WO2018031821A1

WO2018031821A1 - Composite resins with superior optical, mechanical, and therapeutic properties by incorporation of structured microparticles

Info

Publication number: WO2018031821A1
Application number: PCT/US2017/046370
Authority: WO
Inventors: Elijah Shirman; Erica SIISMETS; Joanna Aizenberg
Original assignee: President And Fellows Of Harvard College
Priority date: 2016-08-10
Filing date: 2017-08-10
Publication date: 2018-02-15

Abstract

Curable resins incorporating micro-structured particles, for example inverse opals (IOs), and methods for using same. The curable resin compositions are particularly useful for dental applications.

Description

COMPOSITE RESINS WITH SUPERIOR OPTICAL, MECHANICAL, AND THERAPEUTIC PROPERTIES BY INCORPORATION OF STRUCTURED MICROPARTICLES

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims priority to U.S. Provisional Patent Application No.

62/373,258, filed August 10, 2016, the entire contents of which are hereby incorporated by reference in their entirety.

INCORPORATION BY REFERENCE

[0002] All patents, patent applications and publications cited herein are hereby incorporated by reference in their entirety in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described herein.

FIELD OF THE INVENTION

[0003] The present application relates to composite resins containing structured microparticles. More particularly, the present application relates to curable composite resins that incorporate structured microparticles, such as inverse opals, to provide improved properties.

BACKGROUND

[0004] Composite resins are widely used in fields such as dentistry, cosmetics, 3D printing, and electronics. For example, composite resins for applications in dentistry approach the mechanical durability of amalgam fillings with substantially greater esthetic value. The main esthetic considerations that have been addressed, particularly in the field of composite dental materials, are the development of various hues, translucency, and fluorescence similar to those of natural teeth. In addition, efforts to incorporate components suppressing the development of infections at interfaces as well as components enhancing X-ray contrast, which is important for imaging and diagnostics, are possible.

[0005] It would be beneficial to provide improved composite materials for various applications, wherein the composite materials exhibit improved optical, mechanical, and/or therapeutic properties. For example, there is a demand for dental materials that more closely mimic the appearance and properties of natural enamel. SUMMARY

[0006] In accordance with certain embodiments, a composite resin comprising a curable resin having dispersed therein micro-structured particles is described. In accordance with certain embodiments, the micro- structured particles are direct porous opal, inverse opal and/or compound inverse opals.

[0007] In accordance with certain embodiments, the largest exterior dimension of the micro- structured particles is within the range of 10 nanometers to 500 microns.

[0008] The micro-structured particles may be stoichiometric or non-stoichiometric.

[0009] In accordance with certain embodiments, the micro-structured particle is an oxide selected from the group consisting of silica, zirconia, alumina, titania, yttria, ceria, hafnia, iron oxides, molybdenum oxides, tungsten oxides, rhenium oxides, tantalum oxides, niobium oxides, chromium oxides, scandium oxides, lanthanum oxides, rare earth oxides, thorium oxides, uranium oxides, mixed oxides and combinations thereof.

[0010] In accordance with certain embodiments, the micro-structured particles are compound structures composed of two or more oxides selected from the group consisting of silica, zirconia, alumina, titania, yttria, ceria, hafnia, iron oxides, molybdenum oxides, tungsten oxides, rhenium oxides, tantalum oxides, niobium oxides, chromium oxides, scandium oxides, lanthanum oxides, rare earth oxides, thorium oxides, and uranium oxides.

[0011] In accordance with certain embodiments, the composite resin contains solid components in a range of 5% to 90% by volume.

[0012] In accordance with certain embodiments, the micro-structured particles comprise Si0₂ inverse opal.

[0013] In accordance with certain embodiments, the micro-structured particles comprise Zr0₂.

[0014] In accordance with certain embodiments, the micro-structured particles comprise S1O2 inverse opal filled with Zr0₂.

[0015] In accordance with certain embodiments, wherein the curable resin comprises a thermally-curable or photocurable polymer.

[0016] In accordance with certain embodiments, the curable resin comprises an acrylate- based polymer. In accordance with certain embodiments, the acrylate-based polymer is selected from the group consisting of triethylene glycol dimethacrylate (TEGDMA), bisphenol A glycerolate dimethacrylate (BisGMA), urethane dimethacrylate (UDMA) and mixtures thereof. [0017] In accordance with certain embodiments, the composition may also include camphorquinone (CQ), 4-dimethylaminobenzoic acid ethyl ether (DMABE), 3, 5-di-tert- butyl-4-hydroxytoluene (BHT), and 2-hydroxy-4-methoxybenzophenone (HMBP).

[0018] In accordance with certain embodiments, the curable resin comprises a dimethacrylate resin.

[0019] In accordance with certain embodiments, wherein the micro-structured particles further comprise metals, semiconductors, organometallic compounds, inorganic polymers, organic materials, natural materials, polymeric materials, and mixtures thereof.

[0020] In accordance with certain embodiments, the micro-structured particles comprise nanoparticles that change optical and/or antibacterial properties of the composite resin.

[0021] In accordance with certain embodiments, the micro-structured particles contain structural defects that provide a luminescent appearance to the cured resin and improve curing by slowing light effect.

[0022] In accordance with certain embodiments, the micro-structured particles are compound inverse opals comprising a first material and a second material, wherein the second material fills pores in the inverse opal comprising the first material.

[0023] In accordance with certain embodiments, the resin contains a plurality of different types of micro- structured particles differing in at least one property selected from the group consisting of pore size, composition, particle size, pore fillers, and nanoparticles.

[0024] In accordance with another aspect, the present application discloses a method of applying an uncured resin to a substrate, wherein the uncured resin comprises a curable resin having dispersed therein micro-structured particles and exposing the uncured resin to a curing light having a predetermined curing wavelength, thereby curing the resin.

[0025] In accordance with certain embodiments, the micro-structured particles are inverse opals.

[0026] In accordance with certain embodiments, the inverse opals comprise pores that are filled with a different material than that forming the inverse opal.

[0027] In accordance with certain embodiments, the micro-structured particles are fluorescent under light of the curing wavelength.

[0028] In accordance with certain embodiments, the substrate is a tooth.

