Crosslinked polymer material

Abstract

The present invention relates to a crosslinked polymer material detectable by radiological imaging (radiography or radiology), in particular X-ray imaging, radiography, computed tomography, sciascopy, sciagraphy, comprising a biocompatible polymeric backbone comprising primary groups, linker groups, and radiodense imaging groups; wherein at least part of the primary groups are covalently bonded to the linker groups; and wherein at least part of the imaging groups are covalently bonded to each other and / or to one or more of the linker groups. The present invention further relates to a method to prepare said crosslinked polymer material, and uses of said crosslinked polymer material in biomedical applications such as biofabrication, tissue engineering, and medical devices.

Description

[0001] CROSSLINKED POLYMER MATERIAL

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a crosslinked polymer material detectable by radiological imaging, in particular X-ray imaging, radiography, computed tomography, sciascopy, sciagraphy, and interventional radiology among others, comprising a biocompatible polymeric backbone comprising primary groups, linker groups, and radiodense imaging groups; wherein at least part of the primary groups are covalently bonded to the linker groups; and wherein at least part of the imaging groups are covalently bonded to each other and / or to one or more of the linker groups. The present invention further relates to a method to prepare said crosslinked polymer material, and uses of said crosslinked polymer material in biomedical applications such as biofabrication, tissue engineering, and medical devices.

[0004] BACKGROUND TO THE INVENTION

[0005] Gelatin is a nature-derived biopolymer material with excellent cell-interactive properties and the potential to form a polymer material. As a result, the material has become one of the benchmarks in the field of tissue engineering and biofabrication. However, the biological stability and mechanical properties under physiological conditions of gelatin have to be improved to make it suitable in biomedical applications. The use of photo-crosslinking strategies is of specific interest as these methods are generally characterized by relatively mild conditions allowing cell encapsulation in the polymer material. Photo-crosslinking moreover allows for structuring the material, for instance in additive manufacturing techniques like stereolithography, digital light processing and two-photon polymerization. An often-reported gelatin derivative in this respect is gelatin-methacrylamide (Gel-MOD or Gel-MA) in which the amine groups of gelatin have been modified using methacrylic anhydride yielding crosslinkable methacrylamides.

[0006] Dragusin et al. (Soft Matter, 8, 9589-9602, 2012) reported that gelatin-methacrylamide (Gel-MA) can be crosslinked in combination with 2-hydroxyethyl methacrylate (HEMA) to provide a crosslinked hydrogel. They however found that the resulting crosslinked hydrogel was not fully biodegradable.

[0007] The fate of the polymer material scaffolds in vivo is until now in a large majority of cases monitored via post-mortem histology. There are however reported cases of diagnostic tools to monitor the in vivo behavior of specific polymer material scaffolds. For example, Cellikin et al. (Polymers (Basel) 1 1 , 367, 2019) reported the use of micro-CT to evaluate a gelatin methacrylate - gold nanoparticles hydrogel used for bone tissue engineering. A drawback of reported cases is leaching out of particles from the polymer material, therefore making it difficult to assess whether the signal decrease is due to the biodegradation of the polymer material or due to the particles being released from the polymer material. Other disadvantages include the mechanical properties of the polymer material, and the metabolic activity of cells growing on the polymer material.

[0008] SUMMARY OF THE INVENTION

[0009] It is an object of the present invention to provide a crosslinked polymer material that is detectable by radiological imaging (X-ray, radiography, computed tomography, sciascopy, sciagraphy, etc.), and which overcomes or improves one or more of the disadvantages of the prior art, or at least offers one or more useful alternatives. It is a particular objective of the invention to provide a crosslinked polymer material with sufficient X-ray attenuation, and which is still biologically compatible and chemically stable.

[0010] It is another object of the present invention to provide a method for preparing said crosslinked polymer material detectable by radiological imaging, which overcomes or improves one or more of the disadvantages of the prior art, or at least offers one or more useful alternatives.

[0011] Therefore, in a first aspect, the present invention provides a crosslinked polymer material detectable by radiological imaging, comprising: a biocompatible polymeric backbone comprising primary groups; linker groups; and radiodense imaging groups comprising one or more iodine atoms; wherein at least part of the primary groups are covalently bonded to the linker groups; and wherein at least part of the imaging groups are covalently bonded to each other and / or to one or more of the linker groups.

[0012] According to a preferred embodiment, the present invention provides a crosslinked polymer material as defined herein, wherein the linker groups provide a linker between the primary groups and the imaging groups; wherein crosslinks connecting two or more of the linker groups comprise one or more imaging groups; wherein the imaging groups are covalently bonded to each other and / or to one or more of the linker groups; and wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (IV) wherein

[0013] Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0014] R3 is selected from -H, and -CH3;

[0015] Xi and X2 are each independently selected from a direct bond, -Ci ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0016] Rb is selected from -H, and -CH3; and

[0017] Y is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.

[0018] It was found that the crosslinked polymer material as defined herein, comprising covalently bound radiodense imaging groups comprising one or more iodine atoms, is detectable by radiological imaging, such as X-ray imaging, radiography, computed tomography, sciascopy, skiagraphy, as well as by sonography.

[0019] It is an advantage of the crosslinked polymer material, as defined herein, that the imaging groups, in essence the groups that enable detectability of the material by radiological imaging, are covalently bonded within the structure of the crosslinked polymer material. Therefore, leaching of the imaging groups does not occur, and moreover ensures that the signal from the radiological imaging is proportional to the level of material degrading. It is a further advantage of the crosslinked polymer material, as defined herein, that it can be detected by different imaging techniques, such as radiographical imaging and sonography. This enables the choice between different imaging techniques in terms of cost, radiation, and penetration depth, on a case by case basis.

[0020] It is a further advantage of the crosslinked polymer material, as defined herein, that it has highly tunable mechanical properties. The described examples illustrate that the storage modulus (G') of the crosslinked polymer material can be significantly enhanced, compared to comparative materials. This tunability expands the potential applications of the developed hydrogels, for instance enabling a broader range of cell types to be cultivated with the materials in tissue engineering applications.

[0021] Specifically, for tissue engineering, the crosslinked polymer materials, as defined herein, provide versatility to support various tissue types. For example, they meet the mechanical requirements for soft tissues such as adipose tissue (G' = 0.3-1 .3 kPa), bone osteoid extracellular matrix (G' = 10-15 kPa), and relatively harder tissues like intervertebral discs (G' = 8-93 kPa), among others. Indeed, the crosslinked polymer materials can be used for different tissue engineering applications, such as adipose tissue replacement and reconstruction, bone engineering, bone replacement and bone reconstruction.

[0022] It is a further advantage of the crosslinked polymer material, as defined herein, that it can be shaped by 3D printing, which enables high-resolution fabrication of detailed structures, such as porous scaffolds, and can match any desired design. It is another advantage of the crosslinked polymer materials, as defined herein, that it can be shaped by electrospinning to provide fibres. It is another advantage of the crosslinked polymer material, as defined, that it can be made injectable, for instance by grinding and reswelling of the ground material.

[0023] According to an embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymer backbone is a biopolymer selected from polypeptides, proteins, polysaccharides, and polynucleic acids.

[0024] According to a particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymer backbone is selected from gelatins, collagens, alginates, dextrans, agarose, glycosaminoglycans, chitosans and carrageenans.

[0025] According to an embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymer backbone is a polymer selected from a polyester, a polyamide, a polyether, and any combination thereof; in particular a polylactone. According to an embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the primary groups comprise amine groups and / or hydroxyl groups and / or carboxylic acid groups.

[0026] According to an embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the linker groups comprise propanoic and / or 2-methylpropanoic moieties.

[0027] According to an embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (IVa) wherein

[0028] Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents; and

[0029] R3 is selected from -H, and -CH3.

[0030] According to an embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (IVb) wherein

[0031] Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0032] R3 is selected from -H, and -CH3; and

[0033] Rb is selected from -H, and -CH3.

[0034] According to an embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the imaging groups are represented by formula (V) wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I; Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0035] R3 is selected from -H, and -CH3;

[0036] Xi and X2 are each independently selected from a direct bond, -Ci ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0037] Rb is selected from -H, and -CH3; and

[0038] Y is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.

[0039] According to an embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (Vb) wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;

[0040] R1 and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0041] R3 is selected from -H, and -CH3; and

[0042] Rb is selected from -H, and -CH3. In a second aspect, the present invention provides a method to prepare the crosslinked polymer material as defined herein, the method comprising the steps of: a) providing a biocompatible polymeric backbone comprising primary groups; b) reacting at least part of the primary groups with a pre-linker group introducing agent to covalently bind pre-linker groups comprising at least one C-C double bond with the primary groups; and c) crosslinking at least part of the pre-linker groups with monomers comprising at least one C-C double bond by free radical chain-growth polymerization and / or step-growth polymerization, wherein at least part of the monomers are radiodense imaging monomers comprising one or more iodine atoms.

[0043] According to a preferred embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (VII) wherein

[0044] Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci-ealkyl ; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0045] R3 is selected from -H, and -CH3;

[0046] Xi and X2 are each independently selected from a direct bond, -Ci-ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci-ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents; Rb is selected from -H, and -CH3; and

[0047] Y is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.

[0048] It was also found that the method according to the invention, comprising covalently bonding at least part of the primary groups of the biocompatible polymeric backbone with pre-linker groups comprising at least one C-C double bond, and crosslinking at least part of the C-C double bond comprising pre-linker groups with radiodense imaging monomers comprising at least one C-C double bond and one or more iodine atoms by free radical chain growth or step growth polymerization, provides the crosslinked polymer material as defined herein.

[0049] According to an embodiment, the present invention provides the method as defined herein, wherein the primary groups comprise amine groups and / or hydroxyl groups and / or carboxylic acid groups.

[0050] According to an embodiment, the present invention provides the method as defined herein, wherein the pre-linker group introducing agent in step b) is an acrylating agent, a methacrylating agent, or any combination thereof, thereby providing pre-linker groups comprising acrylic moieties, methacrylic moieties, or any combination thereof.

[0051] According to an embodiment, the present invention provides the method as defined herein, wherein the imaging monomers are represented by formula (VIII) wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;

[0052] R1 and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0053] R3 is selected from -H, and -CH3;

[0054] Xi and X2 are each independently selected from a direct bond, -Ci ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0055] Rb is selected from -H, and -CH3; and

[0056] Y is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.

