Printing Method utilizing the same

FIELD OF THE INVENTION

The present invention relates to a resin composition, in particular suitable for printing, a kit comprising the components of the resin composition, a printing method utilizing the resin composition, a polymer obtained by the printing method, an article comprising or formed from the polymer, and uses thereof.

BACKGROUND

Printing methods may serve for a large variety of purposes. In addition to traditional two-dimensional printing methods that are still widely used, three- dimensional printing methods have gained increasing interest over the past years. Initially developed for preparing prototypes, for instance for design purposes, three-dimensional (3D) printing methods are now more and more utilized for producing highly sophisticated and complex geometric structures that are brought to market as such, for instance in the automobile industry, for producing ornaments and in end-user appliances (Wendel et al., acromol.

Mater. Eng. 293 (2008) 799-809).

Among the known 3D printing methods, so-called solid free-form techniques or rapid prototyping, such as fused deposition modeling (FDM), selective laser sintering (SLS) and 3D printing technology (3DP), in particular stereolithography (SLA) is a very promising technique in view of its high resolution that can hardly be attained with other techniques (Gross et al., Anal. Chem. 86 (2014) 3240- 3253; Liska et a!., J. Coat. Technol. Res. 4 (2007) 505-510). This technique based on photopolymerization is in particular suitable for preparing biomedical products, such as artificial, biologically degradabie bone structures requiring pore sizes between 100 pm and 500 μιη (Lipowiecki et al., J. Biomed. Mater. Res. Part A (2014) accepted; Bose et al., Materials Today 16 (2013) 496-504). Previous bone replacement materials prepared by FDM, SLS or 3DP are mainly based on ceramic materials, such as calcium phosphate or hydroxyapatite, which however suffer from a low mechanical load capacity with increasing porosity. Typical biologically degradabie polymers used as suture material, in particular for surgical suture, are based on polyester polymers, for instance poiycaprolactones (e.g. poly(E-caprolactone)) and poly(a-hydroxy acids) (e.g. polyglycolic acid, polylactic acid and copolymers thereof). However, due to their relatively fast hydrolytic degradation resulting in loss of their mechanical properties, these materials cannot be used as a substitute for hard tissue.

Among the photo- reactive biologically degradabie polymers, poly(propylene fumarate) and poly(trimethylen carbonate-co-caprolactone)~coumarin have proven to be appropriate for preparing porous structures by means of SLA (Melchels et al., Biomaterials 31 (2010) 6121-6130; Cooke et al., J. Biomed. Mater. Res. Part B: Appl. Biomater. 64B (2003) 65-69; Lee et al.,

Biomacromolecules 8 (2007) 1077-1084; Matsuda et al., Macromolecules 33 (2000) 795-800). Microneedles prepared by SLA from acrylated poly(trimethylen carbonate-co-caprolactone) have been subcutaneousiy implanted in rats for one month and have shown a regular degradation by surface erosion similar to that of an alkaline hydrolysis (Matsuda et al., J. Biomed. Mater. Res. 62 (2002) 395- 403). Liska et al. evaluated a variety of photo-reactive polymers as resins used for stereolithography and two-photon absorption (TPA) photopolymerization, respectively, for preparing cellular structures. The monomers mainly based on acrylates, methacrylates as well as acrylamides have proven to be non-cytotoxic and could be structured by stereoiithographic methods by means of digital light processing (PLP) or UV laser microstereolithography with a resolution of 5 to 10 μιη (Liska et al., J. Coat. Technol. Res. 4 (2007) 505-510; Schuster et al, Proceedings LPM 2007 - The 8 ^th Symposium on Laser Precision Microfabrication).

Despite these efforts, the choice of commercially available printing resins is however still limited so that there is a need for the development of new materials and compositions.

Thiol-ene reactions represent an established photopolymerization process used for a variety of appliances, in particular in the optical, biomedical, bioorganic and dental field (Hoyle et al., Angew. Chem. Int. Ed. 49 (2010) 5301-5338).

Advantages of thiol-ene reactions reside in a high reactivity, insensitivity against oxygen, high chemical stability, low shrinkage of the obtained polymers as well as high polymerization yields (Hoyle et al., J. Polym. Sci. Part A: Polym . Chem. 42 (2004) 5301-5338). WO 2013/052328 Al discloses resorbable biocompatible polymers formed by thiol-ene polymerization of vinylesters and vinylcarbonates, which polymers can be used as a biodegradable, resorbable implant.

Thiol-yne photopolymerizations run with a similar mechanism to thiol-ene reactions, and thus they possess the same advantages. However, polymers obtained by thiol-yne reactions have a six-time higher crosslinking degree and consequently a significantly higher glass transition temperature than

corresponding thiol-ene based polymers (Fairbanks et al., Macromolecules 42 (2009) 211-217). Due to the ability of an alkyne moiety to react with two thiol monomers, monofunctional monomers, such as compounds having only one alkyne moiety, may be used in thiol-yne reactions without terminating the polymerization reaction. Thiol-yne based polymers possess high biocompatibility and are thus suitable for the biomedical field. WO 2012/103445 A2 discloses the preparation of biodegradable hydrogels on the basis of a thiol-yne reaction, which hydrogels are described to be suitable for biomedicine, for instance as a substrate for the growth of various cell types. US 2011/0144227 Al discloses biomedical devices containing thiol-ene or thiol-yne shape memory polymers. OBJECTS OF THE INVENTION

In light of the foregoing, the present invention aims at overcoming the above described problems and drawbacks of hitherto available printing resins, in particular the restrictions thereof when used for medical or biomedical appliances. Thus, an object of the present invention is to provide a novel resin composition which may be in particular suitable for printing and which benefits from the advantages of thiol-yne polymerization reactions. Another object is to provide a polymer and an article comprising or formed from the polymer, which is highly biocompatible and biodegradable, has a very low residual monomer content and exhibits low shrinkage.

SUMMARY OF THE INVENTION The present inventors have made diligent studies for solving these objects and have found that when the alkyne functional group-containing component in a resin composition further comprises at least one functional ester group, not only a printing resin having highly biocompatible monomers and being excellently suitable for a 3D printing method, such as stereolithography, with high curing velocity of the resin, very high monomer conversion (thereby substantially avoiding any migration of monomers from the final product) and insensitivity to oxygen during polymerization can be provided, but also the biodegradability of the resulting polymer as well as of an article comprising or formed from the polymer can be appropriately adjusted to the desired needs of a specific medical or biomedical appliance and the shrinkage of the resulting polymer is low due to the formation of a homogenous network as well as the mechanical properties, such as the elastic modulus, are excellent due to its high crosslinking degree, which properties are particularly beneficial in medical or biomedical appliances, such as implantation, bone substitution or replacement, tissue substitution or replacement and/or dental applications. In addition, the composition and a printing method utilizing the composition may be solvent-free which further improves the biocompatibillty of the resulting products due to the absence of any residual solvent. Moreover, additives may be included in the composition, which additives may provide for additional specific tailor-made advantageous properties of the resulting products, as desired. Accordingly, the present invention relates to a resin composition comprising: at least one compound CI having

(i) at least one terminal alkyne functional group, and

(ii) at least one functional ester group; and

at least one compound C2 having at least two thiol functional groups.

The resin composition according to the present invention is in particular suitable for printing.

Accordingly, the present invention further relates to the use of the resin composition according to the present invention as or in an ink.

The components CI and C2 of the resin composition according to the present invention may be in particular provided in a spatially separated manner, for instance in a kit, in particular a kit-of-parts.

Thus, the present invention also relates to a kit comprising :

at least one compound CI having

(i) at least one terminal alkyne functional group, and

(ii) at least one functional ester group; and

at least one compound C2 having at least two thiol functional groups.

Furthermore, the present invention relates to the use of the kit according to the present invention for preparing a resin composition for use as or in an ink. The present invention further relates to a printing method comprising the steps of providing the resin composition according to the present invention, wherein the resin composition further comprises at least one initiator; and

directing an energy source to at least a part of the resin composition so as to cause polymerization of the at least a part of the resin composition and so as to obtain a polymer.

In addition, the present invention relates to a polymer obtainable by the printing method according to the present invention. Moreover, the present invention relates to an article comprising or formed from the polymer according to the present invention.

The polymer and the article obtained according to the present invention can be used for various appliances.

Accordingly, the present invention further relates to the use of the polymer or of the article according to the present invention in a medical or biomedical application. Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become better understood by reference to the following detailed description of embodiments and the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a graphical illustration of the test results of Example 1 Indicating the reaction speeds of the tested alkyne monomers and comparative (meth)acryl monomers and further showing their chemical structural formulas.

Figure 2 is a graphical illustration of the conversion of the content of alkyne and alkene, respectively, during photopolymerisation of 1,4-butanediol dimethacrylate, 1,4-butanediol diacrylate, succinic acid dibut-l-ynyl ester and succinic acid dipropargyl ester obtained by means of real-time FTIR

measurements according to Example 2. Figure 3 shows illustrations of the concentration-dependent cytotoxicity after incubation for 48 h of 1,4-butanediol diacrylate.

Figure 4 shows illustrations of the concentration-dependent cytotoxicity after incubation for 48 h of 1,4-butanediol dimethacrylate.

