A glass-ceramic comprising a combination of fluorapatite, aluminium phosphate and silicone dioxide.

[0426] 2. The glass-ceramic of embodiment 1, comprising at least 85 mol% of said combination, preferably 90 mol% of said combination, more preferably at least 95 mol% of said combination, more preferably at least 98 mol% of said combination.P5523GB00-KN4KE

[0427] 3. The glass-ceramic of embodiment 1, consisting essentially of or consisting of said combination of fluorapatite, aluminium phosphate and silicone dioxide.

[0428] 4. The glass-ceramic of any preceding embodiment, comprising from 3 to 98 mol% fluorapatite, preferably from 10 to 90 mol% fluorapatite, preferably from 20 to 80 mol% fluorapatite.

[0429] 5. The glass-ceramic of any preceding embodiment, comprising from 1 to 70mol% silicone dioxide, preferably from 3 to 50mol% silicone dioxide.

[0430] 6. The glass-ceramic of any preceding embodiment, comprising from 0.1 to 60 mol% aluminium phosphate, preferably from 0.5 to 50 mol% aluminium phosphate.

[0431] 7. The glass-ceramic of any preceding embodiment, comprising less than 1 mol% mullite.

[0432] 8. The glass-ceramic of any preceding embodiment, wherein the molar ratio of Ca:P of the glass is from about 0.5:1 to 3.3:1.

[0433] 9. The glass-ceramic of any preceding embodiment, wherein the molar ratio of Ca : F of the glass-ceramic is from about 48:1 to 0.75:1.

[0434] 10. A glass comprising SiO2, AI2O3, P2O5, CaO and CaF2, wherein the molar ratio of Ca:F of the glass is from about 48:1 to 0.75:1, and wherein the molar ratio of Ca:P of the glass is from about 0.5:1 to 3.3:1, with the proviso that when the glass comprises at least 98 mol% of said SiO2, AI2O3, P2O5, CaO and CaF2, the molar ratio of Ca:P of the glass is from about 0.5:1 to 1.5:1.

[0435] 11. The glass of embodiment 10, comprising at least about 75mol% of SiO2, AI2O3, P2O5, CaO and CaF, preferably comprising at least about 80 mol% of SiO2, AI2O3, P2O5, CaO and CaF2, preferably comprising at least about 85 mol% of SiO2, AI2O3, P2O5, CaO and CaF2, preferably comprising at least about 90 mol% of SiO2, AI2O3, P2O5, CaO and CaF2, more preferably at least about 95 mol% of SiO2, AI2O3, P2O5, CaO and CaF2, more preferably at least about 98 mol% of SiO2, AI2O3, P2O5, CaO and CaF2.

[0436] 12. The glass of embodiment 10, consisting essentially of or consisting of SiO2, AI2O3, P2O5, CaO and CaF2.

[0437] 13. The glass of embodiments 10-12, wherein the AI2O3is present in an amount of from about 5 to about 50 mol%, preferably from about 10 to 30 mol% of the glass.

[0438] 14. The glass of embodiments 10-13, wherein the SiO2is present in an amount of from about 5 to 50 mol%, preferably from about 20 to about 45 mol% of the glass.P5523GB00-KN4KE

[0439] 15. The glass of embodiments 10-14, wherein the P2O5is present in an amount of from about 5 to 50 mol%, preferably from about 10 to about 25 mol% of the glass.

[0440] 16. The glass of embodiments 10-15, wherein the CaO is present in an amount of from 2 to 60mol%, preferably 5 to 40mol% of the glass.

[0441] 17. The glass of embodiments 10-16, wherein the CaF2is present in an amount of from 0.5 to 60mol%, preferably from 1 to 40mol% of the glass.

[0442] 18. The glass or glass-ceramic of any preceding embodiment, comprising TiO2.

[0443] 19. The glass or glass-ceramic of embodiment 18, wherein the TiO2is present in an amount of from about 0.1 to 15mol%, preferably from 0.5-12 mol% of the glass or glass-ceramic.

[0444] 20. The glass or glass-ceramic of any preceding embodiment, comprising a colourant, preferably wherein the colourant is selected from Fe2O3, CeO2, V2O5, V2O3, Er2O3, Tb2O3, Pr2O3, TaO2, MnO2, or combinations thereof.

[0445] 21. The glass or glass-ceramic of embodiment 20, wherein the colourant is present in an amount of 0.1 to 5mol% of the glass or glass-ceramic.