[0057] In a further aspect, the present invention provides a crosslinked polymer material obtainable by the method as defined herein.

[0058] In a further aspect, the present invention provides the crosslinked polymer material as defined herein, or the crosslinked polymer material prepared according to the method as defined herein, for use in human and / or veterinary medicine.

[0059] It was further found that the crosslinked polymer material as defined herein, or the crosslinked polymer material prepared according to the method as defined herein, is particularly suited for use in tissue engineering, biofabrication, and / or as medical device. Without being limited thereto, the crosslinked polymer material may be used for stereolithography, digital light processing, additive manufacturing, 3D-printing, volumetric additive manufacturing, two-photon polymerization, and the like.

[0060] BRIEF DESCRIPTION OF THE DRAWINGS

[0061] Figure 1 , also abbreviated as Fig. 1 , shows a representation of the results of the in vitro degradation analysis performed on selected polymer materials prepared according to example 5a (M2, M4, M8) and comparative example A (CA1 ).

[0062] Figure 2, also abbreviated as Fig. 2, shows a representation of the physico-chemical analysis of crosslinked polymer materials prepared according to example 6 (P5-P6), compared to comparative example B (CB2).

[0063] Figure 3a, also abbreviated as Fig. 3a, shows a representation of the in vitro micro-CT phantom measurement of the gelatin-based crosslinked polymer materials prepared according to example 5a (M2, M4, M8) and (A2, A4, A8) compared to comparative example A (CA1 ) and (CA2), respectively.

[0064] Figure 3b, also abbreviated as Fig. 3b, shows a representation of the in vitro micro-CT phantom measurement of the polycaprolactone-based crosslinked polymer materials prepared according to example 6 (P1 , P2, P3) and (P4, P5, P6) compared to comparative example B (CB1 ) and (CB2), respectively.

[0065] Figure 3c, also abbreviated as Fig. 3c, shows a representation of the in vitro micro-CT phantom measurement of the polycaprolactone-based crosslinked polymer materials prepared according to example 8 (IPA1 and IPA2). The comparative example CB1 is already depicted in Figure 3b.

[0066] Figure 3d, also abbreviated as Fig. 3d, shows a representation of the in vitro micro-CT phantom measurement of the polyethylene glycol)-based crosslinked polymer materials prepared according to example 7 (AUP1 , AUP2, AUP3), compared to comparative example CC1 .

[0067] Figure 4, also abbreviated as Fig. 4, shows a representation of the results of the cell seeding performed on a selected crosslinked polymer material prepared according to example 5a (M4), versus a control experiment (cells seeded on polystyrene tissue culture plate; 48 wells; surface treated, sterile, catalogue number 734-2326; VWR; Radnor, PA, USA).

[0068] Figure 5, also abbreviated as Fig. 5, shows a representation of the results of the cell viability analysis performed on selected polymer materials prepared according to example 5a (M4, A4).

[0069] Figure 6, also abbreviated as Fig. 6, shows a representation of 3D printed phantoms prepared according to example 9.

[0070] Figure 7, also abbreviated as Fig. 7, shows a representation of the results of the in vivo degradation analysis performed on porous 3D moulded porous hydrogels (referred to as scaffolds) or grinded injectable gels (referred to as injectables) made from hydrogel films based on example 5b.

[0071] Figure 8, also abbreviated as Fig. 8, shows a representation of the results of implantation of P2 and CB1 material; Implant volume for CB1 , Avera radiopacity for P2 (Fig. 8A); CAD design, PLA negative scaffold, and SEM micrograph (Fig. 8B), in vivo detectability (Fig. 8C). DETAILED DESCRIPTION OF THE INVENTION

[0072] The present invention will now be further described. In the following passages, different aspects of the invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.

[0073] As mentioned hereinbefore, in a first aspect, the present invention provides a crosslinked polymer material detectable by radiological imaging, comprising: a biocompatible polymeric backbone comprising primary groups; linker groups; and radiodense imaging groups comprising one or more iodine atoms; wherein at least part of the primary groups are covalently bonded to the linker groups; and wherein at least part of the imaging groups are covalently bonded to each other and / or to one or more of the linker groups.

[0074] It was found that the crosslinked polymer material as defined herein may be detectable by radiological imaging, such as X-ray, radiography, computed tomography, sciascopy, sciagraphy, as well as by sonography. The crosslinked polymer material comprises a biocompatible polymeric backbone comprising primary groups, linker groups, and radiodense imaging groups comprising one or more iodine atoms; wherein at least part of the primary groups are covalently bonded to the linker groups; and wherein at least part of the imaging groups are covalently bonded to one or more of the linker groups and / or to each other, thereby providing crosslinking of the biocompatible polymeric backbone. The linker groups provide a linker between the primary groups and the imaging groups.

[0075] When describing the compounds of the invention, the terms used are to be construed in accordance with the definitions provided hereinafter, unless a context dictates otherwise.

[0076] The term "alkyl" by itself or as part of another substituent refers to a fully saturated hydrocarbon of Formula CxHzx+i wherein x is a number greater than or equal to 1 . Alkyl groups may be linear or branched and may be substituted as indicated herein. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. Thus, for example, Ci-4alkyl means an alkyl of one to four carbon atoms. Examples of alkyl groups are methyl, ethyl, n-propyl, i-propyl, butyl, and its isomers (e.g. n-butyl, i-butyl and t-butyl); pentyl and its isomers, hexyl and its isomers, heptyl and its isomers, octyl and its isomers, nonyl and its isomers; decyl and its isomers. Ci-ealkyl includes all linear or branched groups with between 1 and 6 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl, butyl and its isomers (e.g. n-butyl, i-butyl and t-butyl); pentyl and its isomers, hexyl and its isomers.

[0077] The term "optionally substituted alkyl" refers to an alkyl group optionally substituted with one or more substituents (for example 1 to 6 substituents, for example 1 , 2, 3, 4, 5, or 6 substituents, such as 1 , 2, or 3 substituents) at any available point of attachment. When one or more substituents are present, each substituent replaces a hydrogen atom of the alkyl group.

[0078] Where alkyl groups as defined are divalent, i.e., with two single bonds for attachment to two other groups, they are termed "alkylene" groups. Non-limiting examples of alkylene groups includes methylene, ethylene, methylmethylene, trimethylene, propylene, tetramethylene, ethylethylene, 1 ,2-dimethylethylene, pentamethylene and hexamethylene. Similarly, where alkenyl groups as defined above and alkynyl groups as defined above, respectively, are divalent radicals having single bonds for attachment to two other groups, they are termed "alkenylene" and "alkynylene" respectively.

[0079] In the context of the present invention, the alkyl, alkenyl and alkynyl moieties as defined herein may also further comprise one or more heteroatoms, such as selected from N, S or O, in that for example a carbon atom in an alkyl, alkene or alkyne chain is replaced by a heteroatom. When two or more C atoms are replaced by heteroatoms, the heteroatoms may be adjacent or separated, as long as it results in a chemically stable compound, i.e. a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into a therapeutic agent. An example of a stable combination of two adjacent heteroatoms is a disulfide (-S-S-) group. Where a carbon atom in an alkyl, alkenyl or alkynyl chain is replaced by an N atom, the N atom may be N or NH depending on the number of bonds connected to said C atom.

[0080] The term "cycloalkyl" by itself or as part of another substituent refers to a fully saturated cyclic hydrocarbon of Formula CxHzx wherein x is a number greater than or equal to 3. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. Thus, for example, C3-4cycloalkyl means a cycloalkyl of three to four carbon atoms. Examples of cycloalkyl groups are cyclopropyl, cyclobutyl, 2- methylcyclopropyl, cyclopentyl, 2-, 3-, or 4-methylcyclopentyl, and cyclohexyl.

[0081] An “optionally substituted cycloalkyl” refers to a cycloalkyl having optionally one or more substituents (for example 1 to 6 substituents, for example 1 , 2, 3, 4, 5, or 6 substituents, such as 1 , 2, or 3 substituents), selected from those defined above for substituted alkyl.

[0082] When the suffix "ene" is used in conjunction with an alkyl or cycloalkyl group, hereinafter also referred to as “alkylene” or “cycloalkylene” respectively, it is intended to mean the alkyl or cycloalkyl group as defined herein having two single bonds as points of attachment to other groups.

[0083] The terms "heterocycle" or "heterocyclyl" as used herein by itself or as part of another group refer to non-aromatic, fully saturated or partially unsaturated cyclic groups (for example, 3 to 13 member monocyclic, 7 to 17 member bicyclic, or 10 to 20 member tricyclic ring systems, or containing a total of 3 to 10 ring atoms) which have at least one heteroatom in at least one carbon atom-containing ring. Each ring of the heterocyclic group containing a heteroatom may have 1 , 2, 3 or 4 heteroatoms selected from nitrogen atoms, oxygen atoms and / or sulfur atoms, where the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quaternized. The heterocyclic group may be attached at any heteroatom or carbon atom of the ring or ring system, where valence allows. The rings of multiring heterocycles may be fused, bridged and / or joined through one or more spiro atoms.

[0084] The term “aryl" as used herein refers to a polyunsaturated, aromatic hydrocarbyl group having a single ring (i.e. phenyl) or multiple aromatic rings fused together (e.g. naphthalene or anthracene) or linked covalently, typically containing 5 to 10 atoms; wherein at least one ring is aromatic; and wherein optionally one or more carbon atoms in one or more of these rings may be replaced by oxygen, nitrogen or sulfur atoms.

[0085] In the context of the present invention, the term ‘polyether moiety’ is meant to be a chemically defined structure having a repeating ether unit, such as a polyethylene glycol unit (-O-CH2-CH2- ), a polypropylene glycol unit (-O-CH(CH3)-CH2-), and the like, with a limited number of repeating units, such as 1 , 2, 3, 4, 5, or even 10.

[0086] In the context of the present invention, the term ‘primary groups’ refers to chemically defined functional groups present in the biocompatible polymeric backbone that can be further functionalized by a chemical and / or an enzymatic reaction. Examples of such primary groups are amine groups, carboxylic acid groups, and hydroxyl groups. In embodiments of the invention, the primary groups comprised in the biocompatible polymeric backbone are amine groups and / or hydroxyl groups and / or carboxylic acid groups.