Figure 5 shows illustrations of the concentration-dependent cytotoxicity after incubation for 48 h of succinic acid dipropargyl ester.

Figure 6 shows illustrations of the concentration-dependent cytotoxicity after incubation for 48 h of succinic acid dibut-l-ynyl ester.

DETAILLED DESCRIPTION OF THE INVENTION

Hereinafter, details of the present invention and other features and advantages thereof will be described. However, the present invention is not limited to the following specific descriptions, but they are rather for illustrative purposes only.

It should be noted that features described in connection with one exemplary embodiment or exemplary aspect may be combined with any other exemplary embodiment or exemplary aspect, in particular features described with any exemplary embodiment of the resin composition may be combined with any exemplary embodiment of a kit, a printing method, a polymer or an article or with any exemplary embodiment of uses thereof and vice versa, unless specifically stated otherwise.

Where an indefinite or definite article is used when referring to a singular term, such as "a", "an" or "the", a plural of that term is also included and vice versa, unless specifically stated otherwise, whereas the word "one" or the number "1", as used herein, typically means "just one" or "exactly one".

The expression "comprising", as used herein, includes not only the meaning of "comprising", "including" or "containing", but also encompasses "consisting essentially of" and "consisting of".

Unless specifically stated otherwise, the expressions "at least partially", "at least a partial" or "at least a part of", as used herein, may mean at least 5 % thereof, in particular at least 10 % thereof, in particular at least 15 % thereof, in particular at least 20 % thereof, in particular at least 25 % thereof, in particular at least 30 % thereof, in particular at least 35 % thereof, in particular at least 40 % thereof, in particular at least 45 % thereof, in particular at least 50 % thereof, in particular at least 55 % thereof, in particular at least 60 % thereof, in particular at least 65 % thereof, in particular at least 70 % thereof, in particular at least 75 % thereof, in particular at least 80 % thereof, in particular at least 85 % thereof, in particular at least 90 % thereof, in particular at least 95 % thereof, in particular at least 98 % thereof, and may also mean 100 % thereof. In a first aspect, the present invention relates to a resin composition comprising : at least one compound CI having

(i) at least one terminal alkyne functional group, and

(ii) at least one functional ester group ; and

at least one compound C2 having at least two thiol functional groups.

The term "composition", as used herein, may in particular mean that the components (ingredients) of the composition are in close proximity with each other and/or that the components are (intensely) mixed with each other, for instance by using a mixer, a stirrer and/or by shaking, to thereby form the composition. In particular, the components of the compositions may be uniformly distributed or dispersed throughout within the composition. The composition may be in particular solid, semi-solid (pasty) or liquid, in particular a liquid solution or a semi-solid or liquid suspension.

The resin composition may in particular be a photo-reactive and/or a thermo- reactive resin composition. The term "photo-reactive", as used herein, may in particular mean that the resin composition, in particular some or all of its components, undergo a (chemical) reaction upon irradiation with an energy- carrying activation beam, in particular with electromagnetic radiation. The term "thermo-reactive", as used herein, may in particular mean that the resin composition, in particular some or all of its components, undergo a (chemical) reaction upon supplying the resin composition with thermal energy, such as by heating and/or by irradiation with electromagnetic radiation in the infrared or microwave wavelength regions. The resin composition may be in particular suitable for printing, for instance in a printing method according to the present invention. Accordingly, the resin composition may be in particular used as an ink (a printing ink), Le. the resin composition itself may be directly used as an ink. Likewise, the resin composition may be in particular used in an ink (a printing ink), i.e. as a component or an ingredient of an ink together with appropriate one or more further components or ingredients, typically used in an ink.

The resin composition comprises at least two components or ingredients: at least one compound CI (also referred to as "yne component" or "yne monomer") and at least one compound C2 (also referred to as "thiol component" or "thiol monomer")- As it is evident, the resin composition may contain more than one compound CI (such as mixtures of different compounds CI) and/or more than one compound C2 (such as mixtures of different compounds C2), as well as further ingredients or components, which will be described below.

The compound CI has (i) at least one terminal alkyne functional group, and (ii) at least one functional ester group. The term "terminal alkyne functional group", as used herein and as commonly understood by a person skilled in the art, represents a moiety having a carbon- carbon triple bond wherein one of the carbon atoms binds to a hydrogen atom. In other words, a terminal aikyne functional group may be represented by the general formula "-C≡C-H". The terminal alkyne functional group may also be present in protected form, for instance as a silyl (such as trimethylsilyl (TMS)) protected alkyne group and/or as a complex of the carbon -carbon triple bond with for instance dicobalt octacarbonyl. Appropriate deprotection (removal of the protecting group) should then be carried out, as it is well known to a person skilled in the art, prior to the use of the resin composition, for instance in a printing method or in any other intended use thereof where the terminal alkyne functional group is intended to take part in a thiol-yne reaction. The term ester as used herein, correspond to the generally accepted meanings thereof. An ester may be represented by the general formula ^x, -(CO)0-" or "-O(CO)-

The functional ester group enables a degradation of a product (such as a polymer or an article comprising or formed the polymer) obtained after the thiol-yne reaction, for instance by a printing method, in a human or animal body, such as when used as a medical or biomedical device. In addition to the functional ester group, the compound CI may in particular further comprise a carbonate, a carbamate and/or an ether functional group, which might further provide specific desired physiological properties of the product (such as its degree and rate

(speed) of biodegradation under a physiological environment). Other functional groups being more or less hydrolysable/cleavable under physiological conditions may be contained in the compound CI, but also in the compound C2. It might also be advantageous that the product (such as the polymer and/or the article) is at least partially biodegradable and at least partially non-biodegradable, for instance if a certain persistent mechanical support is desired, or that a part of the product biodegrades relatively fast whereas a part of the product biodegrades relatively slowly, which might be in particular advantageous when using the product as an implant, a bone substitute and/or a tissue substitute. Such products may in particular be derived from a resin composition comprising combinations of component CI and C2 containing non degradable thiols.

The terminal alkyne functional group of the compound CI may be in particular any one selected from the group consisting of propargyl, butynyl and pentynyl . Propargyl may be represented by the general formula "-CH ₂ -C≡C-H", butynyl may be represented by the general formulas "-CH2-CH2-C≡C-H" or "-C(CH3)H- C≡C-H" and pentynyl may be represented by the general formulas "-CH2-CH2-

CH ₂ -C≡C-H", ^U -C(CH ₃ )H-CH ₂ -C≡C-H", "-CH ₂ -C(CH ₃ )H-C≡C-H" or ^¾ -C(CH ₃ ) ₂ -C=C- H". The linear (unbranchend) groups thereof, i.e. ^W -CH ₂ -C≡C-H", "-CH ₂ -CH ₂ -C≡C- H" and "-CH ₂ -CH ₂ -CH ₂ -C≡C-H" may be preferred. The present inventors have made the unexpected finding that the larger the carbon atom chain of the terminal alkyne functional group, the higher the reactivity between the terminal alkyne functional group and a thiol group in a thioi-yne reaction, and consequently the faster the resulting crosslinking takes place, which is advantageous for a printing method, in particular a three- dimensional printing method where typically the object to be printed is formed layer by layer requiring the previous layer to be substantially hardened or cured before forming the subsequent layer. Thus, the printing time can be shortened with increasing number of carbon atoms in the terminal alkyne functional group. On the other hand, the present inventors have found that the larger the carbon atom chain of the terminal alkyne functional group, the more flexible the cross- linkages formed, and consequently the mechanical properties of the resulting (polymer) network, in particular its mechanical strength and rigidity, may be impaired, which is not desired when a specific shape and mechanical integrity of the final product or article is an important issue, for instance when used as an implant, a bone substitute and/or a dental product, such as a dental prosthesis. A terminal alkyne functional group of the compound CI of any one selected from the group consisting of propargyl, butynyl and pentynyl has proven to be very appropriate for the purposes of the present invention. In particular, a terminal alkyne functional group of the compound CI of butynyl and/or pentynyl may be preferred in terms of polymerization velocity. In particular, a butynyl group as the at least one terminal alkyne functional group is in particular advantageous in terms of polymerization velocity and mechanical properties of the polymer network formed. In an embodiment, the at least one compound CI may comprise a compound having a functional group selected from the group consisting of a propargyl ester, a butynyi ester and a pentynyl ester. In particular, the at least one compound CI may comprise a compound having a functional group selected from the group consisting of a butynyl ester and a pentynyl ester.

In an embodiment, the at least one compound CI may be represented by any one of the following general formulas (I) to (III) :

wherein

n, m and o represent an integer of from 1 to 1000; and

R ¹ , R ² and R ³ independently from each other represent a linear or branched, saturated or unsaturated, substituted or unsubstituted alkyl group; a linear or branched, saturated or unsaturated, substituted or unsubstituted heteroalkyl group; a saturated or unsaturated, substituted or unsubstituted cycloalkyl group; a saturated or unsaturated, substituted or unsubstituted heterocycloalkyl group; a substituted or unsubstituted aryl group; a substituted or unsubstituted heteroaryl group; a linear or branched, substituted or unsubstituted aralkyi group; or a linear or branched, substituted or unsubstituted alkaryl group. In the general formulas (I) to (III) n, m and o may in particular represent an integer of from 1 to 1000, with a lower range limit of for instance 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25 and/or with an upper range limit of for instance 1000, 900, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 275, 250, 225, 200, 190, 180, 170, 160, 150, 140, 130, 125, 120, 115, 110, 105, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 38, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, including any single combination of lower and upper range limit values.

