Bioresorbable lattice structures and compositions

Abstract

Compounds and compositions are provided which are useful the additive manufacturing of bioresorbable lattice structures particularly additive printing techniques such as vat photopolymerization wherein a composition of one or more photocurable compounds, such as a compound with multiple ethylenically unsaturated groups and a compound with multiple thiol groups, is photopolymerized to create a lattice structure which can optionally be heterogeneous or homogenous and optionally the incorporation of a drug in the photopolymerization process.

Description

BIORESORBABLE LATTICE STUCTURES AND COMPOSITIONSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U. S. Provisional Application No.63 / 715,225, filed November 1, 2024, which is incorporated by reference herein in its entirety.FIELD OF THE DISCLOSURE

[0002] The present disclosure relates generally to the preparation and use of curable compositions, such as photocurable compositions which can be used to create lattice -structures for the support of tissue regeneration. The lattice structure may include a drug eluting compound.BACKGROUND

[0003] Stereolithography (SLA) is a relatively well-developed additive printing technique for preparing three-dimensional (3-D) objects. In stereolithographic methods, light, such as ultraviolet (UV) or visible light, is used to photopolymerize liquid material into designed structures, such as three-dimensional articles, with high accuracy and precision. 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 a liquid photopolymerizable composition that may be referred to as a resin or an ink formulation. The macroscopic properties and degradation profiles of articles produced by SLA depend in part on the polymer chemistry and the processing techniques.

[0005] After SLA polymerization of absorbable macromers with ethylenically unsaturated functional groups, the absorbable polymer segment can be degraded by hydrolytic or enzymatic degradation leaving a non-absorbable polymer (i.e., backbone) from the reacted ethylenically unsaturated groups. For such formulations to be implantable into or onto living bodies, it is desirable that the non-absorbable polymer is water-soluble and has a molecular weight of lower than approximately 20,000 Da so that these degradation products can be excreted by the kidney.

[0006] The present disclosure provides compounds and compositions useful in actiniclight reactive 3-D printing processes, including but not limited to stereolithography (SLA) and digital light processing (DLP) methods for making 3-D photoprinted articles having degradation products, particularly for 3-D photoprinted articles that are desirable for implanted articles, such as medical devices. 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 problems in the prior art discussed in the Background section or associated with 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 the particular problem, which in and of itself may also be inventive.SUMMARY

[0008] In designing parts for medical device implants and drug delivery constructs, lattice structures disclosed herein have been employed to create open pore structures that allow for tunability (meaning that structures may be specifically designed for different conditions) of cell infiltration, cell attachment, drug release, and desired mechanical properties. Open pore structures were previously limited to sponges, woven fabrics, and non-woven scaffolds, but with the increasing combination of technologies in additive manufacturing, software development, and material science, new opportunities have arisen in creating resorbable lattice-based structures through 3D printing. Such tunable structures are critical in the creation of soft and hard tissue regeneration constructs and drug delivery devices.

[0009] in one aspect, the present disclosure provides compositions and articles such as medical devices or portions of medical devices, comprising a lattice structure which can be manufactured through additive manufacturing to create bioresorbable lattice(s)that will degrade in the body under physiological conditions. In another aspect, the present disclosure provides methods to make unique lattice structures that can be tailored using a computer aided design (CAD) and tested through either models or finite element analysis (FEA) to mimic the naturally occurring tissue, and the unique lattice structures are then created with additive manufacturing. These methods present a substantial improvement over previous techniquesof trial-and-error creation, such as for sponge-like material for tissue regeneration.

[0010] In another aspect, the present disclosure provides compositions and articles comprising lattice parts to create drug-eluting devices. Most drug-eluting devices using bioresorbable polymers have been limited to solvent-based processing of thermoplastics to prevent thermal decomposition of drugs. These approaches have limited the construct design and drug release rates from bioresorbable devices. In addition, most of the thermoplastics used in these applications are severely constrained when hydrophilic drugs are used, as polymers like PLGA tend to quickly release hydrophilic drugs. The current invention provides a way of overcoming these challenges through additive manufacturing of bioresorbable photopolymers with a drug. As used herein, the term drug includes bioactive materials for affecting living organisms, and includes, but is not limited to, bioactive agents such as pharmaceutical and therapeutic agents, proteins, receptors, agonists, antagonists, nucleic acid-containing therapeutics or bioactive molecules, protein fragments, diagnostic agents, vitamins, growth factors, therapeutic peptides, antimicrobial agents, pain relieving agents, and other known bioactive agents.

[0011] In brief, 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 such as a thermocuring process that is used in conjunction with a photocuring process. The curing process is useful in manufacturing articles, such as medical devices and coatings. An exemplary curing process is stereolithography (SLA), which is an additive manufacturing process wherein a curable composition according to the present disclosure containing one or more photoreactive compounds, including e.g., a photoreactive macromer, is photopolymerized (photocured) during a process to form a manufactured article. Another exemplary process is a coating process whereby a compound and / or composition of the present disclosure is placed on a surface and then cured by exposure to heat (thermocuring) and / or by exposure to actinic radiation (i.e., photopolymerized or photocured) to provide a coating on the surface. These cured products, i.e., products formed by curing a composition as disclosed herein, may generally be referred to herein as articles, coatings, films, materials and the like. Thus, when the present disclosure is exemplified by preparing an article, it should be understood that a coating or other material can likewise be prepared. In one aspect, the articles, coatings, etc. are biodegradable.

[0012] In one aspect the present disclosure provides biodegradable polymeric materials formed by a curing process. The materials may be articles or may be used to produce articles that have a limited lifetime, such that after some period of time, the article formed from the biodegradable material is no longer present. For example, the material may be a coating on a device, such as a medical device, where the coating degrades after some period of time. In another example, the material may be used to prepare a medical device, for example, a mesh for tissue repair, so that after a time, some or none of the article is present and tissue repair is accomplished. As another example, the medical device may be a tissue adhesive or sealant, where a polymerizable composition of the present disclosure may be applied to a tissue in need of adhesive or sealant, and then that composition is exposed to actinic radiation sufficient to cause photopolymerization of the composition on the tissue.

[0013] According to the present disclosure, in one aspect stereolithography may be used to prepare such materials and articles, using, e.g., compounds and compositions as disclosed herein. The present disclosure addresses concerns about thermo- and photo-cured materials, such as SLA-produced articles, that come into contact with living entities, and include concerns regarding the safety and efficacy of the produced articles, particularly their biocompatibility and cytotoxicity.

[0014] In one aspect, the present disclosure provides for the preparation and use of polymeric compositions, for example comprising one or more chain transfer agents and / or one or more additives. A polymeric composition may include or be made from a photopolymerizable polymer comprising a homopolymer, copolymer, block copolymer, random copolymer, random block copolymer, or combinations thereof. A polymeric composition may include or be made from a thermally curable polymer comprising a homopolymer, copolymer, block copolymer, random copolymer, random block copolymer, or combinations thereof. In one aspect, a polymeric composition is a double network, in that two chemically distinct polymers are present in admixture in the composition, where optionally the double network polymeric composition, after curing, may be characterized as being a solid. In one aspect, a polymeric composition is a single network, in that only single chemically distinct polymers are present in the composition, where optionally the single network polymeric composition, after curing, may be characterized as being a solid. In one aspect, a single network includes a crosslinked polymer. In one aspect, a double networkincludes a crosslinked polymer. Polymeric compositions disclosed herein may be used, e.g., to prepare bioabsorbable implants by an additive manufacturing process.

[0015] In one aspect, the present disclosure provides a composition comprising (1) a compound having multiple photopolymerizable groups, referred to herein as a polyhv, and / or (2) a mixture of two compounds that are thermally reactive with one another (thermocurable) so as to form a polymer, where the two compounds may be referred to herein as polyAl and polyA2 or collectively as polyA (i.e., polyA refers to a mixture of polyAl and polyA2). In one aspect, a composition additionally comprises a photoinitiator. In an aspect, a composition comprises one or more chain transfer agents. In one aspect, a composition additionally comprises one or more additives. In one aspect, the composition additionally comprises a stabilizer. In one aspect, the present disclosure provides a cured, and optionally crosslinked, composition resulting from the photopolymerization of a composition comprising a photoinitiator, optionally, one or more chain transfer agents, optionally, one or more additives, a polyhv and / or a polyA, where this cured (e.g., crosslinked) composition may be said to have a single network, which refers to the network formed from polyhv reacting with itself or polyA reacting with itself. In one aspect, 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, a polyhv and / or a polyA, wherein the photopolymerization of polyhv, and the thermal polymerization of polyAl with polyA2, where each of polyhv and polyA forms an independent network, one or both optionally being a crosslinked network. The two independent networks together form an interpenetrating double network. The double network is thus formed by thermocuring and photocuring a composition having both thermoreactive components (polyAl and polyA2) and at least one photoreactive component (polyhv), a photoinitiator and one or more chain transfer agents, and optionally, one or more additives. In one aspect, photocuring precedes thermocuring. In one aspect, thermocuring precedes photocuring. In one aspect, photocuring and thermocuring occur simultaneously.

[0016] In one aspect, the present disclosure provides a composition comprising 1) a compound having multiple photopolymerizable thiol groups, referred to herein as a polySH, and 2) a compound having multiple photopolymerizable ethylenically unsaturated groups (EU), referred to herein as a polyEU, where polySH and polyEU are photoreactive with oneanother. In one aspect, the composition further comprises a photoinitiator. In one aspect, the composition further comprises one or more chain transfer agents, in one aspect, the composition further comprises one or more additives. In one aspect, the composition further comprises a stabilizer. In one aspect, the present disclosure provides a single network polymeric composition resulting from the photocuring (photopolymerization) of a composition comprising a photoinitiator, one or more chain transfer agents, one or more additives, a polySH and a polyEU. In one aspect, the present disclosure provides a single network crosslinked composition resulting from the photocuring (photopolymerization) of a composition comprising a photoinitiator, one or more chain transfer agents, a polySH and a polyEU. In another aspect, the present disclosure provides a single network crosslinked composition resulting from the photocuring (photopolymerization) of a composition comprising a photoinitiator, one or more chain transfer agents, one or more additives, a stabilizer, a polySH and a polyEU. Exemplary EU groups are acrylate, methacrylate and norbornenyl, where polyEU refers to a compound comprising multiple EU groups, optionally two EU groups, or three EU groups, or four EU groups. As used herein, polyEU or polySH may refer to one or more of a SH moiety (thiol group) or an EU moiety (photopolymerizable ethylenically unsaturated group), and those of skill in the art can determine the intended description thereof.

[0017] In one aspect, disclosed herein are methods and compositions for curing processes, such as 3-D printing, and for making and using the resulting cured articles. For example, the present disclosure provides a method for photopolymerization printing an article comprising, a) exposing for a time to light of suitable wavelength, a photopolymerizable composition comprising a polyEU macromer and a polySH as disclosed herein; optionally in combination with one or more other components such as at least one photoinitiator component and / or at least one light reflective material component comprising a light reflective 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; and forming a printed article comprising a polymerization product of the photopolymerizable composition. In another aspect, the present disclosure provides a method for photopolymerization printing an article comprising, a) exposing for a time to light of suitable wavelength, a photopolymerizable composition comprising a polyhv, polyAl, and polyA2; and b) thermallypolymerizing the polyAl with polyA2; optionally in combination with one or more other components such as at least one photoinitiator component and / or at least one light reflective material component comprising a light reflective 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 printed article comprising a polymerization product of the photopolymerizable composition.

[0018] In one aspect, disclosed herein are methods and compositions for photopolymerization processes, such as a film-forming process including a coating process, and for making and using such photopolymerized materials. For example, the present disclosure provides a method for photopolymerization coating of an article comprising, a) applying a photopolymerizable composition of the present disclosure to a surface, b) exposing for a time to light of suitable wavelength, the photopolymerizable composition comprising polyEU and polySH as disclosed herein; optionally in combination with one or more other components such as at least one photoinitiator component and / or at least one light reflective material component comprising a light reflective 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 solid coating comprising a polymerization product of the photopolymerizable composition.

[0019] In other aspects, the present disclosure provides the polymerization product of a macromer (which may also be referred to as a prepolymer) where the macromer has been polymerized by, e.g., one or more methods disclosed herein. In addition, the present disclosure provides an article, which may be referred to as a polymeric article, produced from a photopolymerizable compound or composition as disclosed herein, optionally by one or more methods as disclosed herein. The photopolymerized macromer or article may be a nontoxic article. In addition, the article made from a photopolymerizable composition which may comprise biodegradable photopolymerized macromers, optionally in admixture with a nontoxic amount of photoinitiator. Optionally, the article may comprise biodegradable photopolymerized macromers, optionally in admixture with a nontoxic amount of stabilizer, and / or one or more chain transfer agents, and / or one or more additives. Optionally, the article may comprise biodegradable photopolymerized macromers, optionally in admixture with a nontoxic amount of UV reflective material. In one aspect, the polymeric article isbiodegradable, in whole or in part, under physiological conditions. However, in an alternative aspect, the polymeric article is not biodegradable under physiological conditions. The present disclosure also contemplates use of nonbiodegradable polymers, macromers, articles, photopolymerizable compositions, in medical devices and other constructs described herein, thus resulting in such materials and compositions being wholly biodegradable, partially biodegradable, or not biodegradable under physiological conditions.

[0020] In addition, the present disclosure provides a photopolymerizable compound, also referred to herein as a macromer, comprising a polyaxial central core (CC) and 2-4 arms of the formula (A)-(B) or (B)-(A) extending from the central core, where at least one of the arms comprise a light-reactive functional group (Q) and (A) is the polymerization product of monomers selected from trimethylene carbonate (also referred to herein as T, or as TMC) and e-caprolactone (also referred to herein as caprolactone, or C, or CAP), while (B) is the polymerization product of monomers selected from glycolide, lactide and p-dioxanone. The macromer may be a photopolymerizable macromer component in compositions and methods as disclosed herein and may be photopolymerized to provide articles. Other macromers may include a photopolymerizable compound that is derived from the following classes of polymers or combination of copolymers of the following categories of polymers: polyesters, polycarbonates, polyanhydrides, polyortho esters, polyhydroxyalkonoates, polyurethanes, polypeptides, polyethers, polythioethers, polyamides, and naturally derived polymers. Some examples of naturally derived polymers are described but not limited to the following: chitosan, hyaluronic acid, pectin, and cellulose. Some examples of polyester may include but are not limited to homopolymers and copolymers derived from lactide, glycolide, caprolactone, and p-dioxanone. Some examples of polycarbonates and polycarbonate esters may include but are not limited to polytrimethlyene carbonate, poly(trimethylene carbonate-co-caprolactone), poly(trimethylene carbonate-co-caprolactone-co-glycolide), and poly(trimethylene carbonate-co-caprolactone-co-lactide). Compositions disclosed herein can comprise biodegradable polymers such as (but not limited to) polymers of lactic and glycolic acids, copolymers of lactic and glycolic acids, poly(ether-co-esters), poly(hydroxybutyrate), polycaprolactone, copolymers of lactic acid and s-aminocapronic acid, lactide polymers, copolymers of poly(hydroxybutyrate) and 3-hydroxyvalerate, polyesters of succinic acid, poly(N-acetyl-D-glucosamine), polydioxanone, cross-linked hyaluronic acid, cross-linkedcollagen, and the like, and combinations thereof. Suitable synthetic polymers can be, for example, polycaprolactone (poly(e-caprolactone), (PCI), polydioxanone (PDO), poly (glycolic acid) (PGA), poly(L-lactic acid) (PLA), poly(lactide-co-glycolide) (PLGA), poly(L-lactide) (PLLA), poly(D, L-lactide) (P(DLLA)), polyethylene glycol) (PEG), montmorillonite (MMT), poly(L-lactide-co-e-caprolactone) (P(LLA-CL)), poly(e-caprolactone-co-ethyl ethylene phosphate) (P(CL-EEP)), poly[bis(p-methylphenoxy) phosphazene] (PNmPh), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly(ester urethane) urea (PEUU), poly(p-dioxanone) (PPDO), polyurethane (PU), polyethylene terephthalate (PET), poly(ethylene-co-vinylacetate) (PEVA), polyethylene oxide) (PEG), poly(phosphazene), poly(ethylene-co-vinyl alcohol), polymer nanoclay nanocomposites, poly(ethylenimine), poly(ethyleneoxide), poly vinylpyrrolidone; polystyrene (PS) and combinations thereof. Particularly suitable polymers include poly (lactic-co-glycolic acid), polydioxanone, polycaprolactone, and combinations thereof. Many biodegradable monomers, copolymers, homo-and hetero-polymers are known in the art, and included herein.

[0021] 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 which is effective to achieve polymerization of the photopolymerizable compound when the composition is exposed to radiation emitted from a light source that delivers light of a selected wavelength suitable to activate the photoinitiator.

[0022] In one aspect, the present disclosure provides a method of 3D-printing, also known as additive printing, e.g., stereolithography, which comprises 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 that composition to light which is effective to activate the photoinitiator, in order to photopolymerize the photopolymerizable compound in the polymerizable composition. In one aspect, the composition is selectively exposed to the light, so that a selected portion of, and not all of, the composition undergoes photopolymerization. In one aspect, the photopolymerizable compound is a mixture including one or more polyhv compounds, e.g., two photopolymerizable compounds denoted herein as polyEU and polySH. In one aspect, one or more photopolymerizable compounds is admixed with one or more thermally reactive compounds, e.g., two thermally reactive compounds denoted herein as polyAl and polyA2.In one aspect, the polymerizable composition further comprises other components, including, but not limited to, one or more stabilizers, one or more photoinitiators, one or more light reflective materials suspended in the composition, one or more chain transfer agents, one or more additives, and one or more dyes.

[0023] The above-mentioned and additional features of the present disclosure and the manner of obtaining them will become apparent, and the disclosure will be best understood by reference to the following more detailed description. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.

[0024] This Brief Summary has been provided to introduce certain concepts in a simplified form that are further described in detail below in the Detailed Description. Except where otherwise expressly stated, this Brief 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.

[0025] The details of one or more embodiments are set forth in the description below. The features illustrated or described in connection with one exemplary embodiment may be combined with the features of other embodiments. Thus, any of the various embodiments described herein can be combined to provide further embodiments. Aspects of the embodiments can be modified, if necessary to employ concepts of the various patents, applications and publications as identified herein to provide yet further embodiments. Other features, objects and advantages will be apparent from the description, the drawings, and the claims.

[0026] The above-mentioned and additional features of the present disclosure and the manner of obtaining them will become apparent, and the disclosure will be best understood by reference to the following more detailed description. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually.BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Exemplary features of the present disclosure, its nature and various advantages will be apparent from the accompanying drawings and the following detailed description of various embodiments. Non-limiting and non-exhaustive embodiments are described with reference to the accompanying drawings, wherein like labels or reference numbers refer tolike parts throughout the various views unless otherwise specified. The sizes and relative positions of elements in the drawings are not necessarily drawn to scale. For example, the shapes of various elements are selected, enlarged, and positioned to improve drawing legibility. The particular shapes of the elements as drawn have been selected for ease of recognition in the drawings. One or more embodiments are described hereinafter with reference to the accompanying drawings in which:

[0028] FIG. 1 shows degradation profile for selected cured compositions of the present disclosure.

[0029] FIG. 2 shows water swelling profiles for selected cured compositions of the present disclosure.

[0030] FIG. 3 shows mass loss profiles for selected cured compositions with and without a chain transfer agent.

[0031] FIG. 4 shows mean cell viability and standard deviation (n=3) determined by MTS assay across resin formulations (A-D) as well as positive (+) and negative (-) controls.

[0032] FIG. 5 shows Voronoi sample structures.

[0033] FIGS. 6A-6C show (a) schematic illustration of the typical mechanical response of porous 3D-printed Voronoi material under compression. Normalized (b) Young's modulus and (c) collapse stress of 3D-printed porous Voronoi structures as a function of slenderness ratio, fitted with exponential trends.

[0034] FIG. 7 shows a basic centered cubic and grid unit cell.

[0035] FIGS. 8A-8B show normalized (a) Young's modulus and (b) collapse stress of 3D-printed porous Voronoi, grid, and BCC structures as a function of rotational angle.

[0036] FIGS. 9A-9D show in vitro release from diameter series that include (A) images of cylinders, (B) cumulative release % of RhB released from solid cylinders (n = 3), (C) zeroorder kinetic fit of in vitro release after plateau, and (D) images of cylinders at 84 d of release. Error bars represent one standard deviation.

[0037] FIGS. 10A-10C shows in vitro release of lattice structures LI to L3 with (A) CAD models of lattice structures, (B) visible light photographs of lattice structures, and (c) cumulative release of RhB from lattice structures (n = 3). Error bars represent one standard deviation.

[0038] FIGS. 11A-11C shows zero-order kinetic fit of in vitro release from LI (A), L2 (B)and L3 (C).

[0039] FIGS. 12A-12C shows in vitro release of latice structures L5, L4, and L2 with (A) CAD models of lattice structures, (B) visible light photographs of lattice structures, and (c) cumulative release of RhB from latice structures (n = 3), Error bars represent one standard deviation.

[0040] FIG. 13 shows Layout Voronoi, Grid, and BCC sample structures.

[0041] FIG. 14 shows the Organic factors of 1,2,5,10,20.

[0042] FIG. 15 shows the Voronoi, Grid, and BCC sample structures, with highlighted beam size for deletion.

[0043] FIG. 16 shows images of printed samples with varying beam size, pore size, geometry, and formulation.

[0044] FIG. 17 shows images of printed samples with varying beam size, pore size, geometry, and formulation.DETAILED DESCRIPTION OF THE DISCLOSURE

[0045] The present disclosure may be understood more readily by reference to the following detailed description of preferred embodiments of the disclosure and the Examples included herein. In reading this detailed description, and 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 this disclosure belongs. The singular terms "a," "an," and "the” include plural referents unless 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, "e.g." is derived from the Latin exempli gratia, and is used herein to indicate a non-limiting example. Thus, the abbreviation "e.g." is synonymous with the term "for example."

[0046] In one aspect, the present disclosure provides compositions which are liquid at a temperature of about room temperature, i.e., about 18°C to about 23°C, and which can undergo curing. The curing process will include photocuring, also referred to herein as photopolymerization, and depending on the composition, may also include thermocuring, also referred to herein as thermopolymerization. Photocuring occurs when the composition is exposed to actinic radiation of selected energy for a selected period of time, to causereaction between the photochemical (also referred to herein as photoreactive or photopolymerizable or the like) components of the composition, and an increase in the average molecular weight of components in the composition. Thermocuring is the corresponding process achieved when the composition is heated above room temperature to a suitable temperature for a suitable length of time, to cause reaction between the thermally reactive (also referred to herein as thermoreactive or thermopolymerizable or the like) components of the composition, and increase the average molecular weight of components in the composition. When the reactants include compounds having three or more photoreactive or thermoreactive chemical groups, then the curing process will provide for a composition having crosslinked components. As used herein, curing refers to photocuring, optionally with thermocuring if the composition has thermally reactive components.

[0047] Compositions of the present disclosure include photoreactive components. Optionally, the compositions may also include thermally reactive components. When a composition includes both thermally and photochemically reactive components, the resulting cured composition may be referred to herein as having a double network or a dual network: a first network formed from the photochemically reactive compounds, and a second network formed from the thermally reactive compounds. When a composition has photochemically reactive components but not thermally reactive components, the resulting cured composition may be referred to herein as having a single network.

[0048] As explained in further detail below, compositions of the present disclosure may comprise one or more compounds having at least two photochemically reactive functional groups, denoted "hv" groups, and may optionally include two or more compounds having at least two thermally reactive functional groups, denoted as "A" groups. The reactive functional groups will be joined to an organic backbone, i.e., a backbone made from atoms including carbon and hydrogen. As a simple example, if the A group is hydroxyl, a thermally reactive compound may be ethylene glycol, i.e., HO-CH2-CH2-OH, where the backbone is -CH2-CH2-.

[0049] When the backbone of a polymeric molecule (compound) includes repeating chemical units, the polymeric molecule (compound) may be referred to herein as a macromer. For example, a reaction between a minor amount of ethylene glycol (referred to as an initiator) and a major amount of a hydroxyl acid or equivalent, e.g., lactic acid or lactide, will result in a polymeric molecule (compound) having two polylactides (repeating lactide units)extending from either end of the ethylene glycol initiator, and also having a hydroxyl group at each of the two termini of the polylactide chains. This polymeric molecule may be referred to herein as a macromer or a compound. In one aspect, compositions of the present disclosure include a macromer as a photochemically reactive component, and / or a macromer as a thermally reactive component.

[0050] 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, a composition of the present disclosure may have a first compound with two or more hydroxyl groups and a second compound with two or more functional groups that are thermally reactive with hydroxyl groups. In one aspect, the hydroxyl group is an example of a nucleophilic group, and an epoxide is an example of an electrophilic group. Thus, in one aspect, a thermally reactive composition of the present disclosure may be described as comprising a compound with two or more nucleophilic groups and a compound having two or more electrophilic groups.