[0087] Radiodensity is a known term in the art, referring to the relative inability of particular waves of electromagnetic radiation, such as radio waves and the X-ray part of the electromagnetic spectrum, to pass through a particular material. The difference of this relative inability is used in radiological imaging techniques as such, but also in combination with radiodense substances, also known as contrast agents. These contrast agents can for instance be passed through the bloodstream to highlight or enhance the contrast of the CT scan or X-ray image. Contrast agents typically contain heavy elements to obtain sufficient attenuation. For this purpose, iodine is most commonly used, because its attenuation coefficients are reasonably high, while its organic compounds are non-toxic and chemically stable.

[0088] The X-ray attenuation coefficients of a given material are determined by its elemental composition, linear attenuation coefficients of those individual elements for a given (X-ray) wavelength, sample density and sample width. The attenuation coefficients for each element have been already measured and published in various studies.

[0089] In the context of the present invention, the terms ‘radiodense imaging groups’, ‘imaging groups’, ‘radiodense imaging groups comprising one or more iodine atoms’ or ‘imaging groups comprising one or more iodine atoms’ are synonymously used for chemically defined moieties comprising one or more iodine atoms, such as 1 , 2, 3, 4, 5, or more iodine atoms, which are susceptible to radiological imaging. Examples of radiological imaging techniques that can be used with the crosslinked polymer materials as defined herein, include X-ray imaging, radiography, computed tomography, sciascopy, skiagraphy. In a preferred embodiment of the invention, the one or more iodine atoms are connected to an sp or sp2hybridized C atom of the imaging groups or imaging monomers.

[0090] The crosslinked polymer material as defined herein may be a hydrogel, i.e. a material capable of binding water in its structure, leading to swelling, but it may also be any other material without the capability of binding water in its structure.

[0091] In the context of the present invention, the term ‘linker groups’ refers to chemically defined moieties providing a linker between a primary group of the biocompatible polymeric backbone and the imaging groups and / or other groups. Consequently, the imaging groups are covalently bonded in the crosslinked polymer material. The imaging groups can form crosslinks connecting two or more of the linker groups of the crosslinked polymer material or they can form grafts on linker groups. Each imaging group may therefore be connected to only a linker group, to two linker groups, to one linker group and one further imaging group, to two further imaging groups, or to one further imaging group.

[0092] Scheme 1 provides a graphical representation of an embodiment of the crosslinked polymer material as defined herein, obtained by radical chain-growth polymerization, comprising a polymeric backbone, linker groups connected to the primary groups of the polymeric backbone, and imaging groups connected to each other and / or to the linker groups. biocompatible polymeric • linker group backbone

[0093] S radiodense imaging group

[0094] Scheme 1. Graphical representation of a crosslinked polymer material as embodied herein

[0095] In embodiments of the invention, the crosslinks connecting two or more of the linker groups of the crosslinked polymer material as defined herein, may comprise one or more imaging groups, such as 1 , 2, 3, 4, 5, 10, 15, or more imaging groups and optionally other groups, such as 1 , 2, 3, 4, 5, 10, 15, or more other groups. Those other groups may be the result of free radical chain growth polymerization of monomers comprising at least one C-C double bond which do not comprise iodine atoms, and are therefore not considered imaging groups, or the result of step growth polymerization of a multifunctional thiol, in essence thiol-ene chemistry. In a particular embodiment, the present invention provides a crosslinked material as defined herein, wherein the crosslinks connecting two or more of the linker groups of the crosslinked polymer material as defined herein, only contain imaging groups.

[0096] It was further found that if more than one iodine atom is present in the imaging groups, this may lead to an enhanced radiodensity, and therefore a higher contrast during radiological imaging. As stated hereinbefore, the imaging groups may comprise one or more iodine atoms, such as 1 , 2, 3, 4, 5, or more iodine atoms. In useful embodiments of the invention, at least part of the imaging groups comprises two or more iodine atoms, such as 2, 3, 4, 5, or more iodine atoms. In preferred embodiments of the invention, at least part of the imaging groups comprises three or more iodine atoms, such as 3, 4, 5, or more iodine atoms. In other useful embodiments of the invention, substantially all, such as about 90 %, 95 %, 99 %, and even 100 %, of the imaging groups comprises three or more iodine atoms, such as 3, 4, 5, or more iodine atoms. In a specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein substantially all, such as about 90 %, 95 %, 99 %, and even 100 %, of the imaging groups comprise three or more iodine atoms. In a more specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein all the imaging groups comprise three or more iodine atoms.

[0097] It was further found that the biocompatible polymeric backbone may be any biopolymer known in the art, such as polypeptides, proteins, polysaccharides, and polynucleic acids. In useful embodiments of the present invention as defined herein, the biocompatible polymer backbone is a biopolymer selected from polypeptides, proteins, polysaccharides, and polynucleic acids. Suitable examples of polypeptides and / or proteins are gelatins, and collagens. Suitable examples of polysaccharides are, alginates, dextrans, agarose, glycosaminoglycans, chitosans and carrageenans. In useful embodiments of the present invention as defined herein, the biocompatible polymer backbone is a biopolymer selected from polypeptides, proteins, polysaccharides, and polynucleic acids. In specific embodiments of the present invention as defined herein, the biocompatible polymer backbone is a biopolymer selected from gelatins, collagens, alginates, dextrans, agarose, glycosaminoglycans, chitosans and carrageenans. In a particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymer backbone is a biopolymer selected from polypeptides, proteins, polysaccharides, and polynucleic acids. In a more particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymer backbone is a biopolymer selected from gelatins, and collagens. In another more particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymer backbone is a biopolymer selected from alginates, dextrans, agarose, glycosaminoglycans, chitosans and carrageenans. In a very specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymer backbone is a gelatin.

[0098] Biopolymers such as polypeptides, proteins, polysaccharides, and polynucleic acids, typically comprise amine groups and / or hydroxyl groups and / or carboxylic acid groups as primary groups throughout the biopolymer.

[0099] It was also found that the biocompatible polymeric backbone may be other polymers known in the art, such as a polyester, a polyamide, a polyether or any combination thereof. In another embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymer backbone is a polymer selected from a polyester, a polyamide, a polyether, and any combination thereof. In a particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymer backbone is a polylactone. In a more particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymer backbone is a polycaprolactone. Depending on the polymerization method used to prepare the polymer, such as condensation polymerization, ring-opening polymerization, the stoichiometry of the monomers, and / or the initiators used, the polymer may comprise amine groups and / or hydroxyl groups and / or carboxylic acid groups as primary groups. Without being limited thereto, the primary groups of the synthetic polymers as defined herein are typically present at two or more ends of the polymer. In the particular case of polycaprolactone, the biocompatible polymeric backbone comprises hydroxyl groups and / or carboxylic acid groups as primary groups. In the more particular case wherein a polyol is used as initiator for the ring-opening polymerization of caprolactone, the resulting polycaprolactone comprises hydroxyl groups as primary groups.

[0100] Scheme 2 provides a graphical representation of another embodiment of a crosslinked polymer material as defined herein, obtained via step-growth polymerization, in particular thiol-ene chemistry, comprising a polymeric backbone, linker groups covalently connected to the primary groups of the polymeric backbone, and imaging groups covalently connected to the linker groups and / or to each other and / or to a multifunctional sulfide compound. biocompatible polymeric linker group backbone > ,

[0101] ® radiodense imaging group multifunctional sulfide

[0102] Scheme 2. Graphical representation of a crosslinked polymer material as embodied herein It appeared that linker groups comprising a propanoic and / or 2-methylpropanoic moiety may lead to improved properties of the crosslinked polymer material. In useful embodiments, the present invention provides the crosslinked polymer material as defined herein, wherein the linker groups comprise a propanoic or a 2-methylpropanoic moiety. The propanoic and / or 2- methylpropanoic moiety may be directly connected to the primary groups of the biocompatible polymeric backbone. For example, when the linker groups comprising a propanoic or a 2- methylpropanoic moiety are covalently connected to an amine primary group, they may form a propanamide or 2-methylpropanamide moiety. When the linker groups comprising a propanoic or a 2-methylpropanoic moiety are covalently connected to a hydroxyl primary group, they may form a propanoic ester or 2-methylpropanoic ester moiety. Alternatively, or complementary, the propanoic and / or 2-methylpropanoic moiety may be indirectly connected to the primary groups of the biocompatible polymeric backbone. For example, when the biocompatible polymeric backbone comprises carboxylic acid groups as primary groups, the propanoic and / or 2- methylpropanoic moiety comprised in the linker groups may be covalently connected to the carboxylic acid group via an amidoalkyl fragment.

[0103] It further appeared that linker groups comprising an A / -propyl amide moiety may lead to improved properties of the crosslinked polymer material. In useful embodiments, the present invention provides the crosslinked polymer material as defined herein, wherein the linker groups comprise an A / -propyl amide moiety. The A / -propyl amide moiety may be directly or indirectly connected to the primary groups of the biocompatible polymeric backbone. For example, when the linker groups comprising an A / -propyl amide moiety are directly covalently connected to an amine primary group, they may form an A / -propyl urea moiety. When the linker groups comprising an A / -propyl amide moiety are directly covalently connected to a hydroxyl primary group, they may form an A / -propyl carbamate moiety.

[0104] It also appeared that improved mechanical properties of the crosslinked polymer material may be obtained, if the biocompatible polymeric backbone is a biopolymer selected from polypeptides, proteins, polysaccharides, and polynucleic acids, comprising amine groups as primary groups, especially when at least 20 % of the amine groups, relative to the total amount of amine groups in the biocompatible polymeric backbone, are covalently bonded to the linker groups. It further appeared that a larger relative amount of amine groups covalently bonded to the linker groups, such as 40 %, 50 %, 55 %, 60 %, 70 %, 75 %, 80 %, 85 %, 90 %, or even substantially all amine groups, such as 95 %, 99 %, or even 100 %, may lead to further improved mechanical properties of the crosslinked polymer material. In useful embodiments of the invention, the biocompatible polymeric backbone comprises amine groups as primary groups, wherein at least 20 % of the amine groups, relative to the total amount of amine groups in the biocompatible polymeric backbone, are covalently bonded to the linker groups preferably at least 30 %, more preferably from 40 to 100 %. In a particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymeric backbone is a biopolymer selected from polypeptides, proteins, polysaccharides, and polynucleic acids, comprising amine groups as primary groups, and wherein at least 20 % of the amine groups, relative to the total amount of amine groups in the biocompatible polymeric backbone, are covalently bonded to the linker groups, preferably at least 30 %, more preferably from 40 to 100 %.