[0446] 22. The glass or glass-ceramic of any preceding embodiment, comprising one or more additional components, preferably wherein the one or more additional components are selected from the group consisting of ZrO2, LiSi, Li2Si2Os, l_i2SiO3, LiSi2, K2O, Na2O, KAISi2O6, Y2O3, CeO2, MgO, Sc2O3, La2O3, B2O3, BaO, SrO, Cr2O3and combinations thereof.

[0447] 23. The glass or glass-ceramic of embodiment 22, wherein the one or more additional components are present in an amount of 0.5 to 10 mol%, preferably from 0.5 to 5 mol%.

[0448] 24. The glass or glass-ceramic of any preceding embodiment, wherein the molar ratio of Ca:P of the glass is from about 0.5:1 to 1.5:1, preferably from about 1:0.9 to 1:1, more preferably from about 1:0.92 to 1:0.96.

[0449] 25. The glass or glass-ceramic of any preceding embodiment, wherein the molar ratio of Ca:P is about 1:0.94.

[0450] 26. The glass or glass-ceramic of any preceding embodiment, wherein the ratio of Ca:F of the mixture is from about 18:1 to 1:1, preferably from about 12:1 to 1.5 to 1.

[0451] 27. A method for preparing a glass, the method comprising the steps of:

[0452] a. Providing a mixture comprising:

[0453] i. SiO2,P5523GB00-KN4KE

[0454] ii. AI2O3,

[0455] iii. P2O5or a source thereof,

[0456] iv. CaO or a source thereof,

[0457] v. CaF2,

[0458] wherein the molar ratio of Ca:F of the mixture is from about 48:1 to 0.75: 1, and

[0459] wherein the molar ratio of Ca:P of the mixture is from about 0.5:1 to 3.3:1, with the proviso that when the mixture comprises at least 98 mol% of components i-v, the molar ratio of Ca:P in the mixture is from about 0.5:1 to 1.5:1;

[0460] b. Melting the mixture to form a molten glass; and

[0461] c. annealing the molten glass.

[0462] 28. The method of embodiment 27, wherein the mixture comprises at least about 75mol% of components i-v, preferably comprising at least about 80mol% of components i-v, preferably comprising at least about 85mol% of components i-v, preferably comprising at least about 90mol% of components i-v, more preferably at least about 95mol% of components i-v, more preferably at least about 98mol% of components i-v.

[0463] 29. The method of embodiment 27, wherein the mixture consists essentially of or consists of components i-v.

[0464] 30. The method of embodiments 27-29, wherein the molar ratio of Ca:P is from about 0.5:1 to 1.5:1, preferably from about 1:0.9 to 1:1, more preferably from about 1:0.92 to 1:0.96.

[0465] 31. The method of embodiments 27-30, wherein the molar ratio of Ca:P is about 1:0.94.

[0466] 32. The method of embodiments 27-31, wherein the ratio of Ca:F of the mixture is from about 18:1 to 1:1, preferably from about 12:1 to 1.5 to 1.

[0467] 33. The method of embodiments 27-32, wherein the AI2O3is present in an amount of from about 5 to about 50 mol%, preferably from about 10 to 30 mol% of the mixture.

[0468] 34. The method of embodiments 27-33, wherein the SiO2is present in an amount of from about 5 to 50 mol%, preferably from about 20 to about 45 mol% of the mixture.P5523GB00-KN4KE

[0469] 35. The method of embodiments 27-34, wherein the P2O5or source thereof, preferably the P2O5, is present in an amount of from about 5 to 50 mol%, preferably from about 10 to about 25 mol% of the mixture.

[0470] 36. The method of embodiments 27-35, wherein the CaO or source thereof, preferably the CaO, is present in an amount of from 2 to 60mol%, preferably 5 to 40mol% of the mixture.

[0471] 37. The method of embodiments 27-36, wherein the CaF2is present in an amount of from 0.5 to 60mol%, preferably from 1 to 40mol% of the mixture.

[0472] 38. The method of embodiments 27-37, wherein the mixture comprises TiO2.

[0473] 39. The method of embodiment 38, wherein the TiO2is present in an amount of from about 0.5 to 15mol%, preferably from 0.5-12 mol% o the mixture.

