Curable compounds and formulations for biomedical applications

Abstract

Curable compounds, hydrogels, modeling materials, and methods of 3D printing are described herein.In some embodiments, the modeling materials for 3D printing described herein comprise one or more compounds having the structure of formula (I) and / or formula (II).Such modeling materials can also comprise additional acrylate components and water.

Description

Cross - reference to related applications

[0001] This application claims priority under 35 U.S.C. § 119 to U.S. Provisional Patent Application No. 63 / 246,604, filed on September 21, 2021, the entire disclosure of which is incorporated herein by reference.

Technical Field

[0002] The present invention relates to compounds and compositions for the manufacture of hydrogel articles, and more particularly to compounds and compositions for additive manufacturing that provide biocompatible hydrogel articles having high biodegradability.

Background Art

[0003] 3D printers form various 3D objects, articles, or parts according to computer - generated files using a shaping material, also known as ink. In some examples, the shaping material is solid at ambient temperature and turns liquid at a high jetting temperature. In other examples, the shaping material is liquid at ambient temperature.

[0004] The shaping material can include various chemical species. The chemical species included in the shaping material can be selected according to various considerations, including but not limited to the desired chemical and / or mechanical properties of the printed article and the operating parameters of the 3D printing apparatus. In recent years, for example, ink compositions for printing hydrogel articles have been developed. Hydrogels are unique materials and have found uses in a wide range of fields, including biological materials. Hydrogel implants that function as scaffolds for tissue regeneration and / or various cell therapies have received considerable attention. Hydrogel scaffolds often need to meet specific physical dimensions and exhibit specific microstructural features for cell / tissue interaction. Achieving these required tolerances using printable hydrogel compositions can be difficult, thereby limiting the effectiveness of hydrogel articles in medical implant applications.

Summary of the Invention

Problems to be Solved by the Invention

[0005] This disclosure intends to describe hydrogels or inks (or shaping materials or polymerizable liquids) for additive manufacturing applications, as well as curable compounds that can be used in or otherwise incorporated into inks (or shaping materials or polymerizable liquids) containing curable compounds. Methods for 3D printing, methods for producing inks (or shaping materials or polymerizable liquids), and articles produced from hydrogels or inks (or shaping materials or polymerizable liquids) are also described herein. [Means for solving the problem]

[0006] In one embodiment, a curable compound is described herein. In some embodiments, such a compound has the structure of formula (I) or the structure of formula (II): [ka] In the formulas, n is an integer between 4 and 40 or between 4 and 20. Furthermore, in some cases, compounds having the structure of formula (I) or formula (II) are liquid at 25°C and 1 atm.

[0007] In another embodiment, hydrogels are described herein. Such hydrogels may contain the compounds described above. Furthermore, in some examples, the hydrogels described herein further include an acrylate component in addition to the compound of formula (I) or formula (II). The hydrogels described herein may also contain additional components, as described further below.

[0008] In yet another embodiment, inks or 3D printing materials or polymerizable liquids are described herein. It should be understood that the terms “ink,” “3D printing material,” and “3D printing liquid” are interchangeable in this disclosure. Furthermore, such materials may be for use in hydrogel formation and / or 3D printing systems or methods. In some embodiments, the 3D printing materials described herein for use in 3D printing comprise one or more compounds having the structure of formula (I) and / or formula (II) above.

[0009] In yet another embodiment, methods for printing or forming 3D articles are described herein. In some embodiments, such methods include the steps of providing an ink, shaping material, or polymerizable liquid described herein, and printing and curing the ink, shaping material, or polymerizable liquid using light to form a hydrogel article, such as a medical implant. Furthermore, in some cases, the ink, shaping material, or polymerizable liquid is provided in a layer-by-layer process.

[0010] In another embodiment, printed 3D articles or objects are described herein, including articles formed from inks, molding materials, or polymerizable liquids described herein.

[0011] These and other embodiments will be described in more detail in the following detailed description. [Modes for carrying out the invention]

[0012] The embodiments described herein can be more readily understood by referring to the following detailed description and examples. However, the compositions, apparatus, and methods described herein are not limited to the specific embodiments shown in the detailed description and examples. It should be recognized that these embodiments are merely illustrative of the principles of the present invention. Numerous modifications and adaptations will be readily apparent to those skilled in the art without departing from the spirit and scope of the invention.

[0013] Furthermore, all ranges disclosed herein should be understood to encompass all subranges contained within them. For example, the range "1.0 to 10.0" should be interpreted to include any subranges beginning with a minimum value greater than or equal to 1.0 and ending with a maximum value less than or equal to 10.0, such as 1.0 to 5.3, or 2 to 9, or 4.7 to 10.0, or 3.6 to 7.9, or 8 to 9.5.

[0014] Furthermore, all scopes disclosed herein should be considered to include the endpoints of that scope unless otherwise specified. For example, the scope "between 5 and 10" should generally be considered to include the endpoints 5 and 10.

[0015] Furthermore, when the phrase "up to" is used in relation to quantity or amount, it should be understood that the quantity is at least a detectable quantity or amount. For example, a material present in an amount "up to" a specified amount can be present in an amount ranging from a detectable amount up to (including) the specified amount.

[0016] Furthermore, in any disclosed embodiment, the terms “substantially,” “approximately,” and “about” may be replaced with “within the range of [a certain percentage]” of the specified, where the percentage may be 0.1, 1, 5, or 10 percent.

[0017] Furthermore, it should be understood that the articles "a" or "an" refer to "at least one" unless the context of their specific use requires a different meaning.

[0018] The terms “3D printing system,” “3D printer,” and “print” broadly describe a variety of solid freeform manufacturing techniques for producing three-dimensional articles or objects, including selective deposition, jetting, fusion deposition modeling, multi-jet modeling, and other additive manufacturing techniques currently known or to be known in the art that use shaping materials or inks to produce three-dimensional articles or objects.

[0019] I. Curing compound In one aspect, curable compounds are described herein. More particularly, the present disclosure contemplates curable compounds that can be used to form, or otherwise incorporated into, hydrogels or inks (or shaping materials or polymeric liquids) for 3D printing applications. One exemplary embodiment of the present disclosure is a compound having the structure of formula (I):

Chemical formula

[0020] Another exemplary embodiment of the present disclosure is a compound having the structure of formula (II):

Chemical formula

[0021] Furthermore, in some implementations, the compound has the structure of formula (I) or formula (II), wherein n is an integer from 4 to 14, 4 to 20, 6 to 30, 10 to 40, or 10 to 20. Other values of n are also possible.

[0022] Furthermore, the compounds described herein are, in some cases, liquids at room temperature or under standard temperature and pressure conditions. For example, in some instances, the compounds described herein are liquids at 25 °C and 1 atm, or have a melting point below about 25 °C. In some embodiments, the compounds described herein are liquids or have a melting point of 0 to 25 °C, 0 to 22 °C, 0 to 20 °C, 5 to 25 °C, 5 to 22 °C, 5 to 20 °C, 10 to 25 °C, 10 to 22 °C, 10 to 20 °C, 15 to 25 °C, 15 to 22 °C, or 15 to 20 °C at 1 atm. Compounds having the melting points described herein may, in some cases, be well-suited for the formation of hydrogels and / or shaping materials.

[0023] The compounds described herein can be prepared in any manner not inconsistent with the technical objectives of this disclosure. For example, in some cases, the compounds described herein are formed from the reaction of poly(ethylene glycol) (PEG) with maleic anhydride (MA). Exemplary reaction protocols are further described in the following specific examples.

[0024] II. Hydrogels In another embodiment, hydrogels are described herein. As will be understood by those skilled in the art, “hydrogel” can be thought of as a gel in which the liquid component is water or aqueous solution. Furthermore, the hydrogels described herein include, or are defined in some embodiments, a network of one or more polymers that swell with or encapsulate water or aqueous solutions or mixtures thereof. In some cases, the hydrogels described herein include a network of polymers produced by curing or polymerizing a curable compound described herein, and / or by curing or polymerizing one or more other polymerizable or curable species described herein, which optionally include a combination with a curable compound of formula (I) or formula (II).