[0051] In addition to being compounds that are useful in thermally curable compositions as disclosed herein, hydroxyl-containing compounds are also useful starting materials for preparing photoreactive compounds. For example, as disclosed herein, hydroxyl groups may be converted to thiol-containing groups. In addition, hydroxyl groups may be converted to groups having an ethylenically unsaturated portion. Thus, the backbones of the hydroxyl-containing compounds as disclosed herein may also be present as the backbone, or a portion of the backbone, of a photochemically reactive compound in the compositions disclosed herein. It should be understood that when the present disclosure provides a compound having two or more hydroxyl groups, the present disclosure simultaneously provides that the backbone of that hydroxyl-containing compound is optionally present in a photochemically reactive compound of the present disclosure.PolyA Compounds

[0052] In one aspect, the present disclosure provides compositions that include two polyA compounds denoted herein as polyAl and polyA2. The compound polyAl has multiple (hence the term "poly") Al groups, where a Al group is thermally reactive with a A2 group. The compound polyA2 has multiple A2 groups, where a A2 group is thermally reactive with a Algroup. Each of polyAl and polyA2 is an organic compound. The term "thermally reactive" means that heat must be applied to a composition comprising polyAl and polyA2 in order for Al and A2 to react with one another. At room temperature, i.e., about 22°C, and in the absence of a catalyst, Al and A2 do not react to any appreciable extent with one another. In one embodiment, the compositions of the present disclosure do not include a catalyst to increase the rate of a thermal reaction. Upon reaction, Al and A2 form one or more covalent bonds so that polyAl and polyA2 become part of a polymeric network, optionally a crosslinked polymeric network.

[0053] In one aspect, a polyhydric compound (also referred to as a polyol) is a polyA compound. For example, an aliphatic polyol having an alkylene group may be used as a polyA. 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 more than two hydroxyl groups, which may be used when crosslinking is desired, include trimethylolpropane, glycerol, pentaerythritol, 1,2,4-butanetriol, and 2,3,4-pentanetriol.

[0054] In one aspect, an aromatic diol may be used as a polyA. Examples include catechol, resorcinol, hydroquinone and the reactions products thereof, for example, the reaction product of reaction products of resorcinol and ethylene carbonate. Other suitable aromatic diols include bisphenol A and 4,4'-dihydroxybiphenyl.

[0055] In one aspect, a polyether diol may be used as a polyA compound. The polyether diol will introduce polyoxyalkylene segments, in other words polyether segments, into a cured composition. The polyether diol may comprise a homopolymer of oxyalkylene groups, or a copolymer of two different oxyalkylene groups. The copolymer may be a random or block copolymer, for example, a diblock copolymer, or a triblock copolymer. Exemplary oxyalkylene moieties include oxyethylene, oxypropylene, oxytrimethylene, and oxytetramethylene.

[0056] In one aspect, a polycarbonate diol may be used as a polyA. Examples include trimethylene carbonate, poly(hexamethylene carbonate) diol, poly(ethylene-carbonate) diol, poly(propylene-carbonate) diol, and poly(butylene-carbonate) diol.

[0057] An exemplary polyA macromer may have a polyaxial central core (CC) and 2-4 arms having repeating units. Such polyA macromers may be referred to herein as polyaxial macromers. In one embodiment, at least two of the arms terminate in a nucleophilic group,e.g., a hydroxyl group or an amine group. In one aspect, the repeating units are all the same, i.e., the arms are a homopolymer. In one aspect, the repeating units are not all the same, i.e., the arms are a copolymer. The copolymer may be a random or block copolymer. For example, and as discussed further below, the arms may have the formula (A)-(B) or (B)-(A) extending from the central core. The arms may be biodegradable or non-biodegradable.

[0058] In one aspect, the arms include ester groups, and the arms may be said to be polyesters. In order to form an ester group, the arms may be prepared, in whole or in part, from hydroxy acids or equivalent. Exemplary hydroxy acids and equivalents include glycolic acid (and its equivalent, glycolide), lactic acid (and its equivalent, lactide), e-caprolactone (C), and p-dioxanone. In one aspect, the arms are all formed from the same monomer, so that the polyaxial macromer has homopolymeric arms. In one aspect, the arms may include a carbonate group. In order to form a carbonate group, the arms may be prepared, in whole or in part, from trimethylene carbonate (also denoted herein as "T").

[0059] In one aspect, the polyA compound may be a polyaxial macromer having a central core and a plurality, e.g., 2-4, copolymeric arms extending from the central core, each arm ending (i.e., terminating) in a thermally reactive group, e.g., a hydroxyl group. The compound may be represented by the formula CC-[armA]nwhere CC represents the central core and n is selected from a number within the ranges of 2-18, or 2-14, or 2-8, or 2-6, or 2-4. Each arm is formed by the polymerization of monomers selected from two groups, the two groups being denoted as group A and group B. Thus, more specifically, in compounds of the present disclosure, CC-[armA]nmay 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 may be shown, where an exemplary terminal functional group is hydroxyl. In the formula, A represents the polymerization product of one or more monomers comprising, and optionally selected only from, 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 1-40, or 1-30, or 1-20, or 1-10. In the formula, B represents the polymerization product of one or more monomers comprising, and optionally selected only 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 the polymerization product B, where q is selected from 1-40, or 1-30, or1-20, or 1-10.

[0060] For example, when compounds of the formula CC-[armA]nare formed from a trifunctional central core, and A is added to CC prior to the addition of B, then compounds of the formula CC-[armA]nmay be written as CC-[(A)p-(B)q-OH]3. If, in this example, A is formed by the polymerization of two Ts and one C, then p would be three and A would be selected from ITT, TTC, TCI, TCC, CCC, CCT, CTC, and CTT, independently within each arm. If, continuing with this example, B is formed by the polymerization of one G, then q would be one and B would be G. In this example, each arm would have a chemical formula selected from TTTG, TTCG, TCTG, TCCG, CCCG, CCTG, CTCG, and CTTG. This exemplary compound may be written as CC-[armA]3where 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 as either CC-[(T, T, C)-(G)-OH]3or CC-[(T, T, C)3-(G)I-OH]3.

[0061] In one aspect, the present disclosure provides a composition comprising a compound having a bifunctional central core and 2 arms extending from the central core, each arm terminating in a hydroxyl group. In one embodiment, the present disclosure provides a composition comprising a compound comprising a trifunctional central core and either 2 or 3 arms extending from the central core, each arm terminating in a hydroxyl group. In one embodiment, the present disclosure provides a composition comprising a compound comprising a tetrafunctional central core and either 2 or 3 or 4 arms extending from the central core, each arm terminating in a hydroxyl group. Each arm in the compound may be a homopolymer or a copolymer, and when a copolymer, may be a random copolymer or a block copolymer, e.g., a block copolymer represented by the formula (A)-(B) or (B)-(A). When the compound is prepared by reacting the central core with monomers of Group A followed by reacting that reaction product with monomer(s) selected from Group B, then the compounds will have the formula CC-[(A)-(B)-OH]. However, when the composition is prepared by reacting the central core with monomers of Group B followed by reacting that reaction product with monomer(s) selected from Group A, then the compounds will have the formula CC-[(B)-(A)-OH].

[0062] In an aspect, the macromer will have a molecular weight of less than 250,000 Da, or less than 200,000 Da, or less than 150,000 Da, or less than 100,000 Da, or less than 50,000 Da, or less than 25,000 Da, or less than 20,000 Da, or less than 15,000 Da, or less than 10,000Da, or less than 9,000 Da, or less than 8,000 Da, or less than 7,000 Da, or less than 6,000 Da, or less than 5,000 Da, or less than 1,000 Da.

[0063] In an aspect, the polyaxial macromers present in a composition all contain the same central core. For example, all of the macromer components of a composition are prepared from trimethylolpropane or pentaerythritol. However, in one aspect, a composition of the present disclosure contains a mixture of polyaxial macromer components, for example, some of the macromer components are triaxial, made from, e.g., trimethylolpropane, and other macromer components of the same composition are tetraaxial, made from, e.g., pentaerythritol.

[0064] In an aspect, the polyaxial macromers of the present disclosure have relatively short arms, e.g., 1-10 monomer residues / arm. A monomer residue, as used herein, refers to the polymerization product of the monomer, i.e., the structure that the monomer has after that monomer has been incorporated into a polymer and is thus providing a monomer residue in that polymer. In one embodiment, when the compounds of the disclosure are used in additive printing, those compounds should be in a fluid state: either the compounds themselves are fluid or the compounds are dissolved in a solvent and / or diluent to provide a fluid composition. If the arms are too long, a composition containing the compound will typically be too viscous to be useful in additive printing such as SLA, unless the composition contains a lot of solvent or diluent to dilute the compound, in which case the additive printing process may need to utilize an undesirably large amount of solvent. Advantageously, when the arms are relatively short, the compounds themselves may be fluid at the application temperature of the additive printing process. In an aspect the application temperature is room temperature, i.e., about 18°C to about 23°C, and the composition is a liquid at this temperature.

[0065] In optional aspects, the compounds and compositions of the present disclosure containing such compounds, can be described by one or more of the following features which characterize the A region (also referred to as a block) of the polyaxial macromer: have a block A which comprises residues formed from trimethylene carbonate (TMC or T), i.e., which are the polymerization product or residue of TMC; have a block A which comprises residues formed from caprolactone (CAP or C); have a block A which comprises residues formed from both TMC and CAP; at least 90% of the residues in block A are residues formed from TMC orCAP; the compound comprises 1-45, or 2-45 residues formed from TMC; the compound comprises 1-15 or 2-15 residues formed from TMC; the compound comprises 1-10 or 2-10 residues formed from TMC; region A has a molecular weight of from 102-2500 g / mol; region A has a molecular weight of 102-1000 g / mol; region A has a molecular weight of 102-900 g / mol; each A region comprises 2-45 monomer residues; each A region comprises 2-15 monomer residues; each A region comprises 2-10 monomer residues.

[0066] In optional aspects, the compounds and compositions of the present disclosure containing such compounds, can be described by one or more of the following features which characterize the B block (also referred to as a region) of the polyaxial macromer: each B block comprise 1-45 or 2-45 monomer residues; each B block comprise 1-15 or 2-15 monomer residues; each B block comprises 1-10 or 2-10 monomer residues.

[0067] In one aspect, a polyamine is a polyA compound. For example, an aliphatic polyamine having an alkylene group may be used as polyA. 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 polyamines having more than two amine groups include polypropylenimine tetramine (also known as Dab-Am-4) and triethylenetetramine. The Huntsman Company sells many suitable polyamines having more than two amine groups, for example polyethertriamine (Huntsman product XTJ-566), JEFFAMINE® ST-404 polyetheramine (Huntsman product (XTJ-586), and JEFFAMINE® T-403 polyetheramine.

[0068] In one aspect, an aromatic diamine may be used as a polyA. Examples include 1,2-diaminobenzene, 1,3-diaminobenzene, 1,4-diaminobenzene, toluene diamine (e.g., 1,2-diamino-3-methylbenzene, l,2-diamino-4-methylbenzene, l,3-diamino-2-methylbenzene, l,3-diaminoe-4-methylbenzene, l,4-diamino-2-methylbenzene, l,4-diamino-3-methylbenzene), alkyl-substituted toluenediamine (e.g., 3,5-diethyltoluene-2,4-diamine and 3,5-diethyltoluene-2,6-diamine), and p-xylyenediamine.

[0069] In one aspect, a polyether diamine may be used as a polyA compound. When a polyether diamine is reacted with a diisocyanate-containing polyA, the result will be a polyether urea moiety. The polyether diamine may comprise a homopolymer of oxyalkylene groups, or a copolymer of two different oxyalkylene groups. The copolymer may be a random or block copolymer, for example, a diblock copolymer, or a triblock copolymer. Exemplaryoxyalkylene moieties include oxyethylene, oxypropylene, oxytrimethylene, and oxytetramethylene.

[0070] In one aspect, a polyisocyanate is a polyA compound. An exemplary polyisocyanate compound is an aliphatic polyisocyanate, such as, without limitation, 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 an aromatic polyisocyanate, such as, without limitation, methylene 4,4'-diphenyl diisocyanate (MDI), 2,4-toluenediisocyanate (TDI), 1,5-naphthalene diisocyanate, and isophorone diisocyanate.

[0071] In one aspect, the polyisocyanate polyA is a macromer having multiple isocyanate groups. Such macromers may be referred to herein as a polyisocyanate macromer. Polyisocyanate macromers may be prepared from the corresponding polyhydroxylated macromers by reaction of the polyhydroxylated macromer with a diisocyanate, e.g., hexamethylene diisocyanate.

[0072] Exemplary polyisocyanate macromers are the reaction product of reactants comprising or consisting of a diisocyanate and either or both of a diamine and a diol, e.g., a polyetherdiamine or a polyetherdiol. Such polyisocyanate macromers have terminal isocyanate groups which are reactive with additional polyamine 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 polyA compound (e.g., a polyA2 compound) having terminal isocyanate groups. This polyA2 polyisocyanate macromer may then be thermally reacted with additional diamine or diol (a polyAl compound) to form a thermocured polymer in a composition of the present disclosure.

[0073] In one aspect the present disclosure provides a polyisocyanate macromer which is the reaction product of a polyisocyanate, e.g., a diisocyanate, and a polyol, e.g., a diol such as a polyetherdiol. Optionally, any one or more of the following may be used to further describe this polyisocyanate macromer and its preparation: the polyol is a diol and the polyisocyanate is a diisocyanate, the diol may be a polyetherdiol comprising 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 an alkylenegroup, where 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 more than two hydroxyl groups, which may be used when crosslinking is desired, include trimethylolpropane, glycerol, pentaerythritol, 1,2,4-butanetriol, and 2,3,4-pentanetriol. The polyol may be an aromatic diol, where examples include catechol, resorcinol, hydroquinone and the reactions products thereof, for example, the reaction products of resorcinol and ethylene carbonate. Other suitable aromatic diols include bisphenol A and 4,4'-dihydroxybiphenyl.

[0074] In one aspect, a polyisocyanate macromer which is the reaction product of a polyisocyanate, e.g., a diisocyanate, and a polyol, e.g., a diol such as a polyetherdiol, provides a polyA2 compound which may be reacted with a polyAl compound such as a polyamine. The reaction product may be described in terms of its structural components rather than in terms of the reactants by which it may be formed. In one aspect the polymer chain is a polyurea, having a plurality of urea groups separated alternately by aliphatic groups (contributed by the aliphatic diamine) and polymeric blocks (contributed by the macromer). In other words, the structure may be described by repeating -[urea-aliphatic-urea-polymer block]- units. The polymer block is a polyurethane, having a plurality of urethane (also known as carbamate) groups separated alternatively by aliphatic groups (contributed by the diisocyanate) and polyether groups. In other words, the structure of the polymer block may 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 more than one of these polyether segments, for example, the polymer contains oxyethylene, oxypropylene and oxytetramethylene groups, where optionally the oxyethylene and oxypropylene are arranged in a block copolymer arrangement (e.g., oxyethylene block-oxypropylene block-oxyethylene block). The polymer block may also be referred to as a polyether polyurethane, and the polymer itself may be referred to as a poly ether urethane urea.

[0075] When the composition includes a polyisocyanate as a polyA compound, e.g., as polyA2, the composition will also include a compound that is reactive with a polyisocyanate, i.e., a polyAl compound such as a polyhydric compound, where reaction of a polyisocyanate and a polyhydric compound create urethane groups. Another example of an isocyanatereactive group is an amine group, so that when a composition contains a polyisocyanate as polyA2, the composition may also include a polyamine compound as polyAl, where reaction of a polyisocyanate and a polyamine creates urea groups.

[0076] In one aspect, the polyA compound is a polyepoxide. Exemplary polyepoxides include, without limitation, a diepoxide, a triepoxide and a tetraepoxide. In one aspect polyA2 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 with molecular weight of about 500 to about 6,000; and polypropylene glycol diglycidyl ether with molecular weight of about 500 to about 6,000.

[0077] The present disclosure provides polyA compounds wherein A is hydroxyl. Such compounds may be converted to polyA compounds wherein A is epoxy to provide polyepoxide compounds of the present disclosure. For instance, a polyhydroxyl compound may be reacted with an excess number of equivalents of epichlorohydrin, followed by treatment with base such as sodium hydroxide, to convert the hydroxyl groups to epoxy groups.

[0078] In an aspect, Al is a nucleophilic group. In one embodiment, polyAl has multiple hydroxyl (-OH) groups. In one embodiment, polyAl has multiple amine groups (-NH2). In an embodiment, polyAl is not reactive with itself. In an embodiment, the only reactive groups present on polyAl are the Al groups, and all of the Al groups are the same, e.g., they are all hydroxyl groups. In an embodiment, the polyAl has two Al groups. In an embodiment, the polyAl has three Al groups. In an embodiment, the polyAl has four Al groups. In an embodiment, the polyAl has more than four Al groups. All other factors being equal, the more Al groups present as part of polyAl, the more crosslinking will occurfrom a composition comprising polyAl.

[0079] In one aspect, A2 is an electrophilic group. In one embodiment, polyA2 has multiple epoxide (-CH(O)CH-) groups. In one embodiment, polyA2 has multiple isocyanate (-N=C=O) groups. In an embodiment, polyA2 is not reactive with itself. In an embodiment, the only reactive groups present on polyA2 are the A2 groups, and all of the A2 groups are the same, e.g., they are all isocyanate groups. In an embodiment, the polyA2 has two A2 groups. In an embodiment, the polyA2 has three A2 groups. In an embodiment, the polyA2 has fourA2 groups. In an embodiment, the polyA2 has more than four A2 groups. All other factors being equal, the more A2 groups present as part of polyA2, the more crosslinking will occur from a composition comprising polyA2.

[0080] in one aspect, polyAl is a polyhydroxyl compound while polyA2 is a polyepoxide.

[0081] In one aspect, polyAl is a polyhydroxyl compound while polyA2 is a polyisocyanate.

[0082] In one aspect, polyAl is a polyamine compound while polyA2 is a polyepoxide.

[0083] In one aspect, polyAl is a polyamine compound while polyA2 is a polyisocyanate.

[0084] In one aspect, polyAl is a polythiol compound while polyA2 is a polyepoxide.

[0085] In one aspect, polyAl is a polythiol compound while polyA2 is a polyisocyanate.

[0086] In an aspect, a composition of the present disclosure includes a photoinitiator. In one aspect, a composition comprises one or more additives. In an aspect, a composition comprises one or more light reflective materials suspended in the composition. In an aspect, a composition comprises one or more stabilizers. In an aspect, a composition comprises one or more chain transfer agents.Polyhv Compounds

[0087] Polyhv compounds of the present disclosure contain a plurality of photopolymerizable groups, hv. Exemplary photopolymerizable groups are ethylenically unsaturated groups, and an exemplary polyhv compound having ethylenically unsaturated groups may be denoted as polyEU. Another exemplary photopolymerizable group is a thiol group, and an exemplary polyhv compound having thiol groups may be denoted as polySH.

[0088] In one aspect, the present disclosure provides multi-arm compounds as described herein, wherein an arm terminates in a hv group, and that hv group is photopolymerizable. In one embodiment, exemplary hv groups may contain a thiol group which is photopolymerizable. In one embodiment, exemplary hv groups may contain a carbon-carbon double bond which is photopolymerizable, e.g., the arm may comprise a vinyl group such as present in an acrylate or methyacrylate group, each having a photopolymerizable carboncarbon double bond.

[0089] The hv group containing a photopolymerizable component, e.g., a photopolymerizable thiol or carbon-carbon double bond, may be introduced into a multi-arm compound as described herein by reaction of the terminal hydroxyl group with a suitablereagent. Methods to convert a hydroxyl group to thiol-containing group or a carbon-carbon double bond containing group are generally known and may be utilized to prepare compounds of the present disclosure, where examples are provided herein.

[0090] While the hv group will contain a photoreactive group, and in particular a photoreactive group that allows for polymerization of the hv-containing macromer, the hv group may also contain additional atoms which influence the photoreactivity of the photoreactive group, e.g., a carbonyl group adjacent to the carbon-carbon double bond as illustrated herein, and / or which were used to introduce the photoreactive group to the macromer, e.g., a succinate ester may be used to introduce a thiol group, as illustrated herein.

[0091] For example, to convert a hydroxyl group to a hv group containing a photopolymerizable carbon-carbon double bond (polyEU), a multi-arm compound having a terminal hydroxyl group as described herein may be reacted with a reactive acrylate, methacrylate, or norbornenyl compound, such as methacrylic anhydride, acrylic anhydride, methyl-5-norbornene-2,3-dicarboxylic anhydride, 5-norbornene-2,3-dicarboxylic anhydride, methacryloyl chloride, or acryloyl chloride.

[0092] For example, to convert a hydroxyl group to a hv group containing a photopolymerizable thiol group (polySH), a multi-arm compound having a terminal hydroxyl group as disclosed herein may undergo an esterification reaction. One method for esterification is to add stoichiometric amounts of macromer and a mercapto carboxyl acid compound in the presence of a carbodiimide (e.g., N, N'-dicyclohexylcarbodiimide) and a catalyst (e.g., dimethylaminopyridine). Exemplary mercapto carboxyl 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-acetyl cysteine. For example, a multi-arm compound having a terminal hydroxyl group as disclosed herein may 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.

[0093] Another exemplary method of forming thiol functionalized macromer (polySH) is to first modify a corresponding hydroxyl terminated macromer to form terminal carboxylic acid groups. One example of this is to react the hydroxyl terminated macromer with a succinic anhydride. With terminal carboxylic acid groups, the macromer can be reacted with mercaptoalcohols by an esterification reaction or with mercapto amines to form amide bonds. Some examples of mercapto alcohols include, but are not limited to, the following: mercapto propanol, mercaptohexanol, mercaptooctanol, and mercapto undecanol. Some examples of mercapto amines include, but are not limited to, the following: cysteine, glutathione, 6-amino-l-hexanethiol hydrochloride, 8-amino-l-octanethiol hydrochloride, and 16-amino-l-hexadecanethiol hydrochloride. For example, a multi-arm compound having a terminal hydroxyl group as disclosed herein may be reacted with succinic anhydride to form an intermediate which is then reacted with cysteine to introduce a terminal thiol group, in which case the polySH compound includes a portion having the formula -C(=O)CH2CH2C(=O)NH-C(COOH)-CH2SH attached to the terminal oxygen of the multi-arm compound.

[0094] Yet another method for forming thiol functionalized macromer polySH is to react a macromer having terminal hydroxyl groups with a lactone monomer having pendant thiol groups. This would occur in a third step ring opening polymerization.

[0095] In one aspect, the polySH compound is a macromer known as a thiomer. In some aspects, the thiol compound is a multi-arm poly(ethylene glycol) (PEG) comprising at least two free thiol groups or a multi-arm poly(ethylene oxide) comprising at least two free thiol groups. Exemplary thiomers include, without limitation, 4arm-PEG2K-SH, 4arm-PEG5K-SH, 4arm-PEG10K-SH, 4arm-PEG20K-SH, 4-arm polyethylene oxide) thiol-terminated, 8arm-PEG10K-SH (hexaglyerol core), 8arm-PEG10K-SH (tripentaerythritol core), 8arm-PEG20K-SH (hexaglyerol core), 8arm-PEG20K-SH (tripentaerythritol core), and 8-arm poly(ethylene oxide) thiol-terminated. These thiomers are available from Millipore Sigma (formerly Sigma Aldrich).

[0096] In one aspect, polySH is not a macromer, but is instead a small molecule having a molecular weight of less than 1000 daltons. Optionally, the small molecule polySH may be water soluble. Examples of such polySH compounds include dithiol compounds, trithiol compounds, and tetrathiol compounds. Exemplary polySH compounds include, without limitation, 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-dithiole; 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.

[0097] In an aspect, a composition of the present disclosure comprises at least one polyhv compound. In an aspect, a composition comprises a photoinitiator. In an aspect, a composition additionally comprises one or more additives. In an aspect, a composition additionally comprises one or more light reflective materials suspended in the composition. In an aspect, a composition additionally comprises one or more stabilizers. In an aspect, a composition additionally comprises one or more chain transfer agents.Photoinitiators

[0098] A photoinitiator refers to an organic (carbon-containing) molecule that creates reactive species when exposed to radiation. In one embodiment the photoinitiator creates a radical reactive species, as opposed to, e.g., a cationic or anionic reactive species. Photoinitiators are well known components for the preparation of photopolymers which find use in photo-curable coatings, adhesives and dental restoratives.