[0029] In accordance with certain embodiments, exposing the uncured resin to a curing light resin cures the resin to a depth of up to about 3mm. [0030] In accordance with certain embodiments, the cured resin more closely matches fluorescence and luminescence properties of the tooth than the same resin without micro- structured particles.

BRIEF DESCRIPTION OF THE DRAWINGS

[0031] The above and other advantages of the present invention will be apparent upon consideration of the following detailed description, taken in conjunction with the

accompanying drawings, in which like reference characters refer to like parts throughout, and in which:

[0032] FIGS. 1 A-1G provides schematics of various composite resins samples, containing structured and non-structured microparticles.

[0033] FIG. 2 shows optical images of the samples from FIGS. 1A-1C in emission, reflection, and transmission modes.

[0034] FIG. 3A, FIG. 3B and FIG. 3C provides scanning electron microscope (SEM) images of the samples from FIGS. 1A-1C, respectively.

[0035] FIG. 4 provides an estimation of the composition of FIG. 1C using

thermogravimetric analysis (TGA).

[0036] FIG. 5 are transmission electron microscope (TEM) images of sample C.

[0037] FIG. 6 provides crystal characterization of the zirconia phase using Raman spectroscopy of sample C and a control sample of zirconia nanocrystals.

[0038] FIG. 7 provides compositional analysis of sample C using X-ray photoelectron spectroscopy (XPS).

[0039] FIG. 8 shows magnified regions of the XPS plots indicating defects-related origin of luminescence.

[0040] FIG. 9A shows SEM images of silica IO opal structures used as resin fillers.

[0041] FIG. 9B shows SEM images of silica and zirconia IO opal structures used as resin fillers.

[0042] FIG. 9C shows SEM images of silica and zirconia compound IO opal structures used as resin fillers.

[0043] FIG. 10A and FIG. 10B provide a comparison of various optical properties of resins containing structured (FIG. 10A) vs. non-structured fillers (FIG. 10B).

[0044] FIG. IOC shows the transmission spectra for resin alone and resin containing structured fillers and resin containing non-structured fillers. [0045] FIG. 10D shows the opalescence parameter for resin containing structured fillers and resin containing non-structured fillers.

[0046] FIG. 10E shows the fluorescence spectra for resin alone and resin containing structured fillers and resin containing non-structured fillers.

[0047] FIGS. 11 A-l IF illustrate variations in optical properties as a function of pore size. FIGS. 11 A, 1 IB and 11C show schematic representation of particles having different pore sizes (360nm, 300nm, and 270nm, respectively) as well as reflectance and transmission images for each. FIGS. 1 ID, 1 IE and 1 IF are graphs of the transmission, reflectance and fluorescence data, respectively for the samples.

[0048] FIGS. 12A, 12B, 12C and 12D illustrate variations in optical properties as a function of composition. FIG. 12E is a graph of transmission percentage v. wavelength for variable 300 nm silica IO percentages. FIG. 12F is a graph of reflection percentage v.

wavelength for variable 300 nm silica IO percentages. FIG. 12G is a graph of fluorescence v. emission wavelength at 365nm excitation for variable 300 nm silica IO percentages.

[0049] FIGS. 13A, 13B and 13C show the influence of microstructuring the filler on the mechanical properties of a composite resin. FIG. 13D is a plot of modulus of elasticity for various filler types. FIG. 13E is a plot of ultimate strength for various filler types.

[0050] FIGS. 14A and 14B show optical images of pure resin (FIG. 14 A) and one containing micro- structured fillers (FIG. 14B) upon indentation with a diamond tip, and a quantitative comparison of the hardness of these two samples is provided in FIG. 14C.

[0051] FIG. 15 provides optical images of composite resins containing various microparticulate fillers: inverse opal, combined, and compound (corresponding to samples A, B, and C in FIGS. 1 A-IC, FIG. 2 and FIGS. 3A-3C) and traditional non-structured nanofiller. For comparison an example of human teeth in emission and reflectance modes are also shown.

[0052] FIG. 16 demonstrates a series of samples containing inverse and compound opal microfillers in fluorescence mode (illuminated with 365 nm light).

[0053] FIG. 17 provides a comparison the optical properties of dental restoration composites incorporating nanostructured fillers to those of natural teeth.

[0054] FIG. 18A is a fluorescence spectra of a series of samples containing resins and micro- structured fillers in accordance with certain embodiments presented herein.

[0055] FIG. 18B provides schematic examples of light-induced processes (energy transfer and slow-light effect) that may occur within the resin containing micro- structured fillers. DETAILED DESCRIPTION OF THE INVENTION

[0056] State of the art composite materials are far from ideal and additional

improvements in their optical, mechanical, and other functional properties are necessary to make them appropriate for various applications. For example, natural enamel exhibits a certain degree of iridescence among other optical effects, which generate their unique appearance. Therefore, in order to achieve natural -looking restorations, a combination of blue spectral component in the reflected light and orange component in the transmitted light are required. Another example relates to the limited penetration depth of the curing light into the composite materials, imposing a requirement for repetitive application of the composite and curing during normal treatment procedures for restorations deeper than a few millimeters.

[0057] The present application discloses compositions and methods for the formation of composite resins with significantly improved esthetic and mechanical properties, as well as increased curing depth and decreased curing time, achieved by incorporating particles with micro- structured architectures. Examples of such particles include those having inverse and compound opal structures. The unique optical effects obtained using the micro- structured particles are due to the interplay between their ability to transmit, reflect, and scatter visible light in a wavelength-selective and angle-dependent fashion, as well as to enhance or suppress the interaction of the materials infiltrated within the photonic structure with light, also in a wavelength-selective and angle-dependent fashion. Such properties can be varied to achieve a desired effect by rationally designing the composition, geometry, periodicity, refractive indices, and other structural and optical properties of the matrix and the infiltrate. For example, a composite with predesigned iridescence, fluorescence, transmittance, opacity, penetration depth of the curing light, and centers emitting at the curing wavelength can be obtained. In particular, microparticles can be engineered to minimize scattering at the wavelength of a curing light. Also, microparticles can be engineered to create internal luminescence at a wavelength appropriate for curing the resin. In both ways, the depth of curing can be increased and the curing time decreased. Furthermore, the microparticles can be designed to substantially enhance the effect of the curing light by other photonic effects such as for example, a "slow light" effect capable of prolonging the interaction time between the light and the resin undergoing curing resulting in more efficient polymerization occurring at deeper locations. The extent of such effects and the specific spectral profile can be controlled by adjusting such parameters as the geometry of the architecture and its degree of order, refractive indices of the microparticles and the resin, and presence of dopants and defects in the structure.

