Methods and compositions including chain transfer agents in absorbing photopolymerizable formulations - Patents.com

Abstract

Compounds and compositions are provided that are useful for additive printing, particularly additive printing techniques such as stereolithography (SLA), in which a composition of one or more photocurable compounds, such as a compound having multiple ethylenically unsaturated groups and a compound having multiple thiol groups, is photopolymerized, optionally the polymerizable composition comprises two or more thermosetting compounds that are reactive with each other, optionally the polymerizable composition comprises one or more chain transfer agents, and optionally is subjected to thermal polymerization to form an article manufactured in solid form.

Description

[Technical field]

[0001] INCORPORATION BY REFERENCE TO PRIORITY APPLICATION Any and all applications for which a foreign or domestic priority claim is identified in the Application Data Sheet filed along with this application are hereby incorporated by reference.

[0002] The present disclosure relates generally to the preparation and use of curable compositions, such as photocurable and thermocurable compositions containing chain transfer agents, and their degradation products, used to prepare articles, such as bioabsorbable implants, by additive manufacturing processes. [Background technology]

[0003] Stereolithography (SLA) is a relatively well-developed additive printing technique for preparing three-dimensional (3D) objects. Stereolithography methods use light, such as ultraviolet (UV) or visible light, to photopolymerize liquid materials with high accuracy and precision into designed structures, such as three-dimensional articles. Thin successive layers are photopolymerized by UV or visible light, for example, under the direction of a sliced ​​CAD (computer-aided design) model.

[0004] SLA generally uses liquid photopolymerizable compositions, which may be referred to as resin or ink formulations. The macroscopic properties and degradation profiles of articles produced by SLA depend in part on the polymer chemistry and processing techniques.

[0005] After SLA polymerization of absorbable macromers with ethylenically unsaturated functional groups, the absorbable polymer segments can be degraded by hydrolysis or enzymatic degradation to leave a non-absorbable polymer (i.e., backbone) from the reacted ethylenically unsaturated groups. For such formulations to be implantable in or on a living body, it is desirable for the non-absorbable polymer to be water soluble and have a molecular weight of less than approximately 20,000 Da, so that these degradation products can be excreted by the kidney. Ethylenically unsaturated polyesters that are free radically polymerized and subsequently degraded are now known to have degradation products, such as the polymer backbone, with molecular weights much greater than 20,000 Da. This may be the case for photopolymerization methods that use biocompatible implantable resins with low photoinitiator concentrations to reduce toxicity from the photoinitiator compound.

[0006] The present disclosure provides compounds and compositions useful in actinic radiation reactive 3D printing processes, including but not limited to stereolithography (SLA) and digital light processing (DLP) methods, for producing 3D photoprinted articles having degradation products, particularly desirable 3D photoprinted articles for implanted articles such as medical devices. The disclosed compounds and compositions have advantages over currently known compounds and compositions for this purpose.

[0007] All of the subject matter discussed in the Background section is not necessarily prior art, and should not be assumed to be prior art merely as a result of its discussion in the Background section. Along these lines, any recognition of a problem in the prior art that is discussed in the Background section or that relates to such subject matter should not be treated as prior art unless expressly stated to be prior art. Instead, the discussion of any subject matter in the Background section should be treated as part of the inventor's approach to a particular problem, and may be the invention in and of itself. Summary of the Invention

[0008] Briefly, in one aspect, the present disclosure provides compounds and compositions useful for reducing degradation products resulting from a curing process, such as a photocuring process, or a thermal curing process used in conjunction with a photocuring process. The curing process is useful for producing articles and coatings, such as medical devices. An exemplary curing process is stereolithography (SLA), which is an additive manufacturing process in which a curable composition according to the present disclosure, containing one or more photoreactive compounds, including, for example, a photoreactive macromer, is photopolymerized (photocured) during the process to form a manufactured article. Another exemplary process is a coating process in which the compounds and / or compositions of the present disclosure are placed on a surface and then cured by exposure to heat (thermal curing) and / or actinic radiation (i.e., photopolymerization or photocuring) to provide a coating on the surface. These cured products, i.e., products formed by curing the compositions disclosed herein, may generally be referred to herein as articles, coatings, films, materials, and the like. Thus, where the present disclosure is illustrated by preparing an article, it is understood that a coating or other material may be prepared as well. In one aspect, the articles, coatings, and the like are biodegradable.

[0009] In one aspect, the present disclosure provides a biodegradable polymeric material formed by a curing process. The material can be used to produce an article with a limited lifespan, such that after a period of time, the article formed from the biodegradable material no longer exists. For example, the material can be a coating on a device, such as a medical device, which degrades after a period of time. In another example, the material can be used to prepare a medical device, such as a mesh for tissue repair, whereby after a period of time, some or none of the article is present and tissue repair is achieved. As another example, the medical device can be a tissue adhesive or sealant, and the polymerizable composition of the present disclosure can be applied to tissue that requires an adhesive or sealant, and then the composition is exposed to sufficient actinic radiation to cause photopolymerization of the composition on the tissue.

[0010] According to the present disclosure, in one embodiment, stereolithography may be used to prepare such materials and articles, for example, using the compounds and compositions disclosed herein. The present disclosure addresses concerns regarding heat- and light-cured materials, such as SLA-generated articles, that come into contact with living organisms, including concerns regarding the safety and efficacy of the generated articles, particularly their biocompatibility and cytotoxicity.

[0011] In one aspect, the present disclosure provides for the preparation and use of polymeric compositions, including, for example, one or more chain transfer agents and / or one or more additives. The polymeric compositions may include or be made from photopolymerizable polymers, including homopolymers, copolymers, block copolymers, random copolymers, random block copolymers, or combinations thereof. The polymeric compositions may include or be made from thermoplastic polymers, including homopolymers, copolymers, block copolymers, random copolymers, random block copolymers, or combinations thereof. In one aspect, the polymeric compositions may be characterized as being double network, where two chemically different polymers are present in the composition in a mixture, and optionally, the double network polymeric composition is solid after curing. In one aspect, the polymeric compositions may be characterized as being single network, where a single polymer is present in the composition, and optionally, the single network polymeric composition is solid after curing. In one aspect, the single network includes a crosslinked polymer. In one aspect, the double network includes a crosslinked polymer. The polymeric compositions disclosed herein may be used, for example, to prepare bioabsorbable implants by additive manufacturing processes. Use of the term polymer is intended to refer to a single chemical or physical type of polymer or to a composition of many individual polymer molecules. In some cases, the term polymer may refer to individual polymer molecules. One of skill in the art will be able to discern from this disclosure the intended meaning and logical meaning of the written terms.

[0012] In one aspect, the disclosure provides a composition comprising (1) a compound having multiple photopolymerizable groups, referred to herein as polyhv, and / or (2) a mixture of two compounds that are thermally reactive (thermosetting) with each other to form a polymer, the two compounds being referred to herein as polyΔ1 and polyΔ2, or collectively referred to as polyΔ (i.e., polyΔ refers to a mixture of polyΔ1 and polyΔ2). In one aspect, the composition additionally comprises a photoinitiator. In an aspect, the composition additionally comprises one or more chain transfer agents. In one aspect, the composition additionally comprises one or more additives. In one aspect, the composition additionally comprises a stabilizer. In one aspect, the disclosure provides a cured, optionally crosslinked composition resulting from photopolymerization of a composition comprising a photoinitiator, optionally one or more chain transfer agents, optionally one or more additives, polyHv, and / or polyΔ, the cured (e.g., crosslinked) composition may be said to have a single network, referring to a network formed from polyhv reacting with itself or polyΔ reacting with itself. In one embodiment, the present disclosure provides a double network composition resulting from a composition comprising a photoinitiator, optionally one or more chain transfer agents, optionally one or more additives, polyhv, and / or polyΔ, where photopolymerization of polyhv and thermal polymerization of polyΔ1 with polyΔ2 results in a double network, one or both of which are optionally crosslinked, where each of polyhv and polyΔ forms an independent network. The two independent networks together form a double network that interpenetrates each other. Thus, the double network is formed by thermally curing and photocuring a composition having both a thermally reactive component (polyΔ1 and polyΔ2) and at least one photoreactive component (polyhv), a photoinitiator and one or more chain transfer agents, and optionally one or more additives. In one embodiment, photocuring precedes thermal curing. In one embodiment, thermal curing precedes photocuring. In one embodiment, photocuring and thermal curing occur simultaneously.

[0013] In one aspect, the disclosure provides a composition comprising 1) a compound having a plurality of photopolymerizable thiol groups, herein referred to as poly-SH, and 2) a compound having a plurality of photopolymerizable ethylenically unsaturated groups, herein referred to as poly-EU, where poly-SH and poly-EU are photoreactive with each other. In one aspect, the composition additionally comprises a photoinitiator. In one aspect, the composition additionally comprises one or more chain transfer agents. In one aspect, the composition additionally comprises one or more additives. In one aspect, the composition additionally comprises a stabilizer. In one aspect, the disclosure provides a single network polymer composition resulting from photocuring (photopolymerizing) a composition comprising a photoinitiator, one or more chain transfer agents, one or more additives, poly-SH, and poly-EU. In one aspect, the disclosure provides a single network crosslinked composition resulting from photocuring (photopolymerizing) a composition comprising a photoinitiator, one or more chain transfer agents, one or more additives, stabilizers, poly-SH, and poly-EU. In another aspect, the disclosure provides a single network crosslinked composition resulting from photocuring (photopolymerizing) a composition comprising a photoinitiator, one or more chain transfer agents, one or more additives, stabilizers, poly-SH, and poly-EU. Exemplary EU groups are acrylate, methacrylate, and norbornenyl, where polyEU refers to a compound containing multiple EU groups, optionally 2 EU groups, or 3 EU groups, or 4 EU groups.

[0014] In one aspect, methods and compositions for curing processes such as 3D printing and for making and using the resulting cured article are disclosed herein.For example, the present disclosure provides a method for photopolymerization printing an article, comprising: a) exposing a photopolymerizable composition comprising polyEU macromer and polySH disclosed herein, optionally combined with one or more other components such as at least one photoinitiator component, and / or at least one light reflecting material component comprising a light reflecting material suspended in the composition, and / or one or more chain transfer agents, and / or at least one stabilizer, and / or one or more additives, to light of a suitable wavelength for a period of time, and forming a printing article comprising the polymerization product of the photopolymerizable composition. In another aspect, the present disclosure provides a method for photopolymerization printing an article, comprising: a) exposing a photopolymerizable composition comprising polyhv, polyΔ1, and polyΔ2 to light of a suitable wavelength for a period of time; b) thermally polymerizing polyΔ1 in combination with polyΔ2, and optionally other components such as at least one photoinitiator component, and / or at least one light reflecting material component comprising a light reflecting material suspended in the composition, and / or at least one stabilizer, and / or one or more chain transfer agents, and / or one or more additives; and forming a printing article comprising the polymerization product of the photopolymerizable composition.

[0015] In one aspect, photopolymerization processes, such as film-forming processes, including coating processes, and methods and compositions for making and using such photopolymerized materials are disclosed herein.For example, the present disclosure provides a method for photopolymerization coating of an article, comprising: a) applying the photopolymerizable composition of the present disclosure to a surface; b) exposing the photopolymerizable composition comprising polyEU and polySH disclosed herein, optionally combined with one or more other components, such as at least one photoinitiator component, and / or at least one light-reflecting material component comprising a light-reflecting material suspended in the composition, and / or at least one stabilizer, and / or one or more chain transfer agents, and / or one or more additives, to light of suitable wavelength for a certain period of time, and forming a solid coating comprising the polymerization product of the photopolymerizable composition.

[0016] In other aspects, the present disclosure provides a polymerization product of a macromer (which may also be referred to as a prepolymer), where the macromer has been polymerized, for example, by one or more methods disclosed herein. Additionally, the present disclosure provides an article, which may be referred to as a polymeric article, produced from a photopolymerizable compound or composition disclosed herein, optionally by one or more methods disclosed herein. The photopolymerized macromer or article may be a non-toxic article. Additionally, the article may include a biodegradable photopolymerized macromer, optionally mixed with a non-toxic amount of a photoinitiator. Optionally, the article may include a biodegradable photopolymerized macromer, optionally mixed with a non-toxic amount of a stabilizer, and / or one or more chain transfer agents, and / or one or more additives. Optionally, the article may include a biodegradable photopolymerized macromer, optionally mixed with a non-toxic amount of a UV-reflective material. In one aspect, the polymeric article is biodegradable in whole or in part under physiological conditions. However, in alternative aspects, the polymeric article is not biodegradable under physiological conditions.

[0017] Additionally, the present disclosure provides photopolymerizable compounds, also referred to herein as macromers, that include a polyaxial central core (CC) and extending from the central core two to four arms of the formula (A)-(B) or (B)-(A), at least one of the arms includes a photoreactive functional group (Q), where (A) is the polymerization product of monomers selected from trimethylene carbonate (also referred to herein as T, or TMC) and ε-caprolactone (also referred to herein as caprolactone, or C, or CAP), and (B) is the polymerization product of monomers selected from glycolide, lactide, and p-dioxanone. The macromers can be the photopolymerizable macromer component in the compositions and methods disclosed herein and can be photopolymerized to provide articles. Other macromers may include photopolymerizable compounds that are derived from the following classes of polymers or are combinations of the following categories of polymers: polyesters, polycarbonates, polyanhydrides, polyorthoesters, polyhydroxyalkonoates, polyurethanes, polypeptides, polyethers, polythioethers, polyamides, and copolymers of naturally derived polymers. Some examples of naturally derived polymers include, but are not limited to: chitosan, hyaluronic acid, pectin, and cellulose. Some examples of polyesters include, but are not limited to, homopolymers and copolymers derived from lactide, glycolide, caprolactone, and p-dioxanone. Some examples of polycarbonates and polycarbonate esters include, but are not limited to, polytrimethylene carbonate, poly(trimethylene carbonate-co-caprolactone), poly(trimethylene carbonate-co-caprolactone-co-glycolide), and poly(trimethylene carbonate-co-caprolactone-co-lactide).

[0018] Optionally, any of the compositions of the present disclosure, before they are cured, may contain an effective amount of at least one photoinitiator, i.e., an amount of photoinitiator effective to effect polymerization of the photopolymerizable compound when the composition is exposed to radiation emitted from a light source delivering a selected wavelength of light suitable for activating the photoinitiator.

[0019] In one aspect, the present disclosure provides a method of additive printing, e.g., 3D printing, also known as stereolithography, comprising providing a polymerizable composition as disclosed herein having a photopolymerizable compound and at least one photoinitiator, and optionally one or more chain transfer agents, one or more additives, and exposing the composition to light effective to activate the photoinitiator to photopolymerize the photopolymerizable compound in the polymerizable composition. In one aspect, the composition is selectively exposed to light, thereby undergoing photopolymerization in selected portions of the composition but not all of it. In one aspect, the photopolymerizable compound is a mixture comprising one or more polyhv compounds, e.g., two photopolymerizable compounds, herein designated polyEU and polySH. In one aspect, the one or more photopolymerizable compounds are mixed with one or more thermally reactive compounds, e.g., two thermally reactive compounds, herein designated polyΔ1 and polyΔ2. In one embodiment, the polymerizable composition further comprises other ingredients including, but not limited to, one or more stabilizers, one or more photoinitiators, one or more light reflecting materials suspended in the composition, one or more chain transfer agents, one or more additives, and one or more pigments.