[0099] Type I photoinitiators are unimolecular free-radical generators; that is upon the absorption of UV-visible light a specific bond within the initiator's structure undergoes homolytic cleavage to produce free radicals. Homolytic cleavage is a bonding pair of electron's even scission into two free radical products. Examples of homolytic cleavage in several common classes of Type I photoinitiators: benzoin ethers, benzyl ketals, a-dialkoxy-aceto-phenones, a-hydroxy-alkyl-phenones, and acyl phosphine oxides. Exemplary commercially available Type I photoinitiators, available from, for example, BASF, BASF SE, Ludwigshafen, Germany, include, but are not limited to, 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™ 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-trimethylbenzoylphosphinates, and sodium phenyl-2,4,6-trimethylbenzoylphosphinates

[0100] Type II photoinitiators require a co-initiator, usually an alcohol or amine, functional groups that can readily have hydrogens abstracted, in addition to the photoinitiator. The absorption of UV-visible light by a Type-ll photoinitiator causes an excited electron state in the photoinitiator that will abstract a hydrogen from the co-initiator, and in the process, splitting a bonding pair of electrons. Benzophenone, thio-xanthones, 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 the free-radicals are generated, the polymerization mechanism is similar to any free-radical polymerization process.

[0101] Optionally, a composition of the present disclosure includes at least one photoinitiator component, typically in 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 photoreactive compounds.Additives

[0102] A composition of the present disclosure may contain an additive, such as one, two, or a plurality of additives, which may or may not be optional. Exemplary additives are described herein. As used herein, "additive" is a broad term, and an additive includes, but is not limited to, one or more light reflective materials that are suspended in the composition; 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. Compositions may contain one or more additives to stabilize an ethylenically unsaturated group(s) and / or chain transfer agent(s). Additives may alter the physical and / or chemical characteristics of such a formulation. Additives alone or as a component of a formulation may be resorbable (biodegradable) or non-resorbable (nonbiodegradable), functionalized or non-functionalized, reactive or non-reactive, and may or may not act as a chain transfer agent. An additive may be bio-degradable, bio-derived (i.e., naturally occurring in part or whole and derived from plant or animal as opposed to synthetically formed), bio-inert (i.e., an additive does not elicit a response when interacting with biological tissue), and may be present in concentrations that are non-toxic to mammals or other living organisms. An example of an additive may be a stabilizer, including, but not limited to, tocopherol, lauryl gallate, or phosphoric acid. Anexample of an additive may be a dye, pigment, and / or actinic absorber, including, but not limited to, D& C Violet No. 2, P-Carotene, lycoprene, or riboflavin. An example of an additive may be an actinic reflective particulate (a light reflective material) including, but not limited to, inorganic or organic compounds, aliphatic or aromatic polymers, or other crystalline solid particulates. An example of an additive may be a diluent or other viscosity modifier, including, but not limited to, poly(ethylene glycol) diacrylate, trimethylolpropane trimethacrylate, or trimethylolpropane tris-mercaptopropionate. An example of an additive may be a Type I photoinitiator including, but not limited to, acyl phosphine oxides and / or a Type II photoinitiator such as thio-xanthones, riboflavin, or camphorquinone with a co-initiator, usually an alcohol or amine.

[0103] In one aspect, a colorant, such as a dye, may be included in the compositions of the present disclosure, and the corresponding cured product. The addition of a dye can achieve the purpose of tailoring a formulation to a desired color. In one aspect, the dye is a non-toxic, biocompatible dye. Such dyes may be present at concentrations of about 2 wt. % or less based on the total weight of the composition. See, for example, PCT / US2016 / 059910, which is incorporated herein for its teaching of the use of dyes. In one embodiment, the dye is present at a concentration of about 0.1-0.3 wt%, which is the FDA-recommended amount for the dye D& C Violet when present in an absorbable suture products. In one embodiment, the dye is present at a concentration of less than 0.5 wt%. In some cases, the dye may impart toxicity to the photopolymerized composition of the present disclosure, if that dye is present at too high of a concentration.

[0104] 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, compositions may comprise a bio-derived dye, pigment or UV absorber. These compounds can be divided into carotenoid, flavonoid, flavone, quinone, porphyrin, diketone and betacyanidine from the viewpoint of chemical structure. Some examples of bio-derived dyes, pigments, and UV absorbers are listed but not limited to betacarotene, chlorophyll, lycoprene, anthocyanins, quercetin, rutin, riboflavin, turmeric, and saffron. A composition may include in the present disclosure may include at least one bioderived dye, pigment, or uv absorber, typically in a total concentration of less than 5 wt%, or less 2 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 photoreactive compounds. In one aspect, the composition with the bioderived dye, pigment, or UV absorber is biocompatible. In one aspect, the composition with the bio-derived dye, pigment, or UV absorber is bioresorbable.

[0105] In one aspect, a light reflective material component comprising a light reflective material may be suspended in the composition, where the light reflective material component modulates the light dose of the composition when compared to the light dose of the composition without the light reflective material. Suitable light reflective materials for optional inclusion in the compositions of the present disclosure are provided in PCT Application No. PCT / US2019 / 026114, filed April 5, 2019, entitled Methods and Compositions for Photopolymerizable Additive Manufacturing, and its related US and overseas applications, each of which is incorporated herein in its entirety.

[0106] A suitable light reflective material comprises light reflective material that reflects UV light, visible light or both. For example, a light reflective material may be or comprise a particulate light reflective material sized less than 500 microns, or sized less than 30 microns, or sized less than 5 microns, or sized less than 1 micron. A light reflective material may be shaped, for example, as a sphere, cube, cone, cuboid, cylinder, pyramid, prism, polyhedron, or irregular shape, or mixtures thereof. In one aspect, a light reflective material has a smooth surface.

[0107] In an aspect, a light reflective material may comprise an inorganic solid including but not limited to titanium dioxide, zinc oxide, barium sulfate, tricalcium phosphate, dicalcium phosphate, monocalcium phosphate, dicalcium diphosphate, calcium triphosphate, tricalcium phosphate, hydroxyapatite, apatite, and tetracalcium phosphate. In an aspect, the light reflective material may comprise organic compounds comprising aliphatic polymers and copolymers including but not limited to polyesters, polyurethanes, polyethers, polyanhydrides, polyamides, polycarbonates, polyketones, polyethylene, polypropylene, polyvinyl alcohol, polytetrafluoroethylene, polyvinyl chloride, polyimides, and polyhydroxy alkanoates or combinations thereof. In an aspect, the light reflective material may comprise organic compounds comprising aromatic polymers and copolymers including but not limited to polyesters, polyurethanes, polyethers, polyanhydrides, polyketones, polyamides, polycarbonates, and polyimides or combinations. In an aspect, the light reflective materialmay comprise organic compounds comprising naturally derived polymers and derivatives including but not limited to cyclodextrins, starch, hyaluronic acid, deacetylated hyaluronic acid, chitosan, trehalose, cellobiose, maltotriose, maltohexaose, chitohexaose, agarose, chitin 50, amylose, glucans, heparin, xylan, pectin, galactan, glycosaminoglycans, dextran, aminated dextran, cellulose, hydroxyalkylcelluloses, carboxyalkylcelluloses, fucoidan, chondroitin sulfate, sulfate polysaccharides, mucopolysaccharides, gelatin, zein, collagen, alginic acid, agar, carrageean, guar gum, gum arabic, gum ghatti, gum karaya, gum konjak, gum tamarind, gum tara, gum tragacanth, locust bean gum, pectins, and xanthan gum. In an aspect, the light reflective material may comprise crystalline organic compounds comprising crystalline aliphatic and aromatic polymers. In an aspect, the light reflective material may comprise crystalline organic compounds comprising crystalline naturally derived polymers and derivatives. In an aspect, a light reflective material may comprise crystalline amino acids and their derivatives. In an aspect, a light reflective material may comprise crystalline fatty acids and their derivatives, including but not limited to palmitic acid, ascorbyl palmitate, lauric acid, glycerol monolaurate, myristic aid, and capric acid. In an aspect, a light reflective material may comprise crystalline peptides.

[0108] In one aspect, the compositions of the present disclosure may contain a diluent. The diluent may be reactive or non-reactive. A reactive diluent undergoes a photopolymerization reaction when exposed to light (UV or visible light) while a non-reactive diluent is inert to such light exposure. An exemplary reactive diluent is PEG-diacrylate (PEG-DA or PEGDA).

[0109] In one aspect, a bioactive agent may be included in a composition of the present disclosure, and the corresponding cured product. Examples of such bioactive agents include, but are not limited to, fibrosis-inducing agents, antifungal agents, antibacterial agents and antibiotics, antimicrobial agents, anti-inflammatory agents, anti-scarring agents, immunosuppressive agents, immunostimulatory agents, antiseptics, anesthetics, antioxidants, cell / tissue growth promoting factors, anti-neoplastic, anticancer agents and agents that support ECM integration.

[0110] Examples of fibrosis-inducing agents include, but are not limited to talcum powder, metallic beryllium and oxides thereof, copper, silk, silica, crystalline silicates, talc, quartz dust, and ethanol; a component of extracellular matrix selected from fibronectin,collagen, fibrin, or fibrinogen; a polymer selected from the group consisting of polylysine, poly(ethylene-co-vinylacetate), chitosan, N-carboxybutylchitosan, and RGD proteins; vinyl chloride or a polymer of vinyl chloride; an adhesive selected from the group consisting of cyanoacrylates and crosslinked poly(ethylene glycol)-methylated collagen; an inflammatory cytokine (e.g., TGFβ, PDGF, VEGF, bFGF, TNFa, NGF, GM-CSF, IGF-a, IL-1, IL-ip, IL-8, IL-6, and growth hormone); connective tissue growth factor (CTGF); a bone morphogenic protein (BMP) (e.g., BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, or BMP-7); leptin, and bleomycin or an analogue or derivative thereof. Optionally, the device may additionally comprise a proliferative agent that stimulates cellular proliferation. Examples of proliferative agents include: dexamethasone, isotretinoin (13-cis retinoic acid), 17-β-estradiol, estradiol, la, 5-dihydroxyvitamin D3, diethylstibesterol, cyclosporine A, L-NA E, all-trans retinoic acid (ATRA), and analogues and derivatives thereof. See, e.g., US 2006 / 0240063, which is incorporated by reference in its entirety. Examples of antifungal agents include, but are not limited to, polyene antifungals, azole antifungal drugs, and Echinocandins. Examples of antibacterial agents and antibiotics include, but are not limited to, erythromycin, penicillins, cephalosporins, doxycycline, gentamicin, vancomycin, tobramycin, clindamycin, and mitomycin. Examples of anti-inflammatory agents include, but are not limited to, non-steriodal 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 a taxane, immunomodulatory agents such as serolimus or biolimus (see, e.g., US 2005 / 0149158, which is incorporated by reference in its entirety). Examples of immunosuppressive agents include, but are not limited to, glucocorticoids, alkylating agents, antimetabolites, and drugs acting on immunophilins such as ciclosporin and tacrolimus. Examples of immunostimulatory agents include, but are not limited to, interleukins, interferon, cytokines, toll-like receptor (TLR) agonists, cytokine receptor agonist, CD40 agonist, Fc receptor agonist, CpG-containing immunostimulatory nucleic acid, complement receptor agonist, or an adjuvant. Examples of antiseptics include, but are not limited to, chlorhexidine and tibezonium iodide. Examples of anesthetic 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 growthfactors, human platelet derived TGF-£, endothelial cell growth factors, thymocyte-activating factors, platelet derived growth factors, fibroblast growth factor, fibronectin or laminin. Examples of antineoplastic / anti-cancer 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.

[0111] The compositions and corresponding cured articles of the present disclosure may contain a mixture of bioactive agents in order to obtain a desired effect. Thus, for example, an antibacterial and an anti-inflammatory agent may be combined in a single article to provide combined effectiveness. One example of an antibacterial sheet is a biodegradable lattice sheet (a part or article) comprising minocycline and rifampin. Another example of an antibacterial sheet is a lattice sheet (a construct or article) comprising polyhexamethylene biguanide.

[0112] Other additives of the photopolymerizable composition are a reactive diluent, a non-reactive diluent, a solvent, a stabilizer, a thixotropic material, a tracer material and a conductive material. The stabilizer, when present, may optionally be selected from the group consisting of tocopherol, gallic acid, ester of gallic acid, butylated hydroxyanisole and combinations thereof. By addition of the appropriate component, a photopolymerized composition (e.g., an article, or piece) of the present disclosure may be colored due to the presence of a dye, or may have any other desired attribute such as having at least a portion of the article that is, but is not limited to, fluorescent, radioactive, reflective, flexible, stiff, pliable, breakable, or a combination thereof.

[0113] In one aspect, a composition of the present disclosure comprising polyhv or a polyA is polymerized in the absence of water, e.g., water is not a diluent in the composition. Specifically, in one aspect, the composition which forms a single or double network, or the single or double network itself, has a moisture (water) content of less than 2500 ppm, or less than 1000 ppm, or less than 500 ppm of water. In one aspect, the photocurable composition of the present disclosure that provides a single network, is an anhydrous composition in that it does not contain more than adventitious water. In one aspect, the photocurable and thermocurable composition of the present disclosure that provides a double network, is an anhydrous composition in that it does not contain more than adventitious water. An anhydrous composition of the present disclosure is not, for example, a hydrogel.

[0114] One challenge to creating formulations with both ethylenically unsaturated compounds and thiol compounds is their tendency to polymerize upon mixing at room temperature prior to the application of stimuli such as lighter heat. Therefore, this can greatly limit the application of these formulations as the working time where their viscosity is constant can be short. Specifically for additive manufacturing using vat photopolymerization, these formulations have issues with a changing viscosity over time. In the present disclosure, biocompatible stabilizers are outlined that may give stability for at least 24 hrs, which should be useful in addressing work time for vat photopolymerization or light assisted photopoymerization. In an aspect, one or more stabilizer compounds may be included in a composition of the present disclosure, and the corresponding cured product.

[0115] In an aspect, a composition comprising a poly(SH) or poly(EU) includes a stabilizer. The stabilizer may be included in the poly(SH), poly(EU) or a combination thereof. In one aspect, the stabilizer is an add-in component. In another aspect, the stabilizer is included as an add-in dissolved in a monomer, diluent, solvent, or combination thereof. In one aspect, the stabilizer is an anti-oxidant. In another aspect, the stabilizer is an acid. Preferably, the acid stabilizer has a pKa between 1 and 5. In another aspect, the stabilizer is selected from a phosphite and phosphonate compound. In another aspect, the stabilizer may include an anti-oxidant, acid, phosphite, phosphonate, and combinations thereof. Examples of anti-oxidant 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-butyl catechol, 1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene (Anox 330TM, Irganox 1330TM), 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, phenyl phosphonic acid, or combinations thereof. Examples of phosphite and phosphonate stabilizers may include but are not limited to triphenyl phosphite, diphenyl isodecyl phosphite, diphenyl isooctylphosphite, or combinations thereof. In one aspect, the stabilizer is soluble in the poly(SH) and / or poly(EU) formulation. A stabilizer may be added in concentrations that achieve biocompatibility. Abiocompatible stabilizer may comprise of tocopherol, gallic acid, ester of gallic acid, butylated hydroxyanisole, or combinations thereof. In one aspect, the stabilizer concentration is less than 100,000 ppm, less than 50,000 ppm, less than 15,000 ppm, less than 15,000 ppm, less than 5,000 ppm, less than 3,000 ppm or less than 1,500 ppm.Photopolymerization Reaction Conditions

[0116] The photopolymerizable compounds polyhv (including polyEU and polySH) as described herein having photopolymerizable groups, and the compositions of the present disclosure that include such compounds, will undergo polymerization upon sufficient exposure to light of appropriate wavelength, optionally in the presence of a photoinitiator, and further optionally in the presence of other components. The choice of appropriate wavelength, time of exposure, and curing agent identity and amount, is selected in view of identity and quantity of the hv group 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.

[0117] In an aspect, a photoinitiator component in a composition of the present disclosure comprises a Type I photoinitiator. In an aspect, a photoinitiator component in a composition of the present disclosure comprise a Type II photoinitiator. In an aspect, a combination of a Type I and a Type II photoinitiator is present in photopolymerization composition of the present disclosure.

[0118] In any of the photopolymerizable compounds and compositions as described herein, hv may be a carbon-carbon double bond, e.g., a vinyl group. Exemplary vinyl groups are an acrylate group and a methacrylate group. Another exemplary carbon-carbon double bond is present in norbornenyl. In additional aspects, the photopolymerizable compound having one or more hv groups undergoes photopolymerization when exposed to light having 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, as examples. In one embodiment, the polyhv compound and related composition undergoes photopolymerization when exposed to UV radiation.

[0119] In any of the photopolymerizable compounds and compositions as described herein, hv may be a thiol group. In additional aspects, the photopolymerizable compound polySH having one or more SH groups undergoes photopolymerization when exposed to actinic radiation, for example, light having a wavelength of 300-450 nm, or 300-425 nm, or350-450 nm, or 350-425 nm, or 365-405 nm, or 450-550 nm, as examples. In one embodiment, the polySH compound and related compositions undergo photopolymerization when exposed to UV radiation. In one embodiment, the polySH compound and related compositions undergo photopolymerization when exposed to visible radiation.

[0120] In one aspect, the present disclosure provides a composition comprising a compound having multiple photopolymerizable thiol groups and a compound having multiple photopolymerizable ethylenically unsaturated groups. The thiol groups and the ethylenically unsaturated groups are reactive with one another 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 compositions may be referred to as light-reactive. This reaction may be referred to as photopolymerization or curing.

[0121] Though not 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 segment can be degraded by hydrolytic 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 lower than approximately 20,000-65,000 Da in order to be cleared by a mammalian kidney. When typical ethylenically unsaturated polyesters are free radically polymerized and subsequently degraded, the backbone molecular weight is often much greater than 20,000-65,000 Da. This is the case in photopolymerizations of biocompatible implantable resins where it is desired that a low amount of photoinitiator is used to reduce toxicity. As disclosed herein, a method to reduce the molecular weight of ethylenically unsaturated polymers is to incorporate at least one chain transfer agent, which can incorporate into the polymeric backbone, terminate the ethylenically unsaturated polymer, and reinitiate ethylenically unsaturated groups. The present disclosures provide specific ranges of ratios of chain transfer agent to ethylenically unsaturated groups so as to modify the molecular weights of the degradation products produced during degradation or resorption of a 3-D printed polymerized article. Further disclosed are biocompatible chemical species to be used in compositions comprising at least one chain transfer agent.

[0122] In one aspect, a composition comprising a photochemically cured reactionproduct of a compound comprising ethylenically unsaturated groups (EU), a photoinitiator, and at least one chain transfer agent, when degraded results in degradation products (or polymeric backbones) that have 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.

[0123] In an aspect, chain transfer agents comprise compounds with functionality reactive groups, including, but not limited to, one or more functional groups comprising thiol, disulfide, aminoalkylthiol, thiocarbonate, xanthate, alcohol, halogen, and / or phosphorous. Examples of chain transfer agents comprise 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-acetyl cysteine, glutathione, bal-introv 2:3-dimercaptopropanol glucoside, isooctylthioglycolate, 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT), 2-(2-carboxyethylsulfanylthiocarbonylsulfanyl)propionic acid, l,8-Dimercapto-3,6-dioxaoctane (DMDO), ethanol, isopropanol, malic acid, lactic acid, formic acid, and sodium hypophosphite.

[0124] A chain transfer agent may be present in a polymerizable composition at a ratio of moles of chain transfer agent functional groups (e.g. thiols) to moles of ethylenically unsaturated groups, of less than 0.80, less than 0.75, or between 0.75 and 0.05. A chain transfer agent may be present in a polymerizable composition at a ratio of moles of chain transfer agent functional groups to moles of ethylenically unsaturated groups of between about 0.03 moles of chain transfer agent functional groups to about 0.80 moles of ethylenically unsaturated groups; from about 0.03 moles of chain transfer agent functional groups to about 0.75 moles of ethylenically unsaturated groups; from about 0.03 moles of chain transfer agent functional groups to about 0.5 moles of ethylenically unsaturated groups; from about 0.03 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 0.80 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 functionalgroups to about 0.25 moles of ethylenically unsaturated groups; or from about 0.05 moles of chain transfer agent functional groups to about 0.15 moles of ethylenically unsaturated groups, and ranges thereinbetween.

[0125] Examples for ethylenically unsaturated macromers are disclosed in PCT Application No. PCT / US2019 / 026098, filed April 5, 2019, and in PCT Application No. PCT / US2019 / 026114, filed April 5, 2019, and their related US and overseas applications, each of which is herein incorporated by reference in its entirety. In an aspect, the ethylenically unsaturated macromer is absorbable.

[0126] For example, disclosed compositions herein comprise a photopolymerizable macromer component comprising macromers (polymers) capable of being photopolymerized that are biodegradable or absorbable or resorbable under physiological conditions. In an aspect, a photopolymerizable macromer component comprises aliphatic or aromatic macromers, polymers and / or oligomers with ethylenically unsaturated end groups. For example, a photopolymerizable macromer component comprises polymers with acrylate end groups. In an aspect, an acrylate end group may be a methacrylate end group. In an aspect, a photopolymerizable macromer comprises light reactive functional end groups, for example, acrylate or methacrylate. In an aspect, a photopolymerizable macromer comprises light reactive functional end groups, for example, thiol groups. In an aspect, a photopolymerizable composition may comprise one or more macromers with light reactive end groups, wherein the light reactive functional end groups, for example, may be acrylate or methacrylate, thiols, or combinations of macromers having different end groups, e.g., some of which have acrylate end groups and some of which have thiol end groups.

[0127] In an aspect, a macromer may comprise a monofunctional, difunctional, trifunctional, tetrafunctional, or pentafunctional photocurable macromer, and in some cases, can comprise a relatively low molecular weight species or a relatively high molecular weight species. In an aspect, a macromer may comprise reactive groups including, but not limited to, the unsaturated functionality of acrylate (including methacrylates), allyl and vinyl-based reactive groups, and thiol reactive groups. Higher functional materials with 4, 5, 6, up to 18 reactive sites are contemplated in the present disclosure. Monomeric materials will typically have molecular weights less than 250 Daltons while oligomeric materials could have molecular weights into the tens of thousands.

[0128] Suitable photoinitiators have been described elsewhere herein. In order for the photoinitiator to successfully cure the light-reactive composition, it is necessary that the absorption bands of the photoinitiator overlap with the emission spectrum of the light source used for curing. Optionally, photopolymerizable compositions disclosed herein comprise at least one photoinitiator that absorbs a wavelength of light in a range between about 10 nm to about 770 nm, or between about 100 nm to about 770 nm, or between about 200 nm to about 770 nm, and all wavelengths between the stated range. In an aspect, a photoinitiator component comprises a photoinitiator that absorbs a wavelength of light of greater than or equal to 300 nm, up to about 770 nm. In an aspect, a photoinitiator component comprises a photoinitiator that absorbs a wavelength of light of greater than or equal to 365 nm, up to about 770 nm. In an aspect, a photoinitiator component comprises a photoinitiator that absorbs a wavelength of light of greater than or equal to 375 nm, up to about 770 nm. In an aspect, a photoinitiator component comprises a photoinitiator that absorbs a wavelength of light of greater than or equal to 400 nm, up to about 770 nm. The photopolymerization conditions of the present disclosure will include exposure of the light-reactive composition to a spectrum of wavelengths from an emission source that can and does provide the desired spectrum of wavelengths suitable for photopolymerization of the composition. Choice of wavelength will depend on the identity of the photoinitiator. Suppliers of commercially available photoinitiators indicate the appropriate wavelength for that particular photoinitiator.

[0129] Free radical generating photoinitiators may be used to achieve polymer curing according to the present disclosure. These photoinitiators may be used to cure a mixture of thiol-containing compounds and ethylenically unsaturated compounds such as disclosed herein. There are two types of free-radical generating photoinitiators, designated as Type I and Type II photoinitiators, which may be used according to the present disclosure, and which are described elsewhere herein.

[0130] Photopolymerizable compositions disclosed herein are made by combining the desired components, typically with stirring to achieve a homogeneous composition. The desired components may be mixed using a homogenizer. For example, a composition as disclosed herein may be prepared by combining ingredients such as those identified above. Optionally, the desired components may include a dispersion agent to aid in suspension. Thelisted components may optionally be heated prior to mixing. The listed components may optionally be placed under vacuum to remove gas bubbles.

[0131] In an aspect, the present disclosure provides a composition comprising a first organic compound (polySH) having multiple thiol groups (SH), a second organic compound (polyEU) having multiple ethylenically unsaturated groups (EU), and a photoinitiator. The relative amounts of polySH and polyEU in the composition may be described in terms of an SH to EU equivalents ratio of X: Y, where X represents the equivalents of SH, Y represents the equivalents of EU, and the total of X and Y is 100. In one aspect, X ranges from 25-75 and Y ranges from 75-25 and the sum of X and Y is 100. In one aspect, X ranges from 30 to 70 and Y ranges from 70 to 30 and the sum of X and Y is 100. In one aspect, X ranges from 40 to 60 and Y ranges from 60 to 40 and the sum of X and Y is 100. In one aspect, X ranges from 45 to 55 and Y ranges from 55 to 45 and the sum of X and Y is 100. In one aspect, the equivalents of X are approximately equal to the equivalents of Y.Thermal Reaction Conditions

[0132] As discussed herein, compositions of the present disclosure may contain polyAl and polyA2, which are reactive with one another upon exposure to elevated temperature. The specific elevated temperature, and the time necessary to achieve reaction between polyAl and polyA2 at that specific elevated temperature, will depend on the specific identities of Al and A2. For many reactions between a nucleophile and an electrophile, a temperature of about 100°C for 30 minutes to 5 hours is sufficient.