[0025] In some embodiments, the hydrogels described herein include or are formed from the curable compounds described above in Section I. Any such curable compound may be included in the hydrogels described herein. For example, in some embodiments, the hydrogels described herein include a compound having the structure of formula (I). In other cases, the hydrogels described herein include a compound having the structure of formula (II). In yet another example, the hydrogels described herein also include a compound having the structure of formula (I) and a compound having the structure of formula (II). In such cases, the compounds having the structures of formula (I) and (II) may be present in the hydrogels described herein in any ratio not inconsistent with the technical objectives of this disclosure. For example, in some embodiments, the compound having the structure of formula (I) is present in an amount at least twice, at least three times, at least five times, or at least ten times the amount of the compound having the structure of formula (II). In some examples, the ratio of formula (I) to formula (II) in the hydrogels described herein is at least 2:1, at least 3:1, at least 5:1, at least 10:1, or at least 100:1.

[0026] The curable compounds described herein may be present in the hydrogel in any amount not inconsistent with the technical objectives of this disclosure. For example, in some cases, a curable compound having the structure of formula (I) or formula (II) (or a cured or polymerized version thereof) may be present in the hydrogel in an amount of 5 to 40% by mass, based on the total weight of the hydrogel. In some implementations, the compound may be present in an amount or concentration of 5 to 35% by mass, 8 to 33% by mass, 10 to 35% by mass, 10 to 30% by mass, 10 to 20% by mass, 10 to 15% by mass, 12 to 25% by mass, 15 to 35% by mass, 20 to 30% by mass, or 5 to 15% by mass, based on the total weight of the hydrogel.

[0027] Furthermore, in some implementations, the hydrogels described herein further comprise or are formed from acrylate components. Such acrylate components may differ from curable compounds having the structure of formula (I) or formula (II). Any acrylate component that is not inconsistent with the technical objectives of this disclosure can be used in such hydrogels. In particular, for the purposes of reference herein, it is observed that the “acrylate” component may comprise one or more chemical species comprising at least one acrylate, methacrylate, acrylamide, or methacrylamide moiety or functional group. Furthermore, the term “(meth)acrylate” should be understood to include acrylate or methacrylate or mixtures or combinations thereof. Similarly, the term “(meth)acrylamide” includes acrylamide or methacrylamide or mixtures or combinations thereof.

[0028] In some cases, the acrylate component includes mono-, di-, tri-, or more functional acrylates. In some examples, the acrylate component includes the acrylate components described in Section III below. For example, in some embodiments, the acrylate component includes one or more hydroxyalkyl acrylates, one or more polyethylene glycol acrylates or diacrylates, and / or one or more hydroxyalkylacrylamides. Other acrylate components may be used.

[0029] The acrylate components described herein (or their cured or polymerized versions thereof) may be present in the hydrogel in any amount not inconsistent with the technical objectives of this disclosure. For example, in some cases, the acrylate components are present in the hydrogel in an amount of 15 to 50% by mass, based on the total weight of the hydrogel. In some implementations, the acrylate components may be present in amounts or concentrations of 15 to 40% by mass, 15 to 30% by mass, 20 to 50% by mass, 20 to 45% by mass, 25 to 40% by mass, 25 to 35% by mass, 30 to 45% by mass, 30 to 50% by mass, 30 to 40% by mass, 35 to 50% by mass, 35 to 45% by mass, or 40 to 50% by mass, based on the total weight of the hydrogel.

[0030] The hydrogels described herein may also contain any amount of water that is not inconsistent with the technical objectives of this disclosure. For example, in some cases, water is present in the hydrogel in an amount of 10–85% by mass or 20–85% by mass, based on the total weight of the hydrogel. In some implementations, water is present in an amount or concentration of 10–60% by mass, 20–80% by mass, 20–50% by mass, 30–80% by mass, 30–60% by mass, 40–80% by mass, 40–60% by mass, 50–80% by mass, or 50–70% by mass, based on the total weight of the hydrogel.

[0031] It should be further understood that water (or the entire hydrogel) may have a pH of about 1 to about 7, about 3 to about 7, or about 4 to about 6. As will be understood by those skilled in the art, such pH values ​​can be obtained, for example, by including Brønsted-Lowry acid or a base. For example, in some cases, a strong acid or a strong base, such as hydrochloric acid or sodium hydroxide, respectively, can be included in the water (or the entire hydrogel) at a desired concentration to provide the desired pH, as will be understood by those skilled in the art. Other proton or hydroxide sources can also be used.

[0032] The hydrogels described herein can be prepared in any manner not inconsistent with the technical objectives of this disclosure. For example, in some cases, the hydrogels described herein are formed by mixing the identified components of the hydrogel and curing or polymerizing the curable or polymerizable components (e.g., curable compounds and acrylate components). Such curing and polymerization may in some cases be carried out in the manner further described below, including in Section IV.

[0033] III. Polymerizable liquids, inks, or molding materials In other embodiments, inks or modeling materials or polymerizable liquids are described herein. Such materials may be for use in hydrogel formation and / or 3D printing systems or methods. In some embodiments, the polymerizable liquids or modeling materials for use in 3D printing described herein comprise compounds having the structure of formula (I) or formula (II) (wherein n is an integer from 4 to 40). Such modeling materials may further comprise an acrylate component and water.

[0034] In certain implementations, the polymerizable liquid includes compounds having the structure of formula (I) and compounds having the structure of formula (II). In other examples, the polymerizable liquid includes compounds having the structure of formula (I) but does not include compounds having the structure of formula (II). In some cases, the polymerizable liquid may include one or more compounds having the structure of formula (I) but substantially no compounds having the structure of formula (II), or may contain compounds having the structure of formula (II) in amounts of less than 5% by mass, less than 3% by mass, or less than 1% by mass, based on the total weight of the polymerizable liquid. In some examples, the ratio (by weight) of compounds having the structure of formula (I) to compounds having the structure of formula (II) is at least 20:1, at least 10:1, at least 5:1, or at least 3:1. In some embodiments, the ratio of compound (I) to compound (II) is 100:1 to 100:0, 100:1 to 50:1, 100:1 to 10:1, 50:1 to 20:1, 50:1 to 10:1, 20:1 to 5:1, or 10:1 to 2:1.

[0035] Furthermore, it should be understood that the polymerizable liquids described herein may contain only one or more compounds having the structure of formula (I). For example, in some implementations, the polymerizable liquid may contain multiple compounds having the structure of formula (I), such as a first compound having the structure of formula (I) with n=4 and a second compound having the structure of formula (I) with n=6. Alternatively, in other implementations, the polymerizable liquid may contain only a single compound having the structure of formula (I), for example, a compound having the structure of formula (I) (wherein n=10), and other compounds having the structure of formula (I) (e.g., n is not equal to 10) may be substantially absent or absent in detectable amounts in the polymerizable liquid. The same applies to compounds having the structure of formula (II) in a manner similar to that described for formula (I) in this paragraph.

[0036] In general, compounds having the structure of formula (I) or formula (II) may be present in the polymerizable liquids described herein in any amount not inconsistent with the purposes of this disclosure. In some embodiments, for example, compounds having the structure of formula (I) or formula (II) are present in amounts of 4 to 40% by mass, based on the total weight of the polymerizable liquid. In some cases, compounds having the structure of formula (I) or formula (II) are present in the polymerizable liquid in amounts of 5 to 35% by mass, 8 to 33% by mass, 10 to 35% by mass, 10 to 30% by mass, 10 to 20% by mass, 10 to 15% by mass, 12 to 25% by mass, 15 to 35% by mass, 20 to 30% by mass, or 5 to 15% by mass, based on the total weight of the polymerizable liquid.

[0037] Referring here to other components of polymerizable liquids, the polymerizable liquids described herein, in some embodiments, further include acrylate components. Any acrylate component that is not inconsistent with the technical objectives of this disclosure may be used. In particular, for the purposes of reference herein, it is observed that the “acrylate” component may include one or more chemical species comprising at least one acrylate, methacrylate, acrylamide, or methacrylamide moiety or functional group. Furthermore, it should be understood that the term “(meth)acrylate” includes acrylate or methacrylate or mixtures or combinations thereof, and the term “(meth)acrylamide” includes acrylamide or methacrylamide or mixtures or combinations thereof.