[0058] Micro- structured fillers can also suppress the tendency of the guest phase to undergo sintering and other phase transitions upon exposure to heat or other means of aging, thus providing for stabilization of advantageous crystal structures or species at the conditions relevant to specific application. The enhancement of the mechanical properties is obtained due to the long-range structural features of the matrix embedded into the resin phase as opposed to a collection of separate particles used in traditional composites. In addition to the unique optical and enhanced mechanical properties, coupled with improved curing, the method allows for the incorporation and encapsulation of other functional components, such as antimicrobial components, X-ray contrast agents and ones used for controlled release of therapeutic species.

[0059] The choice of the method, conditions, and the precursors for creating the microstructures can highly affect the extent of photo-luminescent defects present in the crystalline or amorphous parts of the microstructures. This can influence the optical and functional properties of the microstructures integrated in a composite resin and their contribution to the macroscopic optical appearance of the entire material. Examples for defects include substitutional, interstitial, and/or vacancy defects.

[0060] Inverse opals are ordered, porous structures formed from colloidal crystals, and this structure provides them with many properties. In particular, their porosity facilitates wetting and fluidics studies and applications, and their periodicity facilitates optical and photonic studies and applications. Inverse opals are typically comprised of polymers, metals, or metal oxides, and the specific material can be tailored for particular applications.

[0061] The formation of inverse opal films of titania, alumina, zirconia and other non- silica metal oxide compounds has typically been based mostly on a three-step method. First, a sacrificial direct opal template is formed using colloidal particles, such as polymeric colloidal particles. Then, the preformed direct opal structure is infiltrated (or "backfilled") with a metal oxide precursor to form a matrix around the direct opal structure. Transition metal oxide inverse opals have been made previously with a variety of backfilling methods, including dip-coating, dropcasting, spin coating, or vapor-phase deposition. Then, the templating colloidal particles forming the direct opal structure are removed, leaving behind the metal oxide matrix. For example, calcination, which promotes hydrolysis, crystallization, and sintering of the matrix, in addition to removal of the templating polymeric colloids, is commonly used. Microparticles can be prepared by grinding inverse opals, but can also be obtained bottom up by using patterned substrates for inverse opal growth or via droplet confined self assembly using various emulsification methods.

[0062] Examples of metal oxide precursors used in the conventional method described above include precursors in the form of nanoparticles (e.g., colloidal dispersions) or sol-gel (e.g., water-soluble titanium (IV) bis(ammonium lactato) dihydroxide (TiBALDH)), as well as highly reactive titanium alkoxides for titania; water-soluble aluminum alkoxides stabilized with acetyl acetone for alumina; and highly reactive zirconium alkoxides that can be stabilized with acetyl acetone for zirconia) and various oxide nanoparticles (both

commercially available as well as synthesized precursors).

[0063] In certain embodiments, the inverse opal structures are composed of, or substantially of, a metal oxide matrix and air holes.

[0064] Some other exemplary structures include "compound opals" wherein colloidal particles are present as well as the matrix component. Many different types of colloidal particles can be utilized. The colloids can be made from various materials or mixtures of materials. In certain embodiments, the materials are metals, such as gold, palladium, platinum, tin, silver, copper, rhodium, ruthenium, rhenium, titanium, osmium, iridium, iron, cobalt, nickel or combinations and alloys thereof. In certain embodiments, the materials are semiconductor materials, such as silicon, germanium, silicon doped with group III or V elements, germanium doped with group III or V elements, tin doped with group III or V elements, and combinations thereof. In certain embodiments, the materials include catalysts for chemical reactions. In certain embodiments, the materials are oxides, such as silica, titania, zirconia, alumina, iron oxide, zinc oxide, tin oxide, beryllia, noble metal oxide, platinum group metal oxide, hafnia, molybdenum oxide, tungsten oxides, rhenium oxides, tantalum oxides, niobium oxides, vanadium oxide, chromium oxides, scandium oxides, yttria, lanthanum oxides, ceria, thorium oxides, uranium oxides, other rare earth oxides, mixed oxides and combinations thereof. In certain embodiments, the materials are metal sulfides, metal chalcogenides, metal nitrides, metal pnictides, mixed sulfides or nitrides, and combinations thereof. In certain embodiments, the materials are organometallics, including various metal organic frameworks (MOFs), inorganic polymers (such as silicones), organometallic complexes, and combinations thereof. In certain embodiments, the colloids are made from organic materials, including polymers, natural materials, and mixtures thereof. In certain embodiments, the material is a polymeric material, such as poly(methyl methacrylate) (PMMA), other polyacrylates, other polyalkylacrylates, substituted polyalkylacrylates, polystyrene (PS), poly(divinylbenzene), poly(vinylalcohol) (PVA), and hydrogels. Other polymers of different architectures can be utilized as well, such as random and block copolymers, branched, star and dendritic polymers, and supramolecular polymers. In certain embodiments, the material is a natural material, such as a protein- or

polysaccharide-based material, silk fibroin, chitin, shellac, cellulose, chitosan, alginate, gelatin, and mixtures thereof.

[0065] In certain embodiments, the curable resin has a final solid content of up to about 20% by weight, for example in a range of about 0.05% to about 10% by weight. In certain embodiments, the curable resin has a final solid content of up to 30 w%. In certain embodiments, the curable resin has a final solid content of up to 40 w%. In certain embodiments, the curable resin has a final solid content of up to 50 w%. In certain embodiments, the curable resin has a final solid content of up to 60 w%. In certain embodiments, the curable resin has a final solid content of up to 70 w%. In certain embodiments, the curable resin has a final solid content of up to 80 w%. In certain embodiments, the curable resin has a final solid content of up to 90 w%. In certain embodiments, the curable resin has a final solid content of up to 100 w%.