[0020] Below are some exemplary embodiments of the present disclosure. 1) A composition comprising a first organic compound (polyEU) having a plurality of ethylenically unsaturated groups (EU), optionally a second organic compound (polySH) having a plurality of thiol groups (SH), a photoinitiator, and one (i.e., at least one) chain transfer agent. 2) The composition of embodiment 1, wherein at least one of the first organic compound, the optional second organic compound, the photoinitiator, or the chain transfer agent is bioabsorbable. 3) The composition of embodiment 1, wherein the chain transfer agent is present in a ratio of moles of chain transfer agent functional group (e.g., thiol) to moles of ethylenically unsaturated groups of from 0.03 to 0.80. 4) The composition of embodiment 1, comprising a dye, pigment, or UV absorber that is of biological origin. 5) The composition of embodiment 4, wherein the dye, pigment, or UV absorber is a biologically derived molecule selected from carotenoids, flavonoids, flavones, quinones, porphyrins, diketones, and betacyanidins. 6) The composition of embodiment 4, wherein the dye, pigment, or UV absorber is beta-carotene. 7) The composition of embodiment 1 having an SH to EU equivalent ratio of X:Y, where X is in the range of 25 to 75, Y is in the range of 75 to 25, and the sum of X and Y is 100. 8) The composition of embodiment 1, wherein polySH is water-soluble. 9) The composition of embodiment 1, wherein polySH is bioabsorbable. 10) The composition of embodiment 1, wherein the poly-SH is a macromer. 11) The composition of embodiment 1, wherein poly-SH is a macromer having a molecular weight greater than 1,000 g / mol. 12) The composition of embodiment 1, wherein polySH has a molecular weight of less than 500 g / mol. 13) The composition of embodiment 1, wherein PolyEU is water-soluble. 14) The composition of embodiment 1, wherein PolyEU is bioabsorbable. 15) The composition of embodiment 1, wherein the EU of the PolyEU is an acrylate. 16) The composition of embodiment 1, wherein the EU of the polyEU is a methacrylate. 17) The composition of embodiment 1, wherein EU of the polyEU is norbornenyl. 18) The composition of embodiment 1, wherein the polyEU is a macromer. 19) The composition of embodiment 1, wherein PolyEU is a macromer having a molecular weight greater than 1,000 g / mol. 20) The composition of embodiment 1, wherein at least one of poly-SH and poly-EU further comprises multiple carbonyl groups, and optionally poly-EU comprises multiple carbonyl groups, or optionally poly-SH and poly-EU each comprise multiple carbonyl groups. 21) The composition of embodiment 1, wherein at least one of poly-SH and poly-EU further comprises multiple ester groups, and optionally poly-EU comprises multiple ester groups, or optionally poly-SH and poly-EU each comprise multiple carbonyl groups. 22) The composition of embodiment 1, wherein at least one of PolyEU and PolySH further comprises multiple ester groups and multiple carbonate groups, optionally PolyEU comprises both multiple ester groups and multiple carbonate groups, or optionally both PolySH and PolyEU further comprise both multiple ester groups and multiple carbonate groups. 23) The composition of embodiment 1, wherein at least one of Poly-SH and Poly-EU further comprises multiple ester groups and multiple urethane groups, and optionally Poly-EU further comprises both multiple ester groups and multiple urethane groups, or optionally both Poly-SH and Poly-EU further comprise both multiple ester groups and multiple urethane groups. 24) The composition of embodiment 1, wherein at least one of Poly-SH and Poly-EU further comprises multiple carbonate groups and multiple urethane groups, and optionally Poly-EU further comprises both multiple carbonate groups and multiple urethane groups, or optionally both Poly-SH and Poly-EU further comprise both multiple carbonate groups and multiple urethane groups. 25) The composition of embodiment 1, wherein the plurality of SHs of the polySH are selected from 2, 3, and 4. 26) The composition of embodiment 1, wherein the plurality of EUs in the polyEU is selected from 2, 3, and 4. 27) The composition of embodiment 1, wherein the composition does not contain any volatile materials having a boiling point less than 110° C. 28) The composition of embodiment 1, which is anhydrous. 29) The composition of embodiment 1, which is fluid at room temperature, from about 18° C. to about 22° C. 30) A composition comprising a photochemically cured reaction product of any of the compositions of embodiments 1-29, which upon decomposition results in degradation products (or polymer backbone) having a molecular weight of less than 20,000 Daltons. 31) The composition of embodiment 30, which is bioabsorbable. 32) The composition of embodiment 30, which is solid at 50° C. 33) An additive manufacturing process comprising: a. providing a batt comprising a first composition of any one of embodiments 1-29; b. directing actinic radiation from a light source toward the first composition in the vat, the actinic radiation being effective to induce polymerization of components of the composition to form a second composition; c. forming a solid article comprising the second composition. 34) A composition comprising a first organic compound (polyhv) having a plurality of photopolymerizable groups (hv), a photoinitiator, a second organic compound (polyΔ1) having a plurality of reactive groups Δ1, and a third organic compound (polyΔ2) having a plurality of reactive groups Δ2, wherein Δ1 reacts with Δ2 upon contact and exposure to a temperature greater than 50° C., and optionally a chain transfer agent. 35) The composition of embodiment 34, wherein polyhv is bioabsorbable. 36) The composition of embodiment 34, wherein polyhv is a macromer. 37) The composition of embodiment 34, wherein polyhv is a macromer having a molecular weight greater than 1,000 g / mol. 38) The composition of embodiment 34, wherein polyhv has a molecular weight of less than 500 g / mol. 39) The composition of embodiment 34, wherein polyhv is water-soluble. 40) The composition of embodiment 34, wherein polyhv is polyEU selected from acrylates and methacrylates. 41) The composition of embodiment 34, wherein the hv of polyhv is norbornenyl. 42) The composition of embodiment 34, wherein Δ1 is a nucleophile and Δ2 is an electrophile. 43) The composition of embodiment 34, wherein Δ1 is selected from hydroxyl and amino. 44) The composition of embodiment 34, wherein Δ2 is selected from epoxides and isocyanates. 45) The composition of embodiment 34, wherein at least one of poly hv, poly Delta 1, and poly Delta 2 further comprises multiple carbonyl groups, and optionally poly hv comprises multiple carbonyl groups, or optionally poly hv and at least one of poly Delta 1 and poly Delta 2 comprise multiple carbonyl groups. 46) The composition of embodiment 34, wherein at least one of poly-hv, poly-Δ1, and poly-Δ2 further comprises multiple ester groups, and optionally poly-hv comprises multiple ester groups, or optionally poly-hv and at least one of poly-Δ1 and poly-Δ2 comprise multiple ester groups. 47) The composition of embodiment 34, wherein at least one of poly hv, poly Delta 1, and poly Delta 2 further comprises multiple ester groups and multiple carbonate groups, and optionally poly hv comprises both multiple ester groups and multiple carbonate groups, or optionally at least one of poly hv and poly Delta 1 and poly Delta 2 comprises both multiple ester groups and multiple carbonate groups. 48) The composition of embodiment 34, wherein at least one of polyhv, polyΔ1, and polyΔ2 further comprises multiple ester groups and multiple urethane groups, and optionally polyhv comprises both multiple ester groups and multiple urethane groups, or optionally polyhv and at least one of polyΔ1 and polyΔ2 comprise both multiple ester groups and multiple urethane groups. 49) The composition of embodiment 34, wherein at least one of polyhv, polyΔ1, and polyΔ2 further comprises multiple carbonate groups and multiple urethane groups, and optionally polyhv comprises both multiple carbonate groups and multiple urethane groups, or optionally polyhv and at least one of polyΔ1 and polyΔ2 comprise both multiple carbonate groups and multiple urethane groups. 50) The composition of embodiment 34, wherein the multiple hv of the polyhv are selected from 2, 3, and 4. 51) The composition of embodiment 34, wherein the plurality of Δ1 in the polyΔ1 is selected from 2, 3, and 4. 52) The composition of embodiment 34, wherein the plurality of Δ2 of polyΔ2 is selected from 2, 3, and 4. 53) The composition of embodiment 34, wherein the composition does not contain any volatile materials having a boiling point less than 110° C. 54) The composition of embodiment 34, which is anhydrous. 55) The composition of embodiment 34, which is fluid at a temperature of about 18°C ​​to about 22°C. 56) A composition comprising a photochemically cured reaction product and a thermally cured reaction product of any of the compositions of embodiments 34-55, which when decomposed results in a degradation product (or polymer backbone) having a molecular weight of less than 20,000 Daltons. 57) The composition of embodiment 56, which is bioabsorbable. 58) The composition of embodiment 56, which is solid at 50° C. 59) An additive manufacturing process comprising: a. providing a batt comprising a first composition of any one of embodiments 34-55; b. directing actinic radiation from a light source at the first composition in the vat, the actinic radiation being effective to induce polymerization of components of the first composition to form a second composition comprising a photochemically cured composition; c. applying thermal energy to the second composition comprising the photochemically cured composition to form a third composition comprising a photochemically cured composition and a thermally cured composition. 60) The composition of embodiment 1, comprising a second organic compound, and as further described by any one of embodiments 2-29. 61) The composition of embodiment 1, comprising a second organic compound, and as further described by any two or more of embodiments 2-29. 62) The composition of embodiment 34, comprising a chain transfer agent, and as further described by any one of embodiments 35-55. 63) The composition of embodiment 34, further comprising a chain transfer agent, as further described by any two or more of embodiments 35-55.

[0021] The above and additional features of the present disclosure, and the means for obtaining the same, will become apparent, and the disclosure will be best understood by reference to the following more detailed description, in which: All references disclosed herein are incorporated by reference in their entirety as if each were individually incorporated.

[0022] This Summary is provided to introduce certain concepts in a simplified form that are further described in detail below in the Detailed Description. Unless expressly stated otherwise, this Summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to limit the scope of the claimed subject matter.

[0023] Details of one or more embodiments are set forth in the following description. Features illustrated or described in connection with one exemplary embodiment may be combined with features of other embodiments. Any of the various embodiments described herein may be combined to provide further embodiments. If necessary, aspects of the embodiments may be modified to provide still further embodiments, employing concepts from the various patents, applications, and publications identified herein. Other features, objects, and advantages will become apparent from the description, drawings, and claims.

[0024] The above and additional features of the present disclosure, and the means for obtaining the same, will become apparent, and the disclosure will be best understood by reference to the following more detailed description, in which: All references disclosed herein are incorporated by reference in their entirety as if each were individually incorporated.

[0025] Exemplary characteristics of the present disclosure, its nature, and various advantages will be apparent from the following detailed description of various embodiments and the accompanying drawings. Non-limiting and non-exhaustive embodiments are described with reference to the accompanying drawings, in which like designations or reference numbers refer to like parts throughout the various drawings unless otherwise specified. The sizes and relative positions of elements within the drawings are not necessarily drawn to scale. For example, the shapes of various elements are selected, enlarged, and arranged to improve the readability of the drawings. The particular shapes of the depicted elements are selected for ease of recognition in the drawings. One or more embodiments are described below with reference to the accompanying drawings. [Brief description of the drawings]

[0026] [Figure 1] 1 shows degradation profiles for selected cured compositions of the present disclosure. [Diagram 2] 1 shows water swelling profiles for selected cured compositions of the present disclosure. [Diagram 3] 1 shows the mass loss profile of selected cured compositions with and without the addition of a chain transfer agent. [Figure 4] The mean cell viability and standard deviation (n=3) determined by MTS assay across resin formulations (A-D) and positive (+) and negative (-) controls are shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] The present disclosure may be more readily understood by reference to the following detailed description of preferred embodiments of the present disclosure and examples contained herein. In reading this detailed description, unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure belongs. The singular terms "a", "an" and "the" include plural referents unless the context clearly indicates otherwise. Similarly, the word "or" is intended to include "and" unless the context clearly indicates otherwise. The term "comprises" means "includes". The abbreviation "eg" is derived from the Latin exempli gratia and is used herein to indicate a non-limiting example. Thus, the abbreviation "eg" is synonymous with the term "for example".

[0028] In one aspect, the present disclosure provides compositions that are liquid and capable of undergoing curing at about room temperature, i.e., at temperatures between about 18°C ​​and about 23°C. The curing process may include photocuring, also referred to herein as photopolymerization, and, depending on the composition, may also include thermal curing, also referred to herein as thermal polymerization. Photocuring occurs when the composition is exposed to actinic radiation of a selected energy for a selected period of time to cause a reaction between the photochemical (also referred to herein as photoreactive or photopolymerizable, etc.) components of the composition and an increase in the average molecular weight of the components in the composition. Thermal curing is the corresponding process that is achieved when the composition is heated to a suitable temperature above room temperature for a suitable period of time to cause a reaction between the thermally reactive (also referred to herein as thermally reactive or thermally polymerizable, etc.) components of the composition and an increase in the average molecular weight of the components in the composition. When the reactants include compounds with three or more photoreactive or thermally reactive chemical groups, the curing process thereby provides a composition having crosslinked components. As used herein, curing refers to photocuring, optionally with thermal curing, when the composition has a thermally reactive component.

[0029] The composition of the present disclosure includes a photoreactive component. Optionally, the composition may also include a thermally reactive component. When the composition includes both a thermally reactive component and a photochemically reactive component, the resulting composition may be referred to herein as having a double network or a two-layer network: a first network formed from the photochemically reactive compound and a second network formed from the thermally reactive compound. When the composition includes a photochemically reactive component but does not include a thermally reactive component, the resulting cured composition may be referred to herein as having a single network.

[0030] As described in more detail below, the compositions of the present disclosure may include one or more compounds having at least two photochemically reactive functional groups, designated as "hv" groups, and may optionally include two or more compounds having at least two thermally reactive functional groups, designated as "Δ" groups. The reactive functional groups will be attached to an organic backbone, i.e., a backbone made up of atoms including carbon and hydrogen. As a simple example, when the Δ group is hydroxyl, the thermally reactive compound may be ethylene glycol, i.e., HO-CH2-CH2-OH, where the backbone is -CH2-CH2-.

[0031] When the backbone of a polymer molecule (compound) contains repeating chemical units, the polymer molecule (compound) may be referred to herein as a macromer. For example, the reaction between a small amount of ethylene glycol (called an initiator) and a large amount of a hydroxyl acid or equivalent, such as lactic acid or lactide, will result in a polymer molecule (compound) with two polylactides (repeating lactide units) extending from either end of the ethylene glycol initiator, and with a hydroxyl group at each of the two ends of the polylactide chain. This polymer molecule may be referred to herein as a macromer or compound. In one embodiment, the composition of the present disclosure includes a macromer as a photochemically reactive component and / or a macromer as a thermally reactive component.

[0032] Compounds having two or more hydroxyl groups are exemplary thermally reactive compounds of the present disclosure. Such hydroxyl-containing compounds are thermally reactive with compounds having complementary functional groups, such as epoxide or isocyanate groups. Thus, the compositions of the present disclosure may have a first compound having two or more hydroxyl groups and a second compound having two or more functional groups that are thermally reactive with the hydroxyl groups. In one embodiment, hydroxyl groups are examples of nucleophilic groups, and epoxides are examples of electrophilic groups. Thus, in one embodiment, the thermally reactive compositions of the present disclosure may be described as including compounds having two or more nucleophilic groups and compounds having two or more electrophilic groups.

[0033] In addition to being a compound useful in the thermosetting composition as disclosed herein, hydroxyl-containing compounds are also useful starting materials for preparing photoreactive compounds.For example, as disclosed herein, hydroxyl groups can be converted into thiol-containing groups.In addition, hydroxyl groups can be converted into groups with ethylenic unsaturation.Therefore, the backbone of the hydroxyl-containing compounds disclosed herein can also be present as the backbone or part of the backbone of the photoreactive compound in the composition disclosed herein.When the present disclosure provides a compound with two or more hydroxyl groups, it should be understood that the present disclosure simultaneously provides that the backbone of the hydroxyl-containing compound is optionally present in the photoreactive compound of the present disclosure.

[0034] PolyΔ Compounds In one aspect, the present disclosure provides a composition comprising two polyΔ compounds, herein designated polyΔ1 and polyΔ2. Compound polyΔ1 has a plurality (hence the term "poly") Δ1 groups, which are thermally reactive with Δ2 groups. Compound polyΔ2 has a plurality of Δ2 groups, which are thermally reactive with Δ1 groups. Each of polyΔ1 and polyΔ2 is an organic compound. The term "thermally reactive" means that heat must be applied to a composition comprising polyΔ1 and polyΔ2 in order for Δ1 and Δ2 to react with each other. At room temperature, i.e., about 22° C., and in the absence of a catalyst, Δ1 and Δ2 do not react with each other to any appreciable extent. In one embodiment, the composition of the present disclosure does not include a catalyst that increases the rate of the thermal reaction. Upon reaction, Δ1 and Δ2 form one or more covalent bonds such that polyΔ1 and polyΔ2 become part of a polymer network, optionally a crosslinked polymer network.

[0035] In one embodiment, the polyhydric compound (also referred to as polyol) is a polyΔ compound. For example, an aliphatic polyol having an alkylene group can be used as a polyΔ. Exemplary alkylene groups include ethylene, propylene (branched or linear), butylene (branched or linear), hexylene (branched, linear, or cyclic), and octylene (branched, linear, or cyclic). Exemplary polyols having two or more hydroxyl groups that can be used when crosslinking is required include trimethylolpropane, glycerol, pentaerythritol, 1,2,4-butanetriol, and 2,3,4-pentanetriol.

[0036] In one embodiment, aromatic diols can be used as polyΔ. Examples include catechol, resorcinol, hydroquinone, and their reaction products, such as the reaction product of resorcinol and ethylene carbonate. Other suitable aromatic diols include bisphenol A and 4,4'-dihydroxybiphenyl.

[0037] In one embodiment, polyether diols can be used as polyΔ compounds. Polyether diols introduce polyoxyalkylene segments, or in other words polyether segments, into the cured composition. Polyether diols can include homopolymers of oxyalkylene groups or copolymers of two different oxyalkylene groups. Copolymers can be random or block copolymers, such as diblock copolymers or triblock copolymers. Exemplary oxyalkylene moieties include oxyethylene, oxypropylene, oxytrimethylene, and oxytetramethylene.

[0038] In one embodiment, polycarbonate diols can be used as poly-Δ. Examples include trimethylene carbonate, poly(hexamethylene carbonate) diol, poly(ethylene-carbonate) diol, poly(propylene-carbonate) diol, and poly(butylene-carbonate) diol.

[0039] An exemplary polyΔ macromer may have a polyaxial central core (CC) and 2-4 arms with repeating units. Such polyΔ macromers may be referred to herein as polyaxial macromers. In one embodiment, at least two of the arms terminate with a nucleophilic group, such as a hydroxyl group or an amine group. In one aspect, the repeating units are all the same, i.e., the arms are homopolymers. In one aspect, the repeating units are not all the same, i.e., the arms are copolymers. The copolymers may be random or block copolymers. For example, the arms may have the formula (A)-(B) or (B)-(A) extending from the central core, as discussed further below. The arms may be biodegradable or non-biodegradable.

[0040] In one embodiment, the arms include ester groups and may be referred to as polyesters. To form the ester groups, the arms may be prepared in whole or in part from hydroxy acids or equivalents. Exemplary hydroxy acids and equivalents include glycolic acid (and its equivalent, glycolide), lactic acid (and its equivalent, lactide), ε-caprolactone (C), and p-dioxanone. In one embodiment, the arms are all formed from the same monomer, whereby the multiaxial macromer has homopolymeric arms. In one embodiment, the arms may include carbonate groups. To form the carbonate groups, the arms may be prepared in whole or in part from trimethylene carbonate (also referred to herein as "T").

[0041] In one embodiment, the polyΔ compound can be a multiaxial macromer having a central core and a plurality, e.g., 2-4, copolymer arms extending from the central core, each arm terminating (i.e., terminating) with a thermally reactive group, e.g., a hydroxyl group. The compound has the formula CC-[armΔ] n where CC represents a central core and n is selected from a number in the range of 2 to 18, or 2 to 14, or 2 to 8, or 2 to 6, or 2 to 4. Each arm is formed by polymerization of a monomer selected from two groups, the two groups being designated as Group A and Group B. Thus, more specifically, in the compounds of the present disclosure, CC-[arm Δ] ncan be written as either CC-[(A)p-(B)q-OH]n, or CC-[(B)q-(A)p-OH]n, where each of (A)p-(B)q and (B)q-(A)p represents an arm. Optionally, the terminal functional group of the arm can be shown, an exemplary terminal functional group being hydroxyl. Wherein A represents a polymerization product of one or more monomers including, and optionally selected from only, trimethylene carbonate (T or TMC) and caprolactone (C or CAP), and p represents the number of monomers that have been polymerized to form the polymerization product A, where p is selected from 1 to 40, or 1 to 30, or 1 to 20, or 1 to 10. wherein B represents a polymerization product of one or more monomers including, and optionally selected from, glycolide (G or GLY), lactide (L or LAC), and p-dioxanone (D or DOX), and q represents the number of monomers that have been polymerized to form polymerization product B, where q is selected from 1 to 40, or 1 to 30, or 1 to 20, or 1 to 10.

[0042] For example, the formula CC-[arm Δ] n When a compound of formula CC-[arm Δ] is formed from a trifunctional central core and A is added to CC before the addition of B, n can be described as CC-[(A)p-(B)q-OH]3. In this example, if A is formed by polymerization of two T and one C, then p is 3 and A is selected, independently within each arm, from TTT, TTC, TCT, TCC, CCC, CCT, CTC, and CTT. Continuing this example, if B is formed by polymerization of one G, then q is 1 and B is G. In this example, each arm has a chemical formula selected from TTTG, TTCG, TCTG, TCCG, CCCG, CCTG, CTCG, and CTTG. This exemplary compound can be described as CC-[armΔ]3, where each arm is independently selected from TTTG-OH, TTCG-OH, TCTG-OH, TCCG-OH, CCCG-OH, CCTG-OH, CTCG-OH, and CTTG-OH, or alternatively, from either CC-[(T,T,C)-(G)-OH]3 or CC-[(T,T,C)3-(G)1-OH]3.