[0133] In one aspect, the present disclosure provides a composition comprising a first organic compound (polyhv) having multiple photopolymerizable groups (hv), a photoinitiator, a second organic compound (polyAl) having multiple reactive groups Al, and a third organic compound (polyA2) having multiple reactive groups A2, where Al reacts with A2 upon contact and exposure to a temperature of greater than about 50°C. The relative amounts of polyAl and polyA2 in the composition may be described in terms of a Al to A2 equivalents ratio of X: Y, where X represents the equivalents of Al, Y represents the equivalents of A2, and the total of X and Y is 100. In one aspect, X ranges from 25-75 and Y ranges from 75-25 and the sum of X and Y is 100. In one aspect, X ranges from 30 to 70 and Y ranges from 70 to 30 and the sum of X and Y is 100. In one aspect, X ranges from 40 to 60 and Y ranges from 60 to 40 and the sum of X and Y is 100. In one aspect, X ranges from 45 to 55 and Y ranges from 55 to45 and the sum of X and Y is 100. In one aspect, the equivalents of X are approximately equal to the equivalents of Y.

[0134] In order to expose the composition to elevated temperature, the composition may be placed into an oven. Alternatively, a heat lamp may be directed to the composition, where the head lamp provides infrared radiation that will heat the composition.Additive Manufacturing

[0135] Methods disclosed herein include methods for using curable compositions to make articles, particularly non-toxic and biodegradable articles. For example, a composition disclosed herein may be used as a curable ink or resin in 3-D printing methods. For example, a curable composition as disclosed herein may be used as curable ink or resin in vat polymerization process for 3-D printing. Exemplary vat polymerization processes include stereolithography (SLA, also known as SL), digital light processing (DLP™; Texas Instrument), daylight polymer printing (DPP), Carbon digital light synthesis (Carbon DLS™; Carbon, Inc.) and continuous liquid interface production (CLIP™; Carbon, Inc.). Other suitable methods of additive manufacturing an article using the curable compositions of the present disclosure include binder jetting, material jetting, material extrusion, computed axial lithography, and 2 photon polymerization printing. The present disclosure provides for the use of the curable compositions as disclosed herein in any of the mentioned 3D printing processes.

[0136] Thus, in one aspect, the present disclosure provides a method for vat polymerization, e.g., SLA printing an article, which comprises exposing for a time with light, a photopolymerizable composition comprising at least one photopolymerizable composition as disclosed herein including at least one photoinitiator component that is typically in a total concentration of less than 1.0 wt%. Any of the photopolymerizable compositions disclosed herein may be used in the method for SLA printing an article. For example, the composition may contain polyhv in addition to polyAl and polyA2. As another example, the composition may contain polyEU and polySH. Optionally, the photopolymerizable composition may comprise a reactive diluent or a nonreactive diluent. A reactive diluent is a diluent that participates in the polymerization reaction, for example, the reactive diluent is polymerized with, for example, a macromer. A photopolymerizable composition of the present disclosure may comprise a stabilizer, for example, a free radical stabilizer.

[0137] A method for printing an article by SLA according to the present disclosure maycomprise a secondary curing step comprising curing the printed article with thermal energy. A secondary curing step involves exposing at least a portion of the printed article to thermal energy so that at least a portion of the printed article undergoes a second, heat-induced polymerization reaction. For example, some or all of an article may be exposed to a temperature of about 100°C for about 30 minutes to 5 hours. A secondary curing step may be used to change the properties of the printed article.

[0138] A method for printing an article by SLA according to the present disclosure may comprise pre- and / or post-treatments of a printed article. For example, the printed article may be rinsed after printing, before or after a thermal curing step.

[0139] A printed article is the article resulting after a 3-D printing period is completed. The printed article may be a structure or a portion of a structure. The printed article may be in the form of a film, such as a coating that is printed onto a surface. As used herein, the term printing is used to mean contacting a polymeric composition with a surface and causing the polymeric composition to further polymerize. Printing may involve contacting a polymeric composition with a surface that is then exposed to UV and / or visible light so that the polymeric composition undergoes further polymerization. The surface that the polymeric composition contacts may be any surface including a polymerized layer of the polymeric composition. As mentioned previously, the printed article may undergo a second curing step, by being exposed to elevated temperature.

[0140] A printed article may or may not contain residual amounts of components of a curable composition. For example, a printed article may comprise diluent or photopolymerized diluent, or photoinitiator. In an aspect, a printed article or a curable composition may have additives. Additives, as disclosed herein, may include thixotropic materials, colorants, tracer materials or conductive materials. For example, an additive may be a dye. A printed article may be colored due to the presence of a dye, or may have any desired attribute such as having at least a portion of the article that is, but is not limited to, fluorescent, radioactive, reflective, flexible, stiff, pliable, breakable, or a combination thereof.

[0141] In a common vat printing process, a build platform is lowered from the top of the resin vat downwards by the layer thickness. Actinic radiation is directed into the composition and this light causes photopolymerization (photocuring) of the composition. The build platform continues to move downwards and additional layers are built upon the top ofthe previous layer. After completion, the vat may be drained of excess resin and the printed article collected. This printed article may be subjected to additional treatment. For example, the printed article may be washed to remove excess resin. As another example, particularly in the case where the article contains polyAl and polyA2, the printed article may be exposed to thermal energy to cause thermal curing to occur.

[0142] A method of forming an article by vat polymerization may comprise directing actinic radiation to a vat of a photopolymerizable composition comprising monomers or macromers that are capable of undergoing polymerization, such as monomers or macromers that have functional groups capable of undergoing photopolymerization reactions to form oligomers and / or polymers, such as the polyhv compounds disclosed herein.

[0143] In one aspect, the vat polymerization, e.g. using SLA, is printing an article using a photopolymerizable composition, and directing actinic radiation to the vat of composition at light wavelength from about 10 nm to about 1 mm. As used herein, UV radiation has a wavelength of from about 10-400 nm, while visible radiation has a wavelength of 390-770 nm, and IR radiation has a wavelength of 770 nm -1 mm. In one aspect, the actinic radiation is comprised of one or more wavelengths and / or one or more radiations sources. In an aspect, the photopolymerizable composition may comprise a light reflective material component that causes photopolymerization to occur in a shorter exposure time than would occur without the light reflective material component under the same polymerization conditions. Optionally, if the curable composition contains thermally reactive components polyAl and polyA2, a thermal curing process will be performed before, during, or after the photopolymerization process. Optionally, if the curable composition contains thermally reactive components polyAl and polyA2, a thermal curing process will be performed after the photopolymerization process.

[0144] In one aspect, 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 as disclosed herein comprising at least one photoinitiator that absorbs at a wavelength of light from about 10 nm to about 770 nm. In an aspect, a photoinitiator absorbs at a wavelength of light of greater than or equal to 300 nm. In an aspect, a photoinitiator absorbs at a wavelength of light of greater than or equal to 365 nm. In an aspect, a photoinitiator absorbs at a wavelength oflight of greater than or equal to 375 nm. In an aspect, a photoinitiator absorbs at a wavelength of light of greater than or equal to 400 nm. The photoinitiator in the curable composition is at least one photoinitiator component that comprises a photoinitiator that is a Type I, Type II, a cationic photoinitiator or a combination thereof.

[0145] In one aspect, the present disclosure provides a method of printing an article by vat polymerization, e.g., using SLA in a device for printing by SLA, where the method comprises photopolymerizing or curing a photopolymerizable composition at a depth of less than 150 microns. In an aspect, a method disclosed herein comprises photopolymerizing or curing a photopolymerizable composition at a depth of from about 5 microns to about 50 microns, and all depths thereinbetween.

[0146] In one aspect, the present disclosure provides a method of printing an article by vat polymerization, e.g., using SLA in a device for printing by SLA, where the method comprises photopolymerizable compositions comprising a light reflective material component comprising a light reflective material that is absorbable in physiological conditions. In an aspect, a light reflective material component comprises a light reflective material that is biocompatible for biological organisms. In an aspect, a light reflective material component comprises a light reflective material that polymerizes with at least one of a photopolymerizable macromer, a diluent, a light reflective material, or a combination thereof.

[0147] In one aspect, the present disclosure provides an additive manufacturing process comprising: (a) providing a vat containing a first composition as disclosed herein comprising polyEU and polySH; (b) directing actinic radiation from a light source into the first composition in the vat, where the actinic radiation is effective to induce polymerization of components of the composition so as to form a second composition; (c) forming a solid article comprising the second composition. The step (c) may be accomplished by repeatedly directing actinic radiation at the first composition in the vat, particularly as the build platform is moved. The second composition will be or comprise a photopolymerization product of polyEU and polySH.

[0148] In one aspect, the present disclosure provides an additive manufacturing process comprising: (a) providing a vat containing a first composition as disclosed herein containing polyhv, polyAl and polyA2; (b) directing actinic radiation from a light source into the first composition in the vat, where the actinic radiation is effective to inducepolymerization of photocurable components of the first composition so as to form a second composition comprising photochemically cured composition; and (c) applying thermal energy to the second composition comprising photochemically cured composition so as to form a third composition comprising photochemically cured composition and thermally cured composition. The second composition will be or comprise a photopolymerization product of polyhv. The third composition will be or comprise a double network of the photopolymerization product of polyhv in combination and the thermally induced polymerization product of polyAl and polyA2.

[0149] In one aspect, the present disclosure provides a method of manufacturing an article by 2 photon polymerization printing, comprising curing a curable composition as disclosed herein to form the article. In one aspect, the present disclosure provides a method of manufacturing an article by computer axial lithography, comprising curing a curable composition as disclosed herein to form the article. In one aspect, the present disclosure provides a method of manufacturing an article by material extrusion comprising curing a curable composition as disclosed herein to form the article. In one aspect, the present disclosure provides a method of manufacturing an article by material jetting, comprising curing a curable composition as disclosed herein to form the article. In one aspect, the present disclosure provides a method of manufacturing an article by binder jetting, comprising curing a curable composition as disclosed herein to form the article. In one aspect, the present disclosure provides a method of manufacturing an article by continuous light interface production (CLIP), comprising curing a curable composition as disclosed herein to form the article. In one aspect, the present disclosure provides a method of manufacturing an article by vat polymerization, comprising curing a curable composition as disclosed herein to form the article.Cured Compositions

[0150] The present disclosure comprises an article, additionally referred to herein as a cured composition, a part, or a printed article or a solid article, which may be made by the methods disclosed herein from the compositions disclosed herein. In an aspect, an article may be a medical device. In an aspect, an article may be a portion of a medical device. In an aspect, an article may be porous. In an aspect, an article may be biodegradable under physiological conditions. In an aspect, a biodegradable article may have a degradation time of about threedays to about five years. In an aspect, an article may not be biodegradable. In an aspect, a portion of an article may be biodegradable and a second portion may be non-biodegradable or have a different degradation time from the degradation time of the first portion or the rest of the article.

[0151] As mentioned elsewhere, in one aspect, a cured composition does not contain any appreciable amount of water. For example, in aspects, a cured composition contains less than 2500 ppm water, or less than 1000 ppm water, or less than 500 ppm water. A cured composition is the same as a printed article or may also be described as a part.

[0152] In one aspect, a cured composition will degrade in water or when exposed to aqueous conditions. Thus, in one aspect, a 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 aspect, a cured composition degrades under aqueous conditions to form particulate material rather than, e.g., forming a swollen material, i.e., a material which has absorbed water and is in a swollen state. For example, when the cured composition is placed into a degradation media comprising water at a pH 7.0 to 7.4 phosphate buffer, or in phosphate buffer saline, the cured composition will undergo dissolution in the degradation media. Upon dissolution, such that greater than 50 wt%, or greater than 60 wt%, or greater than 70 wt%, or greater than 80 wt%, or greater than 90 wt% of the total weight of the cured composition has dissolved in the degradation media, the undissolved material will have a particular morphology rather than a swollen morphology.

[0153] In one aspect, cured compositions of the present disclosure demonstrate desirably low swelling when placed in aqueous media. Swelling can be a serious problem when a cured composition is in prolonged contact with aqueous media. For example, when a cured composition is a component of, or all of, a biodegradable implantable medical device, and that device is implanted in a patient, the device may undergo both degradation (which is desirable) and swelling (which may be undesirable). Swelling may be a particular problem towards the end of the implant degradation, i.e., after most of the implant has degraded. However, the problem of swelling, particularly late stage swelling as may be observed after a majority of the implant has degraded (i.e., greater than 50% weight loss, or greater than 60% weight loss, or greater than 70% weight loss, or greater than 80% weight loss, or greater than 90% weight loss), can be mitigated by use of the curable compositions of the presentdisclosure.

[0154] In one embodiment, a disclosed part contains two or more different lattice structures. In one embodiment, the lattice contains a core of one lattice structure and a shell of another lattice structure. In another embodiment, a part contains greater than two different lattice structures. In one aspect, a part is a lattice structure that is homogeneous. In one aspect, the part is a lattice structure that is heterogeneous.

[0155] In one aspect, a part comprises a lattice structure wherein the lattice is derived from a repeating unit cell. A lattice unit cell refers to the smallest repeating unit that forms the structure of the lattice. Examples of unit cells for lattices structures are listed but not limited to simple cubic (sc), body centered cubic (bcc), face centered cubic (fee), simple tetragonal, body centered tetragonal, simple orthorhombic, orthorhombic at the base center, orthorhombic at the body center, orthorhombic at the face center, simple hexagonal, rhombohedral, simple monoclinic, monoclinic at the base center, and triclinic. In another aspect, the part comprises of triply periodic minimal surface (TPMS) unit cells. Examples of these are listed but not limited to gyroid, Schwarz primitive, neovius, and Fisher-Koch. In another aspect, the part comprises custom unit cells from a CAD software. In another aspect, the part comprises a lattice structure wherein there are no repeating unit cells. One example of this is the Voronoi lattice structure. See FIG. 15 for examples of Voronoi, Grid and BCC structures. In another example, the part comprises a structure that is a combination of a repeating unit cell and a randomly generated lattice structure.

[0156] In one aspect, the lattice structure has an organic factor that affects the curvature at each joint of the lattice structure. For example, a lattice organic factor of 1 has no additional curvature to the lattice joints. Wherein, a lattice organic factor of 3 has curved joint that can greatly reduce the stress concentrations within the structure. In one aspect, the lattice structure has an organic factor that ranges from but not limited to 1 to 1.5, 1.1 to 1.5, 1.5 to 2.5, 1 to 2.5, 1 to 3, and 2 to 3, 3 to 5, and 1 to 5.

[0157] In one embodiment, a part with a lattice structure is coated with a second polymer, e.g., a coating polymer. In one aspect, a coating polymer is bioresorbable under physiological conditions and biocompatible. In another aspect, the part with a lattice structure comprises an open pore structure filled with a second polymer. In one aspect, a polymer that fills the porous structure is bioresorbable under physiological conditions andbiocompatible. Examples of synthetic bioresorbable polymers may comprise organic compounds comprising aliphatic polymers and copolymers including but not limited to polyesters, polyurethanes, polyethers, polyanhydrides, polycarbonates, and polyhydroxy alkanoates or combinations thereof. Some naturally derived polymers and proteins are described but not limited to the following: chitosan, hyaluronic acid, gelatin, peptide sequences, collagen, and functionalized analogs. Some examples of polyesters may include but are not limited to homopolymers, random copolymers, and block copolymers derived from lactide, glycolide, caprolactone, and p-dioxanone. Some examples of polycarbonates and polycarbonate esters may include but are not limited to polytrimethlyene carbonate, poly(trimethylene carbonate-co-caprolactone), poly(trimethylene carbonate-co-caprolactone-co-glycolide), and poly(trimethylene carbonate-co-caprolactone-co-lactide). Bioresorbable polymers and copolymers are known to those of skill in the art, and are contemplated for use with disclosed constructs. In one aspect, a coating polymer is not bioresorbable under physiological conditions but is biocompatible. Examples of these may include slip coatings or non slip coatings such as the following: hyaluronan (hyaluronic acid / sodium hyaluronate), polyacrylic acid variants, polyvinylpyrrolidone (PVP), polyethylene glycol / PEG-based polymers, polyacrylamide-type chemistries, L-DOPA (L-3,4-dihydroxyphenylalanine), D-DOPA, dopamine, carbidopa, or poly(NIPAM) (poly(N-isopropylacrylamide).

[0158] In one embodiment, a part comprises a lattice structure wherein the strut size is less than 6 mm, less than 4 mm, less than 2 mm, or less than 1 mm. For example, ranges for the strut size in a lattice may include but are not limited to: 1 pm to 50 pm, 50 pm to 300 pm, 100 pm to 300 pm, 300 pm to 600 pm, 500 pm to 1000 pm, 100 pm to 3000 pm, 50 pm to 3000 pm, or 500 pm to 6000 pm. Often, the strut size can be referred to as the diameter of the strut.

[0159] In one embodiment, a part comprises a lattice structure where struts have a regular cross-section. One of the strut shapes may be selected from the following but not limited to: circle, ellipse, oval, rectangle, square, star, cross, triangle, rhombus, pentagon, hexagon, heart, or other polygons. A part may comprise a lattice with more than one shape for the cross-sectional area of one or more struts. In one embodiment, a part comprises a lattice structure where struts have an irregular shape.

[0160] In one embodiment, a part comprises a lattice structure that may can be formed in many different shapes. One example may be a sheet for a wound product. Another example may be a lattice part that has a tear drop shape for a breast implant. The lattice parts may comprise of many different sizes and shapes to support tissue regrowth where there are voids. A part comprising a lattice may also be referred to as a lattice part.

[0161] In one embodiment, a part comprises a lattice structure with a constant strut size throughout the part. In another embodiment, a part comprises a lattice structure with two or more different strut diameters and may include a range of 2 to 100 different strut diameters. In another embodiment, a part comprises a lattice structure where the strut diameter is a gradient of one diameter to a second different diameter.

[0162] In one embodiment, a part comprises a lattice structure with a pore size that is variable throughout the part. In another embodiment, a part has a lattice structure where the pore size is constant. For cell infiltration into a scaffold, it may be desired that the pore size is greater than 100 pm, greater than 200 pm, or greater than 300 pm. Pore size for a lattice part may be within the following ranges but not limited to: 1 pm to 200 pm 100 pm to 200 pm, 200 pm to 300 pm, 100 pm to 300 pm, 300 pm to 500 pm, 300 pm to 1000 pm, 500 pm to 3000 pm, 100 pm to 3000 pm, 50pm to 3000 pm, or 1500 pm to 10 mm. In one embodiment, a part comprises a lattice structure that has a gradient of pores size throughout the part. A lattice part is a part comprising a lattice, and such a lattice part may have one or more portions of the part that is a lattice, or the part may be completely a lattice structure.

[0163] In one embodiment, a part comprises a lattice structure wherein the beam length is less than 6 mm, less than 3 mm, less than 2 mm, or less than 1 mm. A beam length may be from about 0.1mm to about 10 mm or 0.05 mm to 2 mm. In one embodiment, a lattice part has beam length that is constant throughout the part. In another embodiment, a lattice part has beam length variable all throughout the structure.

[0164] In one embodiment, a part has a lattice structure wherein the materials are resorbable under physiological conditions. In another embodiment, a part has a lattice structure and loses mechanical strength in 1 to 2 months, in 2-4 months, or in 2-6 months. In another embodiment, a part has a lattice structure and loses mechanical strength in 6 to 8 months or loses strength in 6 to 12 months. In another embodiment, a lattice part is made of materials that are biocompatible. In another embodiment, a lattice part is made of materialsthat degrade into biocompatible degradation byproducts. In another embodiment a part has a lattice structure that fully degrades in the body under physiological conditions exhibiting a mass loss of 12 months to 24 months, 9 months to 18 months, 6 to 18 months and 12 months to 36 months, and 24 months to 60 months. Additionally, the lattice part degrades under physiological conditions exhibiting strength loss from 1 day to 1 month, 1 week to 3 months, 2 months to 9 months, 3 months to 18 months, 6 months to 18 months, and 12 months to 36 months.

[0165] In one aspect, one or more drugs, also known as bioactive agents, which may include pharmaceutical compounds, proteins, fragments or proteins; receptors, antagonists, agonists, or other organic or inorganic compounds or molecules that have an effect in a living organism, are incorporated into a photopolymerizable formulation, a curable composition, and that curable composition is printed through an additive manufacturing process, in order to control drug release, a method may comprise tuning the lattice structure for an optimal drug release profile, e.g., choosing particular aspects, such as chemical compounds, particular amounts of such compounds, and / or additive manufacturing printing parameters, such that changes in some or all of these choices, or others, allow for differing characteristics in drug release profiles in a printed article. In one aspect, a drug release profile is a zero order release. In another aspect, a drug release profile is a near zero order release profile. Near zero order will be defined by a release profile that has an R2value of greater than 0.9 when a zero order model is applied to a plot of cumulative release versus time. In one aspect, a drug release profile is a burst release followed by zero order or near zero order. In one aspect, a drug release profile is delayed followed by zero order or near zero order. In one aspect, a drug release profile is classified as first order release. In one aspect, a drug release profile is classified as second order release. In one aspect, a drug release profile is classified as composite of zero order, first order and / or second order first order release.

[0166] In one aspect, a drug is soluble in the photopolymerizable composition. In another aspect, a drug is insoluble in the photopolymerizable composition. In one aspect, the particle size of a drug is less than 100 pm, less than 50 pm, less than 25 pm, less than 10 pm, or less than 5 pm. The range of drug particle size may include but is not limited to 50 nm to 500 nm, 500 nm to 1 pm, 1 pm to 5 pm, 1 pm to 10 pm, 5 pm to 25 pm, and 1 pm to 50 pm.

[0167] In another aspect of the invention, a drug is encapsulated in a polymer particulate, e.g., a drug encapsulated particulate, which is incorporated into the photopolymerizable composition. In one aspect, a drug encapsulated particulate is insoluble in the photopolymerizable composition. In another embodiment, a drug encapsulated particulate is partially soluble in the photopolymerizable composition. An insoluble or partially soluble drug encapsulated particulate may include a particle size of the follow ranges but is not limited to these: 50 nm to 500 nm, 500 nm to 1 pm, 1 pm to 5 pm, 1 pm to 10 pm, 5 pm to 25 pm, and 1 pm to 50 pm. In one aspect, a polymer used to incorporate the drug to form a drug encapsulated particulate is biodegradable and biocompatible under physiological conditions. In another aspect, a polymer used to form a drug encapsulated particulate can be cleared by the body. Some examples of synthetic bioresorbable polymers may comprise organic compounds comprising aliphatic polymers and copolymers including but not limited to polyesters, polyurethanes, polyethers, polyanhydrides, polycarbonates, and polyhydroxy alkanoates or combinations thereof. Some naturally derived polymers and proteins are described but not limited to the following: chitosan, hyaluronic acid, gelatin, collagen, peptide sequences, and functionalized analogs. Some examples of polyester may include but are not limited to homopolymers and copolymers derived from lactide, glycolide, caprolactone, and p-dioxanone. Some examples of polycarbonates and polycarbonate esters may include but are not limited to polytrimethlyene carbonate, poly(trimethylene carbonate-co-caprolactone), poly(trimethylene carbonate-co-caprolactone-co-glycolide), and poly(trimethylene carbonate-co-caprolactone-co-lactide).

[0168] In one aspect, a method of additive manufacturing for making bioresorbable lattice parts may be selected from melt layering (fuse fabrication, FFF or fused deposition modeling, FDM), inkjet printing, photopolymer jetting, stereolithography, selective laser sintering, additive manufacturing systems based on digital optical processing, continuous liquid interface production, selective laser melting, additive manufacturing based on adhesive jetting, additive manufacturing based on multi-jet melting, high speed sintering processes and laminate object modeling. In examples herein, additive e manufacturing process may be a sintering process, melt lamination, light assisted photopoymerization, a vat photopolymerization process.

[0169] In one aspect, a lattice part comprises a drug eluting coating on the part. For example, a coating is bioresorbable and can degrade in the body under physiological conditions. In another aspect, a lattice part is filled with a bioresorbable polymer that comprises a drug and that is drug eluting.