The meaning of the terms "linear", "branched", "saturated", "unsaturated" and "unsubstituted", as used herein, corresponds to the respective well-established meanings thereof, as known to a person skilled in the art. The term

"substituted", as used herein, means that one or more, in particular 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, hydrogen atom(s) of the respective groups are substituted by a substituent. Examples of suitable substituents, include halogen atoms, such as -F, -CI, -Br, -I; -OH, hydroxyalkyl groups (ether), -SH, thioalkyl groups (thioether), =0, carboxyl groups (-COOH) and salts, esters and amides thereof, -NH ₂ , secondary amine groups, tertiary amine groups, nitrile groups and nitro groups. If two or more substituents are present, they may be the same or different and they may be bound to each other to form a ring. The terms

"heteroalkyl group", "heterocycloalkyl group" or "heteroary! group", respectively, represents an alkyl group, a cycloalkyl group or an aryl group, respectively, wherein one or more, in particular 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, carbon atoms are replaced by a hetero atom, such as O, N or S, in particular O and/or N. If more than one hetero atom is contained in a group, these hetero atoms may be the same or different.

Suitable examples of the alkyl group include Ci to C ₂ o alkyl groups, in particular C ₂ to Cio alkyl groups, in particular C ₃ to C ₈ alkyl groups, in particular C ₄ to Ce alkyl groups. Suitable examples of the cycloalkyl group include C3 to C20 cycloaikyl groups, in particular C ₄ to C15 cycloalkyl groups, in particular C ₅ to C10 cycloaikyl groups, in particular C ₆ to C ₈ cycloalkyl groups. Suitable examples of the aryl group include C ₆ to C ₂₀ aryl groups, in particular Ce to Ci6 aryl groups, in particular C ₅ to C14 aryl groups, in particular Ce to C10 aryl groups. In particular, the aryl group may be a phenyl group.

An "aralkyl group", as used herein, denotes a group having an aliphatic and an aromatic moiety, wherein the aliphatic moiety binds to the ester functional group of the respective compounds represented by general formulas (I) to (III), and wherein the aromatic moiety and/or the aliphatic moiety may optional comprise a hetero atom. In other words, an "aralkyl group" represents an alkyl or cycloalkyl group (or a heteroalkyl or heterocycloalkyl group) having an aryi group (or a heteroaryl group) as a substituent. Suitable aliphatic and aromatic moieties of the aralkyl group correspond to the alkyl, cycloalkyl and aryl groups (or heteroalkyl, heterocycloalkyl and heteroaryl groups, respectively), as defined above.

An "alkaryl group", as used herein, denotes a group having an aliphatic and an aromatic moiety, wherein the aromatic moiety binds to the ester functional group of the respective compounds represented by general formulas (I) to (III), and wherein the aliphatic moiety and/or the aromatic moiety may optional comprise a hetero atom. In other words, an "alkaryl group" represents an aryl group (or a heteroaryl group) having an alkyl or cycloalkyl group (or a heteroalkyl or heterocycloalkyl group) as a substituent Suitable aliphatic and aromatic moieties of the alkaryi group correspond to the alkyl, cycloalkyl and aryl groups (or heteroalkyl, heterocycloalkyl and heteroaryl groups, respectively), as defined above. In an embodiment, the at least one compound CI has one terminal alkyne functional group, for instance wherein n, m and o in the above general formulas (I) to (III) is 1. It should be noted that due the presence of a carbon-carbon triple bond in the yne monomer, one monofu notional alkyne monomer can react with two thiol functional groups in a thiol-yne reaction so that the polymerization reaction can proceed (does not terminate) even if only one functional alkine group is present in the yne monomer.

In an embodiment, the at least one compound CI has at least two terminal alkyne functional groups, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more terminal alkyne functional group. Such compounds CI may be in particular advantageous when a low viscosity of the resin composition is not required and/or where a particular strong polymeric network with a large variety of cross-linkages is desired.

Appropriate examples of the at least one compound CI include for instance the following compounds :

The compounds CI as defined herein can be prepared by well-established organic synthesis methods using commercially available starting materials.

For example, a compound having at least one terminal alkyne functional group and at least one ester functional group can be prepared as shown below by way of specific examples. It should be noted that these specific examples are only for illustrative purposes and should not be construed limiting in any way. One approach to for synthesizing compounds having at least one terminal alkyne functional group and at least one ester functional group according to Schotten- Baumann esterification synthesis is illustrated below:

As an alternative approach to the above method, the following method for synthesizing compounds having at least one terminal alkyne functional group an at least one ester functional group by means of Steglich esterification synthesis is illustrated below:

As a further example, a compound having at least one terminal alkyne functional group and at least one ester functional group can be prepared by means of Fischer-Speier esterification synthesis, as illustrated below :

The compound C2 has at least two thiol functional groups.

The term "thiol functional group", as used herein and as commonly understood by a person skilled in the art, represents a functional group represented by the general formula "-SH" which may also be present in protected form represented for instance by the general formula ^W -SZ", wherein "Z" represents a protection group for ^¾ ~SH", i.e. a thiol protection group.

In an embodiment, at least one of the thiol functional groups comprises a thiol protecting group. In other words, at least one of the thiol functional groups may be present in protected form or at least one of the thiol functional groups may be represented by the general formula ^tt -SZ", wherein "Z" represents a protection group for "-SH", i.e. a thiol protection group. The thiol protection group may be in particular selected from the group consisting of an acyl group, a silyl group and a siloxyl group. In case of an acyl thiol protection group, the thiol functional group in particular represents a thioester. In case of a silyl thiol protection group, the thiol functional group in particular represents a silyl thioether. In case of a siloxyl thiol protection group, the thiol functional group in particular represents a silyl thioester.

Suitable examples for an acyl thiol protection group include formyl and acetyl. Suitable examples for a silyl thiol protection group include trimethylsilyl, triethylsilyl, ferf-butyldimethylsilyl, ferf-hexylsilyl, trihexylsi!yl and tripropylsilyl. Suitable examples for a siloxyl thiol protection group include trimethylsiloxyl, triethylsiloxyl, tert-butyldimethylsiloxyl, tert-hexylsiloxyl, trihexytsiloxyl and tripropylsiioxyl.

Appropriate deprotection (removal of the protecting group) should then be carried out, as it is well known to a person skilled in the art, prior to the use of the resin composition, for instance in a printing method or in any other intended use thereof where the thiol functional group is intended to take part in a thiol- yne reaction. For instance, in case of a silyl thiol protection group (a silyl thioether), deprotection may be carried out by reaction with a photoacid, i .e. a compound that generates an acid upon irradiation with electromagnetic radiation. Likewise, in case of an acyl or a siloxyl thiol protection group (a thioester or a silyl thioester), deprotection may be carried out by reaction with a photobase, i.e. a compound that generates a base upon irradiation with electromagnetic radiation.

Accordingly, the resin composition may further comprise at least one photoacid and/or at least one photobase. In particular, in case of a silyl thiol protection group (a silyl thioether), the resin composition may further comprise at least one photoacid and in case of an acyl or a siloxyi thiol protection group (a thioester or a silylthioester), the resin composition may further comprise at least one photobase.

Suitable examples for a photoacid (photoacid generator, PAG) include

- Ionic photoacid generators, in particular

o Onium salts, such as onium salts of aryldiazonium, diaryliodonium

(e.g. Cyracure UVI-6976 available from The Dow Chemical

Company, Esacure 1064 available from Lamberti SpA, QL Cure 211 available from CHANGZHOU TRONLY NEW ELECTRONIC MATERIALS CO., LTD), triarylsulfonium (e.g. Omnicat 440 available from IGM Resins B.V., Irgacure 250 available from BASF SE, Rhodorsii 207 available from Rhodia), triarylselenonium or triarylphosphonium salts that contain complex halides such as BF-f, SbF6 ^~ , AsF ₆ ^~ , B(C ₆ F ₅ )4 ^" or PF ₆ ^" as counter ions,

o Iron arene complexes (e.g. Irgacure 261 available from BASF SE) that contain complex halides such as BF ₄ ^" , SbF ₆ ^~ , AsFe ^" , B(CeF ₅ )4 ^" or PF6 ^" as counter ions,

o Dialkylphenacyl sulfonium salts that contain complex halides such as BF ₄ ^" , SbF6 ^" , AsF6 ^" , B(C ₆ F ₅ ) ₄ ^" or PFe ^" as counter ions - Non-ionic photoacid generators, in particular

o 2-Nitrobenzylester of carboxylic acids

o 2-Nitrobenzylester of sulfonic acids

o Sulfones compounds which generate sulfinic acid upon UV irradiation

o Triarylphosphates

o N-Hydroxyimide sulfonates (e.g. N-Hydroxy-5-norbornene-2,3- dicarboximide perfluoro-l-butanesulfonate)

o Sulfonic acid esters of phenol

o Diazonaphthoquinones

o Imino sulfonates

o Trichloromethyl-l,3,5-triazines (e.g. 2-(4- ethoxystyryl)-4,6- bis(trichloromethyl)-l,3,5-triazine)

and/or mixtures of any one of the foregoing.