[0043] In one aspect, the disclosure provides a composition comprising a compound having a difunctional central core and two arms extending from the central core, each arm terminating in a hydroxyl group. In one embodiment, the disclosure provides a composition comprising a compound having a trifunctional central core and either two or three arms extending from the central core, each arm terminating in a hydroxyl group. In one embodiment, the disclosure provides a composition comprising a compound having a tetrafunctional central core and two, three or four arms extending from the central core, each arm terminating in a hydroxyl group. Each arm in the compound can be a homopolymer or a copolymer, and if a copolymer, can be a random copolymer or a block copolymer, for example, a block copolymer represented by the formula (A)-(B) or (B)-(A). When the compound is prepared by reacting the central core with a monomer of group A, followed by reacting the reaction product with a monomer(s) selected from group B, the compound will have the formula CC-[(A)-(B)-OH]. However, when the composition is prepared by reacting the central core with a monomer of group B, and subsequently reacting the reaction product with a monomer or monomers selected from group A, the compound will have the formula CC-[(B)-(A)-OH].

[0044] In embodiments, the macromers will have a molecular weight of less than 250,000 Da, less than 200,000 Da, less than 150,000 Da, less than 100,000 Da, less than 50,000 Da, less than 25,000 Da, less than 20,000 Da, less than 15,000 Da, less than 10,000 Da, less than 9,000 Da, less than 8,000 Da, less than 7,000 Da, less than 6,000 Da, less than 5,000 Da, less than 1,000 Da.

[0045] In an embodiment, all of the polyaxial macromers present in the composition contain the same central core. For example, all of the macromer components of the composition are prepared from trimethylolpropane or pentaerythritol. However, in one embodiment, the composition of the present disclosure contains a mixture of polyaxial macromer components, for example, some of the macromer components are triaxial, e.g., made from trimethylolpropane, and other macromer components of the same composition are tetraaxial, e.g., made from pentaerythritol.

[0046] In an embodiment, the multiaxial macromers of the present disclosure have relatively short arms, e.g., 1-10 monomer residues / arms. As used herein, monomer residue refers to the product of polymerization of a monomer, i.e., the structure that the monomer has after the monomer is incorporated into a polymer, thus providing the monomer residue to the polymer. In an embodiment, when the compounds of the present disclosure are used for additive printing, these compounds should be in a fluid state, either the compound itself is a fluid or the compound is dissolved in a solvent and / or diluent to provide a fluid composition. If the arms are too long, the composition containing the compound is typically too viscous to be useful for additive printing, such as SLA, unless the composition contains a large amount of solvent or diluent to dilute the compound, in which case the additive printing process may require the utilization of undesirably large amounts of solvent. Advantageously, if the arms are relatively short, the compound itself may be a fluid at the application temperature of the additive printing process. In an embodiment, the application temperature is room temperature, i.e., about 18°C ​​to about 23°C, and the composition is a liquid at this temperature.

[0047] In optional aspects, compounds and compositions of the disclosure containing such compounds can be described by one or more of the following properties characterizing the A region (also referred to as block) of the multiaxial macromer: having a block A that includes residues formed from trimethylene carbonate (TMC or T), i.e., that is the polymerization product or residue of TMC; having a block A that includes residues formed from caprolactone (CAP or C); having a block A that includes residues formed from both TMC and CAP; at least 90% of the residues in block A are the polymerization products or residues of TMC and CAP. the compound comprises 1 to 45 or 2 to 45 residues formed from TMC; the compound comprises 1 to 15 or 2 to 15 residues formed from TMC; the compound comprises 1 to 10 or 2 to 10 residues formed from TMC; region A has a molecular weight of 102 to 2500 g / mol; region A has a molecular weight of 102 to 1000 g / mol; region A has a molecular weight of 102 to 900 g / mol; each A region comprises 2 to 45 monomer residues; each A region comprises 2 to 15 monomer residues; each A region comprises 2 to 10 monomer residues.

[0048] In optional embodiments, the compounds and compositions of the present disclosure containing such compounds can be described by one or more of the following properties characterizing the B blocks (also called regions) of the multiaxial macromer: each B block includes 1 to 45 or 2 to 45 monomer residues; each B block includes 1 to 15 or 2 to 15 monomer residues; each B block includes 1 to 10 or 2 to 10 monomer residues.

[0049] In one embodiment, the polyamine is a polyΔ compound. For example, an aliphatic polyamine having an alkylene group can be used as a polyΔ. Exemplary alkylene groups include ethylene, propylene (branched or linear), butylene (branched or linear), hexylene (branched, linear, or cyclic), and octylene (branched, linear, or cyclic). Exemplary polyamines having two or more amine groups include polypropyleneiminetetramine (also known as Dab-Am-4) and triethylenetetramine. Huntsman sells many suitable polyamines having two or more amine groups, such as polyethertriamine (Huntsman product XTJ-566), JEFFAMINE® ST-404 polyetheramine (Huntsman product XTJ-586), and JEFFAMINE® T-403 polyetheramine.

[0050] In one embodiment, aromatic diamines can be used as polyΔ. Examples include 1,2-diaminobenzene, 1,3-diaminobenzene, 1,4-diaminobenzene, toluene diamines (e.g., 1,2-diamino-3-methylbenzene, 1,2-diamino-4-methylbenzene, 1,3-diamino-2-methylbenzene, 1,3-diaminoe-4-methylbenzene, 1,4-diamino-2-methylbenzene, 1,4-diamino-3-methylbenzene), alkyl-substituted toluene diamines (e.g., 3,5-diethyltoluene-2,4-diamine and 3,5-diethyltoluene-2,6-diamine), and p-xylyenediamine.

[0051] In one embodiment, polyetherdiamines can be used as polyΔ compounds. When polyetherdiamines are reacted with diisocyanate-containing polyΔ, the result is a polyetherurea moiety. The polyetherdiamines can include homopolymers of oxyalkylene groups or copolymers of two different oxyalkylene groups. The copolymers can be random or block copolymers, such as diblock copolymers or triblock copolymers. Exemplary oxyalkylene moieties include oxyethylene, oxypropylene, oxytrimethylene, and oxytetramethylene.

[0052] In one embodiment, the polyisocyanate is a polyΔ compound.Exemplary polyisocyanate compounds are aliphatic polyisocyanates, such as, but not limited to, tetramethylene diisocyanate, l-lysine diisocyanate, lysine ethyl ester diisocyanate, hexamethylene diisocyanate, octamethylene diisocyanate, decamethylene diisocyanate, dodecamethylene diisocyanate, and cyclohexane bis-(methylene isocyanate).Another exemplary polyisocyanate compound is aromatic polyisocyanate, such as, but not limited to, methylene 4,4,-diphenyl diisocyanate (MDI), 2,4-toluene diisocyanate (TDI), 1,5-naphthalene diisocyanate, and isophorone diisocyanate.

[0053] In one embodiment, polyisocyanate poly-Δ is a macromer having multiple isocyanate groups. Such macromers may be referred to herein as polyisocyanate macromers. Polyisocyanate macromers may be prepared from the corresponding polyhydroxylated macromers by reaction of the polyhydroxylated macromer with a diisocyanate, such as hexamethylene diisocyanate.

[0054] An exemplary polyisocyanate macromer is a reaction product of a diisocyanate and a reactant that includes or consists of either or both of a diamine and a diol, such as a polyether diamine or a polyether diol. Such polyisocyanate macromers have terminal isocyanate groups that are reactive with additional polyamines and / or polyhydric compounds. For example, a diisocyanate may be used to form a macromer by reaction with either a diamine or a diol to provide a polyΔ compound (e.g., a polyΔ2 compound) with terminal isocyanate groups. This polyΔ2 polyisocyanate macromer may then be thermally reacted with additional diamines or diols (polyΔ1 compounds) to form a thermoset polymer in the compositions of the present disclosure.

[0055] In one aspect, the present disclosure provides a polyisocyanate macromer that is a reaction product of a polyisocyanate, e.g., a diisocyanate, and a polyol, e.g., a diol such as a polyether diol. Optionally, any one or more of the following may be used to further describe the polyisocyanate macromer and its preparation: the polyol is a diol, the polyisocyanate is a diisocyanate, the diol may be a polyether diol containing at least one type of oxyalkylene sequence selected from the group consisting of oxyethylene, oxypropylene, oxytrimethylene, and oxytetramethylene sequences; the polyol may be an aliphatic polyol having alkylene groups, exemplary alkylene groups include ethylene, propylene (branched or straight chain), butylene (branched or straight chain), hexylene (branched, straight chain, or cyclic), and octylene (branched, straight chain, or cyclic). Exemplary polyols having two or more hydroxyl groups that can be used when crosslinking is desired include trimethylolpropane, glycerol, pentaerythritol, 1,2,4-butanetriol, and 2,3,4-pentanetriol. The polyol can be an aromatic diol, examples of which include catechol, resorcinol, hydroquinone, and their reaction products, such as the reaction product of resorcinol and ethylene carbonate. Other suitable aromatic diols include bisphenol A and 4,4'-dihydroxybiphenyl.

[0056] In one embodiment, a polyisocyanate macromer, which is the reaction product of a polyisocyanate, e.g., a diisocyanate, and a polyol, e.g., a diol, e.g., a polyether diol, provides a polyΔ2 compound that can be reacted with a polyΔ1 compound, e.g., a polyamine. The reaction product can be described in terms of its structural components, rather than in terms of the reactants from which it can be formed. In one embodiment, the polymer chain is a polyurea with multiple urea groups alternately separated by aliphatic groups (contributed by the aliphatic diamine) and polymer blocks (contributed by the macromer). In other words, the structure can be described by repeating -[urea-aliphatic-urea-polymer block]- units. The polymer blocks are polyurethanes with multiple urethane (also known as carbamate) groups alternately separated by aliphatic groups (contributed by the diisocyanate) and polyether groups. In other words, the structure of the polymer blocks can be described by repeating -[urethane-aliphatic-urethane-polyether]- units. The polyether segments may optionally be selected from oxyethylene, oxypropylene, oxytrimethylene, and oxytetramethylene, and in one embodiment, the polymer chain contains multiple of these polyether segments, for example, the polymer contains oxyethylene, oxypropylene, and oxytetramethylene groups, and optionally the oxyethylene and oxypropylene are arranged in a block copolymer configuration (e.g., oxyethylene block-oxypropylene block-oxyethylene block). The polymer blocks may also be referred to as polyether polyurethanes, and the polymer itself may be referred to as a polyether urethane urea.

[0057] When the composition comprises a polyisocyanate as a polyΔ compound, for example as polyΔ2, the composition also comprises a compound that is reactive with the polyisocyanate, i.e. a polyhydric compound, the reaction of the polyisocyanate with the polyhydric compound resulting in urethane groups. Another example of an isocyanate-reactive group is an amine group, whereby when the composition contains a polyisocyanate as polyΔ2, the composition may comprise a polyamine compound as polyΔ1, the reaction of the polyisocyanate with the polyamine resulting in urea groups.

[0058] In one embodiment, the polyΔ compound is a polyepoxide. Exemplary polyepoxides include, but are not limited to, diepoxides, triepoxides, and tetraepoxides. In one embodiment, the polyΔ2 is a diepoxide. Exemplary polyepoxides include diepoxybutane (also known as butane diepoxide, butadiene diepoxide, or 1,2:3,4-diepoxybutane), 1,2,7,8-diepoxyoctane, 1,4-butanediol diglycidyl ether, polyglycerol polyglycidyl ether, ethylene glycol diglycidyl ether, polyethylene glycol diglycidyl ether having a molecular weight of about 500 to about 6,000, and polypropylene glycol diglycidyl ether having a molecular weight of about 500 to about 6,000.

[0059] The present disclosure provides polyΔ compounds where Δ is hydroxyl. Such compounds can be converted to polyΔ compounds where Δ is epoxy to provide polyepoxide compounds of the present disclosure. For example, polyhydroxyl compounds can be reacted with an excess of epichlorohydrin equivalents, followed by treatment with a base such as sodium hydroxide to convert the hydroxyl groups to epoxy groups.

[0060] In an embodiment, Δ1 is a nucleophilic group. In an embodiment, polyΔ1 has multiple hydroxyl (-OH) groups. In an embodiment, polyΔ1 has multiple amine groups (-NH2). In an embodiment, polyΔ1 is not reactive with itself. In an embodiment, the only reactive groups present in polyΔ1 are Δ1 groups, and all of the Δ1 groups are the same, e.g., they are all hydroxyl groups. In an embodiment, polyΔ1 has two Δ1 groups. In an embodiment, polyΔ1 has three Δ1 groups. In an embodiment, polyΔ1 has four Δ1 groups. In an embodiment, polyΔ1 has more than four Δ1 groups. All other factors being equal, the more Δ1 groups present as part of polyΔ1, the more crosslinks will result from a composition comprising polyΔ1.

[0061] In one aspect, Δ2 is an electrophilic group. In one embodiment, polyΔ2 has multiple epoxide (-CH(O)CH-) groups. In one embodiment, polyΔ2 has multiple isocyanate (-N=C=O) groups. In an embodiment, polyΔ2 is not reactive with itself. In an embodiment, the only reactive groups present in polyΔ2 are Δ2 groups, and all of the Δ2 groups are the same, e.g., they are all isocyanate groups. In an embodiment, polyΔ2 has two Δ2 groups. In an embodiment, polyΔ2 has three Δ2 groups. In an embodiment, polyΔ2 has four Δ2 groups. In an embodiment, polyΔ2 has more than four Δ2 groups. All other factors being equal, the more Δ2 groups present as part of polyΔ2, the more crosslinking will result from a composition comprising polyΔ2.

[0062] In one embodiment, poly-Δ1 is a polyhydroxyl compound while poly-Δ2 is a polyepoxide.

[0063] In one embodiment, poly-Δ1 is a polyhydroxyl compound while poly-Δ2 is a polyisocyanate.

[0064] In one embodiment, poly-Δ1 is a polyamine compound while poly-Δ2 is a polyepoxide.

[0065] In one embodiment, poly-Δ1 is a polyamine compound while poly-Δ2 is a polyisocyanate.

[0066] In one embodiment, poly-Δ1 is a polythiol compound while poly-Δ2 is a polyepoxide.

[0067] In one embodiment, poly-Δ1 is a polythiol compound while poly-Δ2 is a polyisocyanate.

[0068] In one embodiment, the composition of the present disclosure includes a photoinitiator. In one embodiment, the composition includes one or more additives. In one embodiment, the composition includes one or more light reflecting materials suspended in the composition. In one embodiment, the composition includes one or more stabilizers. In one embodiment, the composition includes one or more chain transfer agents.

[0069] Polyhν compounds The polyhv compound of the present disclosure contains a plurality of photopolymerizable groups, hv. An exemplary photopolymerizable group is an ethylenically unsaturated group, and an exemplary polyhv compound having an ethylenically unsaturated group can be shown as polyEU. Another exemplary photopolymerizable group is a thiol group, and an exemplary polyhv compound having a thiol group can be shown as polySH.

[0070] In one aspect, the present disclosure provides a multi-arm compound as described herein, wherein the arms terminate with hv groups, and the hv groups are photopolymerizable. In one embodiment, the exemplary hv groups can contain thiol groups that are photopolymerizable. In one embodiment, the exemplary hv groups can contain carbon-carbon double bonds that are photopolymerizable, for example, the arms can contain vinyl groups, such as those present in acrylate or methacrylate groups, each of which has a photopolymerizable carbon-carbon double bond.

[0071] Photopolymerizable moieties, such as photopolymerizable thiols or hν groups containing carbon-carbon double bonds, can be introduced into the multi-arm compounds described herein by reaction of the terminal hydroxyl groups with a suitable reagent. Methods for converting hydroxyl groups to thiol- or carbon-carbon double bond-containing groups are generally known and can be utilized to prepare the compounds of the present disclosure, and examples are provided herein.

[0072] The hv group contains a photoreactive group, particularly a photoreactive group that allows for polymerization of an hv-containing macromer, but the hv group may also contain additional atoms that affect the photoreactivity of the photoreactive group, such as a carbonyl group adjacent to a carbon-carbon double bond as shown herein, and / or additional atoms used to introduce the photoreactive group into the macromer, such as a succinate ester that may be used to introduce a thiol group as shown herein.

[0073] For example, the multi-arm compounds having terminal hydroxyl groups described herein can be reacted with reactive acrylate, methacrylate, or norbornenyl compounds, such as methacrylic anhydride, acrylic anhydride, methyl-5-norbornene-2,3-dicarboxylic anhydride, 5-norbornene-2,3-dicarboxylic anhydride, methacryloyl chloride, or acryloyl chloride, to convert the hydroxyl groups to hν groups containing photopolymerizable carbon-carbon double bonds (polyEU).

[0074] For example, the multi-arm compounds having terminal hydroxyl groups as disclosed herein can undergo an esterification reaction to convert the hydroxyl groups to hν groups containing photopolymerizable thiol groups (polySH). One method for esterification is to add a stoichiometric amount of macromer and a mercaptocarboxylic acid compound in the presence of a carbodiimide (e.g., N,N'-dicyclohexylcarbodiimide) and a catalyst (e.g., dimethylaminopyridine). Exemplary mercaptocarboxylic acids include, but are not limited to, the following compounds: 3-mercaptopropionic acid, thiolactic acid, thioglycolic acid, mercaptobutyric acid, mercaptohexanoic acid, mercaptobenzoic acid, mercaptoundecanoic acid, mercaptooctanoic acid, and n-acetylcysteine. For example, the multi-arm compounds having terminal hydroxyl groups as disclosed herein can be reacted with thiolactic acid, in which case the resulting Q group has the formula -C(=O)-CH2-SH attached to the terminal oxygen of the multi-arm compound.

[0075] Another exemplary method of forming a thiol-functionalized macromer (polySH) is to first modify the corresponding hydroxyl-terminated macromer to form a terminal carboxylic acid group. An example of this is to react the hydroxyl-terminated macromer with succinic anhydride. At the terminal carboxylic acid group, the macromer can be reacted with a mercaptoalcohol by esterification reaction or with a mercaptoamine to form an amide bond. Some examples of mercaptoalcohols include, but are not limited to, mercaptopropanol, mercaptohexanol, mercaptooctanol, and mercaptoundecanol. Some examples of mercaptoamines include, but are not limited to, the following: cysteine, glutathione, 6-amino-1-hexanethiol hydrochloride, 8-amino-1-octanethiol hydrochloride, and 16-amino-1-hexadecanethiol hydrochloride. For example, a multi-arm compound having a terminal hydroxyl group as disclosed herein can be reacted with succinic anhydride to form an intermediate which then reacts with cysteine ​​to introduce a terminal thiol group, in which case the poly-SH compound contains a moiety having the formula -C(=O)CH2CH2C(=O)NH-C(COOH)-CH2SH attached to the terminal oxygen of the multi-arm compound.

[0076] Yet another method for forming the thiol-functionalized macromer polySH is to react a macromer having a terminal hydroxyl group with a lactone monomer having a pendant thiol group, which results in a ring-opening polymerization in the third step.