[0474] 40. The method of embodiments 27-39, wherein the mixture comprises one or more additional components selected from the group consisting of ZrO2, LiSi, Li2Si2Os, l_i2SiO3, LiSi2, K2O, Na2O, KAISi2O6, Y2O3, CeO2, MgO, Sc2O3, La2O3, B2O3, BaO, SrO, Cr2O3and combinations thereof.

[0475] 41. The method of embodiment 40, wherein the one or more additional components are present in an amount of 0.5 to 10mol%, preferably from 0.5 to 5 mol% of the mixture.

[0476] 42. The method of embodiments 27-41, comprising a colourant, preferably wherein the colourant is selected from Fe2O3, CeO2, V2O5, V2O3, Er2O3, Tb2O3, Pr2O3, TaO2, MnO2, or combinations thereof.

[0477] 43. The method of embodiment 42, wherein the colourant is present in an amount of 0.1 to 5mol% of the glass or glass-ceramic.

[0478] 44. The method of embodiments 27-43, wherein, in step b), the mixture is heated to a temperature of from 1400°C to 2200°C.

[0479] 45. The method of embodiments 27-44, wherein, in step b), the molten glass is maintained as said molten glass for 15 to 120 minutes, preferably for 30 to 90 minutes.

[0480] 46. The method of embodiments 27-45, wherein, in step b), the mixture is heated at a rate of from 1 to 50°C / min, preferably from 5 to 30°C / min, more preferably from 5 to 20°C / min.

[0481] 47. The method of embodiments 27-46, wherein step c) involves cooling at a rate of from 1 to 50°C / min.P5523GB00-KN4KE

[0482] 48. A glass obtainable by the method of any of embodiments 27 to 47.

[0483] 49. A method of preparing a glass-ceramic, said method comprising the steps of:

[0484] a. heating the glass of embodiments 10-26 or 48 at a first heating rate to a first temperature,

[0485] b. optionally holding the glass at said first temperature for a first holding time;

[0486] c. After steps a) and b), heating said glass at a second heating rate to a second temperature,

[0487] d. Optionally holding the glass at said second temperature for a second holding time.

[0488] 50. The method of embodiment 49, wherein said first heating rate and said second heating rate are independently selected from l°C / min to 60°C / min, preferably from 3°C / min to 40°C / min, more preferably from 6°C / min to 20°C / min,

[0489] 51. The method of embodiments 49-50, wherein the first heating rate and said second heating rate are the same.

[0490] 52. The method of embodiments 49-51, wherein said first holding time is from 5 minutes to 120 minutes, preferably from 15 minutes to 90 minutes, more preferably from 20 minutes to 75 minutes.

[0491] 53. The method of embodiments 49-52, wherein said second holding time is from 5 minutes to 120 minutes, preferably from 15 minutes to 90 minutes, more preferably from 20 minutes to 75 minutes.

[0492] 54. The method of embodiments 49-53, wherein step b) is conducted or step d) is conducted, preferably wherein both steps b) and d) are conducted.

[0493] 55. The method of embodiment 54, wherein the first heating rate is from 3 to 40°C / min, preferably from 6 to 20°C / min and / or the first holding time is up to 30 minutes.

[0494] 56. The method of embodiment 54 or 55, wherein the second heating rate is from 3 to 40°C / min, preferably from 6 to 20°C / min and / or the second holding time is up to 30 minutes.

[0495] 57. The method of embodiments 49-56, wherein the first temperature is from 450°C to 850°C, preferably from 500°C to 800°C, more preferably from 550°C to 750°C.P5523GB00-KN4KE

[0496] 58. The method of embodiments 49-57, wherein said first temperature within ±150°C of the glass transition temperature (Tg) of the glass, preferably within ±100°C of the glass transition temperature (Tg) of the glass, more preferably within ±50°C of the glass transition temperature (Tg) of the glass, more preferably at the glass transition temperature (Tg) of the glass.

[0497] 59. The method of embodiments 49-58, wherein the second temperature is from 700°C to 1250°C, preferably from 750°C to 1200°C, more preferably from 800°C to 1150°C

[0498] 60. The method of embodiments 49-59, wherein said second temperature is within ±150°C of the peak crystallisation temperature (Tp) of the glass, preferably within ±100°C of the peak crystallisation temperature (Tp) of the glass, more preferably within ±50°C of the peak crystallisation temperature (Tp) of the glass, more preferably at the peak crystallisation temperature (Tp) of the glass.