Incorporation of Functional Materials into Micro-Structured Particles

[0066] The incorporation of a second material component into an opal structure can give rise to synergistic effects, in that it can yield materials with improved or augmented functionalities and properties. In accordance with one aspect, the inverse porous

microparticles are porous structures, such as inverse opals, with pores filled with the resin during the formation of the composite. In accordance with another aspect, the compound particles are porous structures with pores partially or fully filled with a different material prior to their incorporation into the composite resin. An example for such compound particles is a compound-opal-microparticle, e.g., silica inverse-opal-microparticles with zirconia phase partially or fully filled in the pores.

[0067] In certain embodiments, the range of pore size of the micro- structured particles can be from about 10 nm to 20 μπι, more particularly from about 50 nm to 2 μπι and in some cases from about 100 nm to 1 μπι

[0068] In certain embodiments, the phase filling the pores accounts for up to about 100% of the pore volume. In certain embodiments, the phase filling the pores accounts for up to about 90% of the pore volume. In certain embodiments, the phase filling the pores accounts for up to about 80% of the pore volume. In certain embodiments, the phase filling the pores accounts for up to about 70% of the pore volume. In certain embodiments, the phase filling the pores accounts for up to about 60% of the pore volume. In certain embodiments, the phase filling the pores accounts for up to about 50% of the pore volume. In certain embodiments, the phase filling the pores accounts for up to about 40% of the pore volume. In certain embodiments, the phase filling the pores accounts for up to about 30% of the pore volume. In certain embodiments, the phase filling the pores accounts for up to about 20% of the pore volume. In certain embodiments, the phase filling the pores accounts for up to about 10%) of the pore volume. In certain embodiments, the phase filling the pores accounts for up to about 5% of the pore volume.

[0069] In accordance with other aspects, the incorporation of metal nanoparticles into inverse opal structures results in the coupling of photonic and plasmonic properties, providing additional control over the optical properties. Furthermore, incorporation of metal nanoparticles may be advantageous for catalysis, greatly expanding the possible applications of these composite materials. Metal nanoparticles have also been used for the antimicrobial, UV-absorbing, sensing, and electrocatalytic properties. Functional particles that can be incorporated into photonic structures described herein include metal (e.g., gold, silver, platinum, palladium, ruthenium, rhodium, cobalt, iron, nickel, osmium, iridium, rhenium, copper, chromium, bimetals, metal alloys, and the like and combinations thereof) nanoparticles, semiconductor (e.g., silicon, germanium, and the like, pure or doped with elements or compounds of group III or V elements, and combinations thereof) nanoparticles, metal oxide (e.g., silica, titania, zirconia, alumina, iron oxide, zinc oxide, tin oxide, beryllia, noble metal oxide, platinum group metal oxide, hafnia, molybdenum oxide, tungsten oxides, rhenium oxides, tantalum oxides, niobium oxides, vanadium oxide, chromium oxides, scandium oxides, yttria, lanthanum oxides, ceria, thorium oxides, uranium oxides, other rare earth oxides, mixed oxides and combinations thereof and the like) nanoparticles, metal sulfide or nitride nanoparticles, or combinations thereof.

[0070] The microparticles disclosed herein can also include filled and/or hollow structural motifs, such as core-shell, double-shell, and/or mixed shell.

[0071] The micro- structured particles typically have dimensions within a range of 10 nm to 500 microns, more particularly 100 nm to 100 microns and, in some cases, 200 nm to 50 microns. [0072] The micro- structured particles can be made of stoichiometric and nonstoichiometric, pure or mixed (i.e. combinations of) oxides, such as silica, zirconia, alumina, titania, yttria, ceria, hafnia, iron oxides, molybdenum oxides, tungsten oxides, rhenium oxides, tantalum oxides, niobium oxides, chromium oxides, scandium oxides, lanthanum oxides, rare earth oxides, thorium oxides, uranium oxides, and combinations thereof.

[0073] The micro- structured particles may contain various materials or mixtures of materials including metals, semiconductors, organometallic compounds, inorganic polymers, organic materials, natural materials, polymeric materials, and mixtures thereof.

[0074] In accordance with certain aspects, the micro- structured particles are capable of imposing certain restrictions on the material infiltrated in the pores towards its sintering and formation of long-range crystalline regions upon heat treatment or aging, thus providing for the possibility of, for example, high temperature phases of oxides at room temperature, and materials with stable physical and chemical properties over extended periods.

[0075] In accordance with certain aspects, the resin is a thermally- or photo-curable polymer. Such polymers may include, but are not limited to, acrylate-based polymers such as triethylene glycol dimethacrylate (TEGDMA), bisphenol A glycerolate dimethacrylate (BisGMA), and/or urethane dimethacrylate (UDMA). Additional components, such as photoinitiators and photosensitizers, may also be included in the resin composition to facilitate polymerization and stabilization of the resin mixture. A photoinitiator (i.e., a photoinitiator system) may be present in the curable composition. Upon irradiation with actinic radiation the photinitiator initiates the polymerization (or hardening) of the composition. Such photopolymerizable compositions can be free radically polymerizable. The photoinitiator typically has a functional wavelength range from about 250 nm to about 800 nm. Suitable photoinitiators (i.e., photoinitiator systems that include one or more compounds) for polymerizing free radically photopolymerizable compositions can include camphorquinone (CQ), 4-dimethylaminobenzoic acid ethyl ether (DMABE), 3, 5-di-tert- butyl-4-hydroxytoluene (BHT), and 2-hydroxy-4-methoxybenzophenone (HMBP), among others.

[0076] In accordance with certain aspects, the composite resin can be structured to provide controllable properties, such as, iridescence and hues, translucency, and emission.

[0077] In accordance with certain aspects, the composite resin realizes long penetration depth (beyond 1 millimeter, from about l-2mm, or up to about 5mm of the curing light (e.g., 420-485 nm, 2000 mW/cm²). In accordance with certain embodiments, the can be cured at depths over 2mm, such as from about 2-20mm, or in some cases from 2- 10mm.

[0078] In accordance with certain aspects, the composite resin realizes enhanced mechanical properties.