[0077] In one embodiment, the poly-SH compound is a macromer known as a thiomer. In some embodiments, the thiol compound is a multi-arm poly(ethylene glycol) (PEG) containing at least two free thiol groups or a multi-arm poly(ethylene oxide) containing at least two free thiol groups. Exemplary thiomers include, but are not limited to, 4-arm-PEG2K-SH, 4-arm-PEGSK-SH, 4-arm-PEG10K-SH, 4-arm-PEG20K-SH, 4-arm poly(ethylene oxide) thiol terminated, 8-arm-PEG10K-SH (hexaglyerol core), 8-arm-PEG10K-SH (tripentaerythritol core), 8-arm-PEG20K-SH (hexaglyerol core), 8-arm-PEG20K-SH (tripentaerythritol core), and 8-arm poly(ethylene oxide) thiol terminated. These thiomers are available from Millipore Sigma (formerly Sigma Aldrich).

[0078] In one embodiment, the polySH is not a macromer, but instead is a small molecule having a molecular weight of less than 1000 Daltons. Optionally, the small molecule polySH can be water-soluble. Examples of such polySH compounds include dithiol compounds, trithiol compounds, and tetrathiol compounds. Exemplary polySH compounds include, but are not limited to, dithiothreitol (DTT), 1,2-ethanedithiol, 1,3-propanedithiol, 1,4-butanedithiol, 1,5-pentanedithiol, 1,6-hexanedithiol, 1,7-heptanedithiol, 1,8-octanedithiol, 1,9-nonanedithiol, 1,10-decanedithiol, 1,11-undecanedithiol, 1,12-dodecanedithiol, 1,13-tridecanedithiol, 1,14-tetradecanedithiol, 1,16-hexadecanedithiol, dithiolbutylamine (DTBA), tetra(ethylene glycol)dithiol, hexa(ethylene glycol)dithiol, 2-mercaptoethyl ether, 2,2'-thiodiethanethiol, 2,2'- (ethylenedioxy)diethanethiol, propane-1,2,3-trithiol, trimethylolpropane tris(2-mercaptoacetate), trimethylolpropane tris(3-mercaptoacetate), pentaerythrityl tetrathiol, pentaerythritol tetrakis(3-mercaptopropionate), 1,2-dithiane-4,5-diol, lipoic acid (alpha lipoic acid and beta lipoic acid), 3H-1,2-dithiol, 3-propyl-1,2-dithiolane, 3-acetyl-1,2-dithiolane, 1,2-dithiolane-4-carboxylic acid, 1,2-dithiolane-3-pentanol, 1,2,4-dithiazolidine, 1,2-dithiane, 1,2-dithiepane, 1,2-dithiocane, and 1,2-dithiocane-3,8-diol.

[0079] In an embodiment, the composition of the present disclosure comprises at least one polyhv compound. In an embodiment, the composition comprises a photoinitiator. In an embodiment, the composition additionally comprises one or more additives. In an embodiment, the composition additionally comprises one or more light reflecting materials suspended in the composition. In an embodiment, the composition additionally comprises one or more stabilizers. In an embodiment, the composition additionally comprises one or more chain transfer agents.

[0080] Photoinitiators Photoinitiators refer to organic (carbon-containing) molecules that generate reactive species when exposed to radiation. In one embodiment, photoinitiators generate radically reactive species, as opposed to, for example, cationic or anionic reactive species. Photoinitiators are well-known components for the preparation of photopolymers, which are accepted for use in light-curable coatings, adhesives, and dental restoratives.

[0081] Type I photoinitiators are unimolecular free radical generators, i.e., upon absorption of UV-visible light, certain bonds in the initiator's structure undergo homolytic cleavage to generate free radicals. Homolytic cleavage is the homolytic scission of an electronic bond pair to a free radical product. Examples of homolytic cleavage in some common classes of Type I photoinitiators: benzoin ethers, benzil ketals, α-dialkoxy-aceto-phenones, α-hydroxy-alkyl-phenones, and acylphosphine oxides. For example, BASF, BASF Exemplary commercially available Type I photoinitiators available from Ludwigshafen, SE, Germany include Irgacure™ 369, Irgacure™ 379, Irgacure™ 907, Darocur™ 1173, Irgacure™ 184, Irgacure™ 2959, Darocur™ 4265, Irgacure™ 2022, Irgacure™ 500, Irgacure™ 819, Irgacure™ 819-DW, Irgacure™ 2100, Lucirin™ TPO, Lucirin™ These include, but are not limited to, TPO-L, Irgacure™ 651, Darocur™ BP, Irgacure™ 250, Irgacure™ 270, Irgacure™ 290, Irgacure™ 784, Darocur™ MBF, Ivocerin, hand Irgacure™ 754, lithium phenyl-2,4,6-trimethylbenzoylphosphinate, magnesium phenyl-2,4,6-trimethylbenzoylphosphinate, and sodium phenyl-2,4,6-trimethylbenzoylphosphinate.

[0082] Type II photoinitiators require, in addition to the photoinitiator, a coinitiator, usually an alcohol or amine, which is a functional group that can easily abstract hydrogen. Absorption of UV-visible light by the Type II photoinitiator causes an excited electronic state in the photoinitiator that abstracts hydrogen from the coinitiator, breaking up a bond pair of electrons in the process. Benzophenone, thio-xanthone, and benzophenone-type photoinitiators are the most common Type II photoinitiators. Further examples of some common Type II photoinitiators include riboflavin, eosin Y, fluorescein, rose bengal, and camphorquinone. Once free radicals are generated, the polymerization mechanism is similar to any free radical polymerization process.

[0083] Optionally, the compositions of the present disclosure include at least one photoinitiator component, typically at a total concentration of less than 2 wt%, or less than 1.5 wt%, or less than 1 wt%, or less than 0.9 wt%, or less than 0.8 wt%, or less than 0.7 wt%, or less than 0.6 wt%, or less than 0.5 wt%, or less than 0.25 wt%, or less than 0.1 wt%, based on the total weight of the photoreactive compounds.

[0084] Additives The compositions of the present disclosure may contain additives, such as one, two, or more additives, which may be optional or not. Exemplary additives are described herein. As used herein, "additive" is a broad term, and additives include, but are not limited to, one or more light reflecting materials, one or more transfer agents, one or more bioactive agents, one or more dyes, one or more photoinitiators, one or more diluents, and / or one or more stabilizers suspended in the composition. The compositions may contain one or more additives that stabilize the ethylenically unsaturated group(s) and / or the chain transfer agent(s). Additives may modify the physical and / or chemical characteristics of such formulations. Additives, alone or as components of the formulation, may be resorbable (biodegradable) or non-resorbable (non-biodegradable), functionalized or non-functionalized, reactive or non-reactive, and may or may not act as chain transfer agents. Additives may be biodegradable, bio-derived (i.e., partially or wholly naturally occurring and derived from plants or animals rather than synthetically formed), bio-inert (i.e., the additive does not elicit a response when interacting with living tissue), and may be present in concentrations that are non-toxic to mammals or other living organisms. Examples of additives may be stabilizers, including but not limited to tocopherol, lauryl gallate, or phosphoric acid. Examples of additives may be dyes, pigments, and / or actinic radiation absorbers, including but not limited to D&C Violet No. 2, beta-carotene, lycoprene, or riboflavin. Examples of additives may be actinic radiation reflective particles (light reflective materials), including but not limited to inorganic or organic compounds, aliphatic or aromatic polymers, or other crystalline solid particles. Examples of additives may be diluents or other viscosity modifiers, including but not limited to poly(ethylene glycol) diacrylate, trimethylolpropane trimethacrylate, or trimethylolpropane tris-mercaptopropionate. Examples of additives include, but are not limited to, Type I photoinitiators, such as acylphosphine oxides, and / or Type II photoinitiators, such as thio-xanthone, riboflavin, or camphorquinone, along with a coinitiator, which is usually an alcohol or an amine.

[0085] In one aspect, a coloring agent such as a dye may be included in the composition and corresponding cured product of the present disclosure. The addition of a dye may achieve the purpose of matching the formulation to a desired color. In one aspect, the dye is a non-toxic biocompatible dye. Such dyes may be present at a concentration of about 2% by weight or less, based on the total weight of the composition. See, for example, PCT / US2016 / 059910, which is incorporated herein for its teachings of the use of dyes. In one embodiment, the dye is present at a concentration of about 0.1-0.3% by weight, which is the FDA recommended amount for the dye D&C Violet when present in absorbable suture products. In one embodiment, the dye is present at a concentration of less than 0.5% by weight. In some cases, if the dye is present at too high a concentration, the dye may impart toxicity to the photopolymerized composition of the present disclosure.

[0086] In one aspect, higher concentrations of dyes, pigments, or UV absorbers are required to reduce the light penetration depth (Dp) described by Jacob's equation. For these higher concentrations, the composition may contain biologically derived dyes, pigments, or UV absorbers. These compounds can be classified in terms of chemical structure into carotenoids, flavonoids, flavones, quinones, porphyrins, diketones, and beta-cyanidins. Some examples of biologically derived dyes, pigments, and UV absorbers include, but are not limited to, beta-carotene, chlorophyll, lycoprene, anthocyanins, quercetin, rutin, riboflavin, turmeric, and saffron. Compositions that may be included in the present disclosure may include at least one biologically derived dye, pigment, or UV absorber, typically at a total concentration of less than 5% by weight, or less than 2% by weight, or less than 1% by weight, or less than 0.9% by weight, or less than 0.8% by weight, or less than 0.7% by weight, or less than 0.6% by weight, or less than 0.5% by weight, or less than 0.25% by weight, or less than 0.1% by weight, based on the total weight of the photoreactive compound. In one embodiment, the composition having the biologically derived dye, pigment, or UV absorber is biocompatible. In one embodiment, the composition having the biologically derived dye, pigment, or UV absorber is bioabsorbable.

[0087] In one embodiment, a light reflecting material component comprising a light reflecting material can be suspended in the composition, and the light reflecting material component adjusts the light dosage of the composition to a lower level when compared to the light dosage of the composition without the light reflecting material.Suitable light reflecting materials for optional inclusion in the composition of the present disclosure are provided in PCT Application No. PCT / US2019 / 026114, entitled Methods and Compositions for Photopolymerizable Additive Manufacturing, filed on April 5, 2019, and its related U.S. and foreign applications, each of which is incorporated herein in its entirety.

[0088] Suitable light-reflecting materials include light-reflecting materials that reflect UV light, visible light, or both.For example, light-reflecting materials can be or include particulate light-reflecting materials with sizes of less than 500 microns, or less than 30 microns, or less than 5 microns, or less than 1 micron.Light-reflecting materials can be shaped, for example, as spheres, cubes, cones, cubes, cylinders, pyramids, prisms, polyhedrons, or irregular shapes, or mixtures thereof.In one embodiment, light-reflecting materials have a smooth surface.

[0089] In an embodiment, the light reflecting material may include inorganic solids, including but not limited to titanium dioxide, zinc oxide, barium sulfate, tricalcium phosphate, dicalcium phosphate, monocalcium phosphate, dicalcium diphosphate, tricalcium phosphate, hydroxyapatite, apatite, and tetracalcium phosphate. In an embodiment, the light reflecting material may include organic compounds including aliphatic polymers and copolymers, including but not limited to polyesters, polyurethanes, polyethers, polyamides, polyanhydrides, polycarbonates, polyketones, polyethylene, polypropylene, polyvinyl alcohol, polytetrafluoroethylene, polyvinyl chloride, polyimides, and polyhydroxyalkanoates, or combinations thereof. In an embodiment, the light reflecting material may include organic compounds including aromatic polymers and copolymers, including but not limited to polyesters, polyurethanes, polyethers, polyanhydrides, polyketones, polyamides, polycarbonates, and polyimides, or combinations thereof. In embodiments, the light reflecting material may comprise organic compounds including naturally occurring polymers and derivatives, including, but not limited to, cyclodextrin, starch, hyaluronic acid, deacetylated hyaluronic acid, chitosan, trehalose, cellobiose, maltotriose, maltohexaose, chitohexaose, agarose, chitin 50, amylose, glucan, heparin, xylan, pectin, galactan, glycosaminoglycan, dextran, aminated dextran, cellulose, hydroxyalkylcellulose, carboxyalkylcellulose, fucoidan, chondroitin sulfate, sulfate polysaccharides, mucopolysaccharides, gelatin, zein, collagen, alginic acid, agar, carrageean, guar gum, gum arabic, gum ghatti, gum karaya, gum konjac, tamarind gum, tara gum, tragacanth gum, locust bean gum, pectin, xanthan gum. In an embodiment, the light reflecting material may include crystalline organic compounds including crystalline aliphatic and aromatic polymers. In an embodiment, the light reflecting material may include crystalline organic compounds including crystalline naturally occurring polymers and derivatives. In an embodiment, the light reflecting material may include crystalline amino acids and their derivatives.In embodiments, the light reflecting material may include crystalline fatty acids and their derivatives, including, but not limited to, palmitic acid, ascorbyl palmitate, lauric acid, glycerol monolaurate, myristic acid auxiliaries, and capric acid. In embodiments, the light reflecting material may include crystalline peptides.

[0090] In one embodiment, the composition of the present disclosure may contain a diluent. The diluent may be reactive or non-reactive. Reactive diluents undergo photopolymerization reaction when exposed to light (UV or visible light), while non-reactive diluents are inactive to such light exposure. An exemplary reactive diluent is PEG-diacrylate (PEG-DA or PEGDA).

[0091] In one embodiment, bioactive agents may be included in the compositions and corresponding cured products of the present disclosure, examples of such bioactive agents include, but are not limited to, fibrogenic agents, antifungal agents, antibacterial agents and antibiotics, anti-inflammatory agents, anti-scarring agents, immunosuppressants, immunostimulants, antiseptics, anesthetics, antioxidants, cell / tissue growth promoting factors, anti-tumor agents, anti-cancer agents, and agents that support ECM integration.

[0092] Examples of fibrogenic inducers include talcum powder, metallic beryllium and its oxides, copper, silk, silica, crystalline silicate, talc, quartz dust, and ethanol; components of the extracellular matrix selected from fibronectin, collagen, fibrin, or fibrinogen; polymers selected from the group consisting of polylysine, poly(ethylene-co-vinyl acetate), chitosan, N-carboxybutyl chitosan, and RGD protein; vinyl chloride or polymers of vinyl chloride; cyanoacrylates and cross-linked poly(ethylene glycol). inflammatory cytokines (e.g., TGFβ, PDGF, VEGF, bFGF, TNFα, NGF, GM-CSF, IGF-a, IL-1, IL-1β, IL-8, IL-6, and growth hormone); connective tissue growth factor (CTGF); bone plasma protein (BMP) (e.g., BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, or BMP-7); leptin, and bleomycin or an analog or derivative thereof. Optionally, the device may additionally comprise a growth agent to stimulate cell proliferation. Examples of antiproliferative agents include dexamethasone, isotretinoin (13-cis retinoic acid), 17-β-estradiol, estradiol, 1α,25-dihydroxyvitamin D3, diethylstibesterol, cyclosporin A, L-NAME, all-trans retinoic acid (ATRA), and analogs and derivatives thereof. See, for example, US2006 / 0240063, which is incorporated herein by reference in its entirety. Examples of antifungal agents include, but are not limited to, polyene antifungals, azole antifungals, and echinocandins. Examples of antibacterial agents and antibiotics include, but are not limited to, erythromycin, penicillin, cephalosporins, doxycycline, gentamicin, vancomycin, tobramycin, clindamycin, and mitomycin. Examples of anti-inflammatory agents include, but are not limited to, nonsteroidal anti-inflammatory drugs such as ketorolac, naproxen, diclofenac sodium, and fluribiprofen.Examples of anti-scarring agents include, but are not limited to, cell cycle inhibitors such as taxanes, immunomodulators such as cerolimus or biolimus (see, for example, US2005 / 0149158, which is incorporated by reference in its entirety). Examples of immunosuppressants include, but are not limited to, glucocorticoids, alkylating agents, antimetabolites, and drugs that act on immunophilins such as cyclosporine and tacrolimus. Examples of immunostimulants include, but are not limited to, interleukins, interferons, cytokines, toll-like receptor (TLR) agonists, cytokine receptor agonists, CD40 agonists, Fc receptor agonists, CpG-containing immunostimulatory nucleic acids, complement receptor agonists, or adjuvants. Examples of antiseptics include, but are not limited to, chlorhexidine and tibezonium iodide. Examples of anesthetic agents include, but are not limited to, lidocaine, mepivacaine, pyrrocaine, bupivacaine, prilocalne, and etidocaine. Examples of antioxidants include, but are not limited to, antioxidant vitamins, carotenoids, and flavonoids. Examples of cell growth promoting factors include, but are not limited to, epidermal growth factor, human platelet-derived TGF-β, endothelial cell growth factor, thymocyte activating factor, platelet-derived growth factor, fibroblast growth factor, fibronectin, or laminin. Examples of antitumor / anticancer agents include, but are not limited to, paclitaxel, carboplatin, miconazole, leflunamide, and ciprofloxacin. Examples of agents that support ECM integration include, but are not limited to, gentamicin.

[0093] The compositions and corresponding cured articles of the present disclosure may contain a mixture of bioactive agents to achieve a desired effect. Thus, for example, an antibacterial agent and an anti-inflammatory agent may be combined in a single article to provide the combined effectiveness of each agent.

[0094] Other additives of the photopolymerizable composition are reactive diluents, non-reactive diluents, solvents, stabilizers, thixotropic materials, tracer materials, and conductive materials. Stabilizers, when present, can optionally be selected from the group consisting of tocopherol, gallic acid, esters of gallic acid, butylated hydroxyanisole, and combinations thereof. By the addition of appropriate ingredients, the photopolymerizable composition of the present disclosure (e.g., an article, or strip) can be colored by the presence of a dye, or can have any other desired attribute, such as, but not limited to, having at least a portion of the article be fluorescent, emissive, reflective, flexible, rigid, pliable, friable, or combinations thereof.

[0095] In one embodiment, the composition of the present disclosure, including polyhv or polyΔ, is polymerized in the absence of water, e.g., water is not a diluent in the composition. Specifically, in one embodiment, the composition forming the single or double network, or the single or double network itself, has a water content of less than 2500 ppm, or less than 1000 ppm, or less than 500 ppm. In one embodiment, the photocurable composition of the present disclosure that provides a single network is an anhydrous composition in that it does not contain more than extraneous water. In one embodiment, the photocurable and heat curable composition of the present disclosure that provides a double network is an anhydrous composition in that it does not contain more than extraneous water. The anhydrous composition of the present disclosure is not, for example, a hydrogel.