[0499] 61. A glass-ceramic obtainable by the method of embodiments 49-60.

[0500] 62. The glass of embodiments 10-26 or 48, or the glass-ceramic of embodiments 1-9, 18- 26 or 61, wherein the glass is a dental glass or the glass ceramic is a dental glassceramic or wherein the dental glass or dental glass-ceramic is for use in dental applications.

[0501] 63. The glass or glass-ceramic of embodiment 62, wherein the dental glass or dental glassceramic is for the application to, or replacement of at least a part of, a tooth.

[0502] 64. The glass-ceramic of embodiments 62-63, having a fracture toughness of 50% to 200% of an enamel of said tooth.

[0503] 65. The glass-ceramic of embodiments 62-64, having a biaxial flexural strength (BFS) of 50% to 200% of an enamel of said tooth.

[0504] 66. The glass-ceramic of embodiments 62-65, having a microhardness of 50% to 200% of an enamel of said tooth.

[0505] 67. A glass as defined in any of embodiments 10-26, 48 or 62-63, or a glass-ceramic as defined in any of embodiments 1-9, 18-26 or 61-66, for use in therapy.

[0506] 68. A method of treating a patient said method comprising applying the glass as defined in embodiments 10-26, 48 or 62-63 or the glass-ceramic as defined in embodiments 1-9, 18-26 or 61-66 to a patient in need thereof.P5523GB00-KN4KE

[0507] 69. A glass as defined in any of embodiments 10-26, 48 or 62-63 or a glass-ceramic as defined in any of embodiments 1-9, 18-26 or 61-66 for use in a method of preventing or treating a disorder in a tooth of a patient.

[0508] 70. A method of preventing or treating a disorder in a tooth of a patient, the method comprising applying a glass as defined in embodiments 10-26, 48 or 62-63, or the glassceramic as defined in embodiments 1-9, 18-26 or 61-66 to said tooth, or replacing at least a part of said tooth with the glass as defined in embodiments 10-26, 48 or 62-63 or the glass-ceramic as defined in embodiments 1-9, 18-26 or 61-66.

[0509] 71. The method of embodiment 70 or the glass or glass-ceramic for use according to embodiment 69, wherein the disorder is:

[0510] a. dentin hypersensitivity,

[0511] b. tooth wear, or

[0512] c. dental caries.

[0513] 72. A method of cosmetic treatment of a tooth of a patient, said cosmetic method comprising applying the glass of embodiments 10-26, 48 or 62-63 or the glass-ceramic of embodiments 1-9, 18-26 or 61-66 to said tooth, or replacing at least a part of said tooth with the glass of the embodiments 10-26, 48 or 62-63 or the glass-ceramic of embodiments 1-9, 18-26 or 61-66.

[0514] 73. The method of embodiment 72, wherein the cosmetic treatment is the prevention, retardation or reduction of tooth discoloration.

[0515] 74. The method of embodiment 72, wherein the cosmetic treatment is the restoration of at least a part of the physical shape of said tooth.

[0516] 75. The method of embodiments 68 or 70-74, or the glass or glass-ceramic for use according to embodiments 67, 69 or 71, wherein glass or glass-ceramic is applied to said tooth as a dental appliance or prosthesis, such as an inlay, an onlay, a crown, a bridge, or a veneer, or wherein said glass or glass-ceramic is applied as a replacement to at least a part of said tooth.

[0517] 76. The method of embodiments 68 or 70-75, or the glass or glass-ceramic for use according to embodiments 67, 69, 71 or 75, wherein the tooth is a human tooth.

[0518] 77. A glass as defined in any of embodiments 10-26 or 48 or a glass-ceramic as defined in any of embodiments 1-9, 18-26 or 61 for use in orthopaedic applications or for use as a bone substitute or for use in bone regeneration.P5523GB00-KN4KE

[0519] 78. A method for regenerating or replacing bone, said method comprising applying said the glass of embodiments 10-26 or 48 or the glass-ceramics of embodiments 1-9, 18-26 or 61 to a bone in need of regeneration or replacement in a patient in need thereof.

[0520] 79. The method of embodiments 68, 70-76 or 78, or the glass or glass-ceramic for use according to embodiments 67, 69, 71, or 75-77, wherein the patient is a human.