[0105] It also appeared that improved mechanical properties of the crosslinked polymer material may be obtained, if the biocompatible polymeric backbone is a biopolymer selected from polypeptides, proteins, polysaccharides, and polynucleic acids, comprising hydroxyl groups as primary groups, especially when at least 20 % of the hydroxyl groups, relative to the total amount of hydroxyl groups in the biocompatible polymeric backbone, are covalently bonded to the linker groups. It further appeared that a larger relative amount of hydroxyl groups covalently bonded to the linker groups, such as 40 %, 50 %, 55 %, 60 %, 70 %, 75 %, 80 %, 85 %, 90 %, or even substantially all hydroxyl groups, such as 95 %, 99 %, or even 100 %, may lead to further improved mechanical properties of the crosslinked polymer material. In useful embodiments of the invention, the biocompatible polymeric backbone comprises hydroxyl groups as primary groups, wherein at least 20 % of the hydroxyl groups, relative to the total amount of hydroxyl groups in the biocompatible polymeric backbone, are covalently bonded to the linker groups preferably at least 30 %, more preferably from 40 to 100 %. In a particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymeric backbone is a biopolymer selected from polypeptides, proteins, polysaccharides, and polynucleic acids, comprising hydroxyl groups as primary groups, and wherein at least 20 % of the hydroxyl groups, relative to the total amount of hydroxyl groups in the biocompatible polymeric backbone, are covalently bonded to the linker groups, preferably at least 30 %, more preferably from 40 to 100 %.

[0106] It further appeared that improved mechanical properties of the crosslinked polymer material may be obtained, if the biocompatible polymeric backbone is a biopolymer selected from polypeptides, proteins, polysaccharides, and polynucleic acids, comprising both amine groups and carboxylic acid groups as primary groups. Especially when substantially all of the amine groups are covalently bonded to the linker groups, and wherein at least 10 % of the carboxyl acid groups, relative to the total amount of carboxylic acid groups in the biocompatible polymeric backbone, are also covalently linked to the linker groups, this may lead to further improved mechanical properties of the crosslinked polymer material. It further appeared that a larger relative amount of carboxylic groups covalently bonded to the linker groups, such as 15 %, 20 %, 25 %, 30 %, 40 %, 50 %, 60 %, 70 %, 75 %, or more, may lead to further improved mechanical properties of the crosslinked polymer material. In useful embodiments of the invention, the biocompatible polymeric backbone comprises both amine and carboxylic acid groups as primary groups, wherein substantially all of the amine groups, and at least 10 % of the carboxylic acid groups, relative to the total amount of carboxylic acid groups in the biocompatible polymeric backbone, are covalently bonded to the linker groups. In a more particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the biocompatible polymeric backbone is a biopolymer selected from polypeptides, proteins, polysaccharides, and polynucleic acids, comprising both amine and carboxylic acid groups as primary groups, wherein substantially all of the amine groups, and at least 10 % of the carboxylic acid groups, relative to the total amount of carboxylic acid groups in the biocompatible polymeric backbone, are covalently bonded to the linker groups, preferably from 15 to 75 % of the carboxylic acid groups, more preferably from 20 to 50 % of the carboxylic acid groups.

[0107] It was also found that when the crosslinks connecting two or more of the linker groups are substantially, such as about 90 %, 95 %, 99 %, or even 100 %, composed of radiodense imaging groups comprising one or more iodine atoms, this may lead to an enhanced radiodensity. In an embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the crosslinks connecting two or more of the linker groups are substantially composed of radiodense imaging groups comprising one or more iodine atoms. In a specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the crosslinks connecting two or more of the linker groups are fully composed of radiodense imaging groups comprising one or more iodine atoms.

[0108] It was further found that a crosslinked polymer material having an iodine content of at least 1 wt.%, relative to the mass of the crosslinked polymer material, may provide for a suitable contrast when used for radiological imaging. Increasing the iodine content may have a beneficial effect on the contrast of the image obtained during radiological imaging. In useful embodiments of the invention, the crosslinked polymer material has an iodine content of at least 1 wt.%, relative to the mass of the crosslinked polymer material, preferably at least 2 wt.%, more preferably from 5 to 70 wt.%, even more preferably from 10 to 60 wt.%. In a particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the iodine content, relative to the mass of the crosslinked polymer material, is from 1 to 60 wt.%.

[0109] It further appeared that radiodense imaging groups comprising an iodinated aryl moiety may have a beneficial effect on the contrast of the image obtained during radiological imaging. In a particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprise an iodinated aryl moiety represented by formula (I) wherein

[0110] Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; and

[0111] R2 is Ci ealkyl, wherein said -Ci ealkyl is optionally substituted with one or more -OH substituents.

[0112] It also appeared that radiodense imaging groups comprising an iodinated phenyl moiety may have a beneficial effect on the contrast of the image obtained during radiological imaging. In another particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprise an iodinated aryl moiety represented by formula (II) wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;

[0113] R1 and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; and

[0114] R2 is Ci ealkyl, wherein said -Ci ealkyl is optionally substituted with one or more -OH substituents.

[0115] It also appeared that radiodense imaging groups comprising a triiodophenyl moiety may have a beneficial effect on the contrast of the image obtained during radiological imaging. In a more particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprise an iodinated aryl moiety represented by formula (III) wherein

[0116] Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-Rz; each instance of Rais independently selected from -H, and -CH3; and

[0117] R2 is Ci ealkyl, wherein said -Ci ealkyl is optionally substituted with one or more -OH substituents.

[0118] In an even more particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprise an iodinated aryl moiety represented by formula (III) wherein

[0119] Ri and Rr are both -COOH.

[0120] It was found that radiodense imaging groups comprising a propanoic and / or 2-methylpropanoic moiety may lead to improved properties of the crosslinked polymer material. In a particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (IV) wherein

[0121] Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0122] R3 is selected from -H, and -CH3;

[0123] Xi and X2 are each independently selected from a direct bond, -Ci ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0124] Rb is selected from -H, and -CH3; and

[0125] Y is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.

[0126] In a more particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (V) wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;

[0127] Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0128] R3 is selected from -H, and -CH3;

[0129] Xi and X2 are each independently selected from a direct bond, -Ci ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0130] Rb is selected from -H, and -CH3; and

[0131] Y is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.

[0132] In an even more particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (VI) wherein

[0133] Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci-ealkyl ; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0134] R3 is selected from -H, and -CH3; Xi and X2 are each independently selected from a direct bond, -Ci-ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci-ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0135] Rb is selected from -H, and -CH3; and Y is selected from a direct bond, -Ci-ealkylene-, and a polyether moiety.

[0136] In yet an even more particular embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (VI) wherein

[0137] Ri and Rr both -COOH;

[0138] R3 is selected from -H, and -CH3;

[0139] Xi and X2 are each independently selected from a direct bond, -Ci ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0140] Rb is selected from -H, and -CH3; and

[0141] Y is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.

[0142] It was further found that radiodense imaging groups comprising a propanoic ester or 2- methylpropanoic ester moiety may particularly lead to improved properties of the crosslinked polymer material. In a specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (IVa) wherein

[0143] Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents; and

[0144] R3 is selected from -H, and -CH3.

[0145] In a more specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (Va) wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;

[0146] R1 and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents; and

[0147] R3 is selected from -H, and -CH3.

[0148] In an even specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (Via) wherein

[0149] Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents; and

[0150] R3 is selected from -H, and -CH3.

[0151] In yet a more specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (Via) wherein

[0152] R1 and Rr are both -COOH; and

[0153] R3 is selected from -H, and -CH3.

[0154] It was further found that imaging groups comprising a propanamide or 2-methylpropanamide moiety may particularly lead to improved properties of the crosslinked polymer material. In another specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (IVb) wherein

[0155] Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0156] R3 is selected from -H, and -CH3; and

[0157] Rb is selected from -H, and -CH3.

[0158] In another specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (Vb) wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;

[0159] Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0160] R3 is selected from -H, and -CH3; and

[0161] Rb is selected from -H, and -CH3.

[0162] In another specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (Vlb) wherein

[0163] R1 and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0164] R3 is selected from -H, and -CH3; and

[0165] Rb is selected from -H, and -CH3.

[0166] In a more specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (Vlb)

[0167] wherein

[0168] Ri and Rr are both -COOH; R3 is selected from -H, and -CH3; and

[0169] Rb is selected from -H, and -CH3.

[0170] In a further specific embodiment, the present invention provides the crosslinked polymer material as defined herein, wherein the radiodense imaging groups comprising one or more iodine atoms are represented by formula (Vlb’) wherein any instance of R4 is independently selected from -H, -COOH, -NRa-C(O)-R2, and -C(O)- NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;. R3 is selected from -H, and -CH3; and Rb is selected from -H, and -CH3.

[0171] In useful embodiments of the invention, the radiodense imaging groups comprising one or more iodine atoms are represented by any one of formula (IV), (V), (VI), (IVa), (Va), (Via), (I Vb) , (Vb), (Vlb), or (Vlb’); wherein R2 is selected from the list comprising:

[0172] As mentioned hereinbefore, in a second aspect, the present invention provides a method to prepare the crosslinked polymer material as defined herein, the method comprising the steps of: a) providing a biocompatible polymeric backbone comprising primary groups; b) reacting at least part of the primary groups with a pre-linker group introducing agent to covalently bind pre-linker groups comprising at least one C-C double bond with the primary groups; and c) crosslinking at least part of the pre-linker groups with monomers comprising at least one C-C double bond by free radical chain-growth polymerization and / or step-growth polymerization, wherein at least part of the monomers are radiodense imaging monomers comprising one or more iodine atoms.

[0173] It appeared that at least part of the monomers comprising at least one C-C double bond used for crosslinking at least part of the C-C double bond comprising pre-linker groups in step c) should be radiodense imaging monomers comprising one or more iodine atoms, for the crosslinked polymer material to be detectable by radiological imaging.

[0174] It further appeared that when substantially all the monomers comprising at least one C-C double bond are radiodense imaging monomers comprising one or more iodine atoms, this may lead to an enhanced contrast during radiological imaging.