[0096] One challenge for making formulations with both ethylenically unsaturated and thiol compounds is their tendency to polymerize when mixed at room temperature before applying a stimulus such as light or heat. This can therefore significantly limit the application of these formulations, as the working time during which their viscosity remains constant can be short. Specifically, in additive manufacturing using vat photopolymerization, these formulations have problems with viscosity changing over time. In the present disclosure, biocompatible stabilizers are outlined to be able to provide at least 24 hours of stability, which would be useful in addressing the working time for vat photopolymerization. In an embodiment, one or more stabilizer compounds can be included in the compositions of the present disclosure, and the corresponding cured products.

[0097] In an embodiment, the composition comprising poly(SH) or poly(EU) comprises a stabilizer. The stabilizer may be included in poly(SH), poly(EU), or a combination thereof. In one embodiment, the stabilizer is an add-in component. In another embodiment, the stabilizer is included as an add-in dissolved in a monomer, a diluent, a solvent, or a combination thereof. In one embodiment, the stabilizer is an antioxidant. In another embodiment, the stabilizer is an acid. Preferably, the acid stabilizer has a pKa of 1-5. In another embodiment, the stabilizer is selected from phosphite and phosphonate compounds. In another embodiment, the stabilizer may include antioxidants, acids, phosphites, phosphonates, and combinations thereof. Examples of antioxidant stabilizers include, but are not limited to, hydroquinone, mono-tertiary butyl hydroquinone (MTBHQ), 2,5-di-tertiary butyl-hydroquinone (DTBHQ), p-methoxyphenol, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), 2,6-di-tert-butyl-p-cresol, 2,2-methylene-bis-(4-methyl-6-tert-butyl)phenol (MBETBP), p-tert-butylcatechol, 1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene (Anox330™, Irganox1330™), hydroxytoluene butyl ether, tocopherol (all isomers), esters of tocopherol, pyrogallol, lauryl gallate, esters of gallic acid, or combinations thereof. Examples of acid stabilizers may include, but are not limited to, phosphonic acid, phosphorous acid, oxalic acid, succinic acid, gallic acid, ascorbic acid, phenylphosphonic acid, or combinations thereof. Examples of phosphite and phosphonate stabilizers may include, but are not limited to, triphenyl phosphite, diphenyl isodecyl phosphite, diphenyl isooctyl phosphite, or combinations thereof. In one embodiment, the stabilizer is soluble in the poly(SH) and / or poly(EU) formulation. Preferably, the stabilizer is added at a concentration that achieves biocompatibility.Preferably, the biocompatible stabilizer comprises tocopherol, gallic acid, esters of gallic acid, butylated hydroxyanisole, or combinations thereof. In one embodiment, the stabilizer concentration is less than 100,000 ppm, more preferably less than 50,000 ppm, more preferably less than 15,000 ppm, more preferably less than 15,000 ppm, more preferably less than 5,000 ppm, more preferably less than 3,000 ppm, and even more preferably less than 1,500 ppm.

[0098] Photopolymerization reaction conditions The photopolymerizable compounds polyhv (including polyEU and polySH) described herein having photopolymerizable groups, and compositions of the present disclosure that include such compounds, undergo polymerization upon sufficient exposure to light of an appropriate wavelength, optionally in the presence of a photoinitiator, and optionally in the presence of other ingredients. Selection of the appropriate wavelength, exposure time, and identity and amount of curing agent are selected in consideration of the identity and amount of hv groups in the compounds and compositions, as is conventional in the art. Photopolymerization is sometimes referred to as radiation curing, in which case the photoinitiator may be referred to as the curing agent.

[0099] In an embodiment, the photoinitiator component in the composition of the present disclosure comprises a Type I photoinitiator. In an embodiment, the photoinitiator component in the composition of the present disclosure comprises a Type II photoinitiator. In an embodiment, a combination of Type I and Type II photoinitiators is present in the photopolymerizable composition of the present disclosure.

[0100] In any of the photopolymerizable compounds and compositions described herein, hv can be a carbon-carbon double bond, such as a vinyl group. Exemplary vinyl groups are acrylate and methacrylate groups. Another exemplary carbon-carbon double bond is present in norbornenyl. In additional aspects, photopolymerizable compounds having one or more hv groups undergo photopolymerization when exposed to light having, for example, a wavelength of 300-450 nm, or 300-425 nm, or 350-450 nm, or 350-425 nm, or 365-405 nm, or 450-550 nm. In one embodiment, polyhv compounds and related compositions undergo photopolymerization when exposed to UV radiation.

[0101] In any of the photopolymerizable compounds and compositions described herein, hv can be a thiol group. In additional aspects, photopolymerizable compounds polySH having one or more SH groups undergo photopolymerization when exposed to light having a wavelength of, for example, 300-450 nm, or 300-425 nm, or 350-450 nm, or 350-425 nm, or 365-405 nm, or 450-550 nm. In one embodiment, polySH compounds and related compositions undergo photopolymerization when exposed to UV radiation. In one embodiment, polySH compounds and related compositions undergo photopolymerization when exposed to visible radiation.

[0102] In one aspect, the present disclosure provides a composition comprising a compound having a plurality of photopolymerizable thiol groups and a compound having a plurality of photopolymerizable ethylenically unsaturated groups. The thiol groups and the ethylenically unsaturated groups are reactive with each other in the presence of a photoinitiator and upon exposure to suitable actinic radiation. The actinic radiation may alternatively be referred to as light, and the composition may be referred to as photoreactive. This reaction may be referred to as photopolymerization or curing.

[0103] Without wishing to be bound by any particular theory, it is currently understood that after polymerization of absorbable macromers with ethylenically unsaturated functional groups, the absorbable polymer segments may be degraded by hydrolysis or enzymatic degradation leaving a non-absorbable polymer (i.e., backbone) from the reacted ethylenically unsaturated groups. For such formulations to be implantable, the non-absorbable polymer must meet the criteria of being water soluble and having a molecular weight of less than approximately 20,000-65,000 Da in order to be cleared by the mammalian kidney. When typical ethylenically unsaturated polyesters are polymerized with free radicals and subsequently degraded, the backbone molecular weight is often much greater than 20,000-65,000 Da. This is the case in the photopolymerization of biocompatible implantable resins, where small amounts of photoinitiators must be used to reduce toxicity. As disclosed herein, a method of reducing the molecular weight of ethylenically unsaturated polymers is to incorporate at least one chain transfer agent that can be incorporated into the polymer backbone and can terminate the ethylenically unsaturated polymer and re-initiate the ethylenically unsaturated groups. The present disclosure provides specific ranges of ratios of chain transfer agent to ethylenically unsaturated groups to modify the molecular weight of degradation products generated during degradation or resorption of 3D printed polymerized articles. Biocompatible chemical species for use in compositions comprising at least one chain transfer agent are further disclosed.

[0104] In one embodiment, a composition comprising a photochemically cured reaction product of a compound comprising an ethylenically unsaturated group (EU), a photoinitiator, and at least one chain transfer agent, when decomposed, results in decomposition products (or polymer backbones) having a molecular weight of less than 60,000 Daltons, more preferably less than 50,000 Daltons, even more preferably less than 30,000 Daltons, and even more preferably less than 20,000 Daltons.

[0105] In embodiments, chain transfer agents include compounds having functional reactive groups, including, but not limited to, one or more functional groups including thiol, disulfide, aminoalkylthiol, thiocarbonate, xanthate, alcohol, halogen, and / or phosphorus. Examples of chain transfer agents include 1-dodecanethiol, octyl mercaptan, 2,2'-(ethylenedioxy)diethanethiol, 1,6-hexanedithiol, trimethylolpropane tris(3-mercaptopropionate), pentaerythritol tetrakis(3-mercaptopropionate), thioacetic acid, thioglycolic acid, thiolactic acid, N-acetylcysteine, glutathione, Valintrob 2:3-dimercaptopropanol glucoside, isooctyl thioglycolate, 2-(dodecylthiothiocarbonothioylthio)-2-methylpropionic acid (DDMAT), 2-(2-carboxyethylsulfanylsulfanylsulfanylsulfanyl)propionic acid, 1,8-dimercapto-3,6-dioxaoctane (DMDO), ethanol, isopropanol, malic acid, lactic acid, formic acid, and sodium hypophosphite.

[0106] The chain transfer agent may be present in the polymerizable composition in a ratio of moles of chain transfer agent functional group (e.g., thiol) to moles of ethylenically unsaturated groups of less than 0.80, less than 0.75, or from 0.75 to 0.05. The chain transfer agent may be present in the polymerizable composition in a ratio of moles of chain transfer agent functional group (e.g., thiol) to moles of ethylenically unsaturated groups of from about 0.03 moles of chain transfer agent functional group to about 0.80 moles of ethylenically unsaturated groups, from about 0.03 moles of chain transfer agent functional group to about 0.75 moles of ethylenically unsaturated groups, from about 0.03 moles of chain transfer agent functional group to about 0.5 moles of ethylenically unsaturated groups, from about 0.03 moles of chain transfer agent functional group to about 0.25 moles of ethylenically unsaturated groups, from about 0.05 moles of chain transfer agent functional group to about 0.5 moles of ethylenically unsaturated groups, from about 0.03 ... Up to about 0.80 moles of ethylenically unsaturated groups, from about 0.05 moles of chain transfer agent functional groups to about 0.75 moles of ethylenically unsaturated groups, from about 0.05 moles of chain transfer agent functional groups to about 0.50 moles of ethylenically unsaturated groups, from about 0.05 moles of chain transfer agent functional groups to about 0.25 moles of ethylenically unsaturated groups, from about 0.05 moles of chain transfer agent functional groups to about 0.15 moles of ethylenically unsaturated groups, and ranges therebetween, may be present in the polymerizable composition.

[0107] Examples of ethylenically unsaturated macromers are disclosed in PCT Application Nos. PCT / US2019 / 026098, filed April 5, 2019, and PCT Application Nos. PCT / US2019 / 026114, filed April 5, 2019, and their related U.S. and foreign applications, each of which is incorporated herein by reference in its entirety. In an embodiment, the ethylenically unsaturated macromer is absorbable.

[0108] For example, the compositions disclosed herein include a photopolymerizable macromer component that includes a macromer (polymer) that can be photopolymerized that is biodegradable or absorbable or resorbable under physiological conditions. In an embodiment, the photopolymerizable macromer component includes an aliphatic or aromatic macromer, polymer, and / or oligomer with ethylenically unsaturated end groups. For example, the photopolymerizable macromer component includes a polymer with an acrylate end group. In an embodiment, the acrylate end group can be a methacrylate end group. In an embodiment, the photopolymerizable macromer includes a photoreactive functional end group, such as an acrylate or methacrylate. In an embodiment, the photopolymerizable macromer includes a photoreactive functional end group, such as a thiol group. In an embodiment, the photopolymerizable composition can include one or more macromers with photoreactive end groups, where the photoreactive functional end group can be, for example, an acrylate or methacrylate, or a combination of macromers with different end groups, for example, some of which have acrylate end groups and some of which have thiol end groups.

[0109] In embodiments, the macromers may include mono-, di-, tri-, tetra-, or penta-functional photocurable macromers, and in some cases may include relatively low molecular weight or relatively high molecular weight species. In embodiments, the macromers may include reactive groups, including but not limited to acrylate (including methacrylate) unsaturated functional groups, allyl and vinyl reactive groups, and thiol reactive groups. Higher functionality materials having 4, 5, 6, up to 18 reactive sites are contemplated in the present disclosure. Monomeric materials typically have molecular weights below 250 Daltons, while oligomeric materials can have molecular weights in the tens of thousands.

[0110] Suitable photoinitiators are described elsewhere herein. For a photoinitiator to successfully cure a photoreactive composition, it is necessary that the absorption band of the photoinitiator overlaps with the emission spectrum of the light source used for curing. Optionally, the photopolymerizable composition disclosed herein includes at least one photoinitiator that absorbs wavelengths of light ranging from about 10 nm to about 770 nm, or from about 100 nm to about 770 nm, or from about 200 nm to about 770 nm, and all wavelengths in between. In an embodiment, the photoinitiator component includes a photoinitiator that absorbs light at wavelengths of 300 nm or more and up to about 770 nm. In an embodiment, the photoinitiator component includes a photoinitiator that absorbs light at wavelengths of 365 nm or more and up to about 770 nm. In an embodiment, the photoinitiator component includes a photoinitiator that absorbs light at wavelengths of 375 nm or more and up to about 770 nm. In an embodiment, the photoinitiator component includes a photoinitiator that absorbs light at wavelengths of 400 nm or more and up to about 770 nm. The photopolymerization conditions of the present disclosure will include exposure of the photoreactive composition to a spectrum of wavelengths from a light source that can provide a desired spectrum of wavelengths suitable for photopolymerization of the composition. The choice of wavelength will depend on the identity of the photoinitiator. Commercial photoinitiator suppliers will indicate the appropriate wavelengths for their particular photoinitiators.

[0111] Free radical generating photoinitiators may be used to achieve polymer curing in accordance with the present disclosure. These photoinitiators may be used to cure mixtures of thiol-containing compounds and ethylenically unsaturated compounds as disclosed herein. There are two types of free radical generating photoinitiators, designated Type I and Type II photoinitiators, that may be used in accordance with the present disclosure and are described elsewhere herein.

[0112] The photopolymerizable compositions disclosed herein are made by combining the desired components, typically by stirring to achieve a homogenous composition. The desired components can be mixed using a homogenizer. For example, the compositions disclosed herein can be prepared by combining components such as those identified above. Optionally, the desired components can include a dispersant to aid in suspension. The listed components can optionally be heated before mixing. The listed components can optionally be placed under vacuum to remove air bubbles.

[0113] In an embodiment, the disclosure provides a composition comprising a first organic compound (polySH) having a plurality of thiol groups (SH), a second organic compound (polyEU) having a plurality of ethylenically unsaturated groups (EU), and a photoinitiator. The relative amounts of polySH and polyEU in the composition may be described in terms of the Δ1 to Δ2 equivalent ratio of X:Y, where X represents the equivalents of SH, Y represents the equivalents of EU, and the sum of X and Y is 100. In one embodiment, X is in the range of 25 to 75, Y is in the range of 75 to 25, and the sum of X and Y is 100. In one embodiment, X is in the range of 30 to 70, Y is in the range of 70 to 30, and the sum of X and Y is 100. In one embodiment, X is in the range of 40 to 60, Y is in the range of 60 to 40, and the sum of X and Y is 100. In one embodiment, X is in the range of 45 to 55, Y is in the range of 55 to 45, and the sum of X and Y is 100. In one embodiment, the number of equivalents of X is about equal to the number of equivalents of Y.

[0114] Thermal reaction conditions As discussed herein, compositions of the present disclosure may contain polyΔ1 and polyΔ2 that are reactive with each other upon exposure to elevated temperatures. The particular elevated temperature and the time required to achieve a reaction between polyΔ1 and polyΔ2 at that particular elevated temperature will depend on the particular identities of Δ1 and Δ2. For many reactions between nucleophiles and electrophiles, a temperature of about 100° C. for 30 minutes to 5 hours is sufficient.

[0115] In one aspect, the present disclosure provides a composition comprising a first organic compound (polyhv) having a plurality of photopolymerizable groups (hv), a photoinitiator, a second organic compound (polyΔ1) having a plurality of reactive groups Δ1, and a third organic compound (polyΔ2) having a plurality of reactive groups Δ2, where Δ1 reacts with Δ2 upon contact and exposure to a temperature of greater than about 50° C. The relative amounts of polyΔ1 and polyΔ2 in the composition may be described in terms of a Δ1 to Δ2 equivalent ratio of X:Y, where X represents the equivalents of Δ1, Y represents the equivalents of Δ2, and the sum of X and Y is 100. In one aspect, X is in the range of 25-75, Y is in the range of 75-25, and the sum of X and Y is 100. In one aspect, X is in the range of 30-70, Y is in the range of 70-30, and the sum of X and Y is 100. In one embodiment, X is in the range of 40 to 60, Y is in the range of 60 to 40, and the sum of X and Y is 100. In one embodiment, X is in the range of 45 to 55, Y is in the range of 55 to 45, and the sum of X and Y is 100. In one embodiment, the equivalents of X are about equal to the equivalents of Y.

[0116] To expose the composition to high temperatures, the composition can be placed in an oven. Alternatively, a heat lamp can be aimed at the composition, and a headlamp provides infrared radiation that heats the composition.

[0117] Additive Manufacturing The methods disclosed herein include methods for using the curable compositions to make articles, particularly non-toxic and biodegradable articles. For example, the compositions disclosed herein can be used as curable inks or resins in 3D printing methods. For example, the curable compositions disclosed herein can be used as curable inks or resins in a vat polymerization process in 3D printing. Exemplary vat polymerization processes include stereolithography (also known as SLA), digital light processing (DLP™, Texas Instrument), daylight polymer printing (DPP), carbon digital light synthesis (Carbon DLS™, Carbon, Inc.), and continuous liquid interface generation (CLIP™, Carbon, Inc.). Other suitable methods of additively manufacturing articles using the curable compositions of the present disclosure include binder jetting, material jetting, material extrusion, computational axial lithography, and two-photon polymerization printing. The present disclosure provides for the use of the curable compositions disclosed herein in any of the mentioned 3D printing processes.

[0118] Thus, in one aspect, the present disclosure provides a method for vat polymerization, e.g., SLA printing of an article, comprising exposing a photopolymerizable composition comprising at least one photopolymerizable composition disclosed herein, typically comprising at least one photoinitiator component at a total concentration of less than 1.0 wt%, to light for a period of time. Any of the photopolymerizable compositions disclosed herein can be used in the method for SLA printing an article. For example, the composition can contain polyhν in addition to polyΔ1 and polyΔ2. As another example, the composition can contain polyEU and polySH. Optionally, the photopolymerizable composition can include a reactive diluent or a non-reactive diluent. A reactive diluent is a diluent that participates in the polymerization reaction, e.g., a reactive diluent is polymerized, e.g., with a macromer. The photopolymerizable composition of the present disclosure can include a stabilizer, e.g., a free radical stabilizer.

[0119] Methods for printing articles by SLA according to the present disclosure may include a secondary curing step that involves curing the printed article with thermal energy. The secondary curing step involves exposing at least a portion of the printed article to thermal energy, whereby at least a portion of the printed article undergoes a second heat-induced polymerization reaction. For example, part or all of the article may be exposed to a temperature of about 100° C. for about 30 minutes to 5 hours. The secondary curing step may be used to modify the properties of the printed article.

[0120] Methods for printing articles by SLA according to the present disclosure can include pre-treatment and / or post-treatment of the printing article. For example, the printing article can be cleaned after printing, before or after a thermal curing step.

[0121] A printing article is an article resulting after a 3D printing period is completed. A printing article can be a structure or a portion of a structure. A printing article can be in the form of a film, such as a coating, that is printed on a surface. As used herein, the term printing is used to mean contacting a polymer composition with a surface and further polymerizing the polymer composition. Printing can include contacting a polymer composition with a surface and then exposing the polymer composition to UV and / or visible light so that the polymer composition undergoes further polymerization. The surface that the polymer composition contacts can be any surface that contains a polymerized layer of the polymer composition. As previously mentioned, the printing article can undergo a second curing step by being exposed to elevated temperatures.