Suitable examples for a photobase (photobase generator, PBG) include

- Carbamates (e.g. m-nitrophenyl, 3,5-dimethoxybenzyl, l-methy!-l-(3,5- dimethoxyphenyl)ethyl, a-methylnitropiperonyl, o-nitrobenzyl, 3,4- dimethoxy-6-nitrobenzy!, phenyl(o-nitrophenyl)methyl, 2-(2- nitrophenyl)ethyl, 6-nitroveratryl, 4-methoxyphenacyl, 3 ^' 5 '- dimethoxybenzoin carbamates)

- o-Acyloximes

- Ammonium salts

- Su!foamides

- Formamides - Nifedipines

- Amineimides

- a-Aminoketones

- o-Carbamoyloximes

and/or mixtures of any one of the foregoing.

In an embodiment, the at least one compound C2 may be represented by the following general formula (XIII): wherein

z represents an integer of from 2 to 1000;

Z represents - independently from each other on each occurrence - hydrogen or a thiol protecting group;

L represents - independently from each other on each occurrence - a single bond or a divalent group selected from the group consisting of a linear or branched, saturated or unsaturated, substituted or unsubstituted alkylene group; a linear or branched, saturated or unsaturated, substituted or unsubstituted heteroalkylene group; a saturated or unsaturated, substituted or unsubstituted cycloalkylene group; a saturated or unsaturated, substituted or unsubstituted heterocycloalkylene group; a substituted or unsubstituted arylene group; a substituted or unsubstituted heteroarylene group; a linear or branched, substituted or unsubstituted aralky!ene group; a linear or branched, substituted or unsubstituted alkarylene group; or a siiicium containing divalent group; and X represents a z-valent group selected from the group consisting of a linear or branched, saturated or unsaturated, substituted or unsubstituted alkyl group; a linear or branched, saturated or unsaturated, substituted or

unsubstituted heteroalkyl group; a saturated or unsaturated, substituted or unsubstituted cycloalkyl group; a saturated or unsaturated, substituted or unsubstituted heterocycloalkyi group; a substituted or unsubstituted aryl group; a substituted or unsubstituted heteroaryl group; a linear or branched, substituted or unsubstituted aralkyi group; a linear or branched, substituted or unsubstituted alkaryl group; or a silicium containing z-valent group.

In the general formula (XIII), z may in particular represent an integer of from 2 to 1000, with a lower range limit of for instance 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50 and/or with an upper range limit of for instance 1000, 900, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 275, 250, 225, 200, 190, 180, 170, 160, 150, 140, 130, 125, 120, 115, 110, 105, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 38, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, including any single combination of lower and upper range limit values.

The definitions of the terms "linear", "branched", "saturated", "unsaturated", "unsubstituted" and "substituted" may in particular correspond to the above given definitions. Similarly, the definitions and/or suitable examples of the terms "alkylene group", "heteroalkylene group", "cycloalkylene group",

"heterocycloalkylene group", "arylene group", "heteroarylene group", "aralkylene group" and "alkarylene group", respectively, may in particular correspond to the above given definitions and/or suitable examples of the terms "alkyl group", "heteroalkyl group", "cycloalkyl group", "heterocycloalkyl group", "aryl group", "heteroaryl group", "aralkyi group" and "alkaryl group", respectively, except that the groups represented by L are divalent (bivalent) groups, as also indicated by their suffix "-ene". Likewise, the definitions and/or suitable examples of the terms "alkyl group", "heteroalkyl group", "cycloalkyl group", "heterocycloalkyl group", "aryl group", "heteroaryl group", "aralkyi group" and "alkaryl group" represented by X may in particular correspond to the above given definitions, except that the groups represented by X are z-valent groups. The "silicium containing divalent group" and/or the "silicium containing z-valent group" may in particular include groups containing one or more silicium (Si) atoms and optionally further one or more of, for instance, C, O, N, P and/or H atoms. Suitable examples thereof include an Si atom, -[(Si-alkyl) _z ]- (such as -[(Si-CH ₂ ) _Z ]-), -[(Si-0) _z ]- and -[(Si-N) _z ]-.

In an embodiment, Z may represent - independently from each other on each occurrence - hydrogen or a thiol protection group selected from the group consisting of an acyl group, a silyl group and a siloxal group.

In an embodiment, L may - independently from each other on each occurrence - represent a single bond or a divalent group selected from the group consisting of a linear or branched, saturated or unsaturated alkylene group having from 1 to 18 carbon atoms and optionally substituted with one or more hydroxy! groups; - (CO)O-; -O(CO)-; a linear or branched, saturated or unsaturated, divalent alkyl ester group having from 1 to 18 carbon atoms; a linear or branched, saturated or unsaturated, substituted or unsubstituted acylene group having from 1 to 20 carbon atoms; a linear or branched, substituted or unsubstituted a!koxylene group having from 1 to 8 carbon atoms; a saturated or unsaturated, substituted or unsubstituted cycloalkylene group having from 3 to 12 carbon atoms; a substituted or unsubstituted arylene group having from 6 to 16 carbon atoms; or a linear or branched, saturated or unsaturated alkylene group having from 2 to 20 carbon atoms and interspersed with one or more of oxygen, sulfur, a substituted or unsubstituted imine group, -(CO)-, -O(CO)-, -(CO)O-, -0(CO)0- , -(NRio)(CO)0- and/or -0(CO)( Rio)-, wherein Rio represents - independently from each other on each occurrence - a hydrogen atom; a linear or branched, saturated or unsaturated, substituted or unsubstituted alkyl group; a linear or branched, saturated or unsaturated, substituted or unsubstituted heteroa!kyl group; a saturated or unsaturated, substituted or unsubstituted cycloalkyi group; a saturated or unsaturated, substituted or unsubstituted heterocycloalkyl group; a substituted or unsubstituted aryl group; a substituted or unsubstituted heteroaryl group; a linear or branched, substituted or unsubstituted aralkyl group; or a linear or branched, substituted or unsubstituted alkaryl group. In an embodiment, X may represent a z-valent group selected from the group consisting of a linear or branched, saturated or unsaturated alkyl group having from 1 to 18 carbon atoms and optionally substituted with one or more hydroxyl groups; a linear or branched, saturated or unsaturated, z-valent alkyl ester group having from 1 to 18 carbon atoms; a linear or branched, saturated or unsaturated, substituted or unsubstituted acyl group having from 1 to 20 carbon atoms; a linear or branched, substituted or unsubstituted alkoxy group having from 1 to 8 carbon atoms; a saturated or unsaturated, substituted or

unsubstituted cycloalkyl group having from 3 to 12 carbon atoms; a substituted or unsubstituted arylene group having from 6 to 16 carbon atoms; a linear or branched or cyclic group of any one an Si atom, -[(Si-alkyl) _z ]~ (such

as -[(Si-CH2)z] -), -[(Si-O)z] - or -[(Si-N) _z ]-, the group being z times substituted by -L-SH; or a linear or branched, saturated or unsaturated alkyl group having from 2 to 20 carbon atoms and interspersed with one or more of oxygen, sulfur, a substituted or unsubstituted imine group, -(CO)-, -O(CO)-, -(CO)O-, -O(CO)0- , -(NRio)(CO)0- and/or -0(CO)(NRio)-, with Rio being as defined above.

In an embodiment, the at least one compound C2 may have at least two thiol functional groups and at least one, in particular at least two, functional group selected from the group consisting of a silane (an Si atom), a siioxane (-Si-O-), a carbonate, a carbamate, an ether and an ester. In particular, the number of thiol functional groups and the number of functional groups selected from the group consisting of a carbonate, a carbamate, an ether and an ester may be the same or different in the at least one compound C2. For instance, the number of thiol functional groups and/or the number of functional groups selected from the group consisting of a carbonate, a carbamate, an ether and an ester may be 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50 or more and/or 1000, 900, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 275, 250, 225, 200, 190, 180, 170, 160, 150, 140, 130, 125, 120, 115, 110, 105, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 38, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3 or less. Appropriate examples of the at least one compound C2 include for instance the following compounds:

Trimethylpropane tri(3-mercaptopropionate) (T PMP) Further appropriate examples of the at least one compound C2 are shown on pages 23 and 24 of WO 2013/052328 Al, the disclosure of which is incorporated herein by reference.

In an embodiment, the ratio of the number of terminal alkyne functional groups to the number of thiol functional groups may be from 1 : 1.8 to 1: 2.25 in the resin composition, in particular from 1 : 1.85 to 1 :2.2, in particular from 1 : 1.88 to 1: 2.15, in particular from 1 : 1.9 to 1 : 2.1, in particular from 1 : 1.95 to 1 : 2.05, in particular about 1 :2. If the ratio of the number of terminal alkyne functional groups to the number of thiol functional groups in the resin composition lies within the above ranges, the number of residual (after completion of the thiol- yne reaction) reactive groups and the number of residual (after completion of the thiol-yne reaction) monomers in the polymer formed can be minimized, which may be advantageous in particular when the polymer (or an article comprising or formed from the monomer) is used in medical or biomedical appliances.