[0170] In one aspect of the invention, a lattice part comprising one or more drugs may sustain drug release for greater than 7 days, In another aspect, a lattice part comprising one or more drugs may sustain drug release for greater than 20 days. In another aspect, a lattice part comprising one or more drugs may sustain drug release for greater than 40 days. In another aspect, a lattice part comprising one or more drugs may sustain drug release for greater than 60 days. In another aspect, a lattice part comprising one or more drugs may sustain drug release for greater than 100 days., A lattice part comprising one or more drugs may sustain drug release over the following range but is not limited to: 1 to 7 days, 1 to 21 days, 1 to 40 days, 1 to 75 days, and 1 to 100 days. The drug used for drug elution may be hydrophilic or hydrophobic.

[0171] In one aspect, the compression modulus of a lattice part is greater than 1 kPa, greater than 100 kPa, greater than 500 kPa, greater than 1 MPa, or greater than 10 MPa. The compression modulus of the lattice part has a range of the following but not limited to 1 kPa to 100 kPa, 100 kPa to 500 kPa, 500 kPa to 1 MPa, 1 MPa to 10 MPa, and 10 M a to 100 MPa. In one aspect, the collapse stress of lattice part is greater than 0.1 kPa, greater than 10 kPa, than 100 kPa, greater than 500 kPa, than 1 MPa, or greater than 10 MPa. The collapse stress of the lattice part has a range of the following but not limited to 0.1 to 10 Kpa, 1 kPa to 100 kPa, 100 kPa to 500 kPa, 500 kPa to 1 MPa, 1 MPa to 10 MPa, and 10 MPa to 100 MPa.

[0172] In one aspect, a part comprising a lattice structure (e.g., a lattice part) as disclosed herein may have an elongation of greater than 10%, by greater than 30%, greater than 50%, greater than 100%, or greater than 200% when printed via vat photopolymerization or light assisted photopolymerization methods. In one example, a photopolymerizable material to create a part with a lattice structure has an elongation with a range of the following but not limited to: 1% to 10%, 10% to 50%, 30% to 75%, 50% to 100%, 100% to 200%, and 150% to 350% when printed via vat photopolymerization or light assisted photopolymerization methods. In one aspect, a photopolymerizable material to create a part with a lattice structure has a tensile modulus of greater than 0.5 kPa, greater than 1 MPa,than 5 MPa, than 10 MPa, or greater than 30 MPa when printed via vat photopolymerization or light assisted photopolymerization methods. In one example, a photopolymerizable material to create a part with a lattice structure has a tensile modulus with a range of the following but not limited to: 0.5 kPa to 10 kPa, 10 kPa to 100 kPa, 100 kPa to 500 kPa, 500 kPa to 2 MPa, 2 MPa to 10 MPa to 50 MPa, 50 MPa to 500 MPa, 500 MPa to 15 GPa when printed via vat photopolymerization or light assisted photopoymerization methods.

[0173] In one aspect, a lattice structure as disclosed herein has an elongation of greater than 10%, greater than 30%, greater than 50%, greater than 100%, or greater than 200%. In one example, the lattice structure has an elongation with a range of the following but not limited to: 1% to 100%, 10% to 50%, 30% to 75%, 10% to 350%, 50% to 100%, 100% to 200%, and 150% to 350%. In one aspect, the lattice structure has a tensile modulus of greater than 0.5 kPa, greater than 1 MPa, than 5 MPa, than 10 MPa, or greater than 30. In one example, the lattice structure has a tensile modulus with a range of the following but not limited to: 0.5 kPa to 10 kPa, 10 kPa to 100 kPa, 100 kPa to 500 kPa, 500 kPa to 2 MPa, 2 MPa to 10 MPa to 50, 50 MPa to 500 MPa, 500 MPa to 15 GPa.

[0174] In one embodiment, the lattice part has a suture pullout force of 0.1 to 1 N, 0.5 to 2 N, 1 N to 10 N, 10 N to 25 N, 25 N to 50 N, 50 N to 150 N. The suture pullout is conducted by suturing a 2-0 polypropylene suture and pulling the suture on a electromechanical testing system.

[0175] In one embodiment, the lattice part has a flexural rigidity 0.5 pN*m to 2 pN*m, 2 pN*m to 8 pN*m, 5 pN*m to 15 pN*m, 15 pN*m to 75 pN*m, 50 pN*m to 500 pN*m, 500 pN*m to 2000 pN*m, 1000 pN*m to 20,000 pN*m and 0.5 pN*m to 1000 pN*m. These test could be evaluated through ASTM D1388-23 Standard Test Method for Stiffness of Fabrics using the cantilever bending test method.

[0176] In one embodiment, a lattice part comprises at least one additional layer. In one aspect, one or more additional layers added to the lattice part comprise one of the following structures: warp knit textile, weft knit textile, film, foam, sponge, freeze-dried mat, and non-woven construct, though other constructs are contemplated by the present disclosure. In one aspect, additional layer(s) to the lattice part comprise a biodegradable material under physiological conditions. In another aspect, additional layer(s) to the lattice part comprise a non-degradable material. In one aspect, additional layer(s) may be joined tothe lattice structure by applying an adhesive. In another aspect, additional layer(s) may be printed directly onto the lattice part. In another aspect, a lattice part may be printed directly onto an additional layer. In another aspect, an additional layer is attached mechanically to a surface of a lattice part or another layer, or a layer attached to a lattice part. Some examples of mechanical attachment may include but are not limited to surface features, hooks, staples, and suturing. Some examples of biodegradable materials for the additional layer(s) are listed but not limited to polyesters, polycarbonates, polyanhydrides, polyortho esters, polyhydroxyalkonoates, polyurethanes, polypeptides, polyethers, polythioethers, polyamides, and naturally derived polymers. Some examples of naturally derived polymers for additional layer(s) are described but not limited to the following: chitosan, hyaluronic acid, collagen, gelatin, pectin, cellulose or modified version of naturally derived materials. Some examples of polyester may include but are not limited to homopolymers and copolymers derived from lactide, glycolide, caprolactone, and p-dioxanone. Some examples of polycarbonates and polycarbonate esters may include but are not limited to polytrimethlyene carbonate, poly(trimethylene carbonate-co-caprolactone), poly(trimethylene carbonate-co-caprolactone-co-glycolide), and poly(trimethylene carbonate-co-caprolactone-co-lactide). Some example of non-degradable materials for the additional layer(s) may include but are not limited to ultrahigh molecular weight polyethylene (UHMW-PE), polypropylene, an aliphatic polyamide, an aromatic polyamide, polyether-ether ketone, polyalkylene terephthalate, polydimethylsiloxane, silicone, and copolymer or combinations thereof.

[0177] In one aspect, a lattice part is a patient matched medical device, meaning that the lattice part, e.g., medical device, which may or may not also include one or more coatings, one or more additional layers, and / or one or more drugs or drug eluting compositions, has been designed and manufactured specifically for a particular subject or patient, or has a particular structure that may be applicable for particular patent or subject structures or needs.

[0178] In one embodiment, the lattice part is a medical device for wound healing or soft tissue regeneration. In one aspect, the wound healing or soft tissue lattice part will comprise a Voronoi structure or lattice structure with one or more repeating unit cells. In another aspect, the wound healing or soft tissue lattice part will comprise a lattice structure with anisotropic properties.

[0179] The following are some exemplary embodiments of the present disclosure, which may optionally comprise one or more chain transfer agents and / or a beta-carotene compound.1) A composition comprising a first organic compound (polySH) having multiple thiol groups (SH), a second organic compound (polyEU) having multiple ethylenically unsaturated groups (EU), and a photoinitiator. A stabilizer may optionally be present in the composition, where the stabilizer may optionally be selected from the group consisting of tocopherol, gallic acid, ester of gallic acid, butylated hydroxyanisole and combinations thereof.2) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 3-27, wherein the composition has an SH to EU equivalents ratio of X: Y, where X ranges from 25-75 and Y ranges from 75-25 and the sum of X and Y is 100.3) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiment 2, wherein polySH is water soluble.4) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2 or 3, wherein polySH is bioabsorbable.5) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2 or 3 or 4, wherein polySH is a macromer.6) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2 or 3 or 4, wherein polySH is a macromer having a molecular weight of greater than 1,000 g / mol.7) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 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 as disclosed herein, for example any of embodiments 2-7, wherein polyEU is water soluble.9) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example any of embodiments 2-8, wherein polyEU is bioabsorbable. 10) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-9 wherein EU of polyEU is acrylate.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-9, wherein EU of polyEU is methacrylate.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-9, wherein EU of polyEU is norbornenyl.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-7, wherein polyEU is a macromer.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-7, wherein polyEU is a macromer having a molecular weight of greater than 1,000 g / mol.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-14, wherein at least one of polySH and polyEU further has multiple carbonyl groups, where optionally polyEU has multiple carbonyl groups, or where optionally polySH and polyEU each have multiple carbonyl group. ) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-15, wherein at least one of polySH and polyEU further has multiple ester groups, where optionally polyEU has multiple ester groups, or where optionally polySH and polyEU each have multiple ester group.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-15, wherein at least one polyEU and polySH further has multiple ester groups and multiple carbonate groups, where optionally polyEU has both multiple ester groups and multiple carbonate groups, or where optionally both of polySH and polyEU further have both multiple ester groups and multiple carbonate groups.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-15, wherein at least one of polySH and polyEU further has multiple ester groups and multiple urethane groups, where optionally polyEU has both multiple ester groups and multiple urethane groups, or where optionally both of polySH and polyEU further have both multiple ester groups and multiple urethane groups.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-15, wherein at least one of polySH and polyEUfurther has multiple carbonate groups and multiple urethane groups, where optionally polyEU has both multiple carbonate groups and multiple urethane groups, or where optionally both of polySH and polyEU further have both multiple carbonate groups and multiple urethane groups.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-19, wherein the multiple SH of polySH is selected from 2, 3 and 4.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-20, wherein the multiple EU of polyEU is selected from 2, 3 and 4.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-21, which is free of volatile materials having a boiling point of less than 110°C.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-22, which is anhydrous.) The composition of embodiment 1 or any embodiment of embodiment 1 as disclosed herein, for example embodiments 2-23, which is fluid at room temperature of about 18°C to about 22°C.) A composition comprising a photochemically cured reaction product of the compositions of any of embodiments 1-24.) The composition of embodiment 25 which is bioabsorbable.) The composition of embodiment 25 which is a solid at 50°C.) An additive manufacturing process comprising:a. providing a vat containing a first composition of any one of embodiment 1-24; b. directing actinic radiation from a light source into the first composition in the vat, where the actinic radiation is effective to induce polymerization of components of the composition so as to form a second composition; andc. forming a solid article comprising the second composition.) A composition comprising a first organic compound (polyhv) having multiple photopolymerizable groups (hv), a photoinitiator, a second organic compound (polyAl) having multiple reactive groups Al, and a third organic compound (polyA2)having multiple reactive groups A2, where Al reacts with A2 upon contact and exposure to a temperature of greater than 50°C.) The composition of embodiment 29 or any embodiment of embodiment 29, wherein polyhv is bioabsorbable.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30, wherein ppolyhv is a macromer.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 or 31, wherein polyhv is a macromer having a molecular weight of greater than 1,000 g / mol.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 or 31, wherein polyhv has a molecular weight of less than 500 g / mol.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 or 31, wherein polyhv is water soluble.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 34, wherein polyhv is polyEU elected from acrylate and methyacrylate.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 34, wherein hv of polyhv is norbornenyl.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 36, wherein Al is a nucleophile and A2 is an electrophile. ) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 36, wherein Al is selected from hydroxyl and amino. ) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 36, wherein A2 is selected from epoxide and isocyanate. ) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 39, wherein at least one of polyhv, polyAl and polyA2 further has multiple carbonyl groups, where optionally polyhv has multiple carbonyl groups, or where optionally polyhv and at least one of polyAl and polyA2 has multiple carbonyl group.) The composition of embodiment 29 or any embodiment of embodiment 29, for exampie embodiment 30 to 39, wherein at least one of polyhv, polyAl and polyA2 further has multiple ester groups, where optionally polyhv has multiple ester groups, or where optionally polyhv and at least one of polyAl and polyA2 has multiple ester group.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 39, wherein at least one polyhv, polyAl and polyA2 further has multiple ester groups and multiple carbonate groups, where optionally polyhv has both multiple ester groups and multiple carbonate groups, or where optionally polyhv and at least one of polyAl and polyA2 has both multiple ester groups and multiple carbonate groups.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 39, wherein at least one of polyhv, polyAl and polyA2 further has multiple ester groups and multiple urethane groups, where optionally polyhv has both multiple ester groups and multiple urethane groups, or where optionally polyhv and at least one of polyAl and polyA2 has both multiple ester groups and multiple urethane groups.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 39, wherein at least one of polyhv, polyAl and polyA2 further has multiple carbonate groups and multiple urethane groups, where optionally polyhv has both multiple carbonate groups and multiple urethane groups, or where optionally polyhv and at least one of polyAl and polyA2 has both multiple carbonate groups and multiple urethane groups.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 44, wherein the multiple hv of polyhv is selected from 2, 3 and 4.) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 44, wherein the multiple Al of polyAl is selected from 2, 3 and 4.47) The composition of embodiment 29 or any embodiment of embodiment 29, for exampie embodiment 30 to 44, wherein the multipie A2 of polyA2 is selected from 2, 3 and 4.48) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 47, which is free of volatile materials having a boiling point of less than 110°C.49) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 47, which is anhydrous.50) The composition of embodiment 29 or any embodiment of embodiment 29, for example embodiment 30 to 47, which is fluid at a temperature of about 18°C to about 22°C.51) A composition comprising a photochemically cured reaction product and a thermally cured reaction product of the compositions of any of embodiments 29-50.52) The composition of embodiment 51 which is bioabsorbable.53) The composition of embodiment 51 which is a solid at 50°C.54) An additive manufacturing process comprising:a. providing a vat containing a first composition of any one of embodiments 29-50; b. directing actinic radiation from a light source into the first composition in the vat, where the actinic radiation is effective to induce polymerization of components of the first composition so as to form a second composition comprising photochemically cured composition; andc. applying thermal energy to the second composition comprising photochemically cured composition so as to form a third composition comprising photochemically cured composition and thermally cured composition.

[0180] The present disclosure comprises an article, referred to herein as a biodegradable biocompatible photopolymerized lattice part, comprising a biodegradable biocompatible polymeric composition having multiple ethylenically unsaturated groups and at least one photoinitiator, formed to comprise a lattice structure comprising a plurality of repeating or non-repeating unit cells comprising one or more strut sizes of 50 pm to 3000 pm, wherein the lattice part degrades under physiological conditions into a polymeric byproduct with a molecular weight of less than 20,000 Daltons. A lattice part may comprise a Voronoibased lattice structure. A lattice part may isotropic or anisotropic mechanics. A lattice part may comprise a gradient lattice structure wherein one or both of the lattice strut size or pore size changes throughout all or a portion of the part. A lattice part may comprise a lattice structure wherein one or both the lattice strut size or pore size remains constant throughout the part. A lattice part may comprise one or more struts having a cross-sectional shape of a circle, oval, elliptical, square, rectangular, or other polygons. A lattice part may comprise one or more struts having a cross-sectional shape that is irregular. A lattice part may comprise a pore size between 150 pm to 10 mm, or a pore size between 50 pm to 3 mm. A lattice part may comprise a suture pullout strength of 0.1 to 150 N for a 2 mm thick sheet of the material. A lattice part may comprise a flexural rigidity of 0.5 pN*m to 1000 pN*m for a 2 mm thick sheet of the material. A lattice part may comprise an organic factor of between 1 and 3, or an organic factor of between 1 and 2. A lattice part may comprise a cured photopolymerized biodegradable biocompatible polymeric composition, meaning that photopolymerization has occurred to solidify the originally liquid composition, wherein the photopolymerized biodegradable biocompatible polymeric composition of the part comprises an elongation of 1% to 100%, or an elongation of 10% to 350%. A lattice part may comprise all or a portion of one or more repeating unit cells. A lattice part may comprise all or a portion of one or more non-repeating unit cells. A lattice part may comprise a second biodegradable biocompatible composition, such as a biodegradable biocompatible composition disclosed herein, that fills the porous structure. A lattice part may comprise a biodegradable biocompatible polymeric composition comprising at least one chain transfer agent comprising a minimum of one thiol group. A lattice part may be manufactured by a manufacturing technique using vat photopolymerization or light assisted photopolymerization. A lattice part may comprise a biodegradable biocompatible polymeric composition comprising at least one of a biocompatible or naturally derived dye or UV absorber. A lattice part may comprise a biodegradable biocompatible polymeric composition comprising at least one free radical stabilizer. A lattice part may comprise a strength loss between 3 months to 18 months, or a strength loss between 7 days to 3 months. A lattice part may comprise a mass loss of 6 months to 18 months, or a mass loss of 12 months to 36 months. A lattice part may comprise a bioresorbable biocompatible coating. A lattice part may comprise a biodegradable biocompatible polymeric composition comprises a particulate comprising at least one offunctionalized hyaluronic acid, hyaluronic acid, functionalized collagen, collagen, functionalized gelatin, gelatin, peptide sequences, polyester, polycarbonate, polyester carbonate, hydroxyapatite, tricalcium phosphate, and combinations thereof. A lattice part may comprise a surface coating wherein the coating comprises at least one of functionalized hyaluronic acid, hyaluronic acid, functionalized collagen, collagen, functionalized gelatin, gelatin, peptide sequences, polyester, polycarbonate, polyester carbonate, polyethers, chitosan or chitosan derivatives, and combinations thereof. A lattice part may comprise a surface coating wherein the coating comprises at least one or at least one plurality of a particulate comprising at least one of functionalized hyaluronic acid, hyaluronic acid, functionalized collagen, collagen, functionalized gelatin, gelatin, peptide sequences, polyester, polycarbonate, polyester carbonate, hydroxyapatite, tricalcium phosphate, and combinations thereof.

[0181] There are many uses for a lattice part as described herein. A lattice part may comprise all or a portion of a medical device. A lattice part, alone or as a portion of a medical device, may be used as a medical device for wound care treatments, as a tissue scaffold, as a breast implant or in treatments for soft tissue repair.

[0182] A lattice part may comprise one or more bioactive agents. A lattice part may comprise at least one bioactive agent. Disclosed herein is an article, referred to herein as a biodegradable biocompatible photopolymerized lattice part, comprising one or more bioactive agent and a biodegradable biocompatible polymeric composition having multiple ethylenically unsaturated groups and a photoinitiator, formed to comprise a lattice structure comprising a plurality of repeating or non-repeating unit cells comprising one or more strut sizes of 50 pm to 3000 pm, wherein the lattice part degrades under physiological conditions into a polymeric byproduct with a molecular weight of less than 20,000 Daltons. A lattice part comprising one or more bioactive agents may comprise a Voronoi based lattice structure. A lattice part comprising one or more bioactive agents may comprise isotropic or anisotropic mechanics. A lattice part comprising one or more bioactive agents may comprise a gradient lattice structure wherein one or both of the lattice strut size or pore size changes throughout all or a portion of the part. A lattice part comprising one or more bioactive agents may comprise a lattice structure wherein one or both the lattice strut size or pore size remains constant throughout the part. A lattice part comprising one or more bioactive agents maycomprise one or more struts having a cross-sectional shape of a circle, oval, elliptical, square, rectangular, or other polygons. A lattice part comprising one or more bioactive agents may comprise one or more struts having a cross-sectional shape that is irregular. A lattice part comprising one or more bioactive agents may comprise a pore size between 150 pm to 10 mm, or a pore size between 50 pm to 3 mm. A lattice part comprising one or more bioactive agents may comprise a suture pullout strength of 0.1 to 150 N for a 2 mm thick sheet of the material. A lattice part comprising one or more bioactive agents may comprise a flexural rigidity of 0.5 pN*m to 1000 pN*m for a 2 mm thick sheet of the material. A lattice part comprising one or more bioactive agents may an organic factor of between 1 and 3, or an organic factor of between 1 and 2. A lattice part comprising one or more bioactive agents may comprise a cured photopolymerized biodegradable biocompatible polymeric composition, meaning that photopolymerization has occurred to solidify the originally liquid composition, wherein the photopolymerized biodegradable biocompatible polymeric composition of the part comprises an elongation of 1% to 100%, or an elongation of 10% to 350%. A lattice part comprising one or more bioactive agents may comprise all or a portion of one or more repeating unit cells. A lattice part comprising one or more bioactive agents may comprise all or a portion of one or more non-repeating unit cells. A lattice part comprising one or more bioactive agents may comprise a second biodegradable biocompatible material that fills the porous structure. A lattice part comprising one or more bioactive agents may comprise a biodegradable biocompatible polymeric composition comprising a chain transfer agent comprising a minimum of one thiol group. A lattice part comprising one or more bioactive agents may be manufactured by a manufacturing technique using vat photopolymerization or light assisted photopolymerization. A lattice part comprising one or more bioactive agents may comprise a biodegradable biocompatible polymeric composition comprising a biocompatible or naturally derived dye or UV absorber. A lattice part comprising one or more bioactive agents may comprise a biodegradable biocompatible polymeric composition comprising at least one free radical stabilizer. A lattice part comprising one or more bioactive agents may comprise a strength loss between 3 months to 18 months, or a strength loss between 7 days to 3 months. A lattice part comprising one or more bioactive agents may comprise a mass loss of 6 months to 18 months, or a mass loss of 12 months to 36 months. A lattice part comprising one or more bioactive agents may comprise a bioresorbablebiocompatible coating. A lattice part comprising one or more bioactive agents may comprise a biodegradable biocompatible polymeric composition comprises a particulate comprising at least one of functionalized hyaluronic acid, hyaluronic acid, functionalized collagen, collagen, functionalized gelatin, gelatin, peptide sequences, polyester, polycarbonate, polyester carbonate, hydroxyapatite, tricalcium phosphate, and combinations thereof. A lattice part comprising one or more bioactive agents may comprise a surface coating wherein the coating comprises at least one of functionalized hyaluronic acid, hyaluronic acid, functionalized collagen, collagen, functionalized gelatin, gelatin, peptide sequences, polyester, polycarbonate, polyester carbonate, polyethers, chitosan or chitosan derivatives, and combinations thereof.

[0183] A lattice part comprising one or more bioactive agents may comprise at least one bioactive agent with a release profile of a burst release followed by zero order or near zero order release kinetics. A lattice part comprising one or more bioactive agents may comprise at least one bioactive agent having sustained release of over 7 days, or over 20 days, or over 60 days. A lattice part comprising one or more bioactive agents may comprise at least one hydrophobic bioactive agent. A lattice part comprising one or more bioactive agents may comprise at least one hydrophilic bioactive agent. A lattice part comprising one or more bioactive agents may comprise at least one hydrophilic bioactive agent and at least one hydrophobic bioactive agent.

[0184] A lattice part comprising one or more bioactive agents may comprise at least one bioactive agent that is encapsulated. The encapsulation composition may be polymeric, and may comprise polymers known for encapsulation of bioactive materials, and / or polymers disclosed herein. A lattice part comprising one or more bioactive agents may comprise at least one encapsulated bioactive agent in a particulate form, referred to herein as a particulate encapsulated bioactive agent.

[0185] There are many uses for a lattice part comprising one or more bioactive agents as described herein. A lattice part comprising one or more bioactive agents may comprise all or a portion of a medical device. A lattice part comprising one or more bioactive agents, alone or as a portion of a medical device, may be used as a medical device for wound care treatments, as a tissue scaffold, as a breast implant or in treatments for soft tissue repair.

[0186] The disclosure has been described broadly and generically herein. Each of thenarrower species and subgeneric groupings falling within the generic disclosure also form part of the disclosure. This includes the generic description of the disclosure with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

[0187] It is also to be understood that as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural reference unless the context clearly dictates otherwise, the term "X and / or Y" means "X" or "Y" or both "X" and "Y", and the letter "s" following a noun designates both the plural and singular forms of that noun. In addition, where features or aspects of the disclosure are described in terms of Markush groups, it is intended, and those skilled in the art will recognize, that the disclosure embraces and is also thereby described in terms of any individual member and any subgroup of members of the Markush group, and Applicants reserve the right to revise the application or claims to refer specifically to any individual member or any subgroup of members of the Markush group.

[0188] As used herein, nomenclature for compounds, including organic compounds, can be given using common names, IUPAC, IUBMB, or CAS recommendations for nomenclature. When one or more stereochemical features are present, Cahn-lngold-Prelog rules for stereochemistry can be employed to designate stereochemical priority, EIZ specification, and the like. One of skill in the art can readily ascertain the structure of a compound if given a name, either by systemic reduction of the compound structure using naming conventions, or by commercially available software, such as CHEMDRAW™ (Cambridgesoft Corporation, U. S. A.).

[0189] As used in the specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a functional group," "an alkyl,” or "a residue" includes mixtures of two or more such functional groups, alkyls, or residues, and the like.