[0122] The printing article may or may not contain residual amounts of the components of the curable composition. For example, the printing article may include a diluent or photopolymerizable diluent, or a photoinitiator. In an embodiment, the printing article or the curable composition may have additives. The additives, as disclosed herein, may include thixotropic materials, colorants, tracer materials, or conductive materials. For example, the additives may be pigments. The printing article may be colored due to the presence of pigments, or may have any desired attribute, such as, but not limited to, having at least a portion of the article fluorescent, emissive, reflective, flexible, rigid, pliable, friable, or combinations thereof.

[0123] In a typical vat printing process, the build platform is lowered a layer thickness down from the top of a vat of resin. Actinic radiation is directed at the composition, and the light causes photopolymerization (photocuring) of the composition. The build platform continues to move down and additional layers are built on top of the previous layer. Upon completion, the vat can be drained of excess resin and the printing article can be collected. This printing article can be subjected to additional processing. For example, the printing article can be washed to remove excess resin. As another example, the printing article can be exposed to thermal energy to cause thermal curing, especially if the article contains Poly Delta 1 and Poly Delta 2.

[0124] A method of forming an article by vat polymerization can include directing actinic radiation to a vat of a photopolymerizable composition that includes a monomer or macromer that can undergo polymerization, such as a monomer or macromer having functional groups that can undergo a photopolymerization reaction to form an oligomer and / or polymer, such as the poly-hν compounds disclosed herein.

[0125] In one embodiment, vat polymerization, for example using SLA, is printing an article using a photopolymerizable composition by directing actinic radiation at a light wavelength of about 10 nm to about 1 mm onto a vat of the composition. As used herein, UV radiation has a wavelength of about 10 to 400 nm, while visible radiation has a wavelength of 390 to 770 nm, and IR radiation has a wavelength of 770 nm to 1 mm. In one embodiment, the actinic radiation consists of one or more wavelengths and / or one or more radiation sources. In an embodiment, the photopolymerizable composition may include a light-reflecting material component, which allows photopolymerization to occur under the same polymerization conditions with a shorter exposure time than would occur without the light-reflecting material component. Optionally, if the curable composition contains the thermally reactive components polyΔ1 and polyΔ2, a thermal curing process will be performed before, during, or after the photopolymerization process. Optionally, if the curable composition contains the thermally reactive components polyΔ1 and polyΔ2, a thermal curing process will be performed after the photopolymerization process.

[0126] In one embodiment, the present disclosure provides a method of printing an article using vat polymerization, e.g., SLA printing, in a device suitable for printing by SLA. The method includes providing a vat containing a curable composition disclosed herein, including at least one photoinitiator that absorbs at a wavelength of light from about 10 nm to about 770 nm. In an embodiment, the photoinitiator absorbs at a wavelength of light of 300 nm or greater. In an embodiment, the photoinitiator absorbs at a wavelength of light of 365 nm or greater. In an embodiment, the photoinitiator absorbs at a wavelength of light of 375 nm or greater. In an embodiment, the photoinitiator absorbs at a wavelength of light of 400 nm or greater. The photoinitiator in the curable composition is at least one photoinitiator component that includes a photoinitiator that is a Type I, Type II, cationic photoinitiator, or a combination thereof.

[0127] In one embodiment, the present disclosure provides a method of printing an article by vat polymerization using SLA, for example in a device for printing by SLA, the method comprising photopolymerizing or curing a photopolymerizable composition to a depth of less than 150 microns. In an embodiment, the method disclosed herein comprises photopolymerizing or curing a photopolymerizable composition to a depth of about 5 microns to about 50 microns, and all depths in between.

[0128] In one embodiment, the present disclosure provides a method of printing an article by vat polymerization, for example using SLA in a device for printing by SLA, the method comprising a photopolymerizable composition comprising a light reflecting material component comprising a light reflecting material that is absorbable at physiological conditions. In an embodiment, the light reflecting material component comprises a light reflecting material that is biocompatible with a biological organism. In an embodiment, the light reflecting material component comprises a light reflecting material that is polymerized with at least one of a photopolymerizable macromer, a diluent, a light reflecting material, or a combination thereof.

[0129] In one aspect, the present disclosure provides an additive manufacturing process, comprising: (a) providing a vat containing a first composition disclosed herein, comprising polyEU and polySH; (b) directing actinic radiation from a light source to the first composition in the vat, the actinic radiation being effective to induce polymerization of components of the composition to form a second composition; and (c) forming a solid article comprising the second composition. Step (c) may be accomplished by repeatedly directing actinic radiation to the first composition in the vat, particularly as the build platform moves. The second composition is or comprises a photopolymerized product of polyEU and polySH.

[0130] In one aspect, the present disclosure provides an additive manufacturing process, comprising: (a) providing a vat containing a first composition disclosed herein containing polyhv, polyΔ1, and polyΔ2; (b) directing actinic radiation from a light source to the first composition in the vat, the actinic radiation being effective to induce polymerization of the photocurable components of the first composition to form a second composition comprising a photochemically cured composition; and (c) applying thermal energy to the second composition comprising the photochemically cured composition to form a third composition comprising a photochemically cured composition and a thermally cured composition. The second composition is or comprises a photopolymerization product of polyhv. The third composition is or comprises a double network of the combined photopolymerization product of polyhv and the thermally induced polymerization product of polyΔ1 and polyΔ2.

[0131] In one embodiment, the present disclosure provides a method of making an article by two-photon polymerization printing, comprising curing a curable composition disclosed herein to form an article. In one embodiment, the present disclosure provides a method of making an article by computer axial lithography, comprising curing a curable composition disclosed herein to form an article. In one embodiment, the present disclosure provides a method of making an article by material extrusion, comprising curing a curable composition disclosed herein to form an article. In one embodiment, the present disclosure provides a method of making an article by material jetting, comprising curing a curable composition disclosed herein to form an article. In one embodiment, the present disclosure provides a method of making an article by binder jetting, comprising curing a curable composition disclosed herein to form an article. In one embodiment, the present disclosure provides a method of making an article by continuous light interface manufacturing (CLIP), comprising curing a curable composition disclosed herein to form an article. In one embodiment, the present disclosure provides a method of making an article by vat polymerization, comprising curing a curable composition disclosed herein to form an article.

[0132] Curing composition The present disclosure includes articles, additionally referred to herein as printing articles or solid articles, which may be made by the methods disclosed herein from the compositions disclosed herein. In embodiments, the article may be a medical device. In embodiments, the article may be a portion of a medical device. In embodiments, the article may be porous. In embodiments, the article may be biodegradable under physiological conditions. In embodiments, the biodegradable article may have a degradation period of about 3 days to about 5 years. In embodiments, the article may not be biodegradable. In embodiments, a portion of the article may be biodegradable and a second portion may be non-biodegradable or may have a degradation period that is different from the degradation period of the first or remaining portion of the article.

[0133] As noted elsewhere, in one embodiment, the cured composition does not contain any appreciable amount of water. For example, in embodiments, the cured composition contains less than 2500 ppm water, or less than 1000 ppm water, or less than 500 ppm water.

[0134] In one embodiment, the cured composition will degrade in water or when exposed to aqueous conditions. Thus, in one embodiment, the cured composition may be biodegradable, which may be particularly useful when the cured composition is used to form a biodegradable implantable medical device. In one embodiment, the cured composition will degrade under aqueous conditions to form a particulate material, rather than forming, for example, a swollen material, i.e., a material that has absorbed water and is in a swollen state. For example, when the cured composition is placed in a decomposition medium containing water, such as a phosphate buffer at pH 7.0-7.4, or in a phosphate buffer saline solution, the cured composition will undergo dissolution in the decomposition medium. Upon dissolution, the undissolved material will have a particular morphology, rather than a swollen morphology, such that more than 50% by weight, or more than 60% by weight, or more than 70% by weight, or more than 80% by weight, or more than 90% by weight of the total weight of the cured composition is dissolved in the decomposition medium.

[0135] In one aspect, the cured composition of the present disclosure exhibits desirably low swelling when placed in an aqueous medium. If the cured composition is in contact with an aqueous medium for a long time, swelling can be a significant problem. For example, if the cured composition is a component or all of a biodegradable implantable medical device and the device is implanted in a patient, the device may undergo both degradation (which may be desirable) and swelling (which may be undesirable). Swelling can be a particular problem toward the end of implant degradation, i.e., after most of the implant has degraded. However, the problem of swelling, especially the late swelling that may be observed after most of the implant has degraded (i.e., more than 50% weight loss, or more than 60% weight loss, or more than 70% weight loss, or more than 80% weight loss, or more than 90% weight loss), can be mitigated by using the curable composition of the present disclosure.

[0136] Below are some exemplary embodiments of the present disclosure, which may optionally include one or more chain transfer agents and / or beta-carotene compounds. 1) A composition comprising a first organic compound (polySH) having a plurality of thiol groups (SH), a second organic compound (polyEU) having a plurality of ethylenically unsaturated groups (EU), and a photoinitiator. A stabilizer may optionally be present in the composition, the stabilizer may optionally be selected from the group consisting of tocopherol, gallic acid, esters of gallic acid, butylated hydroxyanisole, and combinations thereof. 2) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as the composition of embodiments 3-27, wherein the composition has an SH to EU equivalent ratio of X:Y, where X is in the range of 25 to 75, Y is in the range of 75 to 25, and the sum of X and Y is 100. 3) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as embodiment 2, wherein polySH is water soluble. 4) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as embodiment 2 or 3, wherein polySH is bioabsorbable. 5) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, for example embodiment 2 or 3 or 4, wherein polySH is a macromer. 6) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as embodiment 2 or 3 or 4, wherein polySH is a macromer having a molecular weight greater than 1,000 g / mol. 7) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as embodiment 2 or 3 or 4, wherein polySH has a molecular weight of less than 500 g / mol. 8) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as any of embodiments 2-7, wherein PolyEU is water-soluble. 9) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as any of embodiments 2-8, wherein PolyEU is bioabsorbable. 10) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, for example, embodiments 2-9, wherein the EU of the polyEU is an acrylate. 11) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, for example, embodiments 2-9, wherein the EU of the polyEU is a methacrylate. 12) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, for example, embodiments 2-9, wherein EU of the polyEU is norbornenyl. 13) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, for example, embodiments 2-7, wherein polyEU is a macromer. 14) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, for example, embodiments 2-7, wherein polyEU is a macromer having a molecular weight greater than 1,000 g / mol. 15) The composition of embodiment 1 or any of the embodiments of embodiment 1 disclosed herein, such as embodiments 2-14, wherein at least one of poly-SH and poly-EU further comprises multiple carbonyl groups, and optionally poly-EU comprises multiple carbonyl groups, or optionally each of poly-SH and poly-EU comprises multiple carbonyl groups. 16) The composition of embodiment 1 or any of the embodiments of embodiment 1 disclosed herein, such as embodiments 2-15, wherein at least one of poly-SH and poly-EU further comprises multiple ester groups, and optionally poly-EU comprises multiple ester groups, or optionally poly-SH and poly-EU each comprise multiple ester groups. 17) The composition of embodiment 1 or any of the embodiments of embodiment 1 disclosed herein, such as embodiments 2-15, wherein at least one of PolyEU and PolySH further comprises multiple ester groups and multiple carbonate groups, and optionally PolyEU further comprises both multiple ester groups and multiple carbonate groups, or optionally both PolySH and PolyEU further comprise both multiple ester groups and multiple carbonate groups. 18) The composition of embodiment 1 or any of the embodiments of embodiment 1 disclosed herein, such as embodiments 2-15, wherein at least one of Poly-SH and Poly-EU further comprises multiple ester groups and multiple urethane groups, and optionally Poly-EU further comprises both multiple ester groups and multiple urethane groups, or optionally both Poly-SH and Poly-EU further comprise both multiple ester groups and multiple urethane groups. 19) The composition of embodiment 1 or any of the embodiments of embodiment 1 disclosed herein, such as embodiments 2-15, wherein at least one of Poly-SH and Poly-EU further comprises multiple carbonate groups and multiple urethane groups, and optionally Poly-EU further comprises both multiple carbonate groups and multiple urethane groups, or optionally both Poly-SH and Poly-EU further comprise both multiple carbonate groups and multiple urethane groups. 20) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as embodiments 2-19, wherein the plurality of SHs of the polySH is selected from 2, 3, and 4. 21) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as embodiments 2-20, wherein the plurality of EUs in the polyEU is selected from 2, 3, and 4. 22) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as embodiments 2-21, which does not contain a volatile material having a boiling point less than 110° C. 23) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as embodiments 2-22, which is anhydrous. 24) The composition of embodiment 1 or any embodiment of embodiment 1 disclosed herein, such as embodiments 2-23, which is fluid at room temperature of about 18° C. to about 22° C. 25) A composition comprising the photochemically cured reaction product of any of the compositions of embodiments 1-24. 26) The composition of embodiment 25, which is bioabsorbable. 27) The composition of embodiment 25, which is solid at 50° C. 28) An additive manufacturing process comprising: a. providing a batt comprising a first composition of any one of embodiments 1-24; b. directing actinic radiation from a light source toward the first composition in the vat, the actinic radiation being effective to induce polymerization of components of the composition to form a second composition; c. forming a solid article comprising the second composition. 29) A composition comprising a first organic compound (polyhv) having a plurality of photopolymerizable groups (hv), a photoinitiator, a second organic compound (polyΔ1) having a plurality of reactive groups Δ1, and a third organic compound (polyΔ2) having a plurality of reactive groups Δ2, wherein Δ1 reacts with Δ2 upon contact and exposure to a temperature greater than 50° C. 30) The composition of embodiment 29 or any embodiment of embodiment 29, wherein polyhv is bioabsorbable. 31) The composition of embodiment 29 or any embodiment of embodiment 29, such as embodiment 30, wherein p polyhv is a macromer. 32) The composition of embodiment 29 or any of the embodiments of embodiment 29, such as embodiment 30 or 31, wherein polyhv is a macromer having a molecular weight greater than 1,000 g / mol. 33) The composition of embodiment 29 or any embodiment of embodiment 29, such as embodiment 30 or 31, wherein polyhv has a molecular weight of less than 500 g / mol. 34) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 or 31, wherein polyhv is water-soluble. 35) The composition of embodiment 29 or any of the embodiments of embodiment 29, such as embodiments 30-34, wherein poly-nu is poly-EU selected from acrylates and methacrylates. 36) The composition of embodiment 29 or any embodiment of embodiment 29, such as embodiments 30-34, wherein the hv of polyhv is norbornenyl. 37) The composition of embodiment 29 or any of the embodiments of embodiment 29, such as embodiments 30-36, wherein Δ1 is a nucleophile and Δ2 is an electrophile. 38) The composition of embodiment 29 or any embodiment of embodiment 29, such as embodiments 30-36, wherein Δ1 is selected from hydroxyl and amino. 39) The composition of embodiment 29 or any of the embodiments of embodiment 29, such as embodiments 30-36, wherein Δ2 is selected from epoxides and isocyanates. 40) The composition of embodiment 29 or any of the embodiments of embodiment 29, such as embodiments 30-39, wherein at least one of poly hv, poly Δ1, and poly Δ2 further comprises multiple carbonyl groups, and optionally poly hv comprises multiple carbonyl groups, or optionally poly hv and at least one of poly Δ1 and poly Δ2 comprise multiple carbonyl groups. 41) The composition of embodiment 29 or any of the embodiments of embodiment 29, such as embodiments 30-39, wherein at least one of poly hv, poly Delta 1, and poly Delta 2 further comprises multiple ester groups, and optionally poly hv comprises multiple ester groups, or optionally poly hv and at least one of poly Delta 1 and poly Delta 2 comprise multiple ester groups. 42) The composition of embodiment 29 or any of the embodiments of embodiment 29, such as embodiments 30-39, wherein at least one of poly hv, poly Delta 1, and poly Delta 2 further comprises multiple ester groups and multiple carbonate groups, and optionally poly hv comprises both multiple ester groups and multiple carbonate groups, or optionally at least one of poly hv and poly Delta 1 and poly Delta 2 comprises both multiple ester groups and multiple carbonate groups. 43) The composition of embodiment 29 or any of the embodiments of embodiment 29, such as embodiments 30-39, wherein at least one of poly hv, poly Delta 1, and poly Delta 2 further comprises multiple ester groups and multiple urethane groups, and optionally poly hv comprises both multiple ester groups and multiple urethane groups, or optionally poly hv and at least one of poly Delta 1 and poly Delta 2 comprise both multiple ester groups and multiple urethane groups. 44) The composition of embodiment 29 or any of the embodiments of embodiment 29, such as embodiments 30-39, wherein at least one of poly hv, poly Delta 1, and poly Delta 2 further comprises multiple carbonate groups and multiple urethane groups, and optionally poly hv comprises both multiple carbonate groups and multiple urethane groups, or optionally poly hv and at least one of poly Delta 1 and poly Delta 2 comprise both multiple carbonate groups and multiple urethane groups. 45) The composition of embodiment 29 or any embodiment of embodiment 29, such as embodiments 30-44, wherein the multiple hv of polyhv are selected from 2, 3, and 4. 46) The composition of embodiment 29 or any embodiment of embodiment 29, such as any of embodiments 30-44, wherein the plurality of Δ1 in polyΔ1 is selected from 2, 3, and 4. 47) The composition of embodiment 29 or any embodiment of embodiment 29, such as any of embodiments 30-44, wherein the plurality of Δ2 in polyΔ2 is selected from 2, 3, and 4. 48) The composition of embodiment 29 or any embodiment of embodiment 29, such as embodiments 30-47, which does not contain any volatile materials having a boiling point less than 110° C. 49) The composition of embodiment 29 or any embodiment of embodiment 29, for example, embodiments 30-47, which is anhydrous. 50) The composition of embodiment 29 or any embodiment of embodiment 29, for example, embodiments 30-47, which is fluid at a temperature of about 18° C. to about 22° C. 51) A composition comprising a photochemically cured reaction product of the composition of any of embodiments 29-50 and a thermally cured reaction product. 52) The composition of embodiment 51, which is bioabsorbable. 53) The composition of embodiment 51, which is solid at 50° C. 54) An additive manufacturing process comprising: a. providing a batt comprising the first composition of any one of embodiments 29-50; b. directing actinic radiation from a light source at the first composition in the vat, the actinic radiation being effective to induce polymerization of components of the first composition to form a second composition comprising a photochemically cured composition; c. applying thermal energy to the second composition comprising the photochemically cured composition to form a third composition comprising a photochemically cured composition and a thermally cured composition.

[0137] The disclosure is described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also forms part of the disclosure. This includes the generic description of the invention of the disclosure with a provisio or negative limitation removing any subject matter from that genus, regardless of whether the omitted material is specifically described herein.