In an embodiment, the ratio of the number of terminal alkyne functional groups to the number of thiol functional groups may be smaller than 1 : 2, for instance from 1 :2.01 to 1 : 2.3, in particular from 1 : 2.05 to 1 : 2.25, from 1 : 2.1 to 1 :2.2. If the ratio of the number of terminal alkyne functional groups to the number of thiol functional groups in the resin composition lies within the above ranges, there may remain some thiol functional groups in the polymer formed after completion of the thiol-yne reaction, in particular on the surface of the polymer or of an article comprising or formed from the polymer. Thereby, a surface- modified polymer or article may be obtained. In particular, such remaining or residual thiol functional groups may serve as an anchor or docking site (binding site) capable for coupling the polymer or the article with an additive, such as an organic filler (e.g. heparin) and/or an inorganic filler. The binding (coupling) of the remaining or residual thiol functional group with an additive may be carried out for instance by means of a thiol-ene reaction, such as a thiol-Michael addition, typically catalyzed under basic conditions. The binding (coupling) of the remaining or residual thiol functional group with an additive may also involve the formation of disulfide bonds (disulfide bridges), in particular in case of a protein or a peptide to be coupled with the polymer or article. Thereby, the polymer or article can be imparted with additional physiologically beneficial properties, for instance with anticoagulant properties in case of heparin.

The at least one compound CI may be contained in the resin composition in an amount of from 10 to 90 wt.-%, in particular from 15 to 85 wt.-%, in particular from 20 to 80 wt.-%, in particular from 25 to 75 wt. -%, such as from 20 to 70 wt.-%, from 25 to 65 wt.-%, from 30 to 60 wt.-%, from 35 to 55 wt.-%, from 38 to 52 wt.-% or from 40 to 50 wt.-%.

The at least one compound C2 may be contained in the resin composition in an amount of from 10 to 90 wt.-%, in particular from 15 to 85 wt.-%, in particular from 20 to 80 wt.-%, in particular from 25 to 75 wt.-%, such as from 20 to 70 wt.- , from 25 to 65 wt.-%, from 30 to 60 wt.-%, from 35 to 55 wt.-%, from 38 to 52 wt.-% or from 40 to 50 wt.-%.

In an embodiment, the resin composition may further comprise at least one initiator selected from the group consisting of a photoinitiator and a thermal initiator. The presence of at least one initiator in the resin composition may facilitate the initiation of the reaction between the yne component and the thiol component in a thiol-yne reaction . Thus, the presence of at least one initiator may increase the polymerization speed (velocity) and/or reduce the curing time. As a consequence, the presence of at least one initiator is in particular

advantageous when the resin composition is used as or in an ink for a printing method, in particular a three-dimensional printing method where typically the object to be printed is formed layer by layer requiring the previous layer to be substantially hardened or cured before forming the subsequent layer. In addition by using a photoinitiator and/or a thermal initiator, the thiol-yne reaction can be selectively controlled, in particular in terms of a specific location or area of or within the resin composition where the polymerization is supposed to be initiated/promoted, as desired, for instance by directing an appropriate energy source to the specific location or area, thereby enabling the formation of specific structures with high resolution as a result of a printing method. The term "photoinitiator", as used herein, in particular denotes a compound which can be activated by an energy-carrying activation beam (such as electromagnetic radiation), for instance upon irradiation therewith. Upon activation by an energy-carrying beam, the photoinitiator may be in particular converted into a radical thereof. Thus, the photoinitiator may be in particular a radical generating photoinitiator.

The photoinitiator may be in particular a type I photoinitiator or a type II photoinitiator. The photoinitiator may be in particular an ultraviolet-active photoinitiator and/or a visible light-active photoinitiator. In other words, the photoinitiator may be in particular a compound that can be activated by electromagnetic radiation in the ultraviolet wavelength region (such as the wavelength range of from 10 to 380 nm, in particular from 200 to 380 nm) and or by electromagnetic radiation in the wavelength region of visible light (such as the wavelength range of from 380 to 780 nm)

The term "thermal initiator", as used herein, in particular denotes a compound which can be activated by thermal energy, for instance upon directing thermal energy to the compound, such as by heating and/or by irradiation with

electromagnetic radiation in the infrared wavelength region (such as the wavelength range of from 780 nm to 1 mm) and/or in the microwave wavelength region (such as the wavelength range of from 1 mm to 300 mm). Upon activation by thermal energy, the thermal initiator may be in particular converted into a radical thereof. Thus, the thermal initiator may be in particular a radical generating thermal initiator. The photoinitiator and/or the thermal initiator is not particularly limited, as long as it can be activated by electromagnetic radiation and/or thermal energy to thereby initiate the thioi-yne reaction between the yne component and the thiol component in the resin composition.

In an embodiment, the initiator may be at least one compound selected from the group consisting of a quinone compound, camphorquinone, an azide compound, an azo compound, in particular azobisisobutyronitrile (AIBN), a peroxide compound, in particular benzoyl peroxide, a disulfide compound, a bis-imidazole compound, an alkyl halogenide, an alkyl thiocyanate, a phosphinoxide

compound, a substituted or unsubstituted thioxanthone, a substituted or unsubstituted benzophenone or mixtures thereof. The term "substituted" may in particular correspond to that, as defined above in, as long as the substituent does not substantially reduce the reactivity of the initiator. As it is well known to a person skilled in the art, these compounds may form radicals and/or moieties having unshared valence electrons or at least one unshared electron pair upon activation by an energy source, such as irradiation with an energy-carrying activation beam and/or thermal energy. A particularly suitable example of an initiator, in particular of a photoinitiator represents a mixture of 2-hydroxy-2-rnethyl-l-phenyl propanone and diphenyf 2,4,6-trimethylbenzoyl phosphane oxide, in particular a 50 wt.-%/50 wt.-% mixture thereof. In addition, camphorquinone may be particularly advantageous in view of its high biocompatibility.

Further appropriate examples of initiators, both photoinitiators and thermal initiators, are given on pages 17 to 20 of WO 2013/052328 Al, the disclosure of which is incorporated herein by reference. The content of the at least one initiator may be in particular from 0.1 to 20 wt.- %, such as from 0.2 to 15 wt.-%, in particular from 0.5 to 12.5 wt-%, in particular from 1 to 10 wt-%, in particular from 2 to 8 wt.-%, with respect to the total weight of the resin composition.

In an embodiment, the resin composition may further comprise at least one additive selected from the group consisting of a pigment, an inorganic filler, an organic filler and a stabilizer. By the presence of an additive, such as a pigment, an inorganic filler and/or an organic filler, the products obtained by the thiol-yne reaction, for instance the products of a printing method utilizing the resin composition, may be provided with additional specific tailor-made advantageous properties, as desired. The presence of a stabilizer in the resin composition may be helpful to prevent a premature initiation of the thiol-yne reaction between the yne component and the thiol component. Thus, the presence of at least one stabilizer may improve the storage properties of the resin composition. The pigment may be an organic or an inorganic pigment. The pigment is not particularly limited and any pigment customarily used for printing for example may be used, as long as it does not substantially impair the thiol-yne reaction between the yne component and the thio! component in the resin composition. Suitable examples of pigments are disclosed for instance in paragraphs [0128] to [0138] of WO 2008/074548, column 14, line 39 to column 15, line 46 of US * 6,045,607, pages 12 to 16 of WO 2005/049744 further providing additional references, the disclosures of all of which are incorporated herein by reference. The pigment may be surface-treated so as to improve its dispersibility in the resin composition.

The inorganic filler is not particularly limited, as long as it does not substantially impair the thiol-yne reaction between the yne component and the thiol component in the resin composition. In particular, the inorganic filler may be any one of a calcium carbonate, a calcium phosphate and/or a hydroxyapatite, which are in particular suitable if the product obtained after the thiol-yne reaction, for instance by a printing method, is used as an implant, a bone substitute and/or a dental product, such as a dental prosthesis.

Further appropriate examples of inorganic fillers are disclosed on pages 24 to 27 of WO 2013/052328 Al, the disclosure of which is incorporated herein by reference.

The organic filler is not particularly limited, as long as it does not substantially impair the thiol-yne reaction between the yne component and the thiol component in the resin composition. In particular, the organic filler may be a heparin, a collagen and/or a gelatine, which are in particular suitable if the product obtained after the thiol-yne reaction, for instance by a printing method, is used as an implant, a bone substitute and/or a dental product, such as a dental prosthesis. In addition, the organic filler may comprise physiologically active compounds, such as proteins, peptides, antibodies, drugs, and the like.

Further appropriate examples of organic fillers are disclosed on pages 24 to 27 of WO 2013/052328 Al and the paragraph bridging pages 7 and 8 of WO

2012/103445 A2, the disclosures of which are incorporated herein by reference.