[0038] In some embodiments, the acrylate component comprises hydrophilic mono-, di-, and / or tri(meth)acrylate species. The acrylate component may include, for example, one or more of hydroxyalkyl(meth)acrylates (e.g., hydroxyethyl acrylate), hydroxyalkyl(meth)acrylamides (e.g., N-hydroxyethylacrylamide), ethoxylated trimethylolpropane triacrylate, acryloylmorpholine, and various combinations or mixtures thereof. In some embodiments, the hydroxyalkyl(meth)acrylate comprises hydroxyethyl(meth)acrylate, hydroxypropyl(meth)acrylate, hydroxybutyl(meth)acrylate, and / or mixtures thereof.

[0039] The acrylate components of the polymerizable liquids described herein may also include polyethylene glycol diacrylate (PEGDA). With respect to the polyethylene glycol diacrylate components used herein, the polyethylene glycol diacrylate may include a single polyethylene glycol diacrylate species or polyethylene glycol diacrylate species with different molecular weights. In some embodiments, the species of polyethylene glycol diacrylate component have a weight-average molecular weight of 0.1 kDa to 20 kDa. The molecular weights of individual species of polyethylene glycol diacrylate may be within one or more ranges, for example, those listed in Table 1. Table 1. Molecular weight (kDa) of polyethylene glycol diacrylate [Table 1]

[0040] Any combination or mixture of polyethylene glycol diacrylates with different molecular weights is intended. In some embodiments, the polyethylene glycol diacrylate component comprises a mixture of two or more polyethylene diacrylate species, each having a molecular weight of 0.5 to 5 kDa. The specific composition of the polyethylene glycol diacrylate component can be selected according to several considerations, including but not limited to the crosslinking density, elasticity, tensile strength, and / or mesh size of the resulting hydrogel article.

[0041] The polyethylene glycol diacrylate component may be present in the polymerizable liquid in any amount not inconsistent with the technical objectives described herein. In some embodiments, the polyethylene glycol diacrylate component is present in an amount of 5 to 60% by mass, based on the total weight of the polymerizable liquid. For example, the polyethylene glycol diacrylate component may include 5 to 30% by mass of polyethylene glycol diacrylate species having a molecular weight of 3 to 5 kDa and 2 to 20% by mass of polyethylene glycol diacrylate species having a molecular weight of 0.1 to 1 kDa.

[0042] It should be understood that the acrylate components of the polymerizable liquids described herein may include combinations of acrylate species. For example, in some cases, the acrylate component may be selected from one or more hydroxyalkyl acrylates, one or more polyethylene glycol acrylates, one or more polyethylene glycol diacrylates, one or more hydroxyalkylacrylamides, or combinations thereof. In certain polymerizable liquids, the acrylate component may include only one type of hydroxyalkyl acrylate. In other polymerizable liquids, the acrylate component may include multiple (two or more) hydroxyalkyl acrylates. In yet another polymerizable liquid, the acrylate component may include one polyethylene glycol acrylate and one hydroxyalkylacrylamide. Thus, while this disclosure intends many combinations and compositions of acrylate components that may be included in exemplary implementations, they are not expressly enumerated herein.

[0043] In general, the acrylate components of the polymerizable liquids described herein can be present in the polymerizable liquid in any amount that is not inconsistent with the technical objectives of this disclosure. In some embodiments, for example, the acrylate components are present in an amount or concentration of 15% by mass or more and 50% by mass or less, based on the total weight of the polymerizable liquid. In some implementations, the acrylate components are present in an amount or concentration of 20-45% by mass, 25-40% by mass, 30-40% by mass, 30-50% by mass, 35-50% by mass, or 40-50% by mass, based on the total weight of the polymerizable liquid.

[0044] The polymerizable liquids described herein may also contain water. Water may be present in any amount that is not inconsistent with the technical purposes of this disclosure. For example, in some cases, water may be present in the polymerizable liquid in an amount of 10–85% by mass or 20–85% by mass, based on the total weight of the polymerizable liquid. In some implementations, water may be present in an amount or concentration of 10–60% by mass, 20–80% by mass, 20–50% by mass, 30–80% by mass, 30–60% by mass, 40–80% by mass, 40–60% by mass, 50–80% by mass, or 50–70% by mass, based on the total weight of the polymerizable liquid.

[0045] It should be further understood that water (or the entire polymerizable liquid) may have a pH of about 1 to about 7, about 3 to about 7, or about 4 to about 6. As will be understood by those skilled in the art, such pH values ​​can be obtained, for example, by including Brønsted-Lowry acid or a base. For example, in some cases, a strong acid or a strong base, such as hydrochloric acid or sodium hydroxide, respectively, can be included in the water (or the entire polymerizable liquid) at a desired concentration to provide the desired pH, as will be understood by those skilled in the art. Other proton or hydroxide sources can also be used.

[0046] In some implementations, the polymerizable liquid may further contain one or more additional polymerizable or curable materials that are different from the compound having the structure of formula (I) or formula (II) and different from the acrylate component. In some embodiments, such additional polymerizable or curable materials may include any chemical species having a curable or polymerizable moiety, such as an ethylenically unsaturated moiety, that can participate in the curing or polymerization reaction with the curable compound and / or acrylate component of the polymerizable liquid. Furthermore, in some examples, such additional polymerizable or curable materials are hydrophilic. In some embodiments, one or more additional polymerizable or curable materials may be present in an amount of 1 to 20% by mass, based on the total weight of the polymerizable liquid.

[0047] In some embodiments, the polymerizable liquid described herein further comprises a colorant or a luminescent compound. The luminescent compound may include a structure such that, when exposed to radiation of a specific wavelength, the luminescent compound produces a visible signal. In some implementations, the luminescent compound may include one or more colorants that produce visible wavelengths (e.g., red, green, blue, etc.) when exposed to natural light. When incorporated into a polymerizable liquid, the colorants may be present in amounts of 0.1–5% by mass, 0.1–3% by mass, 0.1–2% by mass, 0.1–1% by mass, 0.1–0.5% by mass, 0.5–5% by mass, 0.5–4% by mass, or 0.5–3% by mass, based on the total weight of the polymerizable liquid.

[0048] The polymerizable liquids described herein also, in some embodiments, include a photoinitiator component for initiating the polymerization of one or more components of the liquid upon exposure to light of an appropriate wavelength. In some embodiments, the photoinitiator component can initiate the polymerization / crosslinking of a curable compound. As described above, acrylate components (and optionally one or more additional polymerizable or curable materials) may also participate in this polymerization.

[0049] Any photoinitiator that is not inconsistent with the purposes of this disclosure can be used. In some embodiments, the photoinitiator preferably includes an alpha-cleavage (single-molecule decomposition process) photoinitiator or a hydrogen-extraction photosensitizer-tertiary amine synergist that is capable of absorbing light at about 250 nm to about 420 nm or about 300 nm to about 385 nm to generate free radicals.

[0050] Examples of alpha-cleavage photoinitiators include Irgacure 184 (CAS 947-19-3), Irgacure 369 (CAS 119313-12-1), and Irgacure 819 (CAS 162881-26-7). An example of a photosensitizer-amine combination is Darocur BP (CAS 119-61-9) containing diethylaminoethyl methacrylate.

[0051] Furthermore, in some examples, suitable photoinitiators include: benzoins, benzoin ethers, e.g., benzoin methyl ether, benzoin ethyl ether and benzoin isopropyl ether, benzoin phenyl ether and benzoin acetate; acetophenones, e.g., 2,2-dimethoxyacetophenone and 1,1-dichloroacetophenone; benzyl ketals, e.g., benzyl dimethyl ketal and benzyl diethyl ketal; anthraquinones, e.g., 2-methylanthraquinone, 2-ethylanthraquinone, 2-tert-butylanthraquinone, 1-chloroanthraquinone and 2-amylanthraquinone; and tri Phenylphosphine, benzoylphosphine oxides, such as 2,4,6-trimethylbenzoyldiphenylphosphine oxide (Lucillin TPO), benzophenones such as benzophenone and 4,4'-bis(N,N'-dimethylamino)benzophenone, thioxanthones and xanthones, acridine derivatives, phenazine derivatives, quinoxaline derivatives, or 1-phenyl-1,2-propanedione, 2-O-benzoyloxime, 1-aminophenyl ketones, or 1-hydroxyphenyl ketones, such as 1-hydroxycyclohexylphenyl ketone, phenyl 1-hydroxyisopropyl ketone, and 4-isopropylphenyl 1-hydroxyisopropyl ketone.