[0175] Scheme 3 provides a graphical representation of an embodiment of the method to prepare the crosslinked polymer material as defined herein, more specifically crosslinking step c) of the method. The left part of the scheme represents a polymeric backbone, pre-linker groups connected to at least part of the primary groups of the polymeric backbone, and radiodense imaging monomers comprising one or more iodine atoms, before the crosslinking reaction; and the right part of the scheme represents a crosslinked polymer material, comprising a polymeric backbone, linker groups connected to at least part of the primary groups of the polymeric backbone, and radiodense imaging groups connected to the linker groups and / or to each other, after free radical chain-growth polymerization, thereby providing crosslinking.

[0176] As a result of the free radical chain-growth polymerization, the pre-linker groups become covalently bonded linker groups, and the imaging monomers become covalently bonded imaging groups. Each imaging monomer thereby becomes covalently bonded to only a linker group, to two linker groups, to one linker group and one further imaging group, to two further imaging groups, or to one further imaging group. biocompatible polymeric ® linker group backbone

[0177] S radiodense ® radiodense imaging monomer imaging group

[0178] Scheme 3. Graphical representation of the crosslinking step of the method as embodied herein

[0179] Scheme 4 provides a graphical representation of another embodiment of the method to prepare the crosslinked polymer material as defined herein, more specifically crosslinking step c) of the method. The left part of the scheme represents a polymeric backbone, pre-linker groups connected to at least part of the primary groups of the polymeric backbone, radiodense imaging monomers comprising one or more iodine atoms, and a multifunctional thiol compound, before the crosslinking reaction; and the right part of the scheme represents a crosslinked polymer material, comprising a polymeric backbone, linker groups connected to at least part of the primary groups of the polymeric backbone, radiodense imaging groups connected to the linker groups and / or to each other and / or to the multifunctional sulfide compound, after step-growth polymerization, thereby providing crosslinking. biocompatible p linker group olymeric backbone

[0180] 5 radiodense ® radiodense imaging monomer imaging group sulfide herein

[0181] In a particular embodiment, the present invention provides the method as defined herein, wherein the primary groups comprised in the biocompatible polymeric backbone comprise amine groups and / or hydroxyl groups and / or carboxylic acid groups.

[0182] It was further found that when substantially all the monomers comprising at least one C-C double bond are radiodense imaging monomers comprising one or more iodine atoms, this may lead to an enhanced contrast during radiological imaging. In an embodiment, the present invention provides the method as defined herein, wherein substantially all, such as about 90 %, 95 %, 99 %, and even 100 %, of the monomers comprising at least one C-C double bond used for crosslinking at least part of the C-C double bond comprising pre-linker groups in step c), are radiodense imaging monomers comprising one or more iodine atoms. In a specific embodiment, the present invention provides the method as defined herein, wherein all the monomers comprising at least one C-C double bond used for crosslinking at least part of the C-C double bond comprising pre-linker groups in step c), are radiodense imaging monomers comprising one or more iodine atoms. It also appeared that if more than one iodine atom is present in the radiodense imaging monomers, this may lead to an enhanced contrast during radiological imaging. In an embodiment, the present invention provides the method as defined herein, wherein at least part of the radiodense imaging monomers used for crosslinking at least part of the C-C double bond comprising pre-linker groups in step c), comprise two or more iodine atoms. In a specific embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers used for crosslinking at least part of the C-C double bond comprising pre-linker groups in step c), comprise two or more iodine atoms.

[0183] It further appeared that radiodense imaging monomers comprising an iodinated aryl moiety may have a beneficial effect on the contrast of the image obtained during radiological imaging. In a particular embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprise an iodinated aryl moiety represented by formula (I) wherein

[0184] Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; and

[0185] R2 is Ci ealkyl, wherein said -Ci ealkyl is optionally substituted with one or more -OH substituents.

[0186] In a more particular embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprise an iodinated aryl moiety represented by formula (II) wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;

[0187] R1 and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; and

[0188] R2 is Ci ealkyl, wherein said -Ci-ealkyl is optionally substituted with one or more -OH substituents.

[0189] In an even more particular embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprise an iodinated aryl moiety represented by formula (III) wherein

[0190] Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; and

[0191] R2 is Ci ealkyl, wherein said -Ci-ealkyl is optionally substituted with one or more -OH substituents.

[0192] In yet an even more particular embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprise an iodinated aryl moiety represented by formula (III) wherein

[0193] R1 and Rr are both -COOH. It was found that radiodense imaging monomers comprising an acrylic or a methacrylic moiety may be particularly suited to crosslink at least part of the C-C double bond comprising pre-linker groups by free radical chain growth polymerization and / or step-growth polymerization. In another particular embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (VII) wherein

[0194] Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of R1 is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci-ealkyl ; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0195] R3 is selected from -H, and -CH3;

[0196] Xi and X2 are each independently selected from a direct bond, -Ci-ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci-ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0197] Rb is selected from -H, and -CH3; and

[0198] Y is selected from a direct bond, -Ci-ealkylene-, and a polyether moiety.

[0199] In a more particular embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (VIII) wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;

[0200] Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci-ealkyl ; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0201] R3 is selected from -H, and -CH3;

[0202] Xi and X2 are each independently selected from a direct bond, -Ci-ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci-ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0203] Rb is selected from -H, and -CH3; and

[0204] Y is selected from a direct bond, -Ci-ealkylene-, and a polyether moiety.

[0205] In an even more particular embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (IX) wherein

[0206] Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci-ealkyl ; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0207] R3 is selected from -H, and -CH3; Xi and X2 are each independently selected from a direct bond, -Ci-ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci-ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0208] Rb is selected from -H, and -CH3; and Y is selected from a direct bond, -Ci-ealkylene-, and a polyether moiety.

[0209] In yet an even more particular embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (IX) wherein

[0210] Ri and Rr are both -COOH;

[0211] R3 is selected from -H, and -CH3;

[0212] Xi and X2 are each independently selected from a direct bond, -Ci ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0213] Rb is selected from -H, and -CH3; and

[0214] Y is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.

[0215] It was further found that imaging monomers comprising an acrylate or a methacrylate moiety may be particularly suited to crosslink at least part of the C-C double bond comprising pre-linker groups by free radical chain growth polymerization and / or step-growth polymerization. In a specific embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (Vila) wherein Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of R1 is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci-ealkyl ; wherein said -Ci-ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents; and

[0216] R3 is selected from -H, and -CH3.

[0217] In a specific embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (Villa)

[0218] (Villa) wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;

[0219] Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci-ealkyl ; wherein said -Ci-ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents; and

[0220] R3 is selected from -H, and -CH3.

[0221] In a specific embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (IXa) wherein

[0222] R1 and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-Rz; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents; and

[0223] R3 is selected from -H, and -CH3.

[0224] In yet an even more specific embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (IXa) wherein

[0225] Ri and Rr are both -COOH; and

[0226] Rs is selected from -H, and -CH3.

[0227] It was further found that imaging monomers comprising an acrylamide or a methacrylamide moiety may be particularly suited to crosslink at least part of the C-C double bond comprising pre-linker groups by free radical chain growth polymerization and / or step-growth polymerization. In another specific embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (VI lb) wherein

[0228] Ar is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0229] R3 is selected from -H, and -CH3; and

[0230] Rb is selected from -H, and -CH3.

[0231] In another specific embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (VI I lb)

[0232] (Vlllb) wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;

[0233] Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0234] R3 is selected from -H, and -CH3; and

[0235] Rb is selected from -H, and -CH3.

[0236] In another specific embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (IXb) wherein

[0237] R1 and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;

[0238] R3 is selected from -H, and -CH3; and

[0239] Rb is selected from -H, and -CH3.

[0240] In a more specific embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (IXb) wherein

[0241] Ri and Rr are both -COOH:

[0242] R3 is selected from -H, and -CH3; and

[0243] Rb is selected from -H, and -CH3.

[0244] In a further specific embodiment, the present invention provides the method as defined herein, wherein the radiodense imaging monomers comprising one or more iodine atoms are represented by formula (IXb’) wherein any instance of R4 is independently selected from -H, -COOH, -NRa-C(O)-R2, and -C(O)- NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;. R3 is selected from -H, and -CH3; and Rb is selected from -H, and -CH3.

[0245] In useful embodiments of the invention, the radiodense imaging monomers comprising one or more iodine atoms are represented by any one of formula (VII), (VIII), (IX), (Vila), (Villa), (IXa), (Vllb), (Vlllb), (IXb), or (IXb’); wherein R2 is selected from the list comprising:

[0246] It was found that any pre-linker group comprising at least one C-C double bond may allow for crosslinking at least part of the pre-linker groups with monomers comprising at least one C-C double bond by free radical chain growth polymerization and / or step-growth polymerization, wherein at least part of the monomers are radiodense imaging monomers comprising one or more iodine atoms. It was however found that acrylic moieties, methacrylic moieties, or any combination thereof, are particularly suited as pre-linker groups comprising at least one C-C double bond and may lead to improved properties of the crosslinked polymer material. In an embodiment, the present invention provides the method as defined herein, wherein the prelinker groups comprising at least one C-C double bond comprise acrylic moieties, methacrylic moieties, or any combination thereof. The acrylic or methacrylic moiety may be directly connected to the primary groups of the biocompatible polymeric backbone. For example, when the pre-linker groups comprising an acrylic or methacrylic moiety are covalently connected to an amine primary group, they may form an acrylamide or methacrylamide moiety. When the prelinker groups comprising an acrylic or methacrylic moiety are covalently connected to a hydroxyl primary group, they may form an acrylate or methacrylate moiety. Alternatively, or complementary, the acrylic or methacrylic moiety may be indirectly connected to the primary groups of the biocompatible polymeric backbone. For example, when the biocompatible polymeric backbone comprises carboxylic acid groups as primary groups, the acrylic or methacrylic moiety comprised in the pre-linker groups may be covalently connected to the carboxylic acid group via an amidoalkyl fragment.

[0247] It was further found that if the biocompatible polymeric backbone comprises amine groups and / or hydroxyl groups as primary groups, an acrylating agent, a methacrylating agent, or any combination thereof, is particularly suited to introduce the pre-linker groups on the primary groups. In a specific embodiment, the present invention provides the method as defined herein, wherein the biocompatible polymeric backbone comprises amine groups and / or hydroxyl groups as primary groups, and wherein the pre-linker group introducing agent is an acrylating agent, a methacrylating agent, or any combination thereof. In a more specific embodiment, the present invention provides the method as defined herein, wherein the biocompatible polymeric backbone comprises amine groups and / or hydroxyl groups as primary groups, and wherein the pre-linker group introducing agent is acryloyl chloride, methacrylic anhydride, or any combination thereof.