[0079] In accordance with certain aspects, the composite resin contains solid components in the range of about 5 to 90%, more particularly from about 10-80% and is certain cases from about 25-50%) by volume.

[0080] In accordance with certain aspects, the structured microparticles provide the means for encapsulation of additional functional components within the structured particles for controllable degree of chemical insulation of these components from the resin and/or controlled release of therapeutics.

[0081] In accordance with certain aspects, the present application provides for the incorporation of photo-luminescent defects within the micro-structured particles. The method may include the use of sacrificial structural elements that introduce defects upon heat treatment performed in the range of room temperature up to 1500°C in an atmosphere of air or other gas mixtures. In certain embodiments, the sacrificial structural elements may be organic molecules, organic and inorganic colloids, transition metal complexes, and/or inorganic salts.

Functionalization of Structured Microparticles

[0082] Structured microparticles can also be functionalized to facilitate processing or provide other properties. In accordance with one embodiment, inverse opals can be functionalized, by means of silanization, in order to promote the infiltration of the resin matrix within the inverse opal pores. The functionalization protocol was adapted from the procedure reported by Karabela and Sideridou. (Effect of the structure of silane coupling agent on sorption characteristics of solvents by dental resin-nanocomposites. Dental

Materials, 24 (2008), 1631-39). Inverse opals were added to a solution of 3- (trimethoxysilyl)propyl methacrylate (MPS) (11 mass percent of the inverse opals), cyclohexane (20mL) and n-propylamine (0.05g). The solution was stirred for 1 hour on a 100 degree Celsius hotplate. Once the solvents had evaporated completely, the inverse opals were then dried in an oven at 85 degrees Celsius for 8 hours. After drying, inverse opals were ground into a micro fine powder, which was sieved (30 μπι) into vials for storage. [0083] In certain embodiments, a substrate can be made from a metal salt or oxide, such as silica, alumina, iron oxide, zinc oxide, tin oxide, alumina silicates, aluminum titanate, beryllia, noble metal oxide, platinum group metal oxide, titania, zirconia, hafnia,

molybdenum oxide, tungsten oxide, rhenium oxide, tantalum oxide, niobium oxide, vanadium oxide, chromium oxide, scandium oxide, yttria, lanthanum oxide, ceria, thorium oxide, uranium oxide, other rare earth oxides, mixed oxides and combinations thereof.

[0084] In other embodiments, the substrate comprises at least one of a metal and a metal alloy, examples of which include stainless steel, ferritic steel (e.g., an iron-chromium alloy), austenitic steel (a chromium-nickel alloy), copper, nickel, brass, gold, silver, titanium, tungsten, tin, aluminum, palladium, and platinum.

[0085] In certain embodiments, the substrate can be made from a ceramic material, such as cordierite, Mullite, zeolite, and natural or synthetic clay.

[0086] In other embodiments, the substrate comprises a combination of composite metal and metal oxide, such as cermet.

[0087] In still other embodiments, the substrate comprises an organic or inorganic material or combination thereof.

[0088] In still other embodiments, the substrate comprises a polymer, such as

polyurethane, and/or comprises at least one of: polyethyleneterephthalate, polystyrene, poly(methyl methacrylate), polyacrylate, polyalkylacrylate, substituted polyalkylacrylate, poly(divinylbenzene), polyvinylpyrrolidone, poly(vinylalcohol), polyacrylamide,

poly(ethylene oxide), polyvinylchloride, polyvinylidene fluoride, polytetrafluoroethylene, other halogenated polymers, hydrogels, organogels, chitin, chitosan, random and block copolymers, branched, star and dendritic polymers, and supramolecular polymers.

[0089] In other embodiments, the substrate can be conductive metal oxide such as indium tin oxide (ITO), fluorine doped tin oxide (FTO) or doped zinc oxide.

[0090] In other embodiments, the substrate can be conductive polymer such as polype- ethyl enedioxythiophene (PEDOT), PEDOT-PSS (polystyrene sulfonate), or a carbon-based conductor (e.g. graphite).

[0091] In still other embodiments, the substrate comprises a natural material, for example including at least one of cellulose, natural rubber (e.g., latex), wool, cotton, silk, linen, hemp, flax, and feather fiber. In some embodiments, the substrate is a tooth. Comparison between resins, resins with nanofillers, and resins with microstructured fillers of this invention

[0092] Schematic examples of different types of composite resins incorporating solid microparticles are shown in FIGS. 1 A-AG. The samples shown include: (A) an example of a conventional composite resin containing silica and zirconia microparticles, (B) a composite resin of this invention containing structured silica microparticles in the form of inverse opals mixed with non-structured zirconia microparticles, and (C) a composite resin of this invention containing silica-inverse-opal microparticles prefilled with zirconia. Note, that while the relative amount of each component (i.e., the weight % of the resin, silica, and zirconia in samples A, B, and C) is the same, the optical, mechanical, and chemical properties of these three composites are substantially different. Although the examples in FIGS. 1 A-2C include only the major and the most common materials currently employed for the formation of composite resins: photo-curable resins, silica, and zirconia, a broad range of other materials can also be used as described above or as known to one of ordinary skill in the art. Additional exemplary schematics of various resins with microparticles are shown in samples D-G of FIGS. 1D-1G: (D) Micro-structured particles of one kind having the same pore size; (E) micro-structured particles (i and ii, which may have the same or different pore size) and optionally containing non-structured fillers (iii and iv, which can be made of the same or different materials and have the same or different particle size). The combination of micro- structured and non- structured particles is referred to herein as the "combined" case; (F) resin containing various micro-structured particles, which incorporate additional materials within their pores, referred here as "compound" case and can contain one or more of the i-iv types of microparticles presented here: (i) pure pores, (ii) nanoparticles incorporated within the pores, (iii) high extent of loading of the additional material within the pores, (iv) completely filled pores; (G) an example of a resin containing a combination of one or more types of various particles in one system as described in FIGS. 1 A-1C. Complex (combinations of) optical, mechanical, therapeutic, and processing (e.g., curing) properties and even synergistic effects can be realized when different types of micro-structured particles are combined in one system, which may also contain a combination of micro- structured and non-structured fillers.