[0052] Suitable photoinitiators may also include acetophenones, 2,2-dialkoxybenzophenones, and 1-hydroxyphenyl ketones, such as 1-hydroxycyclohexylphenyl ketone or 2-hydroxyisopropylphenyl ketone (=2-hydroxy-2,2-dimethylacetophenone), which are operable for use with HeCd laser radiation sources. Furthermore, in some cases, preferred photoinitiators include benzyl ketals, such as benzyldimethyl ketal, which are operable for use with Ar laser radiation sources. In some embodiments, the photoinitiator includes α-hydroxyphenyl ketone, benzyldimethyl ketal, or 2,4,6-trimethylbenzoyldiphenylphosphine oxide or a mixture thereof.

[0053] Another class of suitable photoinitiators includes ionic dye-counterionic compounds that, in some examples, can absorb chemical rays and generate free radicals for polymerization initiation. In some embodiments, polymerizable liquids containing ionic dye-counterionic compounds can polymerize when exposed to visible light within a tunable wavelength range of about 400 nm to about 700 nm. Ionic dye-counterionic compounds and their modes of operation are disclosed in European Patent Application Publication No. 0223587 and U.S. Patents No. 4,751,102; No. 4,772,530; and No. 4,772,541.

[0054] The photoinitiator may be present in the polymerizable liquid described herein in any amount not inconsistent with the purposes of this disclosure. In some embodiments, the photoinitiator is present in an amount up to about 5% by mass, based on the total weight of the polymerizable liquid. In some cases, the photoinitiator is present in an amount ranging from about 0.1% to about 5% by mass, about 0.1% to about 3% by mass, about 0.5% to about 2.5% by mass, or about 1% to about 3% by mass.

[0055] Furthermore, in some implementations, the polymerizable liquid may further contain one or more sensitizers. The sensitizers may be added to increase the effectiveness of one or more photoinitiators, which may also be present. Any sensitizer that is not inconsistent with the purposes of this disclosure may be used. In some cases, the sensitizer comprises isopropylthioxanthone (ITX) or 2-chlorothioxanthone (CTX).

[0056] The sensitizer may be present in the polymerizable liquid in any amount not inconsistent with the purposes of this disclosure. In some embodiments, the sensitizer is present in amounts ranging from about 0.1% to about 3% by mass, about 0.1% to about 2% by mass, about 0.5% to about 2% by mass, or about 0.5% to about 1% by mass, based on the total weight of the polymerizable liquid.

[0057] In some implementations, one or more UV absorbers and / or light stabilizers may be present in the polymerizable liquid at an effective concentration. For example, one or more UV absorbers and / or light stabilizers may be present in an amount of 0.1 to 2% by mass, based on the total weight of the polymerizable liquid. In some embodiments, the UV absorbers and / or light stabilizers are commercially available from BASF in Florham Park, New Jersey, under the trade name TINUVIN®, and from QCR Solutions Corporation under the trade name UV386.

[0058] The polymerizable liquids or inks described herein may have a variety of properties in their cured or uncured states, including properties related to the microstructure of the ink, which may be a composite mixture or other composite material system. In some embodiments, such structural features or other properties relate to the polymerizable liquid in the cured or polymerized state. The “cured” or “polymerized” inks (or shaping materials or polymerizable liquids) used throughout this disclosure include inks (or shaping materials or polymerizable liquids) that are at least partially cured, i.e., contain curable materials or polymerizable components that are at least partially polymerized and / or crosslinked. For example, in some cases, the cured ink (or shaping material or polymerizable liquid) is polymerized or crosslinked by at least about 70%, or at least about 80%. In some embodiments, the cured ink (or shaping material or polymerizable liquid) is polymerized or crosslinked by at least about 85%, at least about 90%, at least about 95%, at least about 98%, or at least 99%. In some examples, the cured ink (or shaping material or polymerizable liquid) is polymerized or crosslinked by about 80% to about 99%. The degree of polymerization or crosslinking can be determined using any protocol or method not inconsistent with the technical objectives of this disclosure, for example, by identifying the proportion of monomers incorporated into the polymer network (e.g., based on the molecular weight of the polymer compared to the molecular weight of the monomers, or based on the total polymer mass compared to the theoretical maximum value of the total polymer mass), or by identifying the amount of monomers that are not incorporated. When multiple methods are used to determine the degree of polymerization or crosslinking, the results of these methods can be averaged to obtain the percentages described herein. It should be further understood that the degree of polymerization or crosslinking described herein is different from the “degree of polymerization” as defined as the number of repeating units in the polymer molecule.

[0059] In some embodiments, the inks (or molding materials or polymerizable liquids) described herein, when cured or polymerized, have an elongation at break of more than 150% when measured according to the method of Example 6. For example, certain articles formed from the polymerization of polymerizable liquids according to this disclosure may have elongations at break of 150-300%, 150-275%, 150-250%, 200-275%, or 200-250% when measured according to the method of Example 6.

[0060] Another exemplary property of a particular polymerizable liquid (or ink or molding material) during polymerization may include a swelling rate in phosphate-buffered saline of less than 30%, less than 20%, less than 15%, or less than 10%, as measured according to the method of Example 7. For example, some articles formed from the polymerization of polymerizable liquids according to the present disclosure may have swelling rates in the range of 0-30%, 0-25%, 0-20%, 0-15%, 1-30%, 1-20%, 1-15%, 5-30%, 5-25%, 5-20%, 5-15%, 10-30%, 10-20%, 10-15%, 15-30%, 15-25%, or 15-20%, as measured according to the method of Example 7.

[0061] The inks (or shaping materials or polymerizable liquids) described herein can be manufactured in any manner not inconsistent with the purposes of this disclosure. In some embodiments, for example, a method for preparing the inks (or shaping materials or polymerizable liquids) described herein comprises the steps of mixing the components of the ink, optionally melting the mixture, and filtering the (optionally melted) mixture. In some cases, the components are mixed and optionally melted at a temperature of about 25°C to about 35°C, or at a temperature in the range of 25 to 55°C, 35 to 65°C, or 45 to 75°C. In some examples where it is desirable or necessary to melt one or more solid components of the ink, the mixing and / or melting can be carried out at a temperature in the range of about 75°C to about 85°C. In some embodiments, the inks described herein are manufactured by placing all the components of the ink in a reaction vessel, optionally heating the resulting mixture, and stirring the resulting mixture at a temperature of about 25°C to about 75°C or at a temperature in the range of about 75°C to about 85°C. Continue stirring (and optionally heating) until the mixture reaches a substantially homogenized liquid (or molten) state. Generally, the liquid (or molten) mixture can be filtered while it is still fluid to remove any large, undesirable particles that may interfere with the spraying, extrusion, or other printing processes. The filtered mixture can then be cooled to ambient temperature (if necessary) and stored until ready for use in the 3D printing system.

[0062] IV. Method for forming 3D articles In another embodiment, methods for forming or "printing" 3D articles or objects (such as hydrogel articles or objects) by additive manufacturing are described herein. Methods for forming 3D articles or objects described herein may include the step of forming a 3D article layer by layer from multiple layers of ink (or build material or polymerizable liquid) described herein (e.g., MJP (Multi-Jet Printing) or SLA (Stereolithography) printing methods). For example, in some examples, an MJP method for printing a 3D article includes the step of selectively depositing layers of the ink described herein in a fluid state onto a substrate such as a build pad of a 3D printing system. This method may further include the step of further curing the ink (e.g., photocuring). Furthermore, curing may include the step of polymerizing one or more polymerizable moieties or functional groups of one or more components of the ink. In some cases, the deposited layers of ink are cured before the deposition of another or adjacent layers of ink. Furthermore, the step of curing one or more layers of deposited ink is carried out in some embodiments by exposing one or more layers to electromagnetic radiation such as UV light, visible light, or infrared light, as described above. Furthermore, in some embodiments, such a method further includes the step of supporting at least one of the ink layers with a support material before or after curing. Any support material that is not inconsistent with the purposes of this disclosure can be used, as will be further described below.