The stabilizer may be in particular a polymerization inhibitor and may be in particular helpful to prevent a premature initiation and/or propagation of the thiol-yne reaction between the yne component and the thiol component. The stabilizer may be in particular comprise any one or more selected from the group consisting of a phenolic antioxidant, a phosphorous containing compound, a hydroquinone, such as hydroquinone monomethyl ether (HQME), a hydroxyl amine and a sterically hindered amine. In particular, the stabilizer may be a hydroquinone, t-butyl catechol, pyrogallol or an ether thereof,

butyihydroxytoluene (BHT, 2,6-di-£ert-butyl-4-methylphenol) and/or butylated hydroxyanisole (BHA, 2-ferf~butyl-4-hydroxyanisole and/or 3~terf-butyl-4- hydroxyanisole). Suitable commercial stabilizers are, for example, Sumi!izer™ GA-80, SumMizer™ GM and Sumilizer™ GS available from Sumitomo Chemical Co. Ltd.; Genorad™ 16, Genorad™ 18 and Genorad™ 20 available from Rahn AG; Irgastab™ UV22 available from BASF SE; Additol™ S (S100, SI 10, S120 and S130) available from Cytec Surface Specialities.

Since excessive addition of these stabilizers or polymerization inhibitors may lower the curing speed, it is preferred that the amount capable of preventing polymerization is determined prior to blending. The amount of a polymerization inhibitor is preferably lower than 5 wt.-%, more preferably lower than 3 wt.-% of the total resin composition.

The content of the at least one additive selected from the group consisting of a pigment, an inorganic filler, an organic filler and a stabilizer, in particular its total content, may be in particular from 0.1 to 60 wt-%, such as from 0.2 to 50 wt.~ %, in particular from 0.5 to 40 wt.- , in particular from 1 to 30 wt.-%, in particular from 2 to 20 wt.~%, with respect to the total weight of the resin composition. Further components or ingredients may be contained in the resin composition.

For example, further monomers other than the above described yne and thiol monomers, for instance vinyl functionalized monomers, may be contained in the resin composition, which may in particular copoiymerize with the yne and/or thiol monomers and which may thereby impart further specific characteristics to the (co-)polymer obtained by polymerizing some or all components of the resin composition. Appropriate examples of vinyl functionalized monomers are disclosed for instance in paragraphs [0025] to [0037] of WO 2013/052328 Al, the disclosure of which is incorporated herein by reference.

Moreover, dispersants, wetting agents and/or sequestering agents (chelating agents) may be contained in the resin composition. In particular, the resin composition may further contain surfactants suitable as dispersants and/or wetting agents, such as anionic surfactants, cationic surfactants, nonionic surfactants and/or amphoiytic surfactants.

Suitable examples of anionic surfactants include surfactants comprising carboxylate, sulfate, phosphate and/or sulfonate groups, for instance amino acid derivatives, fatty alcohol ether sulfates, fatty alcohol sulfates, soaps (such as sodium soaps and/or potassium soaps) alkylpheno! ethoxy!ates, fatty alcohol ethoxylates, alkyl sulfates, olefin sulfates and/or alkyl phosphates.

Suitable examples of cationic surfactants include quaternary ammonium or quaternary phosphonium compounds, for instance tetraalkyl ammonium salts, Ν,Ν-dialkyl imidazoline compounds, dimethyl distearyl ammonium compounds, N-alkyl pyridine compounds and/or ammonium chlorides.

Suitable examples of nonionic surfactants include ethoxylates, for instance ethoxylated addition products of alcohols, such as polyoxyalkylene polyois, amines, fatty acids, alkyl phenols, ethanol amides, polysiloxanes and/or fatty acid esters, aikyl or alkylphenyl polyglycol ether, such as fatty alcohol polyglyco! ether or fatty acid amides, alkyl glycosides, sugar esters, sorbitan esters, polysorbates and/or tria!kyl amine oxides; ester and/or amides pf

poly(meth)acrylic acids with polyalkylene glycols and/or amino polyalkylene glycols, all of which may be terminated by alkyl groups on one side.

Suitable examples of amphoiytic surfactants include amphoteric electrolytes, also called ampholytes, such as amino carboxylic acids and/or betaines.

Suitable commercial examples include Tego Wet and/or Glide from Evonik Industries; Byk 016, 348, UV3500, 9151 from Altana AG; Edaplan 710, 711, 910, 915 from Munzing Chemie GmbH. Further appropriate examples of additional components or ingredients, in particular of dispersants and surfactants, are disclosed on pages 34 to 37 of WO 2013/087427 Al, the disclosure of which is incorporated herein by reference. The resin composition may be solid, semi-solid (pasty) or liquid. Since the yne monomer and/or the thiol monomer are typically liquid, the resin composition may be in particular a solution, an emulsion or a dispersion (in particular a solid- liquid dispersion, such as a suspension). In particular, the resin composition does not form a hydrogel or any other gel-like form. In particular, the resin

composition is not a hydrogel prior to the thiol-yne reaction (prior to

polymerization/curing) nor after the thiol-yne reaction (after polymerization/ curing). Rather, after the thiol-yne reaction (after polymerization/curing) a polymer, in particular a solid or semi-solid (pasty) polymer is formed. The resin composition may be in particular substantially solvent-free, such as substantially water-free. The term "substantially solvent-free", as used herein, may in particular denote that the resin composition comprises not more than 15 wt.-% of a solvent, in particular not more than 10 wt.-%, in particular not more than 5 wt.-%, in particular not more than 2 wt.-%, in particular not more than 1 wt.-%.

Accordingly, the resin composition may in particular contain substantially no solvent, such as a polar solvent or an apolar solvent, for instance water, an alcoholic solvent (such as methanol, ethanol, glycol, 1-propanol, 2-propanol (IPA), propylene glycol, l-butano!, 2-butanol, isobutyl alcohol, butylene glycol, and the like), an ether solvent (such as dimethyl ether, diethyl ether, tert-butyl methyl ether, 1,4-dioxane, tetrahydrofuran (THF), and the like), an ester solvent (such as ethyl acetate, and the like), a carbonate solvent (such as dimethyl carbonate, diethyl carbonate, and the like), a halogenated alkane solvent (such as dichloromethane, trichloromethane, tetrachloromethane, 1,2-dichloroethane, and the like), a nitriie solvent (such as acetonitriie, and the like), an aldehyde or ketone solvent (such as acetone, and the like), an amide solvent (such as dimethylformamide (DMF), and the like), a sulfoxide solvent (such as dimethylsulfoxide (DMSO), and the like), an acid solvent (such as formic acid, acetic acid, and the like), a hydrocarbon solvent (such as pentane, cyclopentane, hexane, cyclohexane, heptane, octane, and the like), or an aromatic solvent (such as benzene, toluene, and the like).

In an embodiment, the at least one compound CI and the at least one compound C2 may form one (single) compound. In other words, the resin composition may comprise (or consist of) at least one compound C3 having

(i) at least one terminal alkyne functional group,

(ii) at least one ester functional group, and

(iii) at least two thiol functional groups.

The at least one terminal alkyne functional group, the at least one ester functional group and/or the at least two thiol functional groups of the compound C3 may in particular be those, as illustrated in the foregoing. In addition, the resin composition comprising at least one compound C3 may further comprise further ingredients or components, as described in detail above, in particular the at least one initiator selected from the group consisting of a photoinitiator and a thermal initiator, the photoacid, the photobase, the at least one additive selected from the group consisting of a pigment, an inorganic filler, an organic filler and a stabilizer, the further monomers other than the yne and thiol monomers, surfactants, dispersants, wetting agents and/or sequestering agents. By comprising at least one compound C3, the resin composition may show particularly advantageous properties, such as a high reaction (polymerization) speed (high curing velocity), a particularly low content of residual monomers, a particularly low shrinkage of the resulting polymer, excellent mechanical properties (such as elastic modulus) of the resulting polymer, and the like.

In a second aspect, the present invention relates to the use of the resin composition according to the present invention as or in an ink, which may be for instance suitable in a printing method, as described in further detail below. In particular, the resin composition may be used as an ink (a printing ink), i.e. the resin composition itself may be directly used as an ink. Alternatively, the resin composition may be used in an ink (a printing ink), i.e. as a component or an ingredient of an ink together with appropriate one or more further components or ingredients, typically used in an ink.

In a third aspect, the present invention relates to a kit comprising :

at least one compound CI having

(i) at least one terminal alkyne functional group, and

(ii) at least one ester functional group; and

at least one compound C2 having at least two thiol functional groups.

The at least one compound CI as well as the at least one compound C2 may in particular be those as defined in detail above with regard to the resin

composition according to the present invention.

The components CI and C2 may be in particular provided in a spatially separated manner in the kit, in particular the kit-of-parts. In particular, the components CI and C2 may be provided in separate compartments of the kit. This might be advantageous if the at least one component CI and/or at least one component C2 are reactive to such an extent that it/they tends/tend to (prematurely) react with the other component/with each other, even when stored in the dark (such as when packaged by means of a light nontransparent material) and/or at low temperature (such as at a temperature of not more than 10 °C, in particular not more than 5 °C, such as not more than 0 °C).