[0093] The optical images of composites corresponding to the samples A, B, and C in the emission, reflection, and transmission modes are shown in FIG 2. The fluorescence image (top) was obtained by illuminating the samples with a 365 nm light-source. [0094] SEM images of cross-sections of the samples are shown in FIGS 3 A to 3C. The images were acquired using a combination of signals from detectors sensitive to back- scattered and secondary electrons. As a result, materials made of different elements appear with different contrast. With respect to the cross section of sample A (FIG. 3 A), on the left image, the white arrows point to the silica particles and the black arrows to the zirconia particles embedded in the resin. A magnification of the area marked with a white dashed rectangle is shown in the right image.

[0095] Scanning electron microscopy images of a cross section of sample B are provided in FIG. 3B. On the left image, the white arrows point to the inverse opal silica microparticles and the black arrows to the non-structured zirconia particles embedded in the resin. The dashed rectangle in the left image marks the area shown in the right image. The dashed rectangle in the right image marks the area magnified in the inset of the right image.

[0096] FIG. 3C includes scanning electron microscopy images of a cross section of sample C. On the left image, the white arrows point to the compound opal microparticles composed of silica inverse opals filled with zirconia nanocrystals embedded in the resin. The dashed rectangle in the left image marks the area shown in the right image. The dashed rectangle in the right image marks the area magnified in the inset of the right image.

[0097] FIG. 4 illustrates an estimation of the composition of compound inverse opal materials of FIG. 1C using thermogravimetric analysis (TGA). The results indicated that the materials were 35% Zr0₂ and 65% Si0₂ by volume.

[0098] FIG. 5 provides transmission electron microscopy images of the compound silica- zirconia inverse opal filler of FIG. 1C. The images indicate a lattice spacing of about 3 Angstroms of a (111) plane.

[0099] FIG. 6 provides crystal characterization of the zirconia phase using Raman spectroscopy of sample C and a control sample of zirconia nanocrystals.

[0100] FIG. 7 provides compositional analysis of sample C using X-ray photoelectron spectroscopy (XPS). The results indicate about 25-35% Zr0₂ by volume.

[0101] FIG. 8 shows magnified regions of the XPS plots indicating defects-related origin of luminescence.

[0102] FIGS. 9 A to 9C show SEM images of various inverse opal structures used as resin fillers. Sample A (FIG. 9A) is an inverse opal of silica. Sample B (FIG. 9B) is a

homogeneous matrix of silicon and zirconia IO. Sample C (FIG. 9C) is a silica and zirconia compound IO (layered matrix). [0103] FIGS. 10A and 10B provide a comparison of various optical properties of resins containing structured vs. non-structured fillers. Optical and SEM images of resins containing structured (FIG. 10A) and non-structured silica microparticles (FIG. 10B) illustrate the improvements associated with the structured microparticles. The transmission spectra (FIG. IOC) show the transmission as a function of wavelength for the resin, resin with structured particles and resin with non- structured particles. Relative opalescence measurements are provided in FIG. 10D, which clearly shows the increased opalescence for the resin with structured particles compared to the resin with non-structured particles. FIG. 10E provides fluorescence spectra for resin, resin with structured particles and resin with non- structured particles as a function of emission wavelength at 365nm excitation.

[0104] FIGS. 11 A to 1 IF illustrate variations in optical properties as a function of pore size. Reflectance, transmission, and fluorescence were measured for three samples having the same composition of the microparticles (100% Si0₂) but different pore sizes (360nm (FIG. 11 A), 300nm (FIG. 1 IB), and 270nm (FIG. 11C)).

[0105] FIGS. 12A to 12D illustrate variations in optical properties as a function of composition. Samples tested were A (100% S1O2), B (80% S1O2, 20% Zr0₂), C (50% S1O2, 50% Zr0₂) and D (20% S1O2, 80% Zr0₂) and each had the same pore size. Transmission, reflectance and fluorescence data are provided in FIGS. 12E to 12G.

[0106] FIGS. 13A to 13E shows the influence of microstructuring the filler on the mechanical properties of a composite resin. Results are provided for stress, modulus of elasticity and ultimate strength for resin; resin with structured particles, and resin with non- structured particles.

[0107] The compression testing procedure of the cured composite samples was performed in accordance with D695 ASTM standard. Samples were cured in molds of 10 mm length and 5 mm diameter. Samples were tested using a commercial universal testing machine (Instron, High Wycombie, UK) using a cross head speed of 1 mm/minute. Tests continued until failure. The compressive stress was calculated by the following equation:

σ = F/A where σ is the compressive force, F is the compressive load and A is the cross sectional area of the sample. The compressive strength is represented by σπιαχ. The strain of the material was calculated by the following formula: ε = Al/lo where ΔΖ is the change in length of the specimen, and Zois is the initial length. The modulus of elasticity, E, the ability of a material to resist plastic deformation, was determined from the slope of the linear portion of the stress - strain curve. Linear regression in MATLAB was used to determine the slope of the curve output by the Instron software.

[0108] FIGS. 14A and 14B show optical images of pure resin and one containing micro- structured fillers upon indentation with a diamond tip, and a quantitative comparison of the hardness of these two samples. Vicker' s hardness testing (indentation) data is also provided for various samples (FIG. 14C). The Vickers hardness test is used to quantitatively assess the hardness of a material, or its ability to resist deformation by means of indenting. The procedure to assess the Vickers hardness of the composite samples was adapted from Beun et al., (Characterization of nanofilled compared to universal and microfilled composites. Dental Materials, 23 (2007), 51-59). Samples were cured and polished into 2 mm by 6 mm diameter cylinders and subjected to indent testing using a microhardness tester with a diamond tip. A load of 200 grams was placed onto the surface of the sample for 30 seconds. The length of the diamond indent was measured using an optical microscope. The Vickers Hardness Number was calculated by the following formula:

VHN = 1854.4P/d2 where VHN is the Vickers hardness in kg/mm², P is the load in grams and d is the length of the diagonals in μπι.