[0248] It was further found that if the biocompatible polymeric backbone comprises carboxylic acid groups as primary groups, the pre-linker groups may be introduced by an aminoalkylacrylate or an aminoalkylmethacrylate via a Fukuyama-Mitsunobu reaction, or a Sheehan-Hess coupling. In a specific example, in the case of a Fukuyama-Mitsunobu reaction, a combination of (2- aminoethyl)methacrylate, triphenylphosphine, triethylamine, and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD) may be used to introduce the pre-linker groups. In a specific example, in the case of a Sheehan-Hess coupling, a combination of (2- aminoethyl)methacrylate, and 1 -ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) or dicyclohexylcarbodiimide (DCC) or diisopropylcarbodiimide (DIC) may be used to introduce the pre-linker groups. In a specific embodiment, the present invention provides the method as defined herein, wherein the biocompatible polymeric backbone comprises carboxylic acid groups as primary groups, and wherein the pre-linker group introducing agent is a combination of a carbodiimide and an aminoalkylacrylate or aminoalkylmethacrylate. In a more specific embodiment, the present invention provides the method as defined herein, wherein the biocompatible polymeric backbone comprises carboxylic acid groups as primary groups, and wherein the pre-linker group introducing agent is a combination of (2-aminoethyl)methacrylate, and 1 -ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) or dicyclohexylcarbodiimide (DCC) or diisopropylcarbodiimide (DIC). In another specific embodiment, the present invention provides the method as defined herein, wherein the biocompatible polymeric backbone comprises carboxylic acid groups as primary groups, and wherein the pre-linker group introducing agent is a combination of an azodicarboxylate, triphenylphosphine, triethylamine, and an aminoalkylacrylate or aminoalkylmethacrylate. In a more specific embodiment, the present invention provides the method as defined herein, wherein the biocompatible polymeric backbone comprises carboxylic acid groups as primary groups, and wherein the pre-linker group introducing agent is a combination of (2-aminoethyl)methacrylate, triphenylphosphine, triethylamine, and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD).

[0249] It also appeared that the ratio of imaging monomers to pre-linker groups may influence the properties of the crosslinked polymer material obtainable by the method. To prepare hydrogel materials, the ratio of imaging monomers to pre-linker groups is preferably from 0.1 to 8, more preferably from 0.2 to 6, even more preferably from 0.3 to 4, yet even more preferably from 0.5 to 2. To prepare crosslinked polymer materials which do not swell in water, such as PCL-based materials, the ratio of imaging monomers to pre-linker groups is preferably from 0.07 to 0.6, more preferably from 0.08 to 0.5, even more preferably from 0.09 to 0.3, yet even more preferably from 0.1 to 0.2.

[0250] In a further aspect, the present invention provides a crosslinked polymer material obtainable by the method as defined herein.

[0251] In a further aspect, the present invention provides a use of the crosslinked polymer material as defined herein, or the crosslinked polymer material prepared according to the method as defined herein. In an embodiment, the present invention provides the use of the crosslinked polymer material as defined herein, in human and / or veterinary medicine. In a particular embodiment, the present invention provides the use of the crosslinked polymer material as defined herein, for tissue engineering and biofabrication. In another particular embodiment, the present invention provides the use of the crosslinked polymer material as defined herein, as medical device. The present invention further provides a use of the crosslinked polymer material as defined herein, or the crosslinked polymer material prepared according to the method as defined herein, in stereolithography, digital light processing, additive manufacturing, 3D-printing, volumetric additive manufacturing or two-photon polymerization.

[0252] In yet a further aspect, the present invention provides the crosslinked polymer material as defined herein, for use in human and / or veterinary medicine. In an embodiment, the present invention provides the crosslinked polymer material as defined herein, for use in tissue engineering or biofabrication.

[0253] The crosslinked polymer material as defined herein may for instance be shaped into a porous or non-porous scaffold suitable for implantation. The crosslinked polymer material may therefore be shaped by techniques known in the art. As mentioned hereinbefore, it is an advantage of the crosslinked polymer material, as defined herein, that it can be shaped by 3D printing.

[0254] The crosslinked polymer material as defined herein may also be dehydrated, ground, and reswollen to provide an injectable hydrogel.

[0255] The present invention further provides a method for the prophylaxis and treatment of human and veterinary disorders, by administering the crosslinked polymer material according to this invention to a subject in need thereof. Such crosslinked polymer materials are particularly suitable in various fields such as tissue engineering and biofabrication. As such the crosslinked polymer material of the present invention is highly useful in the treatment of several human and veterinary disorders. In yet a further aspect, the present invention provides a medical device comprising the crosslinked polymer material as defined herein. Possible examples of medical devices include, but are not limited to, cell carriers, supports and / or scaffolds for tissue engineering purposes; medical implants, such as dental implants, cartilage implants, tendon implants, ligament implants; coatings on existing medical implants; and drug delivery devices.

[0256] The compounds of the present invention can be prepared according to the reaction schemes provided in the examples hereinafter, but those skilled in the art will appreciate that these are only illustrative for the invention and that the compounds of this invention can be prepared by any of several standard synthetic processes commonly used by those skilled in the art of organic chemistry.

[0257] EXAMPLES

[0258] Materials

[0259] Gelatin type B, isolated from bovine hides by an alkaline treatment, provided by Rousselot (Ghent, Belgium). e-Caprolactone (>99%), supplied by Tokyo Chemical Industry (TCI), was dried over calcium hydride (CaHz) and vacuum distilled (120 °C, 10 mbar). 5-amino-2,4,6- triiodoisophthalic acid (95 %), 4-iodoaniline, acryloyl chloride, and acrylic anhydride (> 90 %, 500 ppm MEHQ as stabilizer) were purchased from Fluorochem (Hadfield, UK). Methacrylic anhydride, 1 -ethyl-3-(3-(dimethylamino)propyl)carbodiimide (EDC), Dulbecco’s Modified Eagle Medium (DMEM), allyl isocyanate (98%), ethylene glycol (anhydrous, 99.8%), pentaerythritol tetrakis(3-mercaptopropionate) (>95%), tin(ll) 2-ethylhexanoate (Sn(Oct)2, 92.5-100%), dimethyl terephthalate (99.93%), 5-amino-2,4,6-triiodoisophthalic acid (95 %), polyethylene glycol) (PEG, Mw 2000 g / mol), isophorone diisocyanate (IPDI), 10 v / v% fetal bovine serum, 2 v / v% calcein-acetoxymethyl (Ca-AM), propidium iodide (PI) and deuterium oxide were purchased at Sigma-Aldrich (Diegem, Belgium) and used as received. 2-Aminoethyl methacrylate hydrochloride (AEMA-HCI) was obtained from Polysciences (Conches, France). Dimethyl sulfoxide (DMSO) (99.85%), dimethyl formamide (DMF, 99.85%), and N- hydroxysuccinimide (98%) (NHS) were purchased from Acros (Geel, Belgium). (2,4,6- trimethylbenzoyl)-phenyl-phosphinic acid ethyl ester was purchased from Speedcure TPO-L (Lambson, UK). Ethoxylated and propoxylated pentaerytritol triacrylate, EPPET was purchased from Allnex (Drogenbos, Belgium). Dialysis membranes Spectra / por (MWCO 12 - 14 kDa) were received from polylab (Antwerp, Belgium). The adipose tissue-derived stem cells (ASCs) were purchased from Lonza (Basel, Switzerland). Methods

[0260] Rheological monitoring of crosslinking kinetics

[0261] The crosslinking kinetics were measured using a rheometer Physica MCR-301 (Anton Paar, Sint-Martens-Latem, Belgium) with a parallel plate geometry (upper plate diameter of 25 mm). 300 pL of the sample solution was placed between the plates using a gap setting of 0.35 mm. The edges were trimmed and sealed using silicone grease (Bayer, Sigma-Aldrich, Diegem, Belgium) to prevent sample drying. An oscillation frequency of 1 Hz and a strain of 0.1 % were applied. Next, the solutions were monitored during 5 min at 37 °C and afterwards irradiated using UV-A light (15 min, EXFO Novacure 2000 UV light source at 365 nm using an intensity of 100 mW / cm2). Finally, from the data, the gelation time (tgei) was determined as the time at which the storage modulus (G’) exceeded the loss modulus (G”) of the sample.

[0262] Storage (G’) and loss (G”) moduli of crosslinked polymer films

[0263] The mechanical properties of all crosslinked polymer films (film with 14 mm diameter) were determined using a rheometer Physica MCR-301 (Anton Paar, Sint-Martens-Latem, Belgium) with a parallel plate geometry (diameter of upper plate 15 mm). The storage (G’) and loss (G”) moduli were quantified by means of oscillation rheology (strain 0.1 %, frequency 1 Hz, and normal force 0.6 N). All measurements were performed in triplicate and reported as mean ± SD.

[0264] Tensile testing

[0265] Tensile experiments were performed using a Tinius Olsen Model 1 ST apparatus, equipped with a load cell of 500 N using Horizon as software. Rectangular samples were cut from the crosslinked films (length 14.0 mm, thickness 1 .0 mm, and width 6.00 mm). An initial strain rate of 1 mm / min was used up to a force of 0.1 N after which the strain rate was increased to 10 mm / min. Measurements were performed in triplicate.

[0266] In vitro micro-CT Imaging

[0267] Micro-CT images were acquired with preclinical X-CUBE micro-CT system (MOLECUBES; Ghent, Belgium), in “General-purpose mode” as described in Muller, F. et al. Medical Physics 2022, 49 (5), 3121-3133. Further hardware and software details are also described in the same publication. This mode encompassed a continuous scan, tube voltage 50 kV, tube current 75 pA, 480 projections (each projection has 1 averaging); acquisition per projection 125 ms; total acquisition time 90 s; dose per one bed position 18 mGy. The X-ray source (X-ray tube) was a fixed tungsten anode with a 0.8 mm aluminium filter and a non-variable focal spot size of 33 pm. The flat-panel detector was based on CMOS technology (14-bits) using a Csl scintillator. It consists of 1536 x 864 pixels for an active area of 1 15 mm x 65 mm with a pixel size of 75 pm. The crosslinked film samples (gelatin-based samples, 1 g) have been crushed and filled inside an Eppendorf tube (1 .5 mL size), or the crosslinking solution was directly transferred to an Eppendorf tube (1 .5 mL size), irradiated by UV through an open top to crosslink, and visualized.