Further ingredients or components, as described in detail above with regard to the resin composition according to the present invention, in particular the at least one initiator selected from the group consisting of a photoinitiator and a thermal initiator, the photoacid, the photobase, the at least one additive selected from the group consisting of a pigment, an inorganic filler, an organic filler and a stabilizer, the further monomers other than the yne and thiol monomers, surfactants, dispersants, wetting agents and/or sequestering agents, may be contained independently from each other in any one of the compartment of compound CI and/or the compartment of compound C2 as well as in any additional compartment of the kit.

In particular, the kit may be a two-, three-, four- or multi-component system, such as a 2K system, a 3K system, a 4K system and the like. Prior to use, for instance in a printing method, the components contained in separate compartments of the kit are mixed. The mixing may be carried out manually or (semi-)automatically by an appropriate device or dispenser. The components contained in separate compartments of the kit may be in particular mixed not more than 48 hours, not more than 24 hours, not more than 12 hours, not more than 6 hours, not more than 4 hours, not more than 3 hours, not more than 2 hours, not more than 90 minutes, not more than 60 minutes, not more than 45 minutes, not more than 30 minutes, not more than 25 minutes, not more than 20 minutes, not more than 15 minutes, not more than 10 minutes, not more than 7.5 minutes, not more than 5 minutes, not more than 4 minutes, not more than 3 minutes, not more than 2 minutes, not more than 90 seconds, not more than 60 seconds, not more than 45 seconds, not more than 30 seconds, not more than 25 seconds, not more than 20 seconds, not more than 15 seconds, not more than 10 seconds, not more than 7.5 seconds, not more than 5 seconds, not more than 4 seconds, not more than 3 seconds, not more than 2 seconds, not more than 1 second, prior to use, for instance in a printing method.

In a fourth aspect, the present invention relates to the use of the kit according to the present invention for preparing a resin composition, in particular the resin composition according to the present invention, suitable for use as or in an ink, which may be for instance suitable in a printing method, as described in further detail below. For preparing the resin composition, the components contained in separate compartments of the kit may be mixed. The mixing may be carried out manually or (semi-)automatically by an appropriate device or dispenser.

In a fifth aspect, the present invention relates to a printing method comprising the steps of

providing the resin composition according to the present invention, wherein the resin composition further comprises at least one initiator; and

directing an energy source to at least a part of the resin composition so as to cause polymerization of the at least a part of the resin composition and so as to obtain a polymer.

In an embodiment, the printing method may be a two-dimensional printing method and the resin composition may be provided on a substrate. The term "two-dimensional printing method", as used herein, in particular denotes that the product of the printing method extends in two directions (for example, length and width), but not in a third direction (for example, height). Thus, the product of a two-dimensional printing method may be substantially flat or sheet-like.

The two-dimensional printing method may be in particular an ink-jet printing method or a laser printing method.

The substrate may be flexible, but it may also possess a certain rigidity or may be rigid, as desired. The material of the substrate is not particularly limited and various suitable materials are known to a person skilled in the art. In particular, the substrate may be paper or any other cellulose-based material suitable for printing. Further appropriate substrate materials include polyester, polysulfones, polyarylates, polyacrylates, polycyclic olefins, polyimides, glass or combinations or composites thereof. Merely by way of example, further substrate materials include polyester, such as polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polycarbonate (PC); polysulfones, such as polyethersulfone (PES); polyarylates (PAR); polycyclic olefins (PCO); polyimides (PI); polyolefins, such as polyethylene (PE), polypropylene (PP); vinyl polymers, such as polystyrene (PS), polyvinyl chloride (PVC), polymethyl methacrylate (PMMA) ; polyamides; polyethers; polyketones, such as aromatic polyetherketones (e.g. PEEK); po!ysulfides (e.g. PPS); fluoropolymers, such as poiyvinylidene fluoride (PVDF), polytetrafluoroethylene (such as PTFE), fluorinated ethylene propylene (FEP); liquid crystal polymers; polyepoxides; polyurethanes; polysiloxanes (e.g. PDMS); biopolymers or combinations, copolymers, composites and/or blends thereof, in particular composites or laminates thereof with paper or any other cellulose-based material suitable for printing.

In an embodiment, the printing method may be a three-dimensional printing method. The term three-dimensional printing method", as used herein, in particular denotes that the product of the printing method extends in three directions (for example, length, width and height). Thus, the product of a three-dimensional printing method may be in particular a three-dimensional object. The three-dimensional printing method may be in particular any one selected from the group consisting of stereolithography (SLA), two-photon absorption (TPA) polymerization, digital light processing (DLP), solid ground curing (SGC) and multi jet modeling (MJM). In view of its high resolution, stereolithography (SLA) may be preferred.

In the step of providing the resin composition, the resin composition further comprises an initiator, in particular a photoinitiator and/or a thermal initiator. The initiator may be in particular that as defined in detail above with regard to the resin composition according to the present invention.

In the step of directing an energy source to at least a part of the resin

composition (curing step), a thiol-yne reaction may be caused at the at least a part of the resin composition, to which the energy source has been directed, with the result that the yne component and the thiol components undergo a cross- linking (polymerization) reaction at that part and consequently a polymer is formed at that part of the resin composition, to which the energy source has been directed.

In particular, the energy source may be directed to the at least a part of the resin composition in a controlled manner, in particular controlled by a computer system, so as to form a desired pattern or structure of the resulting polymer,

The term "at least a part of the resin composition" may in particular mean that not 100 % of the resin composition is exposed to the energy source. In particular, the term "at least a part of the resin composition" may mean that at least 5 %, in particular at least 10 %, in particular at least 15 %, in particular at least 20 %, in particular at least 25 %, in particular at least 30 %, in particular at least 35 , in particular at least 40 %, in particular at least 45 %, in particular at least 50 %, in particular at least 55 %, in particular at least 60 %, in particular at least 65 %, in particular at least 70 %, in particular at least 75 %, in particular at least 80 % of the resin composition is exposed to the energy source and it may mean that in particular not more than 95 %, in particular not more than 90 %, in particular not more than 85 %, in particular not more than 80 %, in particular not more than 75 %, in particular not more than 70 %, in particular not more than 65 %, in particular not more than 60 %, in particular not more than 55 %, in particular not more than 50 %, in particular not more than 45 %, in particular not more than 40 %, in particular not more than 35 %, in particular not more than 30 %, in particular not more than 25 %, in particular not more than 20 % of the resin composition is exposed to the energy source.

It might be advantageous to carry out the step of directing an energy source to at least a part of the resin composition under an inert gas atmosphere (such as under a N ₂ , C0 ₂ , or a noble gas, in particular Ar, atmosphere), while it is also possible to carry out this step under ambient gas atmosphere, such as air, or even under (substantially) pure oxygen in view of the intensity of the thiol-yne reaction against oxygen.

The duration of the step of directing an energy source to at least a part of the resin composition is not particularly limited, and may be appropriately selected by a person skilled in the art, depending in particular on the type of the printing method and the components of the resin composition (in particular their reactivity). For instance, suitable times (durations) for directing an energy source may be from 1 ms to 1 h, in particular from 1 s to 1 min.

The intensity of directing an energy source is not particularly limited, and may be appropriately selected by a person skilled in the art, depending in particular on the type of the printing method, the components of the resin composition and the duration of the step. For instance, the ^" intensity may be from 0.01 to 20 W/cm ² , in particular from 0.1 to 5 W/cm ² .

In an embodiment, the step of directing an energy source to at least a part of the resin composition, may comprise or may be followed by a step of post- curing, wherein the initially formed polymer is further or again provided with energy (from an energy source). For instance, in case of stereolithography, the (initially) formed polymer may be further or again irradiated with ultraviolet radiation in a post-curing step.

In an embodiment, the at least one initiator may comprise at least one

photoinitiator and the step of directing an energy source to at least a part of the resin composition may comprise irradiating the at least a part of the resin composition with an energy-carrying activation beam.

The energy-carrying activation beam may in particular comprise electromagnetic radiation (in particular actinic radiation). In particular, the energy-carrying activation beam may be at least one selected from the group consisting of ultraviolet radiation (such as having a wavelength of from 10 to 380 nm, in particular from 200 to 380 nm, in particular from 250 to 380 nm), visible light radiation (such as having a wavelength of from 380 to 780 nm), infrared radiation (such as having a wavelength of from 780 nm to 1 mm, in particular near-infrared radiation having a wavelength of from 780 nm to 1.4 μιη), microwave radiation (such as having a wavelength of from 1 to 300 mm), gamma radiation (such as having a wavelength of from 0.1 to 5 pm), X-ray beam (such as having a wavelength of from 1 pm to 10 nm) or electron beam (such as beta radiation).

In an embodiment, the at least one initiator may comprise at least one thermal initiator and the step of directing an energy source to at least a part of the resin composition comprises directing thermal energy to the at least a part of the resin composition.