[0109] FIG. 15 provides optical images of composite resins containing various microparticulate fillers: inverse opal, combined, and compound (corresponding to samples A, B, and C in FIGS. 1 A-1C, FIG. 2 and FIGS. 3A-3C) and traditional non-structured nanofiller. For comparison an example of human teeth in emission and reflectance modes are also shown. The arrows point to a restoration that has a very different appearance. Note that in these examples the composite containing compound opal microparticles showed the most interesting optical properties, similar to those of natural teeth.

[0110] FIG. 16 demonstrates a series of samples containing inverse and compound opal microfillers in fluorescence mode (illuminated with 365 nm light). The intensity and the peak of the emission can be adjusted by choosing the composition, structure, and preparation procedure in accordance with the description and embodiments provided herein.

[0111] FIG. 17 provides a comparison the optical properties of dental restoration composites incorporating nanostructured fillers to those of natural teeth and to a conventional composite incorporating non- structured filler. The composites incorporating nanostructured fillers provide a more natural appearance similar to that of natural teeth.

[0112] FIG. 18A is a fluorescence spectra of a series of samples containing resins and micro- structured fillers in accordance with certain embodiments. Note that the compound micro- structured fillers produced the highest emission intensity. For the sake of comparison the different types of resins contain the same volume fraction of the various fillers.

[0113] FIG. 18B provides schematic examples of light-induced processes (energy transfer and slow-light effect) that may occur within the resin containing micro- structured fillers and influence the macroscopic appearance, enhance the stability, and capable of facilitating longer curing depth. Various formulations can be used to achieve desired properties. For example, the microparticles can have different sizes such that one provides a particular optical function and another provides a "slow light" function to improve curing properties.

Another type of particles can be included to provide certain mechanical functionality and yet another type can induce curing.

Applications

[0114] Including but not limited to dentistry materials, cosmetic materials, 3D printing photo-curable materials, adhesives, protecting enclosures, photo-luminescent optical elements, iridescent optical elements.

[0115] In accordance with one aspect, a method for using the composite resin disclosed herein is described. The method comprises applying an uncured resin to a substrate, wherein the uncured resin comprises a curable resin having dispersed therein micro-structured particles, and exposing the uncured resin to a curing light having a predetermined curing wavelength, thereby curing the resin. In particularly useful aspects, the substrate is a tooth.

[0116] In accordance with one aspect, the curable resin described herein can be used as a dental composition to treat an oral surface such as tooth, as known in the art. In some embodiments, the compositions can be hardened by curing after applying the dental composition. For example, when the curable dental composition is used as a restorative such as a dental filling, the method generally comprises applying the curable composition to an oral surface (e.g. cavity); and curing the composition. In some embodiments, a dental adhesive may be applied prior to application of the curable dental restoration material described herein. Dental adhesives are also typically hardened by concurrent curing with the highly filled dental restoration composition. The method of treating an oral surface may comprise providing a dental article and adhering the dental article to an oral (e.g. tooth) surface.

[0117] In other embodiments, the compositions can be cured into dental articles prior to applying. For example, a dental article such as a crown may be pre-formed from the curable dental composition described herein. Dental composite (e.g. crowns) articles can be made from the curable composition described herein by casting the curable composition in contact with a mold and curing the composition. Alternatively, dental composites or articles (e.g. crowns) can be made by first curing the composition forming a mill blank and then mechanically milling the composition into the desired article.

[0118] Another method of treating a tooth surface comprises providing a dental composition as described herein wherein the composition is in the form of a (partially cured) curable, self-supporting, malleable structure having a first semi-finished shape; placing the curable dental composition on a tooth surface in the mouth of a subject; customizing the shape of the curable dental composition; and hardening the curable dental composition. The customization can occur in the patient's mouth or on a model outside the patient's mouth.

[0119] As used herein, the terms "about" and "approximately" generally mean plus or minus 10% of the value stated, e.g., a value of about 250 would include 225 to 275, and about 1,000 would include 900 to 1, 100.

EXAMPLES

Example 1

[0120] Macroscopic samples of polystyrene direct opal structures were prepared through evaporation of monodispersed (PDI < 5%) polystyrene colloids with a diameter of 360 nm (additional series of samples with different pore size were prepared in a similar fashion described herein). The structures were infiltrated in three repetitive steps with a silica precursor solution (a mixture of tetraethyl orthosilicate: water: methanol: HC1 in the proportions 5: 2.3 : 4: 0.65) while allowing the structure to dry for ~1 hour in between each infiltration. Then the structures were calcined in air at 500°C for two hours. Part of the IO was ground to obtain a powder with particles dimensions below 30 μπι. The remaining portion was infiltrated with an aqueous solution of zirconia nanocrystals (-20 wt%) in three repetitions and eventually re-calcined. Separately, solutions of zirconia nanocrystals and the silica precursor were dried in vials and the resulting solids were calcined at the same conditions as previously described. All calcined materials were ground to obtain powders with particles smaller than 30 μιη and functionalized with 3-(Trimethoxysilyl)propyl acrylate in order to facilitate their integration into the resin. Sample A (FIG. 1 A) was prepared by combining powders of unstructured silica and zirconia. Sample B (FIG. IB) was prepared by combining structured (inverse opal) silica microparticles with unstructured zirconia. Sample C (FIG. 1C) was prepared using zirconia infiltrated silica inverse opal microparticles (compound opal microparticles). The powders were mixed with a photocurable resin (50 wt% Bis-GMA, 49.22 wt% TEGDMA, 0.3 wt% camphorquinone, 0.3 wt% DMABE, 0.12 wt% BHT, and 0.06 wt% UMBP) transferred into molds and cured for 6-30 sec by illuminating with an LED light-source (420-485 nm, 2000 mw/cm²) used for dental curing. For the demonstration of the effects obtained due to the use of micro- structured particles samples A, B, and C all contain the identical weight % of the same components (i.e. silica, zirconia, and resin). The results shown in FIGS 2-9 clearly demonstrate the superiority of the structured fillers, as compared to non- structured fillers when present in same amount, in terms of their optical, curing and mechanical properties as well as the ability to fine-tune these properties by varying such parameters as the periodicity, refractive index, and crystallinity of the matrix material.