[0268] Cell seeding & cell viability

[0269] The in vitro cell seeding experiments were performed to investigate the biocompatibility of the polymer materials, and whether these materials can support cell growth, according to ISO- 10993. Selected photo-crosslinked and washed polymer materials were sterilized using a 12 h incubation in 70 v / v% ethanol solution followed by 2 h of UV-C irradiation (100 to 280 nm, 15 mW / cm2). Then, these sterilized samples were swollen again at 37 °C in sterile phosphate buffered saline (PBS). Subsequently, adipose tissue-derived stem cells (ASCs) were cultured in Dulbecco’s Modified Eagle Medium (DMEM), supplemented with 10 v / v% fetal bovine serum (FBS) and 1 w / v% penicillin / streptomycin under standard incubator conditions (37 °C, 5% CO2) and with a culture medium change occurring twice a week. ASCs at passage 4 were then seeded at a density of 20,000 ASCs / cm2on the sterilized polymer material samples.

[0270] Next, the biocompatibility of these materials was assessed (by observing the cell morphology and through a live / dead staining) at three consecutive time points (days 1 , 3 and 7). After discarding the culture medium from the cell-seeded constructs, 2 w / v% calcein-acetoxymethyl (Ca-AM) I propidium iodide (PI) staining solution in PBS was added. After incubation of the samples in the dark for 10 minutes, the ASCs were visualized through a green fluorescent protein (GFP) and a Texas Red (TxRed) filter of a fluorescence microscope (Olympus 1X81 with Xcellence Pro software). The percentage viability was quantified using FIJI software.

[0271] In both cases, as a control, the bottom of the well-plate is used. in vitro degradation

[0272] In vitro degradation analysis was performed to investigate the biodegradability of the polymer materials. As a model enzyme, collagenase IV from Clostridium histolyticum metalloproteinase- 2 (MMP-2; 0.5 to 5.0 FALGPA units / mg solid, >125 CDU / mg solid) was used, which mimics the in vivo degradation. Briefly, cylindrical samples (0.8 cm radius, 1 .0 cm height) of selected polymer materials were prepared and incubated in Tris-HCI buffer (0.5 mL, 0.1 M, pH 7.4) in the presence of 0.005% (w / v) NaNs and 5 mM CaCIz at 37 °C for 30 min. Afterwards, 0.5 mL of collagenase solution (200 lU / mL) in Tris-HCI buffer was. The degradation at defined time intervals was stopped by cooling the reaction mixtures with ice and adding EDTA solution (0.1 mL, 0.25 M). Next, the crosslinked polymer materials were washed with ultrapure water and freeze-dried. The residual gel fraction (F) was determined according to the following Equation (1 ): where rrid.t is the dry mass of the sample after degradation at time point t and md,o is the initial mass of the dried sample at t = 0. F was determined in 3 independent measurements and reported as mean ± standard deviation (SD).

[0273] Two-photon polymerization (2PP) 3D-printinci

[0274] Two-photon polymerization was performed using a NanoOne Bio high-resolution 3D printer from UpNano GmbH equipped with a 10x air immersion objective (NA 0.4, WD 3.10 mm, Zeiss). The device was equipped with a femtosecond NIR laser (780 nm center wavelength) with 90 fs pulse length, 80 MHz repetition rate and maximal average laser power of 1000 mW.

[0275] Precursor solutions of 10 w / v% of the precursor material containing different concentrations (0.1 , 0.5, or 1 .0 mM) of the photo-initiator (sodium 3,3'-((((1 E,1 'E)-(2-oxocyclopentane-1 ,3-diylidene) bis (methanylylidene))bis(4,1 -phenylene))bis(methylazanediyl)) dipropanoate; P2CK30,31 ) were utilized. Approximately 50 pL of each solution was placed onto a glass plate which was silanized with 3-(trimethoxysilyl)propyl methacrylate to provide sufficient attachment. The optimal 2PP threshold laser power was determined by printing 100 x 100 x 100 pm3cubes at a constant scanning speed of 100 mm s-1and for varying laser powers (10 to 200 mW). The CAD design was sliced with a layer spacing of 5 pm and hatched with 0.5 pm line spacing. In every layer, the focal spot was scanned in both the x and y directions for all samples.

[0276] After 2PP printing, 2 mL of PBS was added to each sample, and the samples were stored in the incubator at 37 °C for at least 24 h to wash away all non-cross-linked material and induce equilibrium swelling of the microstructures. The samples were analyzed with a confocal microscope (LSM T-PMT, Zeiss). Microscope images were analyzed using Imaged software.

[0277] Example 1

[0278] Gelatin-methacrylamide (Gel-MA) with a degree of substitution (DS) of 66% and 96 % (referred to as gel-MA-70 and gel-MA-100) was prepared according to a protocol described by Van Den Bulcke et al. (Biomacromolecules, vol. 1 , no. 1 , pp. 31-38, 2000). The reaction is represented by the following scheme:

[0279]

[0280] Briefly, 100 g of gelatin type B was dissolved in 1 L phosphate buffer (pH 7.8) at 40 °C. After complete dissolution, 2.5 equivalents of methacrylic anhydride relative to the primary amines present in the (hydroxy-)lysine and ornithine side chains, were added and the mixture was stirred vigorously to obtain a DS of 66, and 96%, respectively. After 1 h, the mixture was diluted using 1 L of double distilled water (DDW) and introduced in dialysis membranes (Spectra / Por MWCO 12 - 14 kDa) during 24 h against DDW. After dialysis, the pH of the mixture was adjusted to 7.4 to mimic the natural ECM more closely using NaOH. Gel-MA-100 (DS 96 %) was isolated using lyophilization (Christ freeze-dryer Alpha 2-4 LSC).

[0281] Example 2

[0282] Gelatin-methacrylamide-aminoethylmethacrylate (Gel-MA-AEMA) with a degree of substitution of 25 % was prepared according to a protocol described by Van Hoorick et al. (Biomacromolecules, vol. 18, no. 10, pp. 3260-3272, 2017). The reaction is represented by the following scheme:

[0283] Briefly, first, the COOH moieties of gel-MA-100 were converted into NHS esters by reaction with 3-{[(ethylimino)methylidene]amino}-N,N-dimethylpropan-1 -amine (EDC) and 1 - hydroxypyrrolidine-2, 5-dione (NHS) (0.50 and 0.75 equivalents respectively to mol. amount of carboxylic acid moieties, respectively) in dry DMSO (10 w / v % solution of gel-MA-100) under inert atmosphere. Afterwards, the activated NHS esters were mixed with 2-aminoethyl methacrylate hydrochloride (AEMA-HCI, 0.5 equivalents respectively to mol. amount of COOH moieties for obtaining a degree of substitution of 25 %) in the presence of 4-tert-butylbenzene- 1 ,2-diol (inhibitor of radicals to prevent polymerization) in dry DMSO. The resulting material was purified by precipitation in acetone, redissolved in DDW and introduced in dialysis membranes (Spectra / Por MWCO 12 - 14 kDa) during 24 h against DDW. After dialysis, the pH of the mixture was adjusted to 7.4 to mimic natural ECM more closely using NaOH and gel-MA-AEMA was isolated using lyophilization (Christ freeze-dryer Alpha 2-4 LSC).

[0284] Example 3a

[0285] Telechelic alkene-functionalized polycaprolactones (2300 and 4000 g / mol, referred to as E-PCL 2300 and 4000, respectively) were prepared following a protocol described in Thijssen et al. (Advanced Materials, vol. 35, no. 19, pp. 2210136, 2023). The reaction is represented by the following scheme:

[0286] First, the poly-e-caprolactone diol was synthesized by the polymerization of e-caprolactone (1 equiv.), in the presence of Sn(Oct)2 (0.5 wt.% with respect to added e-caprolactone), ethylene glycol (1 :17, and 1 :34 stoichiometric ratio initiator to monomer for PCL 2300 and 4000, respectively), and anhydrous toluene (4 M concentration of e-caprolactone), under argon atmosphere. Prior to the polymerization, the air was removed by three freeze-pump-thaw cycles after which the polymerization was stirred for 24 h at 100 °C (the full conversion was monitored with1H NMR). The obtained PCL-diols were further modified to alkene-functionalized PCLs by reaction with 1 .2 equiv. (respectively to the hydroxyl functionalities) of allyl isocyanate for 1 h at 60 °C (the full conversion was monitored with1H NMR spectroscopy). The products were obtained by precipitation into diethyl ether as white solids.

[0287] Example 3b

[0288] Telechelic acrylate-end capped polyethylene glycol) (PEG, Mw 2000 g / mol, referred to as PEG- AUP) was prepared following a protocol described in Houben et al. (Materials Today Chemistry, vol. 4, pp. 84, 89). The reaction is represented by the following scheme:

[0289] First, 100 grams of polyethylene glycol) (PEG, Mw 2000 g / mol) was weighed and melted at 90°C in a 500 ml 3-neck flask with a mechanical stirrer providing stirring of the viscous liquid throughout the reaction. Once in a liquid state, 500 ppm BHT and H3PO4were added. Hereafter, the polymer melt was dried by applying a vacuum and an argon flow directly into the melt. This process was left for 3 hours. The vacuum was removed, and the reaction was placed under an inert atmosphere. The temperature was lowered to 70 °C, and 2 equivalents (compared to PEG) of isophorone diisocyanate (I PDI) were added to the reaction mixture. The reaction temperature was further reduced to 65 °C before the addition of 300 ppm Valikat Bl 2010 as a reaction catalyst. After the addition of the catalyst, the temperature was increased to 75 °C. After 2 hours, the reaction temperature was decreased to 65 °C, and 500 ppm of TPZ and TPP were added. Next, the end-capping agent (ethoxylated and propoxylated pentaerytritol triacrylate, EPPETA, 2 equivalents compared to PEG) was added dropwise, followed by 300 ppm Valikat Bl 2010. After the addition of both compounds, the temperature was increased to 80°C, and the reaction completion was monitored by FTIR spectroscopy (following the decrease of isocyanate peaks in the spectrum). The product was purified by double precipitation in 50 / 50 v / v% n- pentane / diethyl ether (10x excess, volume to weight). The product was dried under vacuum at 60 °C.