The thermal energy may be directed to the at least a part of the resin

composition by specifically heating that part of the resin composition, such as by contact heating. The thermal energy may also be directed to the at least a part of the resin composition by irradiating the at least a part of the resin composition with an energy-carrying activation beam that causes a (local) increase in temperature on and/or in the irradiated part of the resin composition, such as infrared radiation and/or microwave radiation. In particular, the printing method may be a solvent-free printing method. In particular, those solvents as described in detail above with regard to the resin composition according to the present invention are preferably not used in the printing method. In a sixth aspect, the present invention relates to a polymer obtainable by the printing method according to the present invention. The polymer may not only be defined by the components of the resin composition, but also it may be defined by the specific pattern and/or (three-dimensional) structure that it has obtained by the printing method. The chemical structure of the polymer may in particular depend on the components of the resin composition, but also on the specific conditions of the printing method that may influence the degree of crosslinking within the polymer, whereas the geometrical structure of the polymer may in particular depend on the specific conditions of the printing method, such as the specific pattern and/or (three-dimensional) structure imparted to the polymer by the printing method, but also on the components of the resin composition, in particular as regards the flexibility/rigidity of the polymer.

In a seventh aspect, the present invention relates to an article comprising or formed from the polymer according to the present invention. The article may consist of the polymer with or without any further modifications, such as reshaping, or the article may comprise the polymer in addition to further components or ingredients, as desired according to specific purposes. The article may also be formed from the polymer.

In an embodiment, the article may be a medical device or a biomedical device. The medical and/or biomedical device may be in particular selected from the group consisting of an implant, a bone substitute, a tissue substitute and a dental product.

Since a medical and/or biomedical device is typically exposed to a human or animal body upon use, the article should preferably be biocompatible. In particular, the article should not substantially disturb/impart the physiological functions or properties of that part of a human or animal body to be in contact with the article. In addition, the article should not release any harmful compounds or any otherwise detrimental compounds to that part of a human or animal body to be in contact with the article. Since the polymer and

consequently also the article is obtained as a result of a thiol-yne reaction, the polymer has a very low residual monomer content and a low shrinkage so that the polymer as well as the article is not only highly biocompatible, but is also in particular suitable as a medical and/or biomedical device.

In an embodiment, the article (as well as the polymer) may be substantially biodegradable.

The term "substantially" as used herein in particular denotes at least 50%, in particular at least 60%, in particular at least 70%, in particular at least 75%, in particular at least 80%, in particular at least 85%, in particular at least 90%, in particular at least 92.5%, in particular at least 95%, in particular at least 96%, in particular at least 97%, in particular at least 98%, in particular at least 99%, in particular up to 100%, unless specifically stated otherwise.

As explained above, an ester functional group can be relatively easily hydrolysed (for instance enzymatically) under a physiological environment and consequently a product (such as the polymer and/or the article) obtained from a resin composition wherein the at least one component CI comprises an ester functional group is substantially biodegradable and is therefore in particular suitable as an implant, a bone substitute and/or a tissue substitute, which are often intended to gradually degrade and become substituted by natural, physiological material. Thus, a substantially biodegradable article (or polymer) may in particular be derived from a resin composition comprising at least one compound CI comprising an ester functional group. In addition, a substantially biodegradable article (or polymer) may in particular be suitable as an implant, a bone substitute and/or a tissue substitute.

It might also be advantageous that the product (such as the polymer and/or the article) is at least partially biodegradable and at least partially nonbiodegradable, for instance if a certain persistent mechanical support is desired, or that a part of the product biodegrades relatively fast whereas a part of the product biodegrades relatively slowly, which might be in particular advantageous when using the product as an implant, a bone substitute and/or a tissue substitute. Such products may in particular be derived from a resin composition comprising combinations of component CI and C2 containing non degradable thiols. In an eighth aspect, the present invention relates to the use of the polymer or of the article according to the present invention in a medical or biomedical application.

In particular, the medical application comprises any one selected from the group consisting of an implantation, a bone substitution or replacement, a tissue substitution or replacement, and a dental application.

The present invention is further described by the following examples, which are solely for the purpose of illustrating specific embodiments, and are not construed as limiting the scope of the invention in any way.

Examples

Example 1

The maximum reaction speed of various monomers was evaluated by means of Photo Differential Scanning Calorimetry (Photo-DSC). 8 mg of the respective test mixtures consisting of yne monomer (as shown in the following table 1) and thiol monomer (trimethylpropane tri(3-mercaptopropionate), T PMP) as well as 5 wt.- % of a photoinitiator mixture (2-hydroxy-2-methyl~l-phenyl propanone/diphenyl 2,4,6-trimethylbenzoyl phosphane oxide, 50 wt.-%/50 wt.-%) were provided. As comparative test mixtures, acrylate and methacrylate without thiol monomer, but together with 5 wt.-% of the same photoinitiator mixture were provided. The test mixtures were placed in a crucible of aluminium and irradiated with an Omnicure ^® lamp at an intensity of 1 W/cm ² at 50 °C under a nitrogen gas atmosphere to thereby cure the test mixtures. Table 1 shows the results of the maximum reaction speed evaluation of the monomers tested. The times (tmax) for reaching the maximum reaction enthalpy indicate the reactivity of the photo-reactive systems. Figure 1 is a graphical illustration of the test results (tmax) further showing the chemical structural formulas of the tested alkyne monomers and comparative (meth)acryl

monomers.

[Table 1]

* Comparative compounds

As a result, the reaction speeds of the tested monomers according to the present invention were slightly lower than the reaction speed of a comparable acrylate, but significantly higher than the reaction speed of a comparable methacryiate.

Example 2

The reaction kinetics of the monomers listed in Table 1 were further evaluated by means of Real-Rime-FTI spectroscopy. 2 μΙ of the liquid to be tested (alkyne monomer, TMPMP and 5 wt.-% photoinitiator; acrylate or methacryiate, respectively, and 5 wt.-% photoinitiator) were placed between two discs of CaF2 and positioned within the optical path. The samples were irradiated by means of Omnicure ^® S1000 (at 40% of its maximum power) from a distance of 9 cm. Two measurements per second were recorded. The total duration of measurement was 120 seconds.

Figure 2 is a graphical illustration of the conversion of the content of aikyne and alkene, respectively, during photopolymerisation of 1,4-butanediol

dimethacrylate, 1,4-butanediol diacrylate, succinic acid dibut-l-ynyl ester and succinic acid dipropargyl ester obtained by means of real-time FTI

measurements. For illustrating the conversion kinetics in further detail, the peak areas of the aikyne band (at 3280 cm ^-1 ) and of the alkene band (at 1640 cm ^"1 ) of the

(meth)acrylates were integrated by means of the software OPUS from Bruker Corporation. The thus obtained, normalised values are shown in Figures 2. In addition, the content of aikyne and alkene, respectively, was determined after a reaction time of 2 min, which corresponds to the content of residual monomers in %. The results are shown in the following Table 2.

[Table 2]

* Comparative compounds

As it is evident from the results shown in Figures 2, a substantial complete conversion of the alkynes after the thiol-yne reaction was observed, which is in particular advantageous in that it results in a low residual monomer content of 5% or less, as shown in Table 2. In contrast, in case of 1,4-butanediol diacrylate a residual monomer content of 21% was observed even after 2 minutes of irradiation and in case of 1,4-butanediol dimethacrylate a residual monomer content of even 26% was observed. It has thereby been proven that the step growth mechanism of the thiol-yne reaction having a delayed gelling point is far advantageous over the chain growth mechanism of the (meth)acrylates. Due to the substantially lower residual monomer content of polymers obtained by the thiol-yne reaction, less migration of monomers is likely to occur when used as a medicai or biomedical device, which renders these polymers particularly suitable for use as or in a medical or biomedical device.

Example 3 (Biocompatibility) The cytotoxicity of various monomers was determined by a certified laboratory by means of L929 mice fibroblast cells. As a (toxic) positive control, Triton X 100 was added to L929 cells with a final concentration of 1 % (v/v). As a (non-toxic) negative control, a cell culture medium was used. After completion of the incubation, the residual protein content of the cells was determined . A reduction of the protein content from L929 cells by more than 30%, relative to the negative control, was evaluated as cytotoxic (which corresponds to the toxicological concentration limit). From this, the half maximal effective concentration (EC ₅ o), at which 50% of the cells are damaged, can be calculated.

The results obtained from various monomers are shown in Figure 3, 4, 5 and 6.

Table 3 shows the determined concentration limits as well as the ECso values of the monomers tested.

[Table 3] Monomer Concentration limit ECso [mM]

[mM]

1,4-butanediol dimethacrylate* < 0.16 -

1,4-butanediol diacrylate* < 0.16 -

Succinic acid dipropargyl ester 0.4 0.5

Succinic acid dibut-l-ynl ester 1.5 2

Comparative compounds

As it is evident from the results of the cytotoxicological evaluation, all tested a!kyne monomers show a significantly lower cytotoxicity than their respective (meth)acrylate analogues. 1,4-Butanediol diacrylate as well as 1,4-butanediol dimethacrylate have proven to be particularly cytotoxic. An EC50 value of these compounds could not be calculated because the toxic concentration was beneath the detection limit of the measurement method. Among the tested alkyne monomers, in particular Succinic acid dibut-l-ynl ester revealed an excellently low cytotoxicity.

While the present invention has been described in detail by way of specific embodiments and examples, the invention is not limited thereto and various alterations and modifications are possible, without departing from the scope of the invention.