[0190] References in the specification and concluding claims to parts by weight of a particular element or component in a composition denotes the weight relationship between the element or component and any other elements or components in the composition or article for which a part by weight is expressed. Thus, in a compound containing 2 parts by weight of component X and 5 parts by weight component Y, X and Y are present at a weight ratio of 2:5, and are present in such ratio regardless of whether additional components arecontained in the compound.

[0191] A weight percent (wt. %) of a component, unless specifically stated to the contrary, is based on the total weight of the formulation or composition in which the component is included.

[0192] As used herein, when a compound is referred to as a monomer or a compound, it is understood that this is not interpreted as one molecule or one compound. For example, two monomers generally refers to two different monomers, and not two molecules.

[0193] As used herein, the terms "optional" or "optionally" means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.

[0194] As used herein, the terms "about," "approximate," and "at or about" mean that the amount or value in question can be the exact value designated or a value that provides equivalent results or effects as recited in the claims or taught herein. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art such that equivalent results or effects are obtained. In some circumstances, the value that provides equivalent results or effects cannot be reasonably determined. In such cases, it is generally understood, as used herein, that "about" and "at or about" mean the nominal value indicated ±10% variation unless otherwise indicated or inferred. In general, an amount, size, formulation, parameter or other quantity or characteristic is "about," "approximate," or "at or about" whether or not expressly stated to be such. It is understood that where "about,” "approximate," or "at or about" is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise.

[0195] As used herein, the term "subject” can be a vertebrate, such as a mammal, a fish, a bird, a reptile, or an amphibian. Thus, the subject of the herein disclosed methods can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig or rodent. The term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be covered. In an aspect, a mammalian subject is a human. The term "patient" includes human and veterinary subjects.

[0196] As used herein, the terms "administering" and "administration" refer to any method of providing a disclosed composition to a subject.

[0197] As used herein, the terms "comprises," "comprising," "includes," "including," "containing," "characterized by," "has," "having" or any other variation thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. The term "comprising" may also include the limitations associated with the use of "consisting of" or "consisting essentially of".

[0198] The transitional phrase "consisting of' excludes any element, step, or ingredient not specified in the claim, closing the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase "consists of' appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.

[0199] The transitional phrase "consisting essentially of" limits the scope of a claim to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s) of the claimed invention. A "consisting essentially of" claim occupies a middle ground between closed claims that are written in a "consisting of" format and fully open claims that are drafted in a "comprising" format. Optional additives as defined herein, at a level that is appropriate for such additives, and minor impurities are not excluded from a composition by the term "consisting essentially of".

[0200] When a composition, a process, a structure, or a portion of a composition, a process, or a structure, is described herein using an open-ended term such as "comprising," unless otherwise stated the description also includes an embodiment that "consists essentially of" or "consists of" the elements of the composition, the process, the structure, or the portion of the composition, the process, or the structure.

[0201] The articles "a" and "an" may be employed in connection with various elements and components of compositions, processes or structures described herein. This is merely for convenience and to give a general sense of the compositions, processes or structures. Such a description includes "one or at least one" of the elements or components.Moreover, as used herein, the singular articles also include a description of a plurality of elements or components, unless it is apparent from a specific context that the plural is excluded.

[0202] The term "about" means that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and / or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art. In general, an amount, size, formulation, parameter or other quantity or characteristic is "about" or "approximate" whether or not expressly stated to be such.

[0203] The term "or”, as used herein, is inclusive; that is, the phrase "A or B" means "A, B, or both A and B". More specifically, a condition "A or B" is satisfied by any one of the following: A is true (or present) and B is false (or not present); A is false (or not present) and B is true (or present); or both A and B are true (or present). Exclusive "or" is designated herein by terms such as "either A or B" and "one of A or B", for example.

[0204] In addition, the ranges set forth herein include their endpoints unless expressly stated otherwise. Further, when an amount, concentration, or other value or parameter is given as a range, one or more preferred ranges or a list of upper preferable values and lower preferable values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether such pairs are separately disclosed. The scope of the invention is not limited to the specific values recited when defining a range.

[0205] When materials, methods, or machinery are described herein with the term "known to those of skill in the art", "conventional" or a synonymous word or phrase, the term signifies that materials, methods, and machinery that are conventional at the time of filing the present application are encompassed by this description. Also encompassed are materials, methods, and machinery that are not presently conventional, but that will have become recognized in the art as suitable for a similar purpose.

[0206] Unless stated otherwise, all percentages, parts, ratios, and like amounts, are defined by weight.

[0207] All patents, patent applications and references included herein are specifically incorporated by reference in their entireties.

[0208] It should be understood, of course, that the foregoing relates only to preferred embodiments of the present disclosure and that numerous modifications or alterations may be made therein without departing from the spirit and the scope of the disclosure as set forth in this disclosure.

[0209] The following Examples are offered by way of illustration and not by way of limitation. Chemicals were obtained from commercial sources, e.g., MilliporeSigma (St. Louis, MO, USA).EXAMPLES

[0210] Example 1 Hydroxyl Terminated Precursor Polymers

[0211] In one aspect, the present disclosure provides compositions that contain at least one of the compounds denoted as polyhv, polySH, polyEU, polyAl and polyA2. Optionally, each of these compounds may be made from a precursor polymer having hydroxyl groups in lieu of the hv or SH or EU or Al or A2 groups, where optionally the hv, SH, EU, Al or A2 group is joined to the precursor polymer through a suitable linking group. The present Example illustrates the preparation of exemplary hydroxyl-containing precursor polymers.

[0212] Table 1 identifies 16 precursor polymers, uniquely labeled as 3DP 1 through 3DP 16, which may generally be described as having or including compounds of the general formula CC-[arm-OH] according to the present disclosure. The term arm-OH refers to an arm that terminates in a hydroxyl group (OH), i.e., has a hydroxyl end group.

[0213] When the precursor polymer includes compounds that include the formula CC-[(A)-(B)], i.e., when an arm is formed from residues of monomers from Group A (any one or more of trimethylene carbonate and e-caprolactone) which are proximal to (adjacent to) the central core, and residues of monomers from Group B (any one or more of glycolide, lactide and p-dioxanone) which are the distal to (furthest away from) the central core, such precursor polymers may be prepared by reacting a functionalized central core, also referred to herein as an initiator, with one or more monomers from Group A, followed by reacting that reaction product (referred to herein as a precursor prepolymer) with one or more monomers from Group B. The result is a central core bonded to one or more arms, each arm being hydroxyl terminated and having the formula -(A)-(B)-OH. The preparation of such a precursor polymer is illustrated in Example 1A below, where the central core is trifunctional and thefunctionalized central core / initiator is provided by trimethylolpropane.

[0214] Example 1A - Preparation of triaxial 3DP-6 precursor polymer.

[0215] Trimethylene carbonate (1.4 mol) and e-caprolactone (1.4 mol) were copolymerized using trimethylolpropane (0.6 mol) as initiator and stannous octoate (7.0 x 10-5mol) as catalyst, at 130°C for 72 hours to provide a polymer precursor. Glycolide (1.1 mol) and additional stannous octoate (2.1 x 10-4mol) were combined with the polymer precursor at 160°C for 3 hours to provide a precursor polymer having polyglycolide grafts on the ends of the polymer precursor. The amorphous liquid precursor polymer, thus obtained, was devolatilized and characterized by1H NMR spectroscopy, rheometry (viscosity 17,300 cP at shear rate 105 s’1), differential scanning calorimetry (Tg = -45°C) and gel permeation chromatography (Mn = 1884 Da, PDI=1.80).

[0216] When the precursor polymer includes compounds that include the formula CC-[(B)-(A)], i.e., when residues of monomers from Group B (glycolide, lactide and p-dioxanone) are proximal to (adjacent to) the central core, and residues of monomers from Group A (trimethylene carbonate and caprolactone) are the distal to (furthest away from) the central core, such precursor polymers may be prepared by reacting a functionalized central core with one or more monomers from Group B, followed by reacting that reaction product with one or more monomers from Group A. The result is a central core bonded to one or more arms, each arm being hydroxyl terminated and having the formula -(B)-(A)-OH. The preparation of such a precursor polymer is illustrated in Example IB below, where the central core is trifunctional and the functionalized central core is provided by trimethylolpropane.

[0217] Example IB - Preparation of triaxial 3DP-4 precursor polymer.

[0218] In a first step, glycolide (1.1 mol) was polymerized with trimethylolpropane (0.6 mol) as initiator and stannous octoate (7 x 10-5mol) as catalyst, at 160°C for 3 hours to provide a polymer precursor. After completion of the first step, a mixture of equimolar amounts of trimethylene carbonate (1.4 mol) and e-caprolactone (1.4 mol) was copolymerized onto ends of the polymer precursor by adding more stannous octoate (2 x 10-4mol) and reacting at 130°C for 72 hours. The resulting amorphous liquid was devolatilized and characterized by1H NMR spectroscopy, rheometry (viscosity 17,300 cP at shear rate 105 s-1), differential scanning calorimetry (Tg = -45°C) and gel permeation chromatography (Mn = 1909 Da, PDI=1.83).

[0219] Following the procedures outlined in Examples 1A and IB, additional polyester precursor polymers were synthesized as described in Table 1. All linear samples were synthesized with 1,3-propanediol as the bifunctional initiator, all trifunctional prepolymers were prepared with trimethylolpropane, and 4-arm block copolyester compositions were initiated by pentaerythritol as the tetrafunctional initiator. In Table 1, M / 1 refers to the total moles of monomers (M) used to prepare the arms divided by the moles of initiator (I) (also referred to as the functionalized central core) for each of the copolyesters identified in Table 1. Also in Table 1, M / C refers to the total moles of monomers (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 of Table 1 contains a B region, which is characterized in the column titled G / L / p-D, which is shorthand for Glycolide / Lactide / p-Dioxanone segment, and which may either be proximal to the central core (in which case the location of the B region is identified as being central to the precursor polymer) or it is distal to the central core (in which case the location of the B region is identified as being at the end of the precursor polymer, and in which case the B region terminates in a hydroxyl group).

[0220] 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.

[0221] Table 1. Precursor polymer compositionsComposition (mol %)aPrepolymer Name M / 1 M / C Initiator Type G / L / p-DGlycolide TMC Caprolactone D, L-lactide p-Dioxanone 3DP 1 14.3 14,333 Triaxiai Center 2.3 48.8 48.83DP 2 7 14,333 Triaxiai Center 2.3 48.8 48.83DP 3 3.5 14,333 Triaxiai Center 2.3 48.8 48.83DP 4 7 14,000 Triaxiai Center 28.6 35.7 35.73DP 5 7 11,666 Linear Center 14.3 42.9 42.93DP 6 7 14,000 Triaxiai End 28.6 35.7 35.73DP 7 7 11,666 Linear End 14.3 42.9 42.93DP 8 7 14,000 4-arm Center 42.9 28.6 28.63DP 9 7 14,000 Triaxiai End 50 25 253DP 10 7 11,666 Linear End 25 37.5 37.53DP 11 7 14,000 Triaxiai End 75 12.5 12.53DP 12 7 11,666 Linear End 50 25 253DP 13 7 14,000 Triaxiai End 25 25 503DP 14 7 14,000 Triaxiai End 25 25 — 503DP 15 7 11,666 Linear End — 37.5 37.5 253DP 16 7 11,666 Linear End — 37.5 37.5 — 25 3DP 19 7 11,666 Linear End 25 22.5 52.53DP 20 7 11,666 Linear End 20-35 10-25 55-703DP 25 5.25 11,666 Linear End 10-40 1-20 40-653DP 26 5.75 11,666 Linear End 10-40 1-20 40-65

[0222] Table 2. 3DP molecular weights (Mn and Mw) and polydispersity indices (PDI)Precursor Polymer Name Mn (Da) Mw (Da) PDI3DP 4 1909 ± 29 3490±16 1.83 ± 0.033DP 5 2311 ± 23 3766 ± 18 1.63 ± 0.023DP 6 1884 ± 15 3386 ± 36 1.79 ± 0.023DP 7 2168 ± 141 3628 ± 87 1.68 ± 0.083DP 9 1554 ± 37 2569 ± 29 1.65 ± 0.033DP 10 1785 ± 30 2208 ± 73 1.24 ± 0.023DP 11 1389 ± 8 1829 ± 9 1.32 ± 0.013DP 12 1606 ± 5 2410 ± 17 1.50 ± 0.013DP 19 1837 ± 15 2936 ± 23 1.59 ± 0.023DP 20 1881 ± 37 2902 ± 22 1.54 ± 0.053DP 25 1462 ± 11 2087 ± 15 1.43 ± 0.013DP 26 1440 ± 13 1831 ± 3 1.15 ± 0.01

[0223] Example 2 Preparation of Methacrylated Compounds of the Present Disclosure

[0224] Exemplary Polymer of Formula PolyEU

[0225] Table 3 identifies 8 EU-functionalized precursor polymers, uniquely labeled as 3DP 4m (m standing for methacrylate, which is an exemplary ethylenically unsaturated (EU) group) through 3DP 7m and 3DP 9m through 3DP 12m, which may generally be described as having or including compounds of the general formula CC-[arm-EU] according to the present disclosure. The designation arm-EU refers to an arm that terminates in a light-reactive ethylenically unsaturated group, such as an acrylate ("a") or methacrylate ("m") group.

[0226] The methacrylated polymers of Table 3 were prepared from the corresponding precursor polymers of Table 1, that is, 3DP 4m was prepared from 3DP 4, 3DP 5m was prepared from 3DP 5, etc.

[0227] Methacrylation of 3DP 6 to form 3DP 6m

[0228] The 3DP 6 precursor polymer (0.131 moles) was reacted with an excess of methacrylic anhydride, in the presence of 3-tert-2-butyl-4-hydroxyanisole (6.724x10-4 moles), at 120°C for 24 hours. Residual methacrylic anhydride and methacrylic acid byproducts were removed from the crude polymer using a rotary evaporator. The resulting amorphous liquid polymer was characterized using1H NMR spectroscopy, rheometery (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 following the procedure outlined above. The composition and molecular weight results are outlined in Table 3, and the dynamic viscosities are reported in Table 4. In Table3, for 3DP 5m, 40.15 in the TMC column is the total mole% of TMC plus 1,3-propanediol used to make 3DP 5m.

[0229] Table 3. Composition and molecular weight results of methacrylated bioresorbable 3DP formulationsComposition (mol %)PolymerName Glycolide TMC Caprolactone Methacrylate Mn Mw PDI3DP 4m 19.91 28.43 24.66 27.003DP 5m 9.93 40.15 32.87 17.05 2648±182 3999±156 1.51±0.03 3DP 6m 19.94 24.36 28.87 27.43 2162±14 3793±24 1.75±0.02 3DP 7m 9.89 39.38 32.52 18.21 2328±32 3551±14 1.53±0.02 3DP 9m 35.06 15.51 22.16 27.87 1585±55 2946±52 1.86±0.03 3DP 10m 17.3 36.97 27.78 17.95 2140±11 2548±13 1.19±0.004 3DP 11m 50.23 9.34 13.60 26.83 2125±4 2575±6 1.21±0.003 3DP 12m 32.02 26.00 20.98 21.01 1670±8 2588±12 1.55±0.01 3DP 19m 21.58 19.42 45.31 13.69 1826±13 3009±29 1.64±0.01 3DP 20m Not measured 13.59 1984±12 3022±6 1.5±0.093DP 25m Not measured 17.04 1614 ± 14 2232 ± 7 1.38 ± 0.01 3DP 26m Not measured 20.94 1619 ± 9 2035 ± 1 1.26 ± 0.007 3DP 39M Not measured 4381 5231 1.19 3DP 31M Not measured 1849 2979 1.50

[0230] Table 4. Dynamic viscosity of methacrylated 3DP polymersPolymer Name Viscosity at 105 s⁻¹ shear rate (cP)3DP 4m 12700 ± 1413DP 5m 6747 ± 353DP 6m 16400 ± 3463DP 7m 5493 ± 383DP 19m 6555 ± 2163DP 20m 3262 ± 263DP 25m 2044 ± 63DP 26m 1876 ± 26

[0231] Example 3 Preparation of Thiolated Compound of the Present Disclosure

[0232] Exemplary Polymers of Formula PolySH

[0233] A 500 mL 3-neck round bottomed flask equipped with a mechanical stirrer and an addition funnel was charged with 3DP 6 (51.3 g; 0.0665 moles; see Table 1), thiolactic acid (17.243 mL; 20.623 g; 0.1943 moles) and dichloromethane (DCM) (200 mL) in a nitrogen environment. 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 moles) was dissolved in 200 mL DCM. The DCC in DCM solution was then added to the reaction vessel drop wise using an addition funnel over a period of 30 minutes. After the addition of DCC / DCM solution had been completed, 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 continued to stir in nitrogen environment at room temperature for 72 hours. DCM levels were replenished as it evaporated during the reaction. After 72 hours, the reaction mixture was filtered under suction. The filtrate was washed with 2x100 ml 0.25 M HCI and 1x100 mL deionized (DI) water. The organic phase from the extraction was dried over activated molecular sieves (3 A) for 18 hours after which it was filtered under suction. The solvent was removed under vacuum on a rotary evaporator to get a liquid polymeric product (3DP 6t, where "t" indicates thiolated, also referred to herein as a polySH polymer). The amorphous liquid polymer, thus obtained, was characterized by1H NMR spectroscopy, rheometry (viscosity=7690 at shear rate of 99 s-1), and gel permeation chromatography (Mn=1952 Da, PDI=1.62). The table below outlines other thiolated 3DP compounds with n-acetyl cysteine (NAC), thiolactic acid (TLA), and thioglycolic acid (TGA). Each of these were synthesized based on this exemplary synthesis procedure.

[0234] Table 5. Properties of Thiolated 3DP PolymersComposition (mol %)Polymer Viscosity at 100 s⁻¹Glycolide TMC Caprolactone Thiol Mn Mw PDIWameshear rate (cP)3DP 6t (TLA) 22.14 27.64 27.64 22.59 7690 2380 4579 1.92 3DP 6t (NAC) 17.10 21.34 21.34 40.22 116,921 1952 3162 1.62 3DP 10t (NAC) 16.89 25.33 25.33 32.45 42,592 2213 3629 1.64 3DP 19t (TLA) 20.74 18.66 43.55 17.05 5295 2071 3165 1.54 3DP 19t (TGA) 21.32 19.18 44.17 14.74 5904 2202 3487 1.58 3DP 20t (TGA) 21.34 12.81 51.22 14.63 4461 2109 3052 1.45

[0235] Example 4 Preparation of Thiolated Compound of the Present Disclosure

[0236] Generally Described by the Formula PolySH

[0237] Polymers which have hydroxyl groups can be capped with a moiety that replaces the hydroxyl group with a carboxylic acid group. The carboxylic acid groups can thenbe substituted with a thiol containing moiety via an amide or ester bond depending on the functional unit of the substituent employed for bonding. For instance, the hydroxyl end groups of a 3DP precursor polymer (see, e.g., Table 1) can be reacted with succinic anhydride to form a succinated intermediate (3DP-SA), which may in turn be reacted with the amine group present in cysteine to provide a product (3DP 6-SA-Cys) having terminal free thiol groups, which provide exemplary polySH compounds of the present disclosure. This approach is illustrated by the present example.

[0238] Part 1 - formation of 3DP 6-SA: A 250 ml 3-neck round bottomed flask was charged with 3DP 6 (48.9 g; 0.0633 moles, Table 1). The system was placed under vacuum (<0.5 torr) at 40°C for 18 hours to dry the pre-polymer. 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 rotary evaporator to remove residual monomer at room temperature for 18 hours and further 24 hours at 110°C. The structure of the resulting clear amorphous polymer product was confirmed using1H NMR.

[0239] Part 2 - formation of 3DP 6-SA-Cys: A 100 ml 2-neck flask was charged with 3DP 6-SA (10.1 g; 0.0093 moles), L-cysteine (3.39 g; 0.0280 moles) and dichloromethane (DCM) (30 ml). The reactants were stirred at 200 rpm in nitrogen environment. Separately, N'-dicyclohexylcarbodiimide (DCC) (6.35 g, 0.0307 moles) was dissolved in 10 mL DCM. An ice bath was placed around the reaction vessel and DCC / DCM solution was added dropwise. The ice bath was removed after the addition of DCC / DCM solution had been completed and the reactants were allowed to stir at room temperature for 72 hours in nitrogen environment. After 72 hours, the reaction mixture was diluted with 50 ml DCM and filtered under suction. The filtrate was washed with 2x50 mL 0.25 M HCI and 1x50 mL DI water. The organic phase from the extraction was dried over activated molecular sieves (3 A) for 18 hours after which it was filtered under suction. The solvent was removed under vacuum on a rotary evaporated to provide a waxy polymeric product (3DP 6-SA-Cys), the structure of which was confirmed by1H NMR spectroscopy.

[0240] Example 5 Single Polymeric Network from polyEU and polySH

[0241] Thiol terminated 3DP polymers were mixed with methacrylated 3DP polymers in two different ratios. TPO-L photoinitiator was added to each combination at a concentrationof 0.5% (w / w) and the formulation was mixed on a FlackTek high speed mixer for 2 minutes at 2000 rpm followed by 3 minutes at 3000 rpm. The formulation was cured into a film with 0.75 mm thickness. Films were cut into 75mm x 7.5 mm x 0.75mm specimens subjected to accelerated degradation at 50 °C in pH 7.4 phosphate buffer. In FIG. 1, the degradation profiles of 50:50 and 25:753DP 6t TLA / 3DP 10m films are shown. The information in FIG. 1 shows the effect of water swelling for polyEU / polySH single polymeric networks.

[0242] Example 6 Preparation of Isocyanate Terminated Compounds of the Present Disclosure

[0243] Exemplary Polymers of Formula PolyA

[0244] As mentioned in Example 1, hydroxyl-terminated polymers may provide precursor compounds to polyA compounds of the present disclosure. Hydroxyl groups may be converted to thermally reactive groups, e.g., isocyanate group as shown by the present example, which illustrates diisocyanate capping of 3DP 10.

[0245] A 250 ml 3-neck round bottomed flask equipped with a mechanical stirrer and an addition funnel was charged with 3DP 10 (76.7 g; 0.0996 moles). The 3DP 10 was dried at 40°C under reduced pressure for 3 days. After drying, the flask was purged with dry nitrogen, and agitation was started at 220 rpms. The flask was charged with 15 ml of anhydrous toluene and hexamethylene diisocyante (HMDI; 33.5 ml; 0.209 moles). The reaction mixture temperature was increased to 80°C for 2 hours and then allowed to return to room temperature. The polymer mixture was then transferred to a 1-neck flask and placed on a rotary evaporator. The residual toluene and HMDI were removed under reduced pressure on the rotary evaporator. The amorphous liquid polymer, thus obtained was characterized by1H NMR spectroscopy (Polymer - 70.3 wt% Isocyanate - 29.6 wt.%).

[0246] Example 7 Double Polymeric Network from polyEU and polyAl + polyA2

[0247] Double network films were prepared with a photopolymerized methacrylate polymer network and a thermally cured interpenetrating polymer network. 3DP 12m and 3DP 6 precursor polymer (an exemplary polyAl) were mixed in either a 50:50 or 70:30 ratio. TPO-L photoinitiator was added to the mixture at a 0.5% (w / w) concentration with respect to the weight of the methacrylated polymer. Hexamethylenediisocynate (an exemplary polyA2) was added the mixture at a 45% of the number of moles of hydroxyl groups in the precursor polymer (3:1 OH:polymer in case of 3DP6, a triaxial polymer). The formulation was mixedusing a Flacktek high speed mixer for 2 minutes at 2000 rpm followed by 2 minutes at 3000 rpm. The formulation was then cured as a film of 0.75 mm thickness for 10 minutes under UV light at an intensity of 30 mW / cm2. The photocured film was further cured thermally at 1009C for 1 hour.

[0248] The film was cut up into test strips of 75 mm x 7.5 mm x 0.75 mm and subjected to accelerated degradation at 50 °C in pH 7.4 phosphate buffer. Mass loss, water content and mechanical properties of the material were analyzed at different timepoints during the study. The results are shown in FIG. 2. In FIG. 2, the data show the water swelling behavior for urethane and methacrylated polyester double networks. The addition of the urethane network increases the water swelling up to 25-30% mass loss. After 25-30% mass loss, both the 50:503DP12m:3DP 6U and 3DP6u showed substantially less swelling.

[0249] Example 8 Mechanics of Poly(SH) and Poly(EU) Materials

[0250] To evaluate the properties of crosslinked 3DP polymer blends, tensile specimens were created for mechanical testing. For any particular polymer blend, a thiol-terminated 3DP polymer was mixed with one or more methacrylated 3DP polymers (3DPX M) in 25:75 and 50:50 weight ratios where the thiolated polymer was synthesized using thiolactic acid (3DPXTLA), N-acetyl-L-cysteine (3DPX NAC), or thioglycolic acid (3DPXTGA) as described in Example 3. In addition to methacrylated 3DP polymers, select blends at similar ratios were studied with a diluent component of poly-ethylene glycol diacrylate (PEGDA). A photoinitiator, ethyl (2,4,6-trimethylbenzoyl) phenyl phosphinate (TPOL), was added at 0.5% (w / w) and the blend was mixed on a FlackTek high speed mixer for two minutes at 2000 rotations per minute (rpm) followed by three minutes at 3000 rpm.