[0063] Alternatively, a method for printing a 3D article includes: holding ink in a fluid state within a container; selectively applying energy to the ink within the container to solidify at least a portion of a first fluid layer of the ink, thereby forming a first solidified layer defining a first cross-section of the article; raising or lowering the first solidified layer to provide a second fluid layer of ink on the surface of the fluid ink within the container; and selectively applying energy to the ink within the container to solidify at least a portion of a second fluid layer of the ink, thereby forming a second solidified layer defining a second cross-section of the article, wherein the first and second cross-sections are joined to each other in the z-direction. Furthermore, in some such embodiments, the step of selectively applying energy to the ink within the container includes a step of photocuring the ink.

[0064] Furthermore, in some embodiments of the methods described herein, one or more layers of the inks described herein have a thickness of about 10 μm to about 100 μm, about 10 μm to about 80 μm, about 10 μm to about 50 μm, about 20 μm to about 100 μm, about 20 μm to about 80 μm, or about 20 μm to about 40 μm. Other thicknesses are also possible.

[0065] Methods for forming 3D articles by additive manufacturing may also include steps for forming the object in ways other than layer-by-layer methods.

[0066] Furthermore, any ink (or modeling material or polymerizable liquid) described above or below in the specific examples in Section III may be used in the methods herein. For example, in some cases, the methods herein may include the step of supplying a polymerizable liquid comprising a curable compound, an acrylate component, and water to a print bed. This method may further include the step of curing at least a portion of the polymerizable liquid. More specifically, the compositions described herein may be supplied to a print area (e.g., by a 3D printing system), and at least a portion of the supplied composition may be cured (e.g., using electromagnetic radiation directed at the supplied portion of the composition).

[0067] Furthermore, the curing / polymerization processes described herein can be carried out so that a polymerizable liquid (or ink or molding material) forms an article having the physical and / or material properties according to the exemplary embodiments described herein. Further details of various methods, including “material deposition” methods (such as MJP) or “vat polymerization” methods (such as SLA), are provided below.

[0068] A. Material deposition method In the material deposition method, one or more layers of the ink described herein are selectively deposited and cured on a substrate. Curing of the ink may be performed after selective deposition of one layer, each layer, multiple layers, or all layers of the ink.

[0069] In some examples, the inks described herein are selectively deposited in a fluid state onto a substrate, such as a build pad in a 3D printing system. Selective deposition may include, for example, the step of depositing the ink according to pre-selected CAD (computer-aided design) parameters. For example, in some embodiments, a CAD file drawing corresponding to the desired 3D article to be printed is generated and sliced ​​into a sufficient number of horizontal slices. The ink is then selectively deposited layer by layer according to the horizontal slices of the CAD file drawing to print the desired 3D article. The "sufficient" number of horizontal slices is, for example, the number required for the successful printing of the desired 3D article in order to accurately and precisely manufacture the desired 3D article.

[0070] Furthermore, in some embodiments, a pre-selected amount of ink described herein is heated to a suitable temperature and ejected through a suitable inkjet printer printhead or multiple printheads to form layers on the print pad in the print chamber. In some cases, each layer of ink is deposited according to pre-selected CAD parameters. In some embodiments, a piezoelectric printhead is suitable for depositing the ink. Further suitable printheads for depositing the ink and support materials described herein are commercially available from various inkjet printer manufacturers. For example, in some examples, printheads from Xerox, Hewlett-Packard, or Ricoh may be used.

[0071] Furthermore, in some embodiments, the inks described herein remain substantially fluid upon deposition. Alternatively, in other embodiments, the inks exhibit a phase change upon deposition and / or solidify upon deposition. In addition, the temperature of the printing environment can be controlled so that droplets of sprayed ink solidify upon contact with the receiving surface. In other embodiments, droplets of sprayed ink do not solidify upon contact with the receiving surface and remain substantially fluid. Furthermore, in some embodiments, after each layer has been deposited, the deposited material is planarized and cured with electromagnetic radiation (e.g., UV, visible, or infrared) before the deposition of the next layer. Optionally, multiple layers can be deposited before planarization and curing, or multiple layers can be deposited and cured, after which one or more layers can be deposited and then planarized without curing. Planarization corrects the thickness of one or more layers before curing the material by flattening the distributed material and removing excess material to form a uniformly smooth exposed surface or a flat upward surface on the printer's support platform. In some embodiments, planarization is achieved using a wiper device such as a roller, which may rotate in the opposite direction to one or more print directions but not in the opposite direction to one or more other print directions. In some cases, the wiper device comprises a roller and a wiper that removes excess material from the roller. Furthermore, in some cases, the wiper device is heated. In some embodiments, it should be noted that the consistency of the spray ink described herein before curing is preferably sufficient to maintain its shape and not subject to excessive viscous resistance from the planarization device.

[0072] Furthermore, the support material, if used, can be deposited in a manner consistent with the method described above for the ink. The support material can be deposited, for example, according to pre-selected CAD parameters such that the support material is adjacent to or continuous with one or more layers of ink. In some embodiments, the sprayed droplets of the support material solidify or freeze upon contact with the receiving surface. In some cases, the deposited support material is also subjected to planarization, curing, or planarization and curing. Any support material that is not inconsistent with the purposes of this disclosure can be used.

[0073] The layering of ink and support material can be repeated until a 3D article is formed. In some embodiments, the method for printing a 3D article further includes the step of removing the support material from the ink.

[0074] Ink curing may occur after selective deposition of one layer of ink, each layer of ink, multiple layers of ink, or all layers of ink necessary to print a desired 3D article. In some embodiments, partial curing of the deposited ink occurs after selective deposition of one layer of ink, each layer of ink, multiple layers of ink, or all layers of ink necessary to print a desired 3D article. For reference herein, “partially cured” ink is one that can undergo further curing. For example, partially cured ink may be polymerized or crosslinked up to about 30% or up to about 50%. In some embodiments, partially cured ink may be polymerized or crosslinked up to about 60%, about 70%, about 80%, about 90%, or about 95%.

[0075] Partial curing of deposited ink may include irradiating the ink with an electromagnetic radiation source or photocuring the ink (including by the curing radiation described above). Any electromagnetic radiation source that is not inconsistent with the purposes of this disclosure, for example, an electromagnetic radiation source that emits UV, visible light, or infrared light, may be used. For example, in some embodiments, the electromagnetic radiation source may emit light having wavelengths of about 300 nm to about 900 nm, for example, a Xe arc lamp.

[0076] Furthermore, in some embodiments, post-curing is performed after partial curing. For example, in some cases, post-curing is performed after selectively depositing all the layers of ink necessary to form the desired 3D article, after partially curing all the layers of ink, or after both of the aforementioned steps have been performed. Furthermore, in some embodiments, post-curing includes photocuring. Again, any electromagnetic radiation source that is not inconsistent with the purposes of this disclosure can be used in the post-curing process described herein. For example, in some embodiments, the electromagnetic radiation source may be a light source having higher energy, lower energy, or the same energy as the electromagnetic radiation source used for partial curing. If the electromagnetic radiation source used for post-curing has higher energy (i.e., shorter wavelength) than the one used for partial curing, a Xe arc lamp may be used for partial curing and an Hg lamp for post-curing.

[0077] Furthermore, after post-curing, in some cases the deposited ink layer is polymerized or crosslinked by at least about 80%, or at least about 85%. In some embodiments, the deposited ink layer is polymerized or crosslinked by at least about 90%, at least about 95%, at least about 98%, or at least about 99%. In some examples, the deposited ink layer is polymerized or crosslinked by about 80-100%, about 80-99%, about 80-95%, about 85-100%, about 85-99%, about 85-95%, about 90-100%, or about 90-99%.

[0078] B. Vat polymerization It is also possible to form 3D articles from the inks described herein using vat polymerization methods such as SLA. Therefore, in some cases, the method for printing 3D articles described herein includes the steps of holding the inks described herein in a fluid state in a container, and selectively applying energy (in particular, curing radiation) to the ink in the container to solidify at least a portion of the fluid layer of ink, thereby forming a solidified layer that defines the cross-section of the 3D article. Furthermore, the method described herein may further include the step of raising or lowering the solidified layer of ink to provide a new or second fluid layer of unsolidified ink on the surface of the fluid ink in the container, and then selectively applying energy (in particular, curing radiation) again to the ink in the container to solidify at least a portion of the new or second fluid layer of ink, thereby forming a second solidified layer that defines the second cross-section of the 3D article. Furthermore, the first and second cross-sections of the 3D article can be bonded or adhered to each other in the z-direction (or the molding direction corresponding to the raising or lowering direction described above) by the application of energy to solidify the ink. Furthermore, in some examples, the electromagnetic radiation has an average wavelength of 300–900 nm, and in other embodiments, the electromagnetic radiation has an average wavelength of less than 300 nm. In some cases, the curing radiation is provided by a computer-controlled laser beam. In addition, in some cases, the raising or lowering of the solidified layer of ink is performed using an elevator platform placed in a container of fluid ink. The method described herein also includes a step of planarizing a new layer of fluid ink provided by raising or lowering the elevator platform. Such planarization may, in some cases, be performed by a wiper or roller.