[0521] 80. Use of a glass as defined in any of embodiments 10-26 or 48 or the glass-ceramics as defined in embodiments 1-9, 18-26 in a 3D printing resin, or a 3D printing resin comprising a glass as defined in embodiments 10-26 or 48 or the glass-ceramics as defined in embodiments 1-9, 18-26 or 61.

[0522] 81. A method of 3D printing a product comprising a glass as defined in any of embodiments 10-26 or 48 or the glass-ceramics as defined in embodiments 1-9, 18-26, the method comprising the steps of:

[0523] a. providing a 3D printing resin comprising said glass or said glass-ceramic, and

[0524] b. printing said product using said 3D printing resin.

[0525] 82. The method of embodiment 81, the use of embodiment 80, or the 3D printing resin of embodiment 80, wherein said glass or said glass-ceramic is present in an amount of from about 1 to 90wt%, 5 to 80wt%, 15 to 70wt%, 15 to 60wt% or 20 to 50wt% of the 3D printing resin.

[0526] 83. The method of embodiments 81 or 82, the use of embodiment 80 or 82, or the 3D printing resin of embodiment 80 or 82, wherein said glass or said glass-ceramic is provided as a powder in said 3D printing resin.

Claims

P5523GB00-KN4KECLAIMS1. A glass-ceramic comprising a combination of fluorapatite, aluminium phosphate and silicone dioxide.

2. The glass-ceramic of claim 1, wherein the molar ratio of Ca:P of the glass ceramic is from about 0.5:1 to 3.3:1, preferably wherein the molar ratio of Ca:P of the glass ceramic is:a. from 0.5:1 to 2:1,b. from 0.5:1 to 1.5:1c. from about 1:0.9 to 1:1, ord. from about 1:0.92 to 1:0.96.

3. The glass-ceramic of claims 1 or 2, wherein the molar ratio of Ca:F of the glass-ceramic is from about 48:1 to 0.75: 1, preferably from about 18:1 to 1:1, more preferably from about 12:1 to 1.5:1.

4. The glass-ceramic of any preceding claim, comprising TiO2.

5. The glass-ceramic of claim 4, wherein the TiO2is present in an amount of from about 0.1 to 15mol%, preferably from 0.5-12 mol% of the glass-ceramic.

6. The glass-ceramic of any preceding claim, comprising at least 85 mol% of said combination, preferably 90 mol% of said combination, more preferably at least 95 mol% of said combination, more preferably at least 98 mol% of said combination7. A glass-ceramic as defined in of any preceding claim for use in dental applications, preferably wherein the dental glass-ceramic is for the application to, or replacement of at least a part of, a tooth.

8. The glass-ceramic for use according to claim 7, said glass ceramic having a fracture toughness of 50% to 200% of an enamel of said tooth.

9. The glass-ceramic for use according to claim 7 or 8, said glass ceramic having a biaxial flexural strength (BFS) of 50% to 200% of an enamel of said tooth.

10. The glass-ceramic for use according to claims 7 to 9, said glass ceramic having a microhardness of 50% to 200% of an enamel of said tooth.

11. A glass-ceramic as defined in any of claims 1-10, for use in therapy.48P5523GB00-KN4KE12. A glass-ceramic as defined in any of claims 1-10 for use in a method of preventing or treating a disorder in a tooth of a patient, preferably wherein the disorder is dentin hypersensitivity, tooth wear, or dental caries.

13. A method of cosmetic treatment of a tooth of a patient, said cosmetic method comprising applying glass-ceramic as defined in any of claims 1-10 to said tooth, or replacing at least a part of said tooth with the glass-ceramic as defined in any of claims 1-10.

14. A method of cosmetic treatment of a tooth of a patient, said cosmetic method comprising applying glass-ceramic as defined in any of claims 1-10 to said tooth, or replacing at least a part of said tooth with the glass-ceramic as defined in any of claims 1-10, preferably wherein the cosmetic treatment is the prevention, retardation or reduction of tooth discoloration, or wherein the cosmetic treatment is the restoration of at least a part of the physical shape of said tooth.

15. The method of claims 13 or 14, or the glass-ceramic for use according to claims 7-12, wherein the tooth is a human tooth.

16. A glass-ceramic as defined in any of claims 1-10 for use in orthopaedic applications or for use as a bone substitute or for use in bone regeneration.

17. Use of a glass-ceramic as defined in any of claims 1-10 in a 3D printing resin, or a 3D printing resin comprising a glass-ceramic as defined in any of claims 1-10.49

Images