[0251] Each liquid polymer blend was poured between two UV-transparent acrylic sheets with 0.75 mm spacers and cured under a 100 W UV Blak-Ray lamp for 10 minutes. The crosslinked film was removed and cut into tensile specimens with dimensions of 0.75 x 7.5 x 75 mm. The film strips were subjected to mechanical testing on an MTS test frame to evaluate their tensile properties with at least four strips for each blend tested. The test parameters for tensile testing are presented in Table 6. The polymer blends studied and their corresponding tensile properties are reported in Table 7.

[0252] Table 6. Testing ParametersParameter Value UnitsBreak sensitivity 90 %Break threshold 0.5 IbfTest InputsData acquisition rate 70 HzTest speed 2.5 mm / minBreak marker drop 50 %Break marker elongation 0.1 InchGrip separation 1 Inch Calculation Inputs Slack pre-load 1 IbfSlope segment length 20 %Yield offset 0.2 %Yield segment length 2 %

[0253] Table 7. Poly(SH) and Poly(EU) Photopolymerized Tensile MechanicsPeak Stress (kPa) Strain at Break (%) Modulus (MPa) 3DP6 M 29340 38 35225:75 3DP6t TLA:3DP6 M 4020 23 2350:503DP6t TLA DP6 M 750 19 43DP10 M 5950 31 21PEGDA 575 4780 15 3425:75 3DP6t TLA: PEGDA 575 1900 14 1550:50 3DP6t TLA: PEGDA 575 800 13 725:75 3DP6t TLA:3DP10 M 1370 28 650:503DP6t TLA:3DP10 M 450 30 23DP19 M 6630 34 293DP20 M 6430 41 2150:503DP19tTLA:3DP20 400 40 150:503DP19t TGA:3DP20 M 530 65 23DP26 M 4113 42 32

[0254] Example 9 Stability of Poly(SH) and Poly(EU) Compositions

[0255] Part 1 - Polymer blends with and without stabilizers were investigated forpremature crosslinking. A thiol terminated photo-reactive compound was mixed with a methacrylated photo-reactive compound at a 50:50 ratio. Prospective stabilizing compounds were each added to an aliquot of the reactive mixture at varying concentrations. Each formulation blend was mixed on a FlakTek high speed mixer for two minutes at 2000 rotations per minute (rpm) followed by three minutes at 3000 rpm. An aliquot of each blend was transferred to a petri dish and stored at room temperature (RT) or 50°C. The stability of the polymer blends were qualitatively evaluated by the solidification of the blend and the results are reported in table 8.

[0256] Table 8. Stability of methacrylate and thiol terminated photo-reactive resins Photo-reactive Concentration Storage Storage Solidification Stabilizerblends (50:50) (ppm) time (hr) temp (Yes / No) 3DP 19m:3DP 19tCitric acid 5000 16 RT Y TLA3DP 19m:3DP 19tSuccinic acid 5200 96 RT Y TLA3DP 19m:3DP 19tAdipic acid 1000 48 RT Y TLA TMPTM: TMPTT* Phosphoric acid 500 48 50°C N 3DP 20m:3DP 19tLauryi gallate 9000 24 RT N TGA3DP 20m:3DP 19tTocopherol 12000 24 RT N TGA3DP 20m:3DP 19tGallic acid 4000 24 RT N TGA3DP 20m:3DP 19tTriphenylphosphite 9500 24 RT N TGA3DP 20m:3DP 19t Phenylphosphonic4000 24 RT N TGA acid*TMPTM: Trimethylolpropane trimethacrylate; TMPTT: Trimethylolpropane tris(3-mercaptopropionate)

[0257] Part 2 - A thiol-terminated polymer (3DP 19t TGA) was mixed with amethacrylated polymer (3DP 20m) at a 50:50 weight ratio. Selected stabilizers were each added to an aliquot of the liquid polymer blend and the viscosity of the formulations were evaluated by rheometry (25°C at shear rate 100 s-1) at 24 hours to yield a quantitative measurement of stability. The initial viscosity of the resin without a stabilizer was 3920 ± 20 cP. Viscosities of stabilized polymer blends at 24 hours of storage at room temperature are provided in Table 9.

[0258] Table 9. Viscosity of stabilized 3DP 19t TGA and 3DP 20m blend after 24 hours of storageViscosity at 24 hours Stabilizer in polymer blends Concentration (ppm)Viscosity (cP) Increase (%) No stabilizer — SolidifiedAscorbic acid 4400 SolidifiedBHA 4500 4044 3.2 BHT 5400 8797 124 Lauryl gallate 8700 3940 0.5 Gallic acid 5200 4056 3.5 Tocopherol 1000 4021 2.6 Tocopherol 10000 4113 4.9 Tocopherol 100000 3769 - 3.9 Triphenyl phosphite 10000 4046 3.2

[0259] Example 10 - Mechanics of Poly(EU) materials mixed with commercial thiol compounds

[0260] To evaluate the properties of crosslinked 3DP polymers with commercial thiol compounds, tensile specimens were created for mechanical testing. Commercial thiol compounds trimethylolpropane tris(2-mercaptopropionate) (TMPTT) or 1,6-Hexanedithiol (HDM) were added to a methacrylated 3DP polymer (3DP 26m) at 0% mol, 3% mol, 5 % mol and 10 % mol. TPO-L was added at 0.5% (w / w) and the blend was mixed on a FlackTek high speed mixer for two minutes at 2000 rotations per minute (rpm) followed by three minutes at 3000 rpm. Each blend was poured between two UV-transparent acrylic sheets with 0.75 mmspacers and cured under a UV light source for 10 minutes. The crosslinked film was removed and cut into tensile specimens according to standard ASTM D638 type V dog-bone specimen. The dog-bone specimens had a width of 3 mm and 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 tensile testing are presented in Table 10. The polymer blends studied and their corresponding tensile properties are reported in Table 11.

[0261] Table 10. ASTM D638 Type V Testing ParametersParameter Value UnitsBreak sensitivity 90 %Break threshold 0.5 IbfTest InputsData acquisition rate 70 HzTest speed 1 mm / minBreak marker drop 50 %Break marker elongation 0.1 InchGrip separation 1 Inch Calculation Inputs Slack pre-load 1 IbfSlope segment length 20 %Yield offset 0.2 %Yield segment length 2 %

[0262] Table 11. Tensile Mechanics of3DP 26m mixed with Commercial Thiol CompoundsMol (%) Thiol Modulus (Mpa) Elongation (%) Peak Stress (Mpa) 3DP 26m 0 23.7 ± 0.7 29.4 ± 7.9 6.56 ± 1.83 18.7 ± 0.4 31.5 ± 7.5 5.35 ± 1.3 HDT 5 15.7 ± 0.3 29.4 ± 3.5 4.49 ± 0.610 14.9 ± 0.4 41.2 ± 8.8 5.54 ± 1.1 3 20.0 ± 0.3 29.7 ± 5.8 5.31 ± 1.0 TMPTT 5 18.4 ± 0.5 32.9 ± 6.3 5.33 ± 1.010 15.9 ± 0.3 28.9 ± 3.2 3.90 ± 0.6

[0263] Example 11 - Use of TMPTT as chain transfer agent

[0264] Photoreactive resin mixtures were prepared from a 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 12 provides the amounts of TMPTT added to the 3DP20-M resins. Photoinitiator TPO-L was added to the resin mixtures at 0.5% (w / w). The resins were then thoroughly mixed using a FlackTek high speed mixer at 2000 rpm for 2 minutes and further at 3000 rpm for 3 minutes. Each resin blend obtained after mixing was sandwiched between two UV-transparent plates and cured under a 100 W UV blak-ray lamp to create cross-linked films.

[0265] Table 12. Amount of TMPTT added to 3DP20-M to make up the different thiol to methacrylate molar ratios used in the studyMole ratio (thiol:methacrylate) 3DP20-M (g) TMPTT (g) 0 10.0335 0 0.01 10.0297 0.0284 0.03 10.0564 0.0838 0.05 10.0072 0.1386 0.075 10.0615 0.2116 0.1 10.0343 0.2792

[0266] The cross-linked films were milled using a freezer mill. 0.25 g of the milled samples were transferred to a 20 ml scintillation vial. 2.5 mL of DMSO and 2.5 mL of sodium methoxide (NaMeOH) were added to the vials and placed on a heat block at 100 °C for 2 hours. The samples were cooled to room temperature and precipitated in 25 mL of diethyl ether (DEE). The precipitate was collected using centrifugation and then allowed to dry overnight under vacuum. The resulting product was re-dissolved in H2O, lyophilized, and characterized by gel permeation chromatography (GPC).

[0267] Molecular weight results obtained by GPC are provided in Table 13. In Table 13, 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 showsthat adding TMPTT reduced the molecular weight of the poly(methacrylic acid) chains from the photo-polymerized 3DP20-M resins. These changes are attributed to changes in the network structure caused by the chain transfer behavior of the thiol groups during polymerization.

[0268] Table 13. GPC results of thiol-poly(methacrylic acid) kinetic chains from degraded photo-polymerized 3DP20-M resinsMole ratio (thiol:methacrylate) Mw (Da) Mn (Da) Mz (Da) PDI 0 118600 66300 190000 1.79 0.01 40200 15700 101500 2.56 0.03 14200 8500 23100 1.67 0.05 8990 6570 12200 1.37 0.075 6490 5300 7960 1.22 0.1 5460 4700 6350 1.16

[0269] Example 12 Degradation of 3DP20 with TMPTT

[0270] 3DP20-M with TMPTT added at thiol to methacrylate molar ratios of 0 and 0.4 were made into cross-linked films using methods described above. The films were cut by CO laser into 75 mm x 7.5 mm x 0.75 mm strips and subjected to accelerated degradation at 50°C in pH 7.4 phosphate buffer. In FIG. 3, the degradation profiles of the films are shown. As FIG.3 illustrates, adding TMPTT to 3DP20-M increases its degradation rate under accelerated degradation.

[0271] Example 13

[0272] To evaluate the photo-polymerization of resin compositions, formulations were prepared for extrapolation of resin parameters from working curves for vat-polymerization. For each of eight formulations, a methacrylate-terminated polyester carbonate macromer (3DP25-M) was mixed with a similarly functionalized absorbable liquid polymer diluent at 10 percent (w / w) to the 3DP polymer. In all formulations, a chain transfer agent, TMPTT, was added in 7.5 mole-percent of thiol group to total moles of methacrylate groups in the liquid blend. A photo-initiator, ethyl (2,4,6-trimethylbenzoyl) phenylphosphinate (TPO-L), was also added to all formulations in 0.75 weight-percent to theliquid polymer blend (0.85 mole-percent of photo-initiator to total moles of functional groups). Each formulation then received p-carotene or D& C Violet no. 2 as a dye at one of four concentrations: 0.01, 0.1, 1.0, or 2.5 percent by weight to the liquid polymer blend. All formulations were then individually mixed on a FlackTek high speed mixer for three minutes at 3000 rotations per minute.

[0273] Each liquid resin blend was poured onto a glass slide and exposed to UV light of known intensity (i.e., power density) in mW / cm2and a range of exposure times in seconds resulting in cured resin in a range of height (i.e., cure depth). The height of each cured sample was measured using an optical 3D measurement system. For each formulation, heights in millimeters were then plotted against total energy dose as the product of light intensity and exposure time. Logarithmic regression was performed to fit the data to a model used to extrapolate resin parameters of penetration depth (DP) in millimeters, critical energy dose (Ec) in mJ / cm2, and cure time in seconds required for a cure depth of 30 micrometers (Table 14).

[0274] Table 14. Resin parameters of Dp, Ec, and cure time extrapolated from working curves across a range of 6-carotene content within formulations containing ethylenically unsaturated groups and chain transfer agents.Dye Concentration Dp Ec Cure Time at 30 um Dye(wt. %) (mm) (mJ / cm2) (s)0.01 1.164 51.67 1.1780.10 0.664 54.67 1.271P-Carotene1.00 0.121 67.19 1.9142.50 0.033 58.24 3.243 0.01 0.518 58.87 1.3860.10 0.263 64.02 1.594D& C Violet 21.00 0.062 65.55 2.3742.50 0.045 61.26 2.646

[0275] In an additional study to evaluate the photo-polymerization of resins, formulations were similarly prepared for extrapolation of resin parameters from workingcurves across a range of chain transfer agent and stabilizer content. For each of three formulations, a methacrylate-terminated polyester carbonate macromer (3DP25-M) was mixed with a functionalized diluent, trimethylolpropane trimethacrylate (TMPTM), in 5 percent (w / w) of the 3DP polymer. Each formulation received the chain transfer agent, TMPTT, at zero 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 zero 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 photo-initiator to total moles of functional groups). A 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 on a FlackTek high speed mixer for three minutes at 3000 rotations per minute.

[0276] Each liquid resin formulation was treated as previously to create working curves and extrapolate resin parameters of penetration depth (Dp) in millimeters, critical energy dose (Ec) in mJ / cm2, and cure time in seconds required for a cure depth of 30 micrometers (Table 15).

[0277] Table 15. Resin parameters of Dp, Ec, and cure time extrapolated from working curves across a range of stabilizer content within formulations containing ethylenically unsaturated groups and a range of chain transfer agent content.Chain Transfer Agent Stabilizer DP EC Cure Time at 30 |im (wt. %) (wt. %) (mm) (mJ / cm2) (s) 0.00 0.00 1.212 3.044 3.250 1.00 0.00 1.518 2.976 3.373 1.00 0.10 0.981 4.700 4.798

[0278] Example 14

[0279] To assess the cytocompatibility of cured resins, several formulations were prepared for the evaluation of their extractable species by viability assay according to ISO 10993 Biological Evaluation of Medical Devices - Part 5: Tests for in vitro Cytotoxicity. For each of four formulations, a methacrylate-terminated polyester carbonate macromer (3DP20-M or 3DP25-M) was mixed with a similarly functionalized absorbable liquid polymerdiluent in 5 percent (w / w) to the 3DP polymer. In all formulations, TMPTT was added at 10 mole-percent of thiol group to total moles of methacrylate groups in the liquid blend. One formulation received a 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, respectively, of total moles of functional groups). Each formulation also received -carotene as a dye at 0.01 percent (w / w) to the liquid polymer blend. All formulations were then individually mixed on a high speed mixer for three minutes at 3000 rotations per minute. The formulations studied are summarized in Table 16.

[0280] Table 16. Resin formulations and their corresponding additive content studied for the cytotoxicity of their leachable speciesChainMethacrylated Functionalized PhotoFormulation Transfer Stabilizer Dye 3DP Diluent Initiator Identifier Agent (wt. %) (wt. %)Macromer (wt. %) (wt. %)(mol. %)A 20-M 5.0 10.0 0.0 0.75 0.01 B 25-M 5.0 10.0 0.0 0.75 0.01 C 25-M 5.0 10.0 0.1 0.75 0.01 D 25-M 5.0 10.0 0.0 1.00 0.0139 M (50-85wt%) / E 0 1-10 0-0.5 0.1-2.0 0.001-0.231M (20-50wt%)

[0281] Each formulation was cured by UV light into a film, 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 in 70% iso-propanol and treated with UV light.

[0282] For the extraction of cured resin formulations, Eagle's Minimum Essential Medium with 10% (v / v) horse serum served as the elution vehicle. Each sample was submerged in medium at 0.2 g / ml and incubated at 37 degrees Celsius for 24 hours. Analiquot of each extract was added to cell monolayers (mouse fibroblasts, NCTC L-929) across 96-well plates and incubated for 24 hours. An MTS viability assay (MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium)) was applied to each test well, incubated for 1 hour, and measured for absorbance using a microplate reader. For each formulation and control group, mean cell viability was determined by the absorbance of test wells with reference to that of cell culture blanks. The mean cell viability of all groups is shown in FIG. 4 where "+" is the positive control; is the negative control; "A" is the 3DP20-M blend with 0% stabilizer and 0.75% photo-initiator; "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% photo-initiator; and "D" is the 3DP25-M blend with 0% stabilizer and 1.0% photo-initiator. From FIG.4 it can be seen that all formulations (A-D) show a high degree of cell viability interpreted as little to no potential for cytotoxicity.

[0283] Example 15 Preparation of the Bioabsorbable Voronoi Lattice Structures

[0284] 3 Matic (Materialise; Plymouth, Ml), a software program, was used to generate the Voronoi infilled shapes. 19 Voronoi structures were created from the 0.5 in x 0.5 in x 1.0 in STL with pore sizes ranging from 1.4 mm - 2.6 mm, and beam thickness size of 0.15 mm to 1.0 mm as shown in Table 17. The parameter of 2.0 mm pore size or 0.3 mm beam size was held at the center of the analysis, varying the pore size or beam size. Sorted pore size and beam size from smallest to largest was also created in the Voronoi infill. The 20thsample was a fully solid 0.5 in x 0.5 in x 1.0 in part model.

[0285] Table 17. Voronoi Sample ParametersPore Radius Beam Thickness Shape Accuracy Sample Organic Factor(mm) (mm) (mm) 1 1.4 0.3 1.5 0.022 1.6 0.3 1.5 0.023 1.8 0.3 1.5 0.024 2.0 0.3 1.5 0.025 2,2 0,3 1.5 0.026 2.4 0.3 1.5 0.027 2.6 0.3 1.5 0.028 2.0 0.15 1.5 0.029 2.0 0.2 1.5 0.02 10 2.0 0.25 1.5 0.0211 2.0 0.35 1.5 0.0212 2.0 0.6 1.5 0.0213 2.0 1.0 1.5 0.0214 1.4 0.15 1.5 0.0215 1,6 0,2 1.5 0.0216 1.8 0.25 1.5 0.0217 2.2 0.35 1.5 0.0218 2,4 0,6 1.5 0.0219 2.6 1.0 1.5 0.0220 Solid Part

[0286] Once all designs were exported as an STL, they were imported into Formlabs Preform software Version 3,37.5.37 with N = 2 of each sample. They were oriented with the 12.7 in x 12.7 in side on the surface of the build plate (FIG. 5).

[0287] Custom material parameters were used for the printing parameters using Preform(Sommerville, MA). Formlabs Elastic 50A VI (Sommerville, MA) was used as the base material in Print Settings Editor with the modifications in Table 19. An Open Material licensethrough Formlabs was used to print Resin E. Resin E is disclosed in Table 16.

[0288] Table 18. Tensile mechanics of Resin EModulus Elongation At Peak Stress Peak StDev StDev StDev StDev (MPa) Break (%) (MPa) Load (N) 11.87 0.4949 41.362 7.405 3.727 0.6019 32.82 5.171

[0289] Table 19. Study 1 Formlabs Printing ParametersParameter Parameter Detail Units Value Layer Thickness Thickness of Z height per layer mm 0.025 X Correction Scale factor for the X axis tounitless 1.002 Factor account for print scale correctionY Correction Scale factor for the Y axis tounitless 1.002 Factor account for print scale correctionZ Correction Scale factor for the Z axis tounitiess 1.002 Factor account for print scale correctionThe space between theoutermost perimeter laser pathPerimeter toand the model's nominalNominalboundary. A positive value means mm -0.01 Geometrythe laser perimeter will be insetSpacingsmaller than the model's nominalboundary.Energy Density of Laser PowerPerimeter Fillapplied to the outer surface of mJ / cm2150 Exposurethe modelEnergy Density of Laser PowerModel Fillapplied to the interior fill of the mJ / cm2130 ExposuremodelSupports Fili Energy Density of Laser PowermJ / cm2200 Exposure applied to supportsEnergy Density of Laser PowerTop Surface applied to top surfaces of themJ / cm2150 Exposure model. Higher values can reducemodel tackiness.Per layer energy density of laserpower applied to the parts of the Array field of layers,1 @ 200 Overhang Fill model that are overhanging. First with heights in mm2 @ 175 Exposure entry is for the immediate and energy densities3 @ 150 previous layer. Successive values in mJ / cm2are for prior layers.1.0 @ 150 Array field of layers, Heights and energy density of 0.5 @ 400 Early Layer with heights in mmlaser power applied to the model 0.2@ 500 Exposure and energy densitiesfor each early layer provided. 0.1@ 700 in mJ / cm20.0 @ 800 Heights and squeeze speeds to beapplied on early layers. Each entry Array field of layers,Early Layer dictates the height at which the with heights in mm 7 @ 3.0 Squeeze Speed corresponding squeeze speed is and velocities in 0 @ 1.0 applied. Intermediate values are mm / slinearly interpolated.The resin temperature that theOperatingprinter tries to maintain while °C 40 Temperatureprinting.The resin temperature at whichStart the printer starts printing°C 35 Temperature normally, without userintervention.A vector of wipes to do on layer 0,Array field of wiperWipe Behavior 1,..., repeating. 0 means no wipe; Off behavior (binary)1 means full wipe.Wipe Speed Speed of the tank wiper mm / s 20 Initial Wipe Number of tank wipes beforewipes 0 Count printing startsMaximum roller speed whenRoller Squeeze squeezing resin out from undermm / s 3 Speed regions that were lased on theprevious layerWait time after lasing to let thePost Laser Curepart cure before stressing the seconds 3 Waitmaterial by peeling

[0290] Parts were cleaned over 2 cycles using Formlabs Form Wash (Formlabs; Somerville, MA) and Formlabs Finishing Kit (Formlabs; Somerville, MA). The build plate was taken off the Form 3+ and transferred with the samples still attached to a Form Wash station that was filled with a 70 / 30 I PA / Acetone solvent mixture. The parts were washed on the Form Wash for 30 minutes for Cycle 1. The sample parts were removed from the Form3 build plate and put into a Finishing Kit station filled with 100% IPA with a strainer. A 2-inch stir bar was placed below the strainer and stirred at 150 RPM for 10 minutes. The parts were taken out with the strainer and air dried in a fume hood for 60 minutes.

[0291] Once dried, parts were put into a Formlabs Form Cure for final post processing. All parts were arranged with the build plate side on the bottom the of Form curing station. After 30 minutes of curing on the rotating plate at an ambient temperature of 23°C, the parts were flipped 180° so that the side that was on the bottom was now moved so as to be the top surface and cured for another 30 minutes. After curing, all samples were put inside a desiccant cabinet at 5% target humidity for storage until mechanical testing was performed.

[0292] Example 16 Mechanical Testing and Analysis of Voronoi Cubes

[0293] 3D-printed Voronoi cubes with varying pore and beam sizes were tested in compression mode using a Discovery HR-2 rheometer (TA Instruments, Delaware, USA) witha 20 mm flat plate geometry. The samples were compressed vertically, with the initial sample length being 1 inch, and a compression rate of 1.27 mm / min, following ASTM D695-23 standards. The relative density (RD) was determined as the ratio between the mass of the porous material and the apparent volume of the 3D-printed cubes. The Young's modulus was calculated from the slope of the linear elasticity region in the compressive stress-strain curves (FIG. 6a), while the collapse stress was identified as the value within the plateau region of these plots. The slenderness ratio was calculated as the ratio of pore size to beam size. The results of compression test on different Voronoi structures are reported in Table 20.

[0294] Table 20. Geometrical and mechanical properties of 3D-printed Voronoi cubes Pore Bean RelativeYoung Modulus Collapse stress Slenderness Sample size size density, RD(kPa) (kPa) ratio (mm) (mm) (gr / ml)1 1.40 0.15 0.14±0.00 18.88±2.48 1.36±0.21 9.33 2 1.40 0.30 0.27±0.01 221.89±12.73 27.74±0.58 4.67 3 1.60 0.20 0.15±0.00 44.60±5.47 2.95±0.12 8.00 4 1.60 0.30 0.23±0.00 159.86±5.56 13.82±0.05 5.33 5 1.80 0.25 0.16±0.00 67.63±3.06 4.44±0.49 7.20 6 1.80 0.30 0.19±0.01 118.48±5.11 9.04±0.84 6.00 7 2.00 0.15 0.07±0.00 1.83±0.24 0.26±0.02 13.33 8 2.00 0.20 0.11±0.00 18.12±0.72 1.25±0.00 10.00 9 2.00 0.25 0.14±0.00 45.75±2.22 3.16±0.00 8.00 10 2.00 0.30 0.16±0.01 70.23±4.56 4.99±0.01 6.67 11 2.00 0.35 0.18±0.00 96.16±1.66 7.95±0.00 5.71 12 2.00 0.60 0.28±0.00 244.70±1.17 21.54±0.00 3.33 13 2.00 1.00 0.45±0.00 609.45±16.95 92.83±0.00 2.00 14 2.20 0.30 0.13±0.00 56.61±0.79 3.36±0.11 7.33 15 2.20 0.35 0.16±0.00 80.45±0.16 5.24±0.71 6.29 16 2.40 0.30 0.11±0.00 30.58±3.05 2.08±0.06 8.00 17 2.40 0.60 0.22±0.00 149.62±3.87 11.49±0.95 4.0018 2.60 0.30 0.10±0.00 26.97±0.97 1.62±0.20 8.67 19 2.60 1.00 0.32±0.00 325.30±11.91 33.01±2.24 2.60 Solid20 - 1.17±0.01 8690.50±122.32 8950.00±1989.95Part

[0295] The normalized mechanical properties (Young's modulus and collapse stress) of 3D-printed Voronoi materials, relative to their relative density (RD), were plotted against the slenderness ratio in FIGs. 6b and 6c, respectively. These plots were presented on a semi-logarithmic scale, with an exponential trend fitted to the data. As a result, these graphs can serve as master curves for predicting the mechanical properties of 3D-printed Voronoi structures. Alternatively, desired mechanical properties can be achieved by adjusting the geometric features, such as pore size and beam size, of the 3D-printed constructs.