[0079] It should be further understood that the process described above can be repeated a desired number of times to provide a 3D object. For example, in some cases, this process can be repeated "n" times, where n could be up to approximately 100,000, up to approximately 50,000, up to approximately 10,000, up to approximately 5,000, up to approximately 1,000, or up to approximately 500. Accordingly, in some embodiments, the method for printing a 3D article described herein may include the steps of: selectively applying energy (e.g., curing radiation) to ink in a container to solidify at least a portion of the nth fluid layer of ink, thereby forming an nth solidified layer defining the nth cross-section of the 3D article; raising or lowering the nth solidified layer of ink to provide an (n+1)th unsolidified ink layer on the surface of the fluid ink in the container; selectively applying energy to the (n+1)th ink layer in the container to solidify at least a portion of the (n+1)th ink layer to form an (n+1)th solidified layer defining the (n+1)th cross-section of the 3D article; raising or lowering the (n+1)th solidified layer of ink to provide an (n+2)th unsolidified ink layer on the surface of the fluid ink in the container; and repeatedly performing the above steps to form a 3D article. Furthermore, it should be understood that one or more steps of the methods described herein, such as the step of selectively applying energy (e.g., curing radiation) to a layer of ink, can be performed according to an image of a 3D article in a computer-readable format. Common methods of 3D printing using stereolithography are described further, among other things, in U.S. Patent Nos. 5,904,889 and 6,558,606.

[0080] By performing the printing process described above, it is possible to provide 3D articles printed from the inks described herein having high feature resolution. The “feature resolution” of an article may, for reference in this specification, be the smallest controllable physical feature size of the article. The feature resolution of an article may be described in terms of units of distance such as microns (μm) or dots per inch (dpi). As will be understood by those skilled in the art, higher feature resolution corresponds to higher dpi values, while distance values ​​in μm are lower. In some cases, articles formed by depositing or solidifying the inks described herein may have a feature resolution of about 500 μm or less, about 200 μm or less, about 100 μm or less, or about 50 μm or less, including at high temperatures. In some embodiments, articles may have a feature resolution of about 50 μm to about 500 μm, about 50 μm to about 200 μm, about 50 μm to about 100 μm, or about 100 μm to about 200 μm. Similarly, in some examples, the articles described herein have a feature resolution of at least about 100 dpi, at least about 200 dpi, at least about 250 dpi, at least about 400 dpi, or at least about 500 dpi. In some cases, the feature resolution of the articles is about 100 dpi to about 600 dpi, about 100 dpi to about 250 dpi, or about 200 dpi to about 600 dpi.

[0081] In the vat polymerization method described above, the ink may be partially cured as described in Section IV.A above. For example, in some embodiments, the step of selectively applying energy to the ink in a container to solidify at least a portion of the fluid layer of the ink may include the step of partially curing at least a portion of the fluid layer of the ink. In other embodiments, the partial curing of at least a portion of the fluid layer of the ink may occur after a first layer of ink has been provided and solidified, before or after a second layer of ink has been provided and solidified, or before or after one, more, or all of the subsequent layers of ink have been provided or solidified.

[0082] Furthermore, in some embodiments of the vat polymerization methods described herein, post-curing may be performed after partial curing or after the desired 3D article has been formed, as described in Section IV.A above. The desired 3D article may be, for example, an article corresponding to a design in a CAD file.

[0083] V. Printed Articles In another embodiment, printed 3D articles are described herein. In some embodiments, printed 3D articles are formed from inks (or molding materials or polymerizable liquids) described herein. Any ink (or molding materials or polymerizable liquids) described herein can be used. For example, in some cases, the ink comprises a curable compound having the structure of formula (I) or formula (II), an acrylate component, and water. Furthermore, in some cases, printed 3D articles described herein are primarily formed from polymer networks resulting from the curing or polymerization of the curable compound and acrylate component. Articles described herein may also be hydrogel articles, or articles formed from hydrogels and exhibiting hydrogel properties.

[0084] Hydrogel articles printed according to the methods described herein can find applications in a variety of fields, including the medical field. Hydrogel articles may, for example, be medical implants. Hydrogel medical implants can be used for tissue regeneration and / or function as scaffolds for cell seeding and / or proliferation. It is also possible to form mimics of biological tissues or organs using the hydrogels or polymerizable liquids described herein. [Examples]

[0085] Some specific embodiments of curable compounds, hydrogels, inks (or molding materials or polymerizable liquids), methods, and articles are further illustrated in the following non-limiting embodiments.

[0086] Example 1 A curable compound denoted as MA-PEG200-MA was prepared as follows. This species has the structure of formula (I), where n corresponds to the PEG portion having a weight-average molecular weight of approximately 200.

[0087] Add 216.66 grams of PEG200 to a two-necked 1-liter round-bottom flask equipped with a Teflon®-coated stirring magnet, stopper, and 24 / 40 adapter. Place the round-bottom flask (reaction vessel) in a 65°C oil bath with a condenser installed. Transfer 218.92 grams of maleic anhydride to the reaction vessel via a glass funnel. Stir at 65°C until completely dissolved and homogeneous. After flowing dry elitehouse nitrogen into the headspace of the round-bottom flask for approximately 30 seconds, place the stopper while gently flowing dry elitehouse nitrogen over the top of the condenser.

[0088] After 3 hours, the initial infrared (IR) spectroscopy time point was recorded. Reflux at 65°C was continued for approximately 36 hours. After confirming the product by IR, reflux was stopped.

[0089] Example 2 A curable compound denoted as MA-PEG400-MA is prepared as follows. This species has the structure of formula (I), where n corresponds to the PEG portion having a weight-average molecular weight of approximately 400.

[0090] Add 430 grams of PEG400 to a two-necked 1-liter round-bottom flask equipped with a Teflon®-coated stirring magnet, stopper, and 24 / 40 adapter. Place the round-bottom flask in a 65°C oil bath with a condenser installed. Transfer 220 grams of maleic anhydride to the reaction vessel via a glass funnel. Stir at 65°C until the flask contents are completely dissolved and homogenized. After supplying nitrogen gas to the headspace of the round-bottom flask for approximately 30 seconds, place the stopper while gently flowing nitrogen over the top of the condenser.

[0091] After 3 hours, IR spectroscopy is performed on sample aliquots from the reaction vessel to provide the initial IR time point. Reflux is continued at 65°C for approximately 36 hours. After confirming the product by IR, reflux is stopped.

[0092] Example 3 A curable compound denoted as MA-PEG600-MA is prepared as follows. This species has the structure of formula (I), where n corresponds to the PEG portion having a weight-average molecular weight of approximately 600.

[0093] Add 650 grams of PEG600 to a two-necked 2-liter round-bottom flask equipped with a Teflon®-coated stirring magnet, stopper, and 24 / 40 adapter. Place the round-bottom flask in a 65°C oil bath with a condenser installed. Transfer 220 grams of maleic anhydride to the reaction vessel via a glass funnel. Stir at 65°C until the flask contents are completely dissolved and homogenized. After supplying inert gas (nitrogen, dry) to the headspace of the round-bottom flask for approximately 30 seconds, place the stopper while gently flowing dry inert gas (nitrogen) over the top of the condenser.

[0094] After 3 hours, IR spectroscopy is performed on sample aliquots from the reaction vessel to provide the initial IR time point. Reflux is continued at 65°C for approximately 36 hours. After confirming the product by IR, reflux is stopped.

[0095] Example 4 A curable compound denoted as MA-PEG1000-MA is prepared as follows. This species has the structure of formula (I), where n corresponds to the PEG portion having a weight-average molecular weight of approximately 1000.