Example 2

[0121] Microparticles with IO structures (pore size 300 nm) were prepared using the same procedure as described above, with the colloidal dispersion containing metal-oxide precursors of both silica and zirconia in proportions corresponding to 0, 20, 50, and 80 mol% of zirconia in the final IO (representative images of IO with different compositions are shown in FIG 9). Pure silica IO microparticles were prepared with pore diameters of 270, 300, and 360 nm. The influence of the pore size and composition of the microparticulate filler on the optical and mechanical properties of the resulting composite resins were qualitatively and quantitatively characterized as shown in FIGs 10-14. The results clearly demonstrate the superiority of the structured fillers, as compared to non- structured fillers when present in same amount, in terms of their optical, processing/curing and mechanical properties as well as the ability to fine-tune these properties by varying such parameters as the periodicity, refractive index, and crystallinity of the matrix material.

[0122] Modifications to the materials and quantities as well as employment of other top- down or bottom-up techniques (i.e. self-assembly, photolithography, micro-imprinting, electrochemical deposition/etching, structure preserving chemical transformation, acoustic templating, etc. and their combinations) may result in the formation of structured microparticles that can be used for the preparation of composite resins as described in the current disclosure without departing from the essence of the invention.

[0123] Upon review of the description and embodiments provided herein, those skilled in the art will understand that modifications and equivalent substitutions may be performed in carrying out the invention without departing from the essence of the invention. Thus, the invention is not meant to be limiting by the embodiments described explicitly above.

Claims

CLAIMS What is claimed is:

1. A composite resin comprising a curable resin having dispersed therein micro-structured particles.

2. The composite resin of claim 1, wherein the micro- structured particles are direct porous opal, inverse opal and/or compound opals.

3. The composite resin of claim 1 or 2, wherein the largest exterior dimension of the micro- structured particles is within the range of 10 nanometers to 5mm.

4. The composite resin of any one of the preceding claims, wherein the micro- structured particles are stoichiometric.

5. The composite resin of any one of claims 1-3, wherein the micro- structured particles are non-stoichiometric.

6. The composite resin of any one of the preceding claims, wherein the micro- structured particles comprise an oxide selected from the group consisting of silica, zirconia, alumina, titania, yttria, ceria, hafnia, iron oxides, molybdenum oxides, tungsten oxides, rhenium oxides, tantalum oxides, niobium oxides, chromium oxides, scandium oxides, lanthanum oxides, rare earth oxides, thorium oxides, uranium oxides, mixed oxides and combinations thereof.

7. The composite resin of any one of claims 1-5, wherein the micro- structured particles comprise compound structures composed of two or more oxides selected from the group consisting of silica, zirconia, alumina, titania, yttria, ceria, hafnia, iron oxides, molybdenum oxides, tungsten oxides, rhenium oxides, tantalum oxides, niobium oxides, chromium oxides, scandium oxides, lanthanum oxides, rare earth oxides, thorium oxides, and uranium oxides.

8. The composite resin of any one of the preceding claims, wherein the composite resin contains solid components in a range of 0.5% to 99.5% by volume.

9. The composite resin of any one of the preceding claims, wherein the micro- structured particles comprise S1O2 inverse opal.

10. The composite resin of any one of the preceding claims, wherein the micro- structured particles comprise ZrCh.

11. The composite resin of any one of the preceding claims, wherein the micro- structured particles comprise S1O2 inverse opal filled with ZrCh.

12. The composite resin of any one of the preceding claims, wherein the curable resin comprises a thermally-curable or photocurable polymer.

13. The composite resin of claim 12, wherein the curable resin comprises an acrylate-based polymer.

14. The composite resin of claim 13, wherein the acrylate-based polymer is selected from the group consisting of triethylene glycol dimethacrylate (TEGDMA), bisphenol A glycerolate dimethacrylate (BisGMA), urethane dimethacrylate (UDMA) and mixtures thereof.

15. The composite resin of any one of the preceding claims, further comprising camphorquinone (CQ), 4-dimethylaminobenzoic acid ethyl ether (DMABE), 3, 5-di-tert- butyl-4-hydroxytoluene (BHT), and 2-hydroxy-4-methoxybenzophenone (HMBP).

16. The composite resin of any one of the preceding claims, wherein the curable resin comprises a dimethacrylate resin.

17. The composite resin of any one of the preceding claims, wherein the micro- structured particles further comprise metals, semiconductors, organometallic compounds, inorganic polymers, organic materials, natural materials, polymeric materials, and mixtures thereof.

18. The composite resin of claim 17, wherein the micro-structured particles comprise nanoparticles that change optical and/or antibacterial properties of the composite resin.

19. The composite resin of any one of the preceding claims, wherein the micro- structured particles comprise structural defects that provide at least one of: luminescent appearance to the cured resin and improve curing by slowing light effect.

20. The composite resin of any one of claims 1-8, wherein the micro-structured particles are compound inverse opals comprising a first material and a second material, wherein the second material fills pores in the inverse opal comprising the first material.

21. The composite resin of any one of claims 1-8, wherein the resin contains a plurality of different types of micro-structured particles differing in at least one property selected from the group consisting of pore size, composition, particle size, pore fillers, and nanoparticles.

22. A method comprising: applying an uncured resin to a substrate, wherein the uncured resin comprises a curable resin having dispersed therein micro-structured particles; and exposing the uncured resin to a curing light having a predetermined curing wavelength range, thereby curing the resin.

23. The method of claim 22, wherein the micro- structured particles are inverse opals.

24. The method of claim 23, wherein the inverse opals comprise pores that are filled with a different material than that forming the inverse opal.

25. The method of any one of claims 22 to 24, wherein the micro-structured particles are fluorescent under light of the curing wavelength.

26. The method of any one of claims 22-25, wherein the substrate is a tooth.

27. The method of any one of claims 22-26, wherein exposing the uncured resin to a curing light resin cures the resin to a depth of up to about 5mm.

28. The method of claim 26, wherein the cured resin more closely matches the color, opaqueness, fluorescence and luminescence properties of the tooth than the same resin containing fillers that are not micro- structured but of the same chemical composition.

29. The method of claim 26, wherein the cured resin more closely matches the mechanical properties of the tooth than the same resin containing fillers that are not micro- structured but of the same chemical composition.