[0296] Example 17 Preparation of the Bioabsorbable Body-center Cubic and Simple Cubic Lattice Structures

[0297] Materialise was used to generate the Voronoi, Grid, and BCC infilled with tilted cell generation to study isotropic compression. 4 Voronoi structures were created from the 0.5 x 0.5 x 1.0 in STL with pore sizes of 1.5 mm and angle of cell generation varied at 0°, 15°, 30°, and 45° across the x-axis as shown in Table 21. 4 Grid structures were created from the 0.5 x 0.5 x 1.0 in STL with pore sizes of 2.12 mm and angle of cell generation varied at 0°, 15°, 30°, and 45° across the x-axis as shown in Table 21. BCC structures were created from the 0.5in x 0.5in x l. Oin STL with pore sizes of 2.54mm and angle of cell generation varied at 0°, 15°, 30°, and 45° across the x-axis as shown in Table 21. All structures were made with the same beam thickness of 0.3mm, organic factor of 1.5, shape accuracy of 0.02 mm. For VP printability, a 1.0mm thick 12.7mm x 12.7mm rectangular prism was attached to the top and bottom of all parts. All loose beams were deleted from the part except those attached to the rectangular prism layers. (FIG. 14).

[0298] Table 21. Voronoi, Grid, and BCC Sample ParametersPore Beam Shape Unit Cell Tilt Lattice OrganicSample Radius Thickness Accuracy AlongX-Axis Cell Factor(mm) (mm) (mm) (°) 1 Voronoi 1.5 0.3 1.5 0.02 0 2 Voronoi 1.5 0.3 1.5 0.02 15 3 Voronoi 1.5 0.3 1.5 0.02 30 4 Voronoi 1.5 0.3 1.5 0.02 45 5 Grid 2.1166 0.3 1.5 0.02 0 6 Grid 2.1166 0.3 1.5 0.02 15 7 Grid 2.1166 0.3 1.5 0.02 30 8 Grid 2.1166 0.3 1.5 0.02 45 9 BCC 2.54 0.3 1.5 0.02 0 10 BCC 2.54 0.3 1.5 0.02 15 11 BCC 2.54 0.3 1.5 0.02 30 12 BCC 2.54 0.3 1.5 0.02 45

[0299] A Cubic Grid unit ceil and body-centered cubic (bcc) unit cell were designed in Solidworks SP3.1 (FIG. 7). A 3D Sketch was used to design the unit cell shape. Each linear component of the structure was independently made in its own sketch. The length, width, and height of the unit cell were made to be 5 mm. This measurement was changed in Materialise when making the lattice structures. The file was exported as an. IGES file for Materialise use in their software to make lattice patterns. A 0.5 in x 0.5 in x 1.0 in rectangular prism was designed in SolidWorks SP3.1 and exported as an. STL file.

[0300] Parts were printed, post-processed, and mechanically tested using the same settings and methods as in Example 15. Specifically, 3D-printed Voronoi, grid, and BCC cubes with varying angles were tested in compression mode using a Discovery HR-2 rheometer (TA Instruments, Delaware, USA) with a 20 mm flat plate geometry at a compression rate of 1.27 mm / min, following ASTM D695-23 standards. The relative density (RD) was calculated as the ratio of the mass of the porous material to the apparent volume of the 3D-printed cubes.Consistent with the data analysis in Example 15, the Young's modulus was determined from the slope of the linear elasticity region in the compressive stress-strain curves (FIG. 8A), while the collapse stress was identified within the plateau region of these curves (FIG. 8B). The results of the compression tests on various Voronoi structures are summarized in Table 22. The result for the solid part was taken from Example 15, as this data point was identical between the two examples.

[0301] Table 22. Mechanical properties of3D-printed Voronoi, grid, and BCC cubes at various angles

[0302] The normalized mechanical properties (Young's modulus and collapse stress) of 3D-printed Voronoi materials, relative to their relative density (RD), were plotted against the rotational angle in FIG.s 8a and 8b, respectively. These graphs showed that the Voronoi structure was independent of the rotation angle, exhibiting fully isotropic mechanical properties. In contrast, the grid and BCC structures displayed anisotropic mechanicalproperties, with changes observed as the angle varies from 0 to 45 degrees. The grid structure showed a strong decreasing trend in elastic modulus as the angle increases, while the BCC structure exhibited an increasing trend. Although the grid and BCC structures were just two examples of many possible ordered lattices, they demonstrated that, unlike ordered structures, the Voronoi structures uniquely maintained isotropic behavior in mechanical properties.

[0303] Example 19 Drug release from solid cylinders

[0304] Cylindrical solid models that were 12 mm in height and 6 mm, 3 mm or 1 mm in diameter were generated using CAD software SolidWorks SP3.1. To evaluate the effects of print geometry on the release of model drug rhodamine B (RhB), a base resin containing 3DP 26m with 1 to 15 mol% trimethylolpropane tris(3-mercaptopropionate) (TMPTT), 0.1 to 1 wt.% ethyl(2,4,6-Trimethylbenzoyl)-phenyl phosphinate (TPO-L), and 0.01 to 1 wt.% betacarotene was prepared. RhB was then added to the base resin at 0.2 wt%. The RhB loaded resin was used to print solid cylinders listed below (Table 23) using a Kudo 3D Micro DLP-VP (Dublin, CA) printer equipped with a 365 nm LED UV light source. The layer thickness chosen, and light irradiance used to print the parts were 30 pm and 45 mW / cm2, respectively. After printing, excess resin was removed from cylinders using a Kimwipe. Afterwards, the cylinders were post cured for 200 s under a UV spot lamp (Dymax BlueWave 200) at an irradiance of 45 mW / cm2.

[0305] Table 23. Geometric parameters of solid cylindersDiameter (mm) Height (mm) SA (mm2) Volume (mm3) SA / V1 12 39.218 9.38 4.183 12 127.035 84.42 1.506 12 282.392 338.24 0.83

[0306] To evaluate the release, the RhB loaded cylinders were placed in a 50 mL centrifuge tube. 20 mL, 10 mL and 4 mL of pH 7.40.01 M phosphate buffered saline (PBS) was added to the 6 mm, 3 mm, and 1 mm cylinders, respectively. The samples were placed in an incubating shaker at 37°C under constant oscillation at 50 rpm. At each designated time point,1 mL of the release medium was collected, and the absorbance was measured using a UV / Vis spectrophotometer (Perkin Elmer Lambda 365+). The amount of drug released at each timepoint was quantified by extrapolating against a standard curve on known concentrations in PBS using the UV / Vis spectrophotometer. At this point, the remainder of the release medium was removed and replenished before placing the samples back in the incubating shaker. The cumulative release (%) was calculated using the equation shown below:100 (eq. 1)where Ctis the amount of drug released at time t, CM is the amount of drug released before time t, and Co is the initial amount of drug.

[0307] As seen in FIGS. 9A-9D, increasing the SA / V ratio of the cylinders increased the release of RhB from the 3D-printed cylinders. Furthermore, the release profile of the 1 mm cylinder closely matches a zero-order kinetic profile which is desired in drug delivery applications (FIG. 9C). Degradation differences between the cylinders were also observed with the 1 mm cylinder showing a higher structural integrity than the 3 mm and 6 mm cylinders (FIG. 9D). This highlights a simple way of tuning print geometry to achieve constant and sustained drug release.

[0308] Example 20 RhB release from lattice structures

[0309] Cylindrical lattice models were generated using CAD software Altair sulis by arraying a nodal unit cell that was 6 mm in diameter and 12 mm in height. The same RhB loaded resin formulation used in the solid cylinder (Example 19) study was used to evaluate the effects of the lattice models on the release of RhB. The RhB loaded resin was used to print lattice models listed below (Table 24) using a Kudo 3D Micro DLP-VP printer equipped with a 365 nm LED UV light source. The same layer thickness and light irradiance used in the previous study were also used for this study. After printing, excess resin was removed from the lattice structures using a Kimwipe. Afterwards, the lattice structures were post cured for 200 s under a UV spot lamp (Dymax Blue Wave 200) at an irradiance of 45 mW / cm2.

[0310] Table 24. Geometric parameters of lattice structures

[0311] To evaluate RhB release from the lattice structures, the lattice parts were placed in a 50 mL centrifuge tube and 20 ml of pH 7.40.01 M phosphate buffered saline (PBS) was added. The samples were placed in an incubating shaker at 37°C under constant oscillation at 50 rpm. At each designated time point, 1 mL of the release medium was collected, and the absorbance was measured using a UV / Vis spectrophotometer (Perkin Elmer Lambda 365+). The amount of drug released at each timepoint was quantified by extrapolating against a standard curve on known concentrations in PBS using the UV / Vis spectrophotometer. At this point, the remainder of the release medium was removed and replenished before placing the samples back in the incubating shaker. The cumulative release (%) was calculated using equation 1.

[0312] RhB release from lattice structure L1-L3 is shown in FIGS. 10A-10C. In this series, the gyroid lattice type was held constant, but unit cell size of the array varied. This in turn changed the strut length and surface area to volume ratio (SA / V) of the printed structures with a decrease in strut length and an increase in SA / V corresponding to decreasing unit cell size. In this study, the pore-size of the structures were kept constant. The in vitro release results (FIG. 10C) showed that decreasing the unit cell size increased the release of RhB. Interestingly, the RhB release profile from L3 was concave downward, typical of diffusion control release. However, the release profile from LI and L2 were sigmoidal, which cannot be explained by diffusion alone. This sigmoidal release is explained by a time-dependent increase in effective RhB diffusivity, caused by degradation of the polymer network. Furthermore, fitting the release profile to a zero-order kinetic model (corresponding to constant drugrelease over time which is often preferred in drug delivery applications) showed that L2 which has a unit cell size of 3 mm and a strut length of 1.4 mm showed the closest fit (FIGS. 11A-11C). This result indicates that there is an optimal unit cell size or strut length in a lattice structure that allows for the interplay of degradation and diffusion to yield constant release of a drug over time. In this study, this was evident with the L2 lattice structure.

[0313] The effect of pore-size on the RhB release was also investigated. In the L4, L2, and L5 lattice structures, the unit cell size and strut length were held constant, but the poresize was modified from 2.45 mm, 1.6 mm, and 0.75 mm, respectively. FIGS. 12A-12C show that cumulative release of RhB from the lattice structures with different pore-sizes. While the L4 and L2 sample had similar release profiles, the L5 sample had lower release showing approximately 60% release at 112 d compared to the 80% release showed by the L4 and L2 samples. This was explained to be due to the effect of pore wetting through the relatively hydrophobic polymer network channels of the smaller pores. This result exemplifies the importance of lattice pore-size in drug release from lattice devices.

[0314] Example 21 Hyaluronic acid loaded formulations

[0315] Hyaluronic acid (800 kDa) was added to a Resin E composition at concentrations of 0, 5, or 10 weight-percent (wt.%). In some case, a polyglycolide microparticulate (A6E3) was added at concentrations of 5%. All formulations were then individually mixed on a high speed mixer for two minutes at 2000 rotations per minute (rpm) and three minutes at 3000 rpms.

[0316] The effect of unit cell geometry, pore-size, beam-size, and the inclusion of additives such as Hyaluronic acid was also investigated for flexural rigidity, suture pull out force, suture pull out elongation, compressive stress and modulus. Hardness values of solid samples were also measured in the Shore A hardness scale. Images of 3D printed parts were taken to observe the sample under magnification (FIG. 16 and FIG. 17).

[0317] Table 25. Characteristics of different lattice structures

[0318] Table 26. Hardness and Compressive modulus and stress of different lattice structures

[0319] All references disclosed herein, including patent references and non-patent references, are hereby incorporated by reference in their entirety as if each was incorporated individually.

[0320] It is to be understood that the terminology used herein is for the purpose of describing specific embodiments only and is not intended to be limiting. It is further to be understood that unless specifically defined herein, the terminology used herein is to be given its traditional meaning as known in the relevant art.

[0321] Reference throughout this specification to "one embodiment" or "an embodiment" and variations thereof means that a particular feature, structure, or characteristic described in connection with the 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.

[0322] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents, i.e., one or more, unless the content and context clearly dictates otherwise. It should also be noted that the conjunctive terms, "and" and "or"are generally employed in the broadest sense to include "and / or" unless the content and context clearly dictates inclusivity or exclusivity as the case may be. Thus, the use of the alternative (e.g., "or") should be understood to mean either one, both, or any combination thereof of the alternatives. In addition, the composition of "and" and "or" when recited herein as "and / or" is intended to encompass an embodiment that includes all of the associated items or ideas and one or more other alternative embodiments that include fewer than all of the associated items or ideas.

[0323] Unless the context requires otherwise, throughout the specification and claims that follow, the word "comprise" and synonyms and variants thereof such as "have" and "include", as well as variations thereof such as "comprises" and "comprising" are to be construed in an open, inclusive sense, e.g., "including, but not limited to." The term "consisting essentially of" limits the scope of a claim to the specified materials or steps, or to 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 the materials, methods, and examples are illustrative and not intended to be limiting.

[0324] Any headings used within this document are only being utilized to expedite its review by the reader, and should not be construed as limiting the disclosure or claims in any manner. Thus, the headings and Abstract of the Disclosure provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.

[0325] Where a range of values is provided herein, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges is also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure.

[0326] For example, any concentration range, percentage range, ratio range, or integer range provided herein is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and onehundredth of an integer), unless otherwise indicated. Also, any number range recited herein relating to any physical feature, such as polymer subunits, size or thickness, are to 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.

[0327] All of the U. S. patents, U. S. patent application publications, U. S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and / or listed in the Application Data Sheet, are incorporated herein by reference, in their entirety. Such documents may be incorporated by reference for the purpose of describing and disclosing, for example, materials and methodologies described in the publications, which might be used in connection with the presently described disclosure. The publications discussed above and throughout the text are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the inventors are not entitled to antedate any referenced publication by virtue of prior disclosure.

[0328] All patents, publications, scientific articles, web sites, and other documents and materials referenced or mentioned herein are indicative of the levels of skill of those skilled in the art to which the disclosure pertains, and each such referenced document and material is hereby incorporated by reference to the same extent as if it had been incorporated by reference in its entirety individually or set forth herein in its entirety. Applicants reserve the right to physically incorporate into this specification any and all materials and information from any such patents, publications, scientific articles, web sites, electronically available information, and other referenced materials or documents.

[0329] 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 the disclosure.

[0330] Furthermore, the written description portion of this patent includes all claims. Furthermore, all claims, including all original claims as well as all claims from any and all priority documents, are hereby incorporated by reference in their entirety into the writtendescription portion of the specification, and Applicants reserve the right to physically incorporate into the written description or any other portion of the application, any and all such claims. Thus, for example, under no circumstances may the patent be interpreted as allegedly not providing a written description for a claim on the assertion that the precise wording of the claim is not set forth in haec verba in written description portion of the patent.

[0331] The claims will be interpreted according to law. However, and notwithstanding the alleged or perceived ease or difficulty of interpreting any claim or portion thereof, under no circumstances may any adjustment or amendment of a claim or any portion thereof during prosecution of the application or applications leading to this patent be interpreted as having forfeited any right to any and all equivalents thereof that do not form a part of the prior art.

[0332] Other nonlimiting embodiments are within the following claims. The patent may not be interpreted to be limited to the specific examples or nonlimiting embodiments or methods specifically and / or expressly disclosed herein. Under no circumstances may the patent be interpreted to be limited by any statement made by any Examiner or any other official or employee of the Patent and Trademark Office unless such statement is specifically and without qualification or reservation expressly adopted in a responsive writing by Applicants.

Claims

CLAIMSWhat is claimed is:

1. A biodegradable biocompatible photopolymerized lattice part, comprising a biodegradable biocompatible polymeric composition having multiple ethylenically unsaturated groups and a photoinitiator, formed to comprise a lattice structure comprising a plurality of repeating or non-repeating unit cells comprising one or more strut sizes of 50 pm to 3000 pm, wherein the lattice part degrades under physiological conditions into a polymeric byproduct with a molecular weight of less than 20,000 Daltons.

2. The lattice part of Claim 1, comprising a Voronoi based lattice structure.

3. The lattice part of Claim 1, having isotropic mechanics.

4. The lattice part of Claim 1, comprising a gradient lattice structure wherein one or both of the lattice strut size or pore size changes throughout the part.

5. The lattice part of Claim 1, comprising one or more struts having a cross-sectional shape of a circle, oval, elliptical, square, rectangular, or other polygons.

6. The lattice part of Claim 1, comprising one or more struts having a cross-sectional shape that is irregular.

7. The lattice part of Claim 1, comprising a pore size between 150 pm to 10 mm.

8. The lattice part of Claim 1, comprising a pore size between 50 pm to 3 mm.

9. The lattice part of Claim 1, comprising a suture pullout strength of 0.1 to 150 N for a 2 mm thick sheet of the material.

10. The lattice part of Claim 1, comprising a flexural rigidity of 0.5 pN*m to 1000 pN*m for a 2 mm thick sheet of the material.

11. The lattice part of Claim 1, comprising an organic factor of between 1 and 3.

12. The lattice part of Claim 1, comprising an organic factor of between 1 and 2.

13. The lattice part of Claim 1, comprising wherein the photopolymerized biodegradable biocompatible polymeric composition of the part comprises an elongation of 1% to 100%.

14. The lattice part of Claim 1, wherein the photopolymerized biodegradable biocompatible polymeric composition comprises an elongation of 10% to 350%.

15. The lattice part of Claim 1, comprising all or a portion of a lattice structure of one or more repeating unit cells, or all or a portion of a lattice of one or more non-repeating unit cells.

16. The lattice part of Claim 1, further comprising a second biodegradable biocompatible material composition that fills the porous structure.

17. The lattice part of Claim 1, wherein the biodegradable biocompatible polymeric composition comprises a chain transfer agent comprising a minimum of one thiol group.

18. The lattice part of Claim 1, made by a manufacturing technique using vat photopolymerization or light assisted photopolymerization.

19. The lattice part of Claim 1, wherein the biodegradable biocompatible polymeric composition comprises a biocompatible or naturally derived dye or UV absorber.

20. The lattice part of Claim 1, wherein the biodegradable biocompatible polymeric composition comprises at least one free radical stabilizer.

21. The lattice part of Claim 1, comprising a strength loss between 3 months to 18 months.

22. The lattice part of Claim 1, comprising a strength loss between 7 days to 3 months.

23. The lattice part of Claim 1, comprising a mass loss of 6 months to 18 months.

24. The lattice part of Claim 1, comprising a mass loss of 12 months to 36 months.

25. The lattice part of Claim 1, further comprising a bioresorbable biocompatible coating.

26. The lattice part of Claim 1, wherein the biodegradable biocompatible polymeric composition comprises a particulate comprising at least one of functionalized hyaluronic acid, hyaluronic acid, functionalized collagen, collagen, functionalized gelatin, gelatin, peptide sequences, polyester, polycarbonate, polyester carbonate, hydroxyapatite, tricalcium phosphate, and combinations thereof.

27. The lattice part of Claim 1, further comprising a surface coating wherein the coating comprises at least one of functionalized hyaluronic acid, hyaluronic acid, functionalized collagen, collagen, functionalized gelatin, gelatin, peptide sequences, polyester, polycarbonate, polyester carbonate, polyethers, chitosan or chitosan derivatives, and combinations thereof.

28. The lattice part of Claim 1, wherein the lattice part is at least a portion of a medical device or is a medical device, and is used as a medical device for wound care treatments, as a tissue scaffold, as a breast implant or in treatments for soft tissue repair.

29. The lattice part of Claim 1, further comprising at least one bioactive agent.

30. The lattice part of Claim 29, comprising a Voronoi based lattice structure.

31. The lattice part of Claim 29, having isotropic mechanics.

32. The lattice part of Claim 29, comprising a gradient lattice structure wherein one or both of the lattice strut size or pore size changes throughout the part.

33. The lattice part of Claim 29, comprising one or more struts having a cross-sectional shape of a circle, oval, elliptical, square, rectangular, or other polygons.

34. The lattice part of Claim 29, comprising one or more struts having a cross-sectional shape that is irregular.

35. The lattice part of Claim 29, comprising a pore size between 150 pm to 10 mm.

36. The lattice part of Claim 29, comprising a pore size between 50 pm to 3 mm.

37. The lattice part of Claim 29, comprising a suture pullout strength of 0.1 to 150 N for a 2 mm thick sheet of the material.

38. The lattice part of Claim 29, comprising a flexural rigidity of 0.5 pN*m to 1000 pN*m for a 2 mm thick sheet of the material.

39. The lattice part of Claim 29, comprising an organic factor of between 1 and 3.

40. The lattice part of Claim 29, comprising an organic factor of between 1 and 2.

41. The lattice part of Claim 29, comprising wherein the photopolymerized biodegradable biocompatible polymeric composition of the part comprises an elongation of 1% to 100%.

42. The lattice part of Claim 29, wherein the photopolymerized biodegradable biocompatible polymeric composition comprises an elongation of 10% to 350%.

43. The lattice part of Claim 29, comprising all or a portion of a lattice structure of one or more repeating unit cells, or all or a portion of a lattice of one or more non-repeating unit cells.

44. The lattice part of Claim 29, further comprising a second biodegradable biocompatible material composition that fills the porous structure.

45. The lattice part of Claim 29, wherein the biodegradable biocompatible polymeric composition comprises a chain transfer agent comprising a minimum of one thiol group.

46. The lattice part of Claim 29, made by a manufacturing technique using vat photopolymerization or light assisted photopolymerization.

47. The lattice part of Claim 29, wherein the biodegradable biocompatible polymeric composition comprises a biocompatible or naturally derived dye or UV absorber.

48. The lattice part of Claim 29, wherein the biodegradable biocompatible polymeric composition comprises at least one free radical stabilizer.

49. The lattice part of Claim 29, comprising a strength loss between 3 months to 18 months.

50. The lattice part of Claim 29, comprising a strength loss between 7 days to 3 months.

51. The lattice part of Claim 29, comprising a mass loss of 6 months to 18 months.

52. The lattice part of Claim 29, comprising a mass loss of 12 months to 36 months.

53. The lattice part of Claim 29, further comprising a bioresorbable biocompatible coating.

54. The lattice part of Claim 29, wherein the biodegradable biocompatible polymeric composition comprises a particulate comprising at least one of functionalized hyaluronic acid, hyaluronic acid, functionalized collagen, collagen, functionalized gelatin, gelatin, peptide sequences, polyester, polycarbonate, polyester carbonate, hydroxyapatite, tricalcium phosphate, and combinations thereof.

55. The lattice part of Claim 29, further comprising a surface coating wherein the coating comprises at least one of functionalized hyaluronic acid, hyaluronic acid, functionalized collagen, collagen, functionalized gelatin, gelatin, peptide sequences, polyester, polycarbonate, polyester carbonate, polyethers, chitosan or chitosan derivatives, and combinations thereof.

56. The lattice part of Claim 29, comprising at least one bioactive agent with a release profile of a burst release followed by zero order or near zero order release kinetics.

57. The lattice part of Claim 29, comprising at least one bioactive agent having sustained release of over 7 days.

58. The lattice part of Claim 29, comprising at least one bioactive agent having sustained release of over 20 days.

59. The lattice part of Claim 29, comprising at least one bioactive agent having sustained release of over 60 days.

60. The lattice part of Claim 29, comprising at least one hydrophobic bioactive agent.

61. The lattice part of Claim 29, comprising at least one hydrophillic bioactive agent.

62. The lattice part of Claim 29, wherein the biodegradable biocompatible polymeric composition further comprises at least one particulate encapsulated bioactive agent.

63. The lattice part of Claim 53, wherein the biodegradable biocompatible coating further comprises at least one particulate encapsulated bioactive agent.

64. The lattice part of Claim 29, wherein the lattice part is at least a portion of a medical device or is a medical device, and is used as a medical device for wound care treatments, as a tissue scaffold, as a breast implant or in treatments for soft tissue repair.

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