[0096] Add 1,080 grams of PEG1000 to a two-necked 2-liter round-bottom flask equipped with a Teflon®-coated stirring magnet, stopper, and 24 / 40 adapter. Place the round-bottom flask in a 65°C oil bath with a condenser installed. Transfer 220 grams of maleic anhydride to the reaction vessel via a glass funnel. Stir at 65°C until the flask contents are completely dissolved and homogenized. Supply dry nitrogen to the headspace of the round-bottom flask for approximately 30 seconds, then place the stopper while gently flowing dry nitrogen over the top of the condenser.

[0097] After 3 hours, IR spectroscopy is performed on sample aliquots from the reaction vessel to provide the initial IR time point. Reflux is continued at 65°C for approximately 36 hours. After confirming the product by IR, reflux is stopped.

[0098] Example 5 Table 2 provides formulations of polymerizable liquids (or hydrogels or molding materials) according to several embodiments described herein. In Table 2, "Comp." means "composition," and the amounts listed for a given composition are mass percentages based on the total weight of the composition. It should be understood that all components of a given composition total 100 mass percent. Table 3 provides the components of compositions 1 to 6. Table 4 provides the elongation at break (EOB) of compositions 1 to 6, as measured as described in Example 6 below.

[0099] It should be noted that compositions 1 to 6 contain various amounts of the components described herein (as shown in Table 2). Furthermore, compositions 4 to 6 use different species of formula (I), where the integer n is modified to approximately correspond to the weight-average molecular weights of 200, 600, and 1000 of the PEG portion of formula (I) (as shown in Table 3). As shown in Table 4, all compositions 1 to 6 have an EOB of 150-300%. Furthermore, in Table 3, "QY" refers to quinoline yellow. Table 2. Exemplary Compositions [Table 2]

[0100] Table 3. Ingredients [Table 3]

[0101] Table 4. Elongation at break [Table 4]

[0102] In addition to compositions 1 to 6, several comparative compositions were prepared. Specifically, comparative compositions 1 to 3 were prepared in the same manner as compositions 1 to 6. Comparative compositions 1 to 3 can be compared in particular with composition 6. The components of comparative compositions 1 to 3 were the same as those of composition 6, except that each of comparative compositions 1 to 3 completely excluded the curable compound of formula I. In comparative composition 1, the compound of formula I was replaced with water. Therefore, comparative composition 1 contained 47.8% by mass of water instead of 12.8% by mass of water. In comparative composition 2, the curable compound of formula I was replaced with an equivalent poly(ethylene glycol) diacrylate. Therefore, comparative composition 2 contained 35% by mass of PEGDA as the alternative curable component. In comparative composition 3, the curable compound of formula I was replaced with monomer triacrylate (TAC) without the PEG portion. Therefore, comparative composition 3 contained 35% by mass of TAC as the alternative curable component.

[0103] As described in Example 7 below, the EOB was measured for each of the comparative compositions 1 to 3. As shown in Table 5, comparative compositions 1 to 3, which excluded the curable compounds of formula I or formula II described herein, each had an EOB value of less than 150%. Table 5. Elongation at break [Table 5]

[0104] The additional compositions according to the present invention are provided using the amounts shown in Table 6 below. The amounts in Table 6 refer to the mass % of each component of the identified composition, based on the total weight of the composition. Also, "PI" stands for "photoinitiator". Furthermore, in all cases of Table 6 below, water provides a balance of components so that it reaches 100% by mass (e.g., 10-60% by mass of water). Table 6. Composition ingredients [Table 6]

[0105] Example 6 Tensile tests of printed articles to determine the elongation at break were performed as follows: The test formulation (ink, molding material, or polymerizable liquid) was printed onto a horizontally oriented ring with a thickness of 20 μm using a digital photovoltaic (DLP) printer at room temperature (approximately 23-25°C). The ring had a neck region with a specified 1 mm × 1 mm square cross-section. The ring was removed from the printer platform and the uncured material was washed away (e.g., by placing the ring in phosphate-buffered saline (PBS) or water for 10 minutes or less at room temperature). The ring was then loaded into a dynamic mechanical analysis (DMA) system and stretched vertically at 100% strain per minute (at room temperature) until the instrument reached maximum strain or the sample broke, thereby obtaining the elongation at break (EOB). The modulus of elasticity was determined by determining the slope of the first 10% strain.

[0106] Example 7 Swelling of the prints was identified and measured in both the ink itself and in PBS as follows: 8 mm diameter and 3 mm thickness discs were printed with the test formulation (the ink, printing material, or polymerizable liquid of interest) and then placed in a shallow dish. Each disc was measured using a Zeiss microscope to determine the print diameter. To measure swelling in phosphate-buffered saline (PBS), the discs were immersed in Dulbecco's PBS(++). The discs were covered with at least approximately 5 times the volume of the disc in solution. The diameter of the discs was then measured sequentially at different time points over the following week to assess shrinkage, swelling, or swelling over time. Final swelling was quantified as [final diameter (mm) - initial diameter (mm)] / initial diameter (mm).

[0107] Several additional, non-limiting, exemplary embodiments are provided below.

[0108] Embodiment 1. Compound having the structure of formula (I): [ka] In the formula, n is an integer between 4 and 40.

[0109] Embodiment 2. Compound having the structure of formula (II): [ka] In the formula, n is an integer between 4 and 40.

[0110] Embodiment 3. The compound according to Embodiment 1 or Embodiment 2, wherein n is an integer from 4 to 14 or from 4 to 20.

[0111] Embodiment 4. The compound according to any of the previous embodiments, wherein the compound is a liquid at 25°C and 1 atm.

[0112] Embodiment 5. A hydrogel comprising any of the compounds of the preceding embodiments.

[0113] Embodiment 6. The hydrogel according to Embodiment 5, wherein the compound is present in the hydrogel in an amount of 10 to 35% by mass based on the total weight of the hydrogel.

[0114] Embodiment 7. The hydrogel according to Embodiment 5 or Embodiment 6, further comprising an acrylate component.

[0115] Embodiment 8. The hydrogel according to Embodiment 7, wherein the acrylate component is present in an amount of 35 to 50% by mass based on the total weight of the hydrogel.

[0116] Embodiment 9. A hydrogel according to any one of Embodiments 5 to 7, wherein the acrylate component comprises one or more hydroxyalkyl acrylates.

[0117] Embodiment 10. A hydrogel according to any one of Embodiments 5 to 7, wherein the acrylate component comprises one or more polyethylene glycol acrylates or diacrylates.

[0118] Embodiment 11. A hydrogel according to any one of Embodiments 5 to 7, wherein the acrylate component comprises one or more hydroxyalkylacrylamides.

[0119] Embodiment 12. A hydrogel according to any one of Embodiments 5 to 11, wherein water is present in the hydrogel in an amount of 20 to 85% by mass based on the total weight of the hydrogel.

[0120] Embodiment 13. A polymerizable liquid for forming a hydrogel article, Compounds having the structure of formula (I) or formula (II) (wherein n is an integer between 4 and 40); [ka] Acrylate components; and water A polymerizable liquid containing [a certain substance].

[0121] Embodiment 14. The polymerizable liquid according to Embodiment 13, wherein the polymerizable liquid comprises a compound having the structure of formula (I).

[0122] Embodiment 15. A polymerizable liquid according to Embodiment 13 or Embodiment 14, wherein a compound having the structure of formula (I) or formula (II) is present in an amount of 10 to 35% by mass based on the total weight of the polymerizable liquid.

[0123] Embodiment 16. A polymerizable liquid according to any one of Embodiments 13 to 15, wherein the acrylate component comprises one or more hydroxyalkyl acrylates.

[0124] Embodiment 17. A polymerizable liquid according to any one of Embodiments 13 to 16, wherein the acrylate component comprises one or more polyethylene glycol acrylates or diacrylates.

[0125] Embodiment 18. A polymerizable liquid according to any one of Embodiments 13 to 17, wherein the acrylate component comprises one or more hydroxyalkylacrylamides.

[0126] Embodiment 19. A polymerizable liquid according to any one of Embodiments 13 to 18, wherein the acrylate component is present in an amount of 15 to 50% by mass or 35 to 50% by mass, based on the total weight of the polymerizable liquid.

[0127] Embodiment 20. A polymerizable liquid according to any one of Embodiments 13 to 19, wherein water is present in an amount of 20 to 85% by mass or 10 to 50% by mass, based on the total weight of the polymerizable liquid.