[0138] As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise, and the term "X and / or Y" means either "X" or "Y," or both "X" and "Y," and the letter "s" following a noun is to be understood to indicate both the plural and the singular form of that noun. In addition, when features or aspects of the disclosure are described in terms of a Markush group, it is intended that the disclosure encompasses, and is thus described in terms of, the individual members of the Markush group and any subgroups of the members, and applicants reserve the right, and one of ordinary skill in the art will recognize, to amend their application or claims to specifically refer to the individual members or any subgroups of the members of the Markush group.

[0139] The following examples are offered by way of illustration and not by limitation. Chemicals were obtained from commercial sources, such as MilliporeSigma (St. Louis, MO, USA). EXAMPLES

[0140] Example 1 Hydroxyl-terminated precursor polymer In one aspect, the present disclosure provides a composition containing at least one of the compounds designated as polyhv, polySH, polyEU, polyΔ1, and polyΔ2. Optionally, each of these compounds can be made from a precursor polymer having a hydroxyl group instead of the hv or SH or EU or Δ1 or Δ2 group, and optionally the hv, SH, EU, Δ1, or Δ2 group is attached to the precursor polymer via a suitable linking group. This example illustrates the preparation of an exemplary hydroxyl-containing precursor polymer.

[0141] Table 1 identifies 16 precursor polymers, uniquely designated as 3DP 1 through 3DP 16, which may be generally described as having or including compounds of the general formula CC-[arm-OH] in accordance with the present disclosure. The term arm-OH refers to an arm that terminates with a hydroxyl group (OH), i.e., has a hydroxyl end group.

[0142] When the precursor polymer comprises a compound having the formula CC-[(A)-(B)], i.e., the arms are formed from residues of monomers from group A (any one or more of trimethylene carbonate and ε-caprolactone) proximal (adjacent) to the central core, and residues of monomers from group B (any one or more of glycolide, lactide, and p-dioxanone) distal (furthest) to the central core, such precursor polymers can be prepared by reacting a functionalized central core, also referred to herein as initiator, with one or more monomers from group A, followed by reacting the reaction product (referred to herein as precursor prepolymer) with one or more monomers from group B. The result is a central core attached to one or more arms, each arm terminated with a hydroxyl and having the formula -(A)-(B)-OH. The preparation of such a precursor polymer is shown in Example 1A below, where the central core is trifunctional and the functionalized central core / initiator is provided by trimethylolpropane. Example 1A - Preparation of triaxial 3DP-6 precursor polymer.

[0143] Trimethylene carbonate (1.4 mol) and ε-caprolactone (1.4 mol) were used as the reaction initiator, trimethylolpropane (0.6 mol), and stannous octoate (7.0 × 10 -5 The copolymerization was carried out at 130° C. for 72 hours using glycolide (1.1 mol) and additional stannous octoate (2.1×10 -4 mol) was mixed with the polymer precursor at 160° C. for 3 hours to provide a precursor polymer having polyglycolide grafts at the ends of the polymer precursor. The amorphous liquid precursor polymer thus obtained was devolatilized and 1 H NMR spectroscopy, rheometry (shear rate 105 s -1 It was characterized by thermal expansion coefficient (Tg) of 17,300 cP, differential scanning calorimetry (Tg = -45 °C), and gel permeation chromatography (Mn = 1884 Da, PDI = 1.80).

[0144] When the precursor polymer comprises a compound having the formula CC-[(B)-(A)], i.e., the residues of monomers from group B (glycolide, lactide, and p-dioxanone) are proximal (adjacent) to the central core and the residues of monomers from group A (trimethylene carbonate and caprolactone) are distal (furthest) to the central core, such precursor polymers can be prepared by reacting a functionalized central core with one or more monomers from group B, followed by reacting the reaction product with one or more monomers from group A. The result is a central core attached to one or more arms, each arm terminated with a hydroxyl and having the formula -(B)-(A)-OH. The preparation of such a precursor polymer is shown in Example 1B below, where the central core is trifunctional and the functionalized central core is provided by trimethylolpropane. Example 1B - Preparation of triaxial 3DP-4 precursor polymer.

[0145] In the first step, glycolide (1.1 mol) was reacted with trimethylolpropane (0.6 mol) as initiator and stannous octoate (7 × 10 -5 The polymerisation was carried out at 160 °C for 3 h using 1.4 mol of stannous octoate as catalyst to provide the polymer precursor. After the completion of the first step, a mixture of equimolar amounts of trimethylene carbonate (1.4 mol) and ε-caprolactone (1.4 mol) was added to more stannous octoate (2 × 10 -4 The resulting amorphous liquid was removed by volatilization, and the resulting mixture was cooled to 130° C. for 72 hours to copolymerize the polymer precursor at its terminal. 1 H NMR spectroscopy, rheometry (shear rate 105 s -1 It was characterized by thermal expansion coefficient (Tg) of 17,300 cP, differential scanning calorimetry (Tg = -45 °C), and gel permeation chromatography (Mn = 1909 Da, PDI = 1.83).

[0146] Following the procedures outlined in Examples 1A and 1B, additional polyester precursor polymers were synthesized as described in Table 1. All linear samples were synthesized using 1,3-propanediol as the difunctional initiator, all trifunctional prepolymers were prepared using trimethylolpropane, and the four-arm block copolyester compositions were initiated with pentaerythritol as the tetrafunctional initiator. In Table 1, M / I refers to the total moles of monomer (M) used to prepare the arms (also referred to as the functionalized central core) divided by the moles of initiator (I) for each of the copolyesters identified in Table 1. Also in Table 1, M / C refers to the total moles of monomer (M) used to prepare the arms divided by the total moles of catalyst (C) used to prepare each of the copolyester prepolymers identified in Table 1. Each of the precursor polymers in Table 1 contains a B region, characterized by a row entitled G / L / pD, which is an abbreviation for glycolide / lactide / p-dioxanone segment, which can be either proximal to the central core (in which case the location of the B region is specified to be in the middle of the precursor polymer) or distal to the central core (in which case the location of the B region is specified to be at the end of the precursor polymer, in which case the B region terminates in a hydroxyl group).

[0147] Selected molecular weight results obtained by gel permeation chromatography (GPC) for selected precursor polymers prepared as illustrated in Example 1 are provided in Table 2. In Table 2, Mn refers to number average molecular weight, Mw refers to weight average molecular weight, PDI refers to polydispersity (i.e., Mw / Mn), and Da refers to Daltons. [Table 1] [Table 2]

[0148] Example 2 Preparation of Methacrylated Compounds of the Present Disclosure Representative polymers of the formula PolyEU Table 3 identifies eight EU-functionalized precursor polymers, uniquely designated 3DP 4m (where m represents an exemplary ethylenically unsaturated (EU) group, methacrylate) through 3DP 7m and 3DP 9m through 3DP 12m, which may be generally described as having or including a compound of the general formula CC-[arm-EU] in accordance with the present disclosure. The designation arm-EU refers to an arm that terminates in a photoreactive ethylenically unsaturated group, such as an acrylate ("a") or methacrylate ("m") group.

[0149] The methacrylated polymers in Table 3 were prepared from the corresponding precursor polymers in Table 1, i.e., 3DP 4m was prepared from 3DP 4, 3DP 5m was prepared from 3DP 5, etc.

[0150] Methacrylation of 3DP 6 to produce 3DP 6m 3DP 6 precursor polymer (0.131 moles) was reacted with excess methacrylic anhydride in the presence of 3-tert-2-butyl-4-hydroxyanisole (6.724×10-4 moles) at 120° C. for 24 hours. Residual methacrylic anhydride and methacrylic acid by-products were removed from the crude polymer using a rotary evaporator. The resulting amorphous liquid polymer was 1 Characterization was performed using H NMR spectroscopy, rheometry (viscosity 16,400 cP at shear rate 105 s-1), differential scanning calorimetry (Tg=-38°C), and gel permeation chromatography (Mn=2162 Da, PDI=1.75). Each 3DP formulation was methacrylated according to the procedure described above. The composition and molecular weight results are summarized in Table 3, and the dynamic viscosity is reported in Table 4. In Table 3, for 3DP 5m, the 40.15 in the TMC column is the total mole % of TMC+1,3-propanediol used to make the 3DP 5m. [Table 3] [Table 4]

[0151] Example 3 Preparation of Thiolated Compounds of the Present Disclosure Exemplary polymers of formula polySH To a 500 mL 3-neck round bottom flask equipped with a mechanical stirrer and an addition funnel, 3DP 6 (51.3 g, 0.0665 mol, see Table 1), thiolactic acid (17.243 mL, 20.623 g, 0.1943 mol), and dichloromethane (DCM) (200 mL) were added under nitrogen. The contents of the reaction vessel were stirred at 200 rpm and the reaction vessel was cooled using an ice bath. Separately, N,N'-dicyclohexylcarbodiimide (DCC) (44.5 g, 0.2157 mol) was dissolved in 200 mL of DCM. The DCC in DCM solution was then added dropwise to the reaction vessel using an addition funnel over a period of 30 min. After the addition of the DCC / DCM solution was complete, the ice bath was removed. 4-Dimethylaminopyridine (DMAP) (2.366 g, 0.0193 moles) was added to the reaction vessel using a powder funnel. The reaction mixture was kept stirring at room temperature under nitrogen for 72 hours. The DCM level that evaporated during the reaction was replenished. After 72 hours, the reaction mixture was filtered under suction. The filtrate was washed with 2×100 mL of 0.25 M HCl and 1×100 mL of deionized (DI) water. The organic phase from the extraction was dried over activated molecular sieves (3 Å) for 18 hours and then filtered under suction. The solvent was removed under vacuum on a rotary evaporator to obtain a liquid polymer product (3DP 6t, where "t" indicates thiolation, also referred to herein as poly-SH polymer). The amorphous liquid polymer thus obtained was subjected to HPLC analysis using a HPLC-MS / ... 1 H NMR spectroscopy, rheometry (99s -1 The compound was characterized by viscosity (Mn=1952 Da, PDI=1.62 at a shear rate of 100 ng / ml) and gel permeation chromatography (Mn=1952 Da, PDI=1.62). The following table outlines other thiolated 3DP compounds with n-acetylcysteine ​​(NAC), thiolactic acid (TLA), and thioglycolic acid (TGA). Each of these was synthesized according to this exemplary synthetic procedure. [Table 5]

[0152] Example 4 Preparation of Thiolated Compounds of the Present Disclosure Generally described by the formula polySH Polymers bearing hydroxyl groups can be capped with moieties that replace the hydroxyl groups with carboxylic acid groups. The carboxylic acid groups can then be replaced with thiol-containing moieties via amide or ester bonds, depending on the functional units of the substituents used for conjugation. For example, the hydroxyl end groups of 3DP precursor polymers (see, for example, Table 1) can be reacted with succinic anhydride to form a succinylated intermediate (3DP-SA), which in turn can be reacted with the amine groups present in cysteine ​​to provide a product with a terminal free thiol group (3DP 6-SA-Cys), providing an exemplary poly-SH compound of the present disclosure. This approach is illustrated by this example.

[0153] Part 1 - Preparation of 3DP 6-SA: 3DP 6 (48.9 g, 0.0633 moles, Table 1) was added to a 250 mL three-neck round bottom flask. The system was placed under vacuum (<0.5 torr) at 40° C. for 18 hours to dry the prepolymer. After 18 hours, the system was purged with nitrogen and succinic anhydride (19.0 g, 0.1900 moles) was added to the reaction vessel. The reaction mixture was stirred at 50 rpm at 120° C. for 24 hours. The polymer thus obtained was cooled to room temperature and devolatilized on a rotary evaporator to remove residual monomers at room temperature for 18 hours and at 110° C. for another 24 hours. The structure of the resulting transparent amorphous polymer product was: 1 Confirmed using 1 H NMR.

[0154] Part 2 - Preparation of 3DP 6-SA-Cys: To a 100 mL 2-neck flask was added 3DP 6-SA (10.1 g, 0.0093 mol), L-cysteine ​​(3.39 g, 0.0280 mol), and dichloromethane (DCM) (30 mL). The reaction was stirred at 200 rpm under nitrogen. Separately, N'-dicyclohexylcarbodiimide (DCC) (6.35 g, 0.0307 mol) was dissolved in 10 mL of DCM. An ice bath was placed around the reaction vessel and the DCC / DCM solution was added dropwise. After the addition of the DCC / DCM solution was complete, the ice bath was removed and the reaction was stirred at room temperature under nitrogen for 72 hours. After 72 hours, the reaction mixture was diluted with 50 mL of DCM and filtered under suction. The filtrate was washed with 2 x 50 mL of 0.25 M HCl and 1 x 50 mL of DI water. The organic phase from the extraction was dried over activated molecular sieves (3 Å) for 18 h and then filtered under suction. The solvent was removed under vacuum on a rotary evaporator to give the waxy polymer product (3DP 6-SA-Cys), the structure of which was 1 Confirmed by 1 H NMR spectroscopy.

[0155] Example 5 Single polymer networks from polyEU and polySH The thiol-terminated 3DP polymer was mixed with the methacrylated 3DP polymer in two different ratios. TPO-L photoinitiator was added to each combination at a concentration of 0.5% (w / w) and the formulations were mixed in a Flacktek high-speed mixer at 2000 rpm for 2 minutes followed by 3000 rpm for 3 minutes. The formulations were cured into 0.75 mm thick films. The films were cut into 75 mm x 7.5 mm x 0.75 mm specimens that were subjected to accelerated degradation at 50°C in phosphate buffer, pH 7.4. The degradation profiles of 50:50 and 25:75 3DP 6t TLA / 3DP 10m films are shown in Figure 1. The information in Figure 1 shows the effect of water swelling on polyEU / polySH single polymer networks.

[0156] Example 6 Preparation of the Isocyanate-Terminated Compounds of the Present Disclosure Exemplary Polymers of Formula PolyΔ As mentioned in Example 1, hydroxyl-terminated polymers can provide precursor compounds to the poly-Δ compounds of the present disclosure. The hydroxyl groups can be converted to thermally reactive groups, such as isocyanate groups, as shown by this example illustrating the diisocyanate capping of 3DP 10.

[0157] 3DP 10 (76.7 g, 0.0996 mol) was added to a 250 mL 3-neck round bottom flask equipped with a mechanical stirrer and an addition funnel. 3DP 10 was dried under vacuum at 40° C. for 3 days. After drying, the flask was purged with dry nitrogen and stirring was started at 220 rpm. To the flask, 15 ml of anhydrous toluene and hexamethylene diisocyanate (HMDI, 33.5 ml, 0.209 mol) were added. The reaction mixture temperature was raised to 80° C. for 2 hours and then allowed to cool to room temperature. The polymer mixture was then transferred to a 1-neck flask and placed on a rotary evaporator. Residual toluene and HMDI were removed under reduced pressure on the rotary evaporator. The amorphous liquid polymer thus obtained was dissolved in H 1 It was characterized by NMR spectroscopy (polymer-70.3 wt.%, isocyanate-29.6 wt.%).

[0158] Example 7 Double polymer networks from polyEU and polyΔ1+polyΔ2 Dual network films were prepared using photopolymerized methacrylate polymer networks and thermally cured interpenetrating polymer networks. 3DP 12m and 3DP 6 precursor polymers (exemplary PolyΔ1) were mixed in either a 50:50 or 70:30 ratio. TPO-L photoinitiator was added to the mixture at a concentration of 0.5% (w / w) relative to the weight of the methacrylated polymer. Hexamethylene diisocyanate (exemplary PolyΔ2) was added to the mixture at 45% of the moles of hydroxyl groups in the precursor polymer (3DP6, 3:1 OH:polymer for triaxial polymers). The formulations were mixed using a Flacktek high-speed mixer at 2000 rpm for 2 minutes, followed by 3000 rpm for 2 minutes. The formulations were then cured as 0.75 mm thick films under UV light at an intensity of 30 mW / cm2 for 10 minutes. The photocured films were further thermally cured at 100°C for 1 hour.

[0159] The films were cut into test strips of 75 mm x 7.5 mm x 0.75 mm and subjected to accelerated degradation at 50 °C in phosphate buffer, pH 7.4. The mass loss, water content, and mechanical properties of the materials were analyzed at different time points during the test period. The results are shown in Figure 2. In Figure 2, the data show the water swelling behavior of a urethane and methacrylated polyester double network. The addition of the urethane network increases the water swelling up to a maximum of 25-30% mass loss. After 25-30% mass loss, both the 50:50 3DP12m:3DP 6U and 3DP6u showed substantially less swelling.

[0160] Example 8 Mechanics of poly(SH) and poly(EU) materials. To evaluate the properties of the crosslinked 3DP polymer blends, tensile specimens were prepared for mechanical testing. For any particular polymer blend, the thiol-terminated 3DP polymer was mixed with one or more methacrylated 3DP polymers (3DPX M) in weight ratios of 25:75 and 50:50, where the thiolated polymers were synthesized using thiolactic acid (3DPX TLA), N-acetyl-L-cysteine ​​(3DPX NAC), or thioglycolic acid (3DPX TGA) as described in Example 3. In addition to the methacrylated 3DP polymers, select blends of similar ratios were tested using a diluent component of poly-ethylene glycol diacrylate (PEGDA). The photoinitiator ethyl (2,4,6-trimethylbenzoyl)phenylphosphinate (TPOL) was added at 0.5% (w / w) and the blends were mixed in a FlackTek high-speed mixer at 2000 revolutions per minute (rpm) for 2 minutes, followed by 3000 rpm for 3 minutes.