[0128] Embodiment 21. The polymerizable liquid according to any one of Embodiments 13 to 20, wherein the polymerizable liquid further comprises one or more additional polymerizable or curable materials that are different from the compound having the structure of formula (I) or formula (II) and are different from the acrylate component.

[0129] Embodiment 22. The polymerizable liquid according to Embodiment 21, wherein one or more additional polymerizable or curable materials are present in an amount of 1 to 20% by mass based on the total weight of the polymerizable liquid.

[0130] Embodiment 23. The polymerizable liquid according to any one of Embodiments 13 to 22, wherein the polymerizable liquid further comprises one or more colorants.

[0131] Embodiment 24. The polymerizable liquid according to Embodiment 23, wherein one or more colorants are present in an amount of 0.1 to 5% by mass or 0.1 to 1% by mass, based on the total weight of the polymerizable liquid.

[0132] Embodiment 25. A polymerizable liquid according to any one of Embodiments 13 to 24, wherein the polymerizable liquid further comprises a photoinitiator component.

[0133] Embodiment 26. The polymerizable liquid according to Embodiment 25, wherein the photoinitiator component is present in an amount of 0.1 to 5 or 0.1 to 3% by mass, based on the total weight of the polymerizable liquid.

[0134] Embodiment 27. A polymerizable liquid according to any one of Embodiments 13 to 26, wherein the liquid has a break elongation of more than 150% when polymerized, as measured according to the method of Example 6.

[0135] Embodiment 28. A polymerizable liquid according to any one of Embodiments 13 to 26, wherein, when measured according to the method of Example 7, the liquid has a swelling rate of less than 20% in phosphate-buffered saline when polymerized.

[0136] Embodiment 29. A method for printing a three-dimensional hydrogel article, A step of providing a polymerizable liquid according to any of embodiments 13 to 28; and A process of printing a polymerizable liquid and curing it with light to form a hydrogel article. Methods that include...

[0137] Embodiment 30. The method according to Embodiment 29, wherein the polymerizable liquid is provided in a layer-by-layer process.

[0138] Embodiment 31. The method according to Embodiment 29 or Embodiment 30, wherein the hydrogel article is a medical implant.

[0139] Embodiment 32. A printed three-dimensional article formed from a polymerizable liquid according to any of Embodiments 13 to 28.

[0140] All patent documents referenced herein are incorporated in their entirety by reference. Various embodiments of the present invention have been described to serve various purposes of the present invention. It should be recognized that these embodiments are merely illustrative of the principles of the present invention. Numerous modifications and adaptations thereof will be readily apparent to those skilled in the art without departing from the spirit and scope of the present invention.

Claims

1. A polymerizable liquid for forming hydrogel articles, Compounds having the structure of formula (I) or formula (II) (wherein n is an integer from 4 to 40); 【Chemistry 1】 Acrylate components; and water Includes, The acrylate component comprises one or more hydroxyalkyl acrylates. A polymerizable liquid characterized by the following features.

2. A polymerizable liquid for forming hydrogel articles, Compounds having the structure of formula (I) or formula (II) (wherein n is an integer from 4 to 40); 【Chemistry 2】 Acrylate components; and water Includes, The acrylate component comprises one or more polyethylene glycol acrylates or diacrylates. A polymerizable liquid characterized by the following features.

3. A polymerizable liquid for forming hydrogel articles, Compounds having the structure of formula (I) or formula (II) (wherein n is an integer from 4 to 40); 【Transformation 3】 Acrylate components; and water Includes, The acrylate component comprises one or more hydroxyalkylacrylamides. A polymerizable liquid characterized by the following features.

4. The polymerizable liquid according to any one of claims 1 to 3, characterized in that the polymerizable liquid contains a compound having the structure of formula (I).

5. The polymerizable liquid according to any one of claims 1 to 3, characterized in that the compound having the structure of formula (I) or formula (II) is present in an amount of 4 to 40% by mass based on the total weight of the polymerizable liquid.

6. The polymerizable liquid according to any one of claims 1 to 3, characterized in that the acrylate component is present in an amount of 15 to 50% by mass based on the total weight of the polymerizable liquid.

7. The polymerizable liquid according to any one of claims 1 to 3, characterized in that the water is present in an amount of 20 to 85% by mass based on the total weight of the polymerizable liquid.

8. A polymerizable liquid for forming hydrogel articles, Compounds having the structure of formula (I) or formula (II) (wherein n is an integer from 4 to 40); 【Chemistry 4】 Acrylate components; and water Includes, The polymerizable liquid further comprises one or more additional polymerizable or curable materials that are different from the compound having the structure of formula (I) or formula (II) and different from the acrylate component. A polymerizable liquid characterized by the following features.

9. The polymerizable liquid according to claim 8, characterized in that the one or more additional polymerizable or curable materials are present in an amount of 1 to 20% by mass based on the total weight of the polymerizable liquid.

10. The polymerizable liquid according to any one of claims 1 to 3 and 8, characterized in that the polymerizable liquid further comprises one or more colorants.

11. The polymerizable liquid according to claim 10, characterized in that the one or more colorants are present in an amount of 0.1 to 5% by mass based on the total weight of the polymerizable liquid.

12. The polymerizable liquid according to any one of claims 1 to 3 and 8, characterized in that the polymerizable liquid further comprises a photoinitiator component.

13. The polymerizable liquid according to claim 12, characterized in that the photoinitiator component is present in an amount of 0.1 to 5 weight percent based on the total weight of the polymerizable liquid.

14. A method for printing three-dimensional hydrogel articles, A step of providing a polymerizable liquid according to any one of claims 1 to 3 and 8; and The process involves printing the polymerizable liquid and curing it with light to form a hydrogel article. A method characterized by including

15. The method according to claim 14, characterized in that the polymerizable liquid is provided in a layer-by-layer process.

16. The method according to claim 14, characterized in that the hydrogel article is a medical implant.

17. A printed three-dimensional article formed from a polymerizable liquid according to any one of claims 1 to 3 and 8.

18. A hydrogel comprising a compound having the structure of formula (I): 【Transformation 5】 In the formula, n is an integer between 4 and 40. The hydrogel further contains an acrylate component, The acrylate component comprises one or more hydroxyalkyl acrylates. A hydrogel characterized by the following features.

19. A hydrogel comprising a compound having the structure of formula (I): 【Transformation 6】 In the formula, n is an integer between 4 and 40. The hydrogel further contains an acrylate component, The acrylate component comprises one or more polyethylene glycol acrylates or diacrylates. A hydrogel characterized by the following features.

20. A hydrogel comprising a compound having the structure of formula (I): 【Transformation 7】 In the formula, n is an integer between 4 and 40. The hydrogel further contains an acrylate component, The acrylate component comprises one or more hydroxyalkylacrylamides. A hydrogel characterized by the following features.

21. A hydrogel comprising a compound having the structure of formula (II): 【Transformation 8】 In the formula, n is an integer between 4 and 40. The hydrogel further contains an acrylate component, The acrylate component comprises one or more hydroxyalkyl acrylates. A hydrogel characterized by the following features.

22. A hydrogel comprising a compound having the structure of formula (II): 【Chemistry 9】 In the formula, n is an integer between 4 and 40. The hydrogel further contains an acrylate component, The acrylate component comprises one or more polyethylene glycol acrylates or diacrylates. A hydrogel characterized by the following features.

23. A hydrogel comprising a compound having the structure of formula (II): 【Chemistry 10】 In the formula, n is an integer between 4 and 40. The hydrogel further contains an acrylate component, The acrylate component comprises one or more hydroxyalkylacrylamides. A hydrogel characterized by the following features.

24. The hydrogel according to any one of claims 18 to 23, characterized in that n is an integer from 4 to 20.

25. The hydrogel according to any one of claims 18 to 23, characterized in that the compound is liquid at 25°C and 1 atm.

26. The hydrogel according to any one of claims 18 to 23, characterized in that the compound is present in the hydrogel in an amount of 5 to 40% by mass based on the total weight of the hydrogel.

27. The hydrogel according to any one of claims 18 to 23, characterized in that the acrylate component is present in an amount of 15 to 50% by mass based on the total weight of the hydrogel.

28. The hydrogel according to any one of claims 18 to 23, characterized in that water is present in the hydrogel in an amount of 20 to 85% by mass based on the total weight of the hydrogel.

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