[0161] Each liquid polymer blend was poured between two UV-transparent acrylic sheets with a 0.75 mm spacer and cured under a 100 W UV Blak-Ray lamp for 10 minutes. The crosslinked films were removed and cut into tensile specimens with dimensions of 0.75 × 7.5 × 75 mm. The film strips were subjected to mechanical testing in an MTS test frame to evaluate their tensile properties with at least four strips for each blend tested. The test parameters in the tensile test are listed in Table 6. The polymer blends tested and their corresponding tensile properties are reported in Table 7. [Table 6] [Table 7]

[0162] Example 9 Stability of poly(SH) and poly(EU) compositions Part 1 - Polymer blends with and without stabilizer were examined for premature crosslinking. Thiol-terminated photoreactive compounds were mixed with methacrylated photoreactive compounds in a 50:50 ratio. Proactive stabilizing compounds were added to each aliquot of the reactive mixture at various concentrations. Each formulation blend was mixed in a FlakTek high speed mixer at 2000 revolutions per minute (rpm) for 2 minutes, followed by 3000 rpm for 3 minutes. Aliquots of each blend were transferred to petri dishes and stored at room temperature (RT) or 50°C. Polymer blend stability was qualitatively assessed by blend solidification, and the results are reported in Table 8. [Table 8] *-TMPTM: Trimethylolpropane trimethacrylate, TMPTT: Trimethylolpropane tris(3-mercaptopropionate)

[0163] Part 2 - The thiol-terminated polymer (3DP 19t TGA) was mixed with the methacrylated polymer (3DP 20m) in a 50:50 weight ratio. Selected stabilizers were each added to aliquots of the liquid polymer blend and the viscosity of the formulations was evaluated by rheometry (25°C at a shear rate of 100s-1) at 24 hours to obtain a quantitative measure of stability. The initial viscosity of the resin without stabilizer was 3920±20 cP. The viscosity of the stabilized polymer blends at room temperature for 24 hours storage is shown in Table 9. [Table 9]

[0164] Example 10 Mechanics of poly(EU) materials blended with commercial thiol compounds To evaluate the properties of 3DP polymers crosslinked with commercial thiol compounds, tensile specimens were prepared for mechanical testing. Commercial thiol compounds trimethylolpropane tris(2-mercaptopropionate) (TMPTT) or 1,6-hexanediol (HDM) were added to methacrylated 3DP polymer (3DP 26m) at 0%, 3%, 5%, and 10% mol. TPO-L was added at 0.5% (w / w) and the blends were mixed in a FlackTek high-speed mixer at 2000 revolutions per minute (rpm) for 2 minutes followed by 3000 rpm for 3 minutes. Each blend was poured between two UV-transparent acrylic sheets with a 0.75 mm spacer and cured under a UV light source for 10 minutes. The crosslinked films were removed and cut into tensile specimens according to standard ASTM D638 Type V dog-bone specimens. The dog-bone specimens had a width of 3 mm and a thickness of 0.75 mm. The samples were subjected to mechanical testing on an MTS test frame to evaluate their tensile properties. The test parameters for the tensile test are shown in Table 9. The polymer blends tested and their corresponding tensile properties are reported in Table 10. [Table 10] [Table 11]

[0165] Example 11 Use of TMPTT as a chain transfer agent Photoreactive resin mixtures were prepared from methacrylated macromer (3DP20-M) with trimethylolpropane tris(2-mercaptopropionate) (TMPTT) added as a chain transfer agent at thiol to methacrylate molar ratios of 0, 0.01, 0.03, 0.05, 0.075, and 0.1. Table 10 provides the amount of TMPTT added to the 3DP20-M resin. Photoinitiator TPO-L was added to the resin mixture at 0.5% (w / w). The resin was then thoroughly mixed using a FlackTek high-speed mixer at 2000 rpm for 2 minutes and then at 3000 rpm for 3 minutes. Each resin blend obtained after mixing was sandwiched between two UV-transparent plates and cured under a 100W UV blak-ray lamp to produce crosslinked films. [Table 12]

[0166] The crosslinked film was ground using a cryo-mill. 0.25 g of the ground sample was transferred to a 20 mL scintillation vial. 2.5 mL of DMSO and 2.5 mL of sodium methoxide (NaMeOH) were added to the vial and placed in a heating block at 100° C. for 2 hours. The sample was cooled to room temperature and precipitated into 25 mL of diethyl ether (DEE). The precipitate was collected using centrifugation and then dried under vacuum overnight. The resulting product was redissolved in H2O, lyophilized, and characterized by gel permeation chromatography (GPC).

[0167] The molecular weight results obtained by GPC are provided in Table 11. In Table 11, Mn refers to number average molecular weight, Mw refers to weight average molecular weight, PDI refers to polydispersity (i.e., Mw / Mn), and Da refers to Daltons. The data show that adding TMPTT reduced the molecular weight of poly(methacrylic acid) chains from photopolymerized 3DP20-M resin. These changes are attributed to changes in the network structure caused by the chain transfer behavior of thiol groups during polymerization. [Table 13]

[0168] Example 12 Decomposition of 3DP20 with TMPTT 3DP20-M doped with TMPTT at thiol to methacrylate molar ratios of 0 and 0.4 was crosslinked using the method described above. The films were cut into 75 mm x 7.5 mm x 0.75 mm strips by a CO2 laser and subjected to accelerated degradation at 50 °C in phosphate buffer, pH 7.4. The degradation profile of the films is shown in Figure 3. As Figure 3 shows, adding TMPTT to 3DP20-M increases its degradation rate under accelerated degradation.

[0169] Example 12 To evaluate the photopolymerization of the resin compositions, formulations were prepared for the extrapolation of resin parameters from the working curves in the vat polymerization. For each of the eight formulations, a methacrylate-terminated polyester carbonate macromer (3DP25-M) was mixed with a similarly functionalized absorbing liquid polymer diluent at 10% (w / w) relative to the 3DP polymer. In all formulations, the chain transfer agent TMPTT was added at 7.5 mole percent of thiol groups relative to the total moles of methacrylate groups in the liquid blend. The photoinitiator ethyl (2,4,6-trimethylbenzoyl)phenylphosphinate (TPO-L) was also added to all formulations at 0.75% by weight relative to the liquid polymer blend (0.85 mole percent of photoinitiator relative to the total moles of functional groups). Each formulation then received β-carotene or D&C Violet No. 2 as the dye at one of four concentrations: 0.01, 0.1, 1.0, or 2.5 wt% in the liquid polymer blend. All formulations were then mixed individually in a FlackTek high speed mixer at 3000 revolutions per minute for 3 minutes.

[0170] Each liquid resin blend was poured onto a glass slide and tuned in mW / cm 2The UV light was exposed to a range of known intensities (i.e., power density) in 1000 nm and a range of exposure times in seconds, resulting in cured resins at a range of heights (i.e., cure depths). The height of each cured sample was measured using an optical 3D measurement system. The height in millimeters was then plotted against the total energy as a product of light intensity and exposure time for each formulation. A logarithmic regression was performed to determine the penetration depth in millimeters (D P ), mJ / cm 2 The critical energy at C The data was fitted to a model used to extrapolate resin parameters of cure time in seconds required for a cure depth of 30 micrometers (Table 12). [Table 14]

[0171] In additional tests evaluating the photopolymerization of the resins, formulations were similarly prepared for the extrapolation of resin parameters from the work curves over a range of chain transfer agent and stabilizer contents. For each of the three formulations, a methacrylate-terminated polyester carbonate macromer (3DP25-M) was mixed with a functionalized diluent, trimethylolpropane trimethacrylate (TMPTM), at 5 percent (w / w) of the 3DP polymer. Each formulation received a chain transfer agent, TMPTT, at 0 or 1 weight percent of the liquid blend (2.79 mole percent of thiol groups to total moles of methacrylate groups). Each formulation also received a stabilizer, tocopherol, at 0 or 0.1 percent (w / w) of the chain transfer agent. In all formulations, TPO-L was added at 0.5 percent (w / w) of the liquid polymer blend (0.54 mole percent of photoinitiator to total moles of functional groups). The dye, D&C Violet 2, was also added to each formulation at 0.025 percent (w / w) of the liquid blend. All formulations were then individually mixed in a FlackTek high speed mixer at 3000 revolutions per minute for 3 minutes.

[0172] Each liquid resin formulation was processed as described above to generate a working curve and measure the penetration depth in millimeters (DP ), mJ / cm 2 The critical energy at C ), and the resin parameters of cure time in seconds required for a cure depth of 30 micrometers were extrapolated (Table 13). [Table 15]

[0173] Example 14 To evaluate the cytocompatibility of the cured resins, several formulations were prepared for evaluation of their extractable species by viability assay according to ISO10993 Biological Evaluation of Medical Devices-Part 5:Tests for in vitro Cytotoxicity. For each of the four formulations, a methacrylate-terminated polyester carbonate macromer (3DP20-M or 3DP25-M) was mixed with a similarly functionalized absorbent liquid polymer diluent at 5 percent (w / w) relative to the 3DP polymer. In all formulations, TMPTT was added at 10 mole percent of the thiol groups relative to the total moles of methacrylate groups in the liquid blend. One formulation received the stabilizer tocopherol at 0.1 percent (w / w) of the chain transfer agent. TPO-L was also added to each formulation at 0.75 or 1 weight percent of the liquid polymer blend (0.98 or 1.11 mole percent of the total moles of functional groups, respectively). Each formulation also received β-carotene as a pigment at 0.01 percent (w / w) relative to the liquid polymer blend. All formulations were then mixed individually in a high speed mixer at 3000 revolutions per minute for 3 minutes. The formulations tested are summarized in Table 14. [Table 16]

[0174] Each formulation was cured into a film by UV light, cut into individual specimens, and combined into three samples for each formulation group. Control specimens were similarly cut from sheets of natural rubber and high density polyethylene as positive (+) and negative (-) controls, respectively, and combined into three samples per control group. All samples were disinfected by rinsing with 70% iso-propanol and treated with UV light.

[0175] For extraction of the cured resin formulations, Eagle's minimum essential medium supplemented with 10% (v / v) horse serum served as the elution vehicle. Each sample was immersed in medium at 0.2 g / ml and incubated at 37°C for 24 hours. Aliquots of each extract were added to cell monolayers (mouse fibroblasts, NCTC L-929) across 96-well plates and incubated for 24 hours. MTS viability assay (MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) was added to each test well, incubated for 1 hour, and absorbance was measured using a microplate reader. For each formulation and control group, the average cell viability was determined by the absorbance of the test wells in reference to the absorbance of a cell culture blank. The average cell viability of all groups is shown in Figure 4, where "+" indicates the positive control and "-" indicates the negative control. 4, "A" is the 3DP20-M blend with 0% stabilizer and 0.75% photoinitiator, "B" is the 3DP25-M blend with 0% stabilizer and 0.75% photoinitiator, "C" is the 3DP25-M blend with 0.1% stabilizer and 0.75% photoinitiator, and "D" is the 3DP25-M blend with 0% stabilizer and 1.0% photoinitiator. From Figure 4, it can be seen that all formulations (A-D) exhibit a high degree of cell viability which translates into little or no potential for cytotoxicity.

[0176] All references disclosed herein, including patent and non-patent references, are incorporated by reference in their entirety as if each was incorporated individually.

[0177] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. It is further understood that, unless specifically defined herein, terms used herein are to be given their traditional meaning as known in the relevant art.

[0178] References throughout this specification to "one embodiment" or "an embodiment" and variations thereof mean that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0179] As used herein and in the appended claims, the singular forms "a," "an," and "the" include the plural, i.e., one or more, unless the content and context clearly dictate otherwise. It should also be noted that the connector terms "and" and "or" are generally used in their broadest sense, including "and / or," unless the content and context clearly dictate inclusiveness or exclusiveness as may be the case. Thus, the use of alternatives (e.g., "or") should be understood to mean either one, both, or any combination thereof of the alternatives. In addition, the "and" and "or" configurations, when recited herein as "and / or," are intended to encompass embodiments including all of the associated items or ideas, as well as one or more other alternative embodiments including less than all of the associated items or ideas.

[0180] Unless the context otherwise requires, throughout this specification and the following claims, the term "comprise" and its synonyms and variations, such as "have" and "include," and variations thereof, such as "comprises" and "comprising," are to be interpreted in an open and inclusive sense, e.g., "including, but not limited to." The term "consisting essentially of" limits the scope of a claim to certain materials or steps, or those that do not materially affect the basic and novel characteristics of the claimed disclosure. In case of conflict, the present specification, including explanations of terms, will control. In addition, all materials, methods, and examples are illustrative and not intended to be limiting.

[0181] The headings used within this document are merely utilized to facilitate the reader's review thereof and should not be construed as limiting the scope of the disclosure or the claims in any manner. Thus, the headings and abstracts of the disclosure provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.

[0182] Where a range of values ​​is provided herein, it is understood that, to the tenth of the unit of the lower limit, each intervening value between the upper and lower limits of that range, and any other stated or intervening value in that stated range, is encompassed within the disclosure, unless the context clearly dictates otherwise. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, subject to any specifically excluded limit of a given range, and are encompassed within the disclosure. Where a stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.

[0183] For example, any concentration range, percentage range, ratio range, or integer range provided herein should be understood to include any integer value within the recited range, and fractions thereof, where appropriate (such as tenths and hundredths of integers), unless otherwise indicated. Also, any numerical range recited herein relating to any physical property, such as polymer subunits, size, or thickness, should be understood to include any integer within the recited range, unless otherwise indicated. As used herein, the term "about" means ±20% of the indicated range, value, or structure, unless otherwise indicated.

[0184] All U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications, and / or non-patent publications mentioned in this application and / or listed in the application data sheet are incorporated herein by reference in their entirety. Such documents may be incorporated by reference, for example, for the purpose of describing and disclosing the materials and methodologies described in the publications and may be used in connection with the disclosure set forth herein, the above and throughout the context publications being provided solely for their disclosure prior to the filing date of this application. Nothing herein should be construed as an admission that the inventors are not entitled to antedate any cited publication by virtue of prior disclosure.

[0185] All patents, publications, scientific articles, websites, and other documents and materials referenced or mentioned in this specification are indicative of the level of skill of one of ordinary skill in the art, and each such referenced document and material is incorporated herein by reference as if it were individually incorporated by reference in its entirety or as if set forth in its entirety herein. Applicant reserves the right to physically incorporate into this specification all materials and information from any such patents, publications, scientific articles, websites, electronically available information, and other referenced materials or documents.

[0186] In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments, along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by this disclosure.

[0187] Moreover, the written description portion of this patent includes all claims. Moreover, all claims, including all original claims and all claims from any and all priority documents, are incorporated by reference in their entirety into the written description portion of this specification, and the applicant reserves the right to physically incorporate any and all such claims into the written description or any other portion of the application. Thus, for example, under no circumstances may a patent be construed as not providing a written description of the claims in response to an assertion that the exact wording of the claims is not set forth in the written description portion of the patent.

[0188] The claims will be interpreted according to law. However, regardless of the alleged or perceived ease or difficulty of interpreting any claim or portion thereof, under no circumstances will any adjustment or modification of the claims or portions thereof during the prosecution of the application(s) leading to this patent be construed as a forfeiture of any and all equivalents thereof that do not form part of the prior art.

[0189] Other non-limiting embodiments are within the scope of the following claims. This patent should not be construed as limited to the specific examples or non-limiting embodiments or methods specifically and / or explicitly disclosed herein. Under no circumstances should the patent be construed as limited by any statements made by the examiner or other staff or employees of the Patent and Trademark Office, unless such statements have been specifically and without limitation or qualification expressly adopted in the written answer given by the applicant.

Claims

1. A composition comprising: a first organic compound (poly-EU) having a plurality of ethylenically unsaturated groups (EU); optionally, a second organic compound (poly-SH) having a plurality of thiol groups (SH); a photoinitiator; and at least one chain transfer agent present in a molar ratio of chain transfer agent functional groups (e.g., thiol) to moles of ethylenically unsaturated groups of 0.03 to 0.

80.

2. The composition according to claim 1, wherein at least one of the first organic compound, the optional second organic compound, the photoinitiator, or the chain transfer agent is biocompatible.

3. The composition according to claim 1, further comprising one or more dyes, pigments or UV absorbers that are biogenic molecules from carotenoids, flavonoids, flavones, quinones, porphyrins, diketones, and betacyanidins.

4. The composition according to claim 1, having an SH to EU equivalent ratio of X:Y, where X is in the range of 25 to 75, Y is in the range of 75 to 25, and the sum of X and Y is 100.

5. The composition according to claim 1, wherein the poly-SH is water-soluble or biocompatible.

6. The composition according to claim 1, wherein the poly-SH is a macromer having a molecular weight greater than 1,000 g / mol.

7. The composition according to claim 1, wherein the poly-EU is water-soluble or biocompatible.

8. The composition according to claim 1, wherein the EU of the poly-EU is acrylate, methacrylate, or norbornenyl.

9. The composition according to claim 1, wherein the poly-EU is a macromer having a molecular weight greater than 1,000 g / mol.

10. The composition according to claim 1, wherein the plurality of SH of the poly-SH are selected from 2, 3, and 4.

11. The composition according to claim 1, wherein the plurality of EU of the poly-EU are selected from 2, 3, and 4.

12. The composition according to claim 1, comprising no volatile materials having a boiling point less than 110°C.

13. A composition comprising a photochemically cured reaction product of the composition according to claim 1, which, when decomposed, yields a decomposition product (or polymer backbone) having a molecular weight of less than 20,000 Daltons.

14. The composition according to claim 13, which is biocompatible.

15. The composition according to claim 13, which is solid at 50°C.

16. An additive manufacturing process comprising: (a) providing a vat containing the first composition according to claim 1; (b) directing actinic radiation from a light source towards the first composition within the vat, the actinic radiation being effective to induce polymerization of the components of the composition to form a second composition; (c) forming a solid article comprising the second composition, an additive manufacturing process. (Claim 17) A composition comprising a first organic compound (poly hν) having a plurality of photopolymerizable groups (hν), a photoinitiator, a second organic compound (poly Δ1) having a plurality of reactive groups Δ1, and a third organic compound (poly Δ2) having a plurality of reactive groups Δ2, wherein Δ1 reacts with Δ2 upon contact and exposure to a temperature above 50° C., and optionally comprising a chain transfer agent. (Claim 18) The composition according to claim 17, wherein poly hν is bioabsorbable. (Claim 19) The composition according to claim 17, wherein poly hν is a macromer having a molecular weight greater than 1,000 g / mol. (Claim 20) The composition according to claim 17, wherein poly hν has a molecular weight less than 500 g / mol. (Claim 21) The composition according to claim 17, wherein poly hν is water-soluble. (Claim 22) The composition according to claim 17, wherein poly hν is a poly EU selected from acrylates and methacrylates. (Claim 23) The composition according to claim 17, wherein hν of poly hν is norbornenyl. (Claim 24) The composition according to claim 17, wherein the plurality of hν of poly hν are selected from 2, 3, and 4. (Claim 25) The composition according to claim 17, wherein the plurality of Δ1 of poly Δ1 are selected from 2, 3, and 4. (Claim 26) The composition according to claim 17, wherein the plurality of Δ2 of poly Δ2 are selected from 2, 3, and 4. (Claim 27) A composition comprising a photochemically cured reaction product and a thermally cured reaction product of the composition according to any one of claims 13 to 26, which, when decomposed, yields a decomposition product (or polymer backbone) having a molecular weight of less than 20,000 daltons. (Claim 28) The composition according to claim 27, which is bioabsorbable. (Claim 29) The composition according to claim 27, which is solid at 50° C. (Claim 30) An additive manufacturing process comprising: (a) providing a vat containing a first composition according to any one of claims 17 to 26; (b) directing actinic radiation from a light source towards the first composition within the vat, the directing being effective to induce polymerization of components of the first composition such that the actinic radiation forms a second composition that includes a composition cured photochemically; (c) applying thermal energy to the second composition that includes a composition cured photochemically so as to form a third composition that includes a composition cured photochemically and a composition cured thermally; wherein the additive manufacturing process comprises the foregoing.

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