[0290] Example 4a

[0291] To prepare a 5-acrylamido-2,4,6-triiodoisophthalic acid (ATIPA) monomer, 5-amino-2,4,6- triiodoisophthalic acid (4.80 g, 8.60 mmol) was first dissolved in dry acetonitrile (30 mL) in a round bottom flask. Afterwards, the reflux condenser was attached and flushed the apparatus with inert gas (3 cycles of vacuum-nitrogen cycles). Subsequently, the flask was cooled with ice bath and the concentrated sulfuric acid (98%, 10 pL, 0.10 mmol) and acrylic anhydride (3.1 mL, 3.3 g, 26.2 mmol) were added dropwise to the mixture. Afterwards, the reaction was slowly heated to 80 °C and left to stir for 65 hours. Then, the reaction mixture was cooled to room temperature, reaction mixture was filtered and washed with cold acetonitrile (= 3x10 mL, three times). The product was isolated as dry white powder (= 98% yield). The reaction is represented by the following scheme:

[0292] Example 4b

[0293] N-(4-iodophenyl)-acrylamide (IPA) monomer was prepared following a protocol described in Fortin et al. (European Journal of Medicinal Chemistry, vol. 45, no. 7, pp. 2928, 2937). The reaction is represented by the following scheme:

[0294] To prepare a N-(4-iodophenyl)-acrylamide (IPA) monomer, 4-iodoaniline (5.0 g, 22.8 mmol) was first dissolved in dry acetonitrile (MeCN, 120 mL) together with anhydrous NazCOs (4.8 g, 45.7 mmol) in a round bottom flask. Subsequently, the flask was cooled in an ice bath before acryloyl chloride (2.8 mL, 3.1 g, 34.2 mmol in 5.0 mL of dry DCM) was added dropwise to the mixture. Afterwards, the reaction was slowly heated to room temperature and left to stir for 16 hours. After the reaction, the mixture was filtered and the solvent was evaporated. The product was recrystallized from dichloromethane / hexane (1 :10) as a white solid (Yield, 56 %).

[0295] Example 5a

[0296] Gelatin-based polymer materials were prepared by a combination of one of the gelatin-based materials prepared in example 1 (gel-MA-100), or example 2 (gel-MA-AEMA), with the ATIPA monomer prepared in example 4a. The reagents were dissolved in various ratios in dry DMSO or milliQ at 50 °C. The concentration of gelatin-based material + ATIPA monomer was around 10 wt. % for all prepared solutions (exact masses and molar amounts are summarized in Table 1 ). These solutions were prepared in dark glass vials and protected from light. Subsequently, Li- TPO-L (8 mg / mL solution in ultrapure water; 2 mol.% relative to the number of MA and AEMA moieties in the reaction mixture) was added to the mixture and flushed with argon for 2 min. Afterwards, the solution was injected between two parallel glass plates (moulds) separated by a 1 mm thick silicone spacer and covered with a thin poly(tetrafluoroethylene) sheet. Next, these moulds were irradiated from both sides with UV-A light (365 nm, 100 mW / cm2) for 1 h.

[0297] After the photopolymerization, the polymer material films were washed (ethanol / water 70:30 (v / v) mixture) for 24 h (solvent was replaced with fresh solvent at least 5 times during 24 h) and subsequently in ultrapure water or PBS (140 mM, pH = 7.4) for another 24 h (solvent was replaced with fresh solvent at least 5 times during 24 h).

[0298] Table 1 provides an overview of polymer materials prepared according to example 5a; mgeiis the mass of the corresponding starting material; ITIATIPA is the mass of ATI PA in the reaction mixtures; and OATIPA / HMA+AEMA is the ratio of molar amounts of ATIPA and MA+AEMA moieties in the reaction mixtures.

[0299] Table 1. Specification of reaction mixtures

[0300] Wgel niATIPA OATIPA

[0301] Code Starting material

[0302] (mg) (mg) / / ?MA+AEMA

[0303] M2 Gel-MA-100 100.0 45.7 2.0

[0304] M4 Gel-MA-100 100.0 91 .4 4.0

[0305] M8 Gel-MA-100 100.0 182.8 8.0

[0306] A2 Gel-AEMA 57.6 45.7 2.0

[0307] A4 Gel-AEMA 57.6 91 .4 4.0

[0308] A8 Gel-AEMA 57.6 182.8 8.0

[0309] Example 5b

[0310] Gelatin-based polymer materials were prepared by a combination of either one of the gelatinbased materials prepared in example 1 , being gel-MA-70 and gel-MA-100, or example 2 (gel- MA-AEMA) with the ATIPA monomer prepared in example 4a. The reagents were dissolved in a ratio nATiPA / nwiA in milliQ (exact masses and molar amounts are summarized in Table 1 ) and the ATIPA monomer was neutralized with minute amounts of 2.5M NaOH, in order to avoid possible negative effect of carboxylates during the in vivo study. These solutions were prepared in dark glass vials and protected from light. Subsequently, Li-TPO-L (8 mg / mL solution in ultrapure water; 2 mol.% relative to the number of MA and AEMA moieties in the reaction mixture) was added to the mixture and flushed with argon for 2 min. Afterwards, the solution was either injected between two parallel glass plates (moulds) separated by a 1 mm thick silicone spacer and covered with a thin poly(tetrafluoroethylene) sheet or soaked into a PLA negative scaffold (indirect 3D printing). Next, these moulds were irradiated from both sides with UV-A light (365 nm, 100 mW / cm2) for 1 h. The PLA negative scaffold was then dissolved in chloroform (42 h), and the obtained indirectly printed porous hydrogels were washed with ethanol (70%) for 24 h and with milliQ for 24 h. The resulting materials are referred to as G70I, G1001, and GAEMAI, respectively.

[0311] Table 2 provides an overview of polymer materials prepared according to example 5b; mgeiis the mass of the corresponding starting material; ITIATIPA is the mass of ATI PA in the reaction mixtures; and UATIPA / HMA+AEMA is the ratio of molar amounts of ATIPA and MA+AEMA moieties in the reaction mixtures.

[0312] Table 2. Specification of reaction mixtures

[0313] Starting mgeiHJATIPA OATIPA

[0314] Code material (mg) (mg) / / ?MA+AEMA

[0315] G70I Gel-MA-70 100 31 .0 2.0

[0316] G100I Gel-MA-100 100 46.0 2.0

[0317] GAEMAI Gel-MA-AEMA 100 80.0 2.0

[0318] Comparative example A

[0319] Polymer materials CA3, CA1 , and CA2 were prepared according to example 5a by using either one of the gelatin-based materials prepared in example 1 , being (gel-MA-70) and (gel-MA-100), or example 2 (gel-MA-AEMA), respectively, without addition of the ATIPA monomer.

[0320] In vitro degradation analysis was performed to investigate the effect of MA and ATIPA content on the biodegradability of selected polymer materials with ATIPA (M2, M4, M8) and without ATIPA (CA1 ), as described above. Figure 1 shows that crosslinked polymer materials without ATIPA (CA1 based on gel-MA-100) and selected gel-MA-100-based crosslinked polymer materials (M2, M4, M8) degraded quickly with zero-order kinetics. In contrast to gel-MA based crosslinked polymer materials crosslinked with HEMA, as reported by Dragusin et al., it was surprisingly found that gel-MA based crosslinked polymer materials crosslinked with ATIPA may be fully biodegradable. It was moreover found that the ATIPA content allows to tune the biodegradability.

[0321] Example 6

[0322] Polycaprolactone based crosslinked polymer materials were prepared by dissolving the PCL starting materials prepared in example 3 with the ATIPA monomer prepared in example 4a in DMF (0.45 mL to 1 g of PCL) at 50 °C in a dark glass vial to protect the solution from light. The solution was also sonicated to ensure a proper mixing of all components and bubbled with argon. When all the components were properly dissolved and mixed, the TPO-L initiator (10 mg in each crosslinking solution), and the pentaerythritol tetrakis(3-mercaptopropionate) (1 eq. respectively to the double bonds in the corresponding PCL starting material (E-PCL)) were added to the mixture (exact masses and molar amounts are summarized in Table 2). The resulting solutions were bubbled with argon once more (for 1 min) and injected between two parallel glass plates covered with a thin poly(tetrafluoroethylene) sheet and separated by a 0.5 thick silicone spacer. Next, the moulds were irradiated from both sides with UV-A light (365 nm, 100 mW / cm2) for 30 min.

[0323] After the photopolymerization, the obtained films were washed with DMF overnight dried in desiccator under vacuum for another 3 d to obtain white yellowish films, herein referred to as P1 -P3 (materials containing E-PCL 2300), and P4-P6 (materials containing E-PCL 4000).

[0324] Table 3 provides an overview of polymer materials prepared according to example 6; mpci is the mass of the corresponding starting material; ITIATIPA is the mass of ATIPA in the reaction mixtures; and HATIPA / nene is the ratio of molar amounts of ATIPA and double bonds from allyl-end group of selected PCLs.

[0325] Table 3. Specification of reaction mixtures mpcL mATIPA rtATIPA

[0326] Code Starting material

[0327] (9) (mg) / nene

[0328] P1 E-PCL 2300 1 .0 40.0 0.066

[0329] P2 E-PCL 2300 1 .0 80.0 0.131

[0330] P3 E-PCL 2300 1 .0 160.0 0.262

[0331] P4 E-PCL 4000 1 .0 40.0 0.131

[0332] P5 E-PCL 4000 1 .0 80.0 0.262

[0333] P6 E-PCL 4000 1 .0 160.0 0.524

[0334] Comparative example B

[0335] Polymer materials CB1 and CB2 were prepared according to example 6 by using the PCL starting materials prepared in example 3, E-PCL 2300 and E-PCL 4000 respectively, without addition of the ATIPA monomer.

[0336] Example 7

[0337] Polyethyleneglycol based crosslinked polymer materials were prepared by dissolving PEG- AUPs starting materials prepared in example 3b with the ATIPA monomer prepared in example 4a in milliQ (0.45 mL to 1 g of PEG-AUP) at 50 °C in a dark glass vial to protect the solution from light. The solubility of AATIPA in milliQ was improved by using minute amounts of NaOH. When all the components were properly dissolved and mixed, the Li-TPO-L initiator 1 wt% solution (2 mol% respectively to the double bonds in PEG-AUP) was added to the crosslinking mixture. The resulting solutions were bubbled with argon once more (for 1 min) and injected between two parallel glass plates covered with a thin poly(tetrafluoroethylene) sheet and separated by a 0.5 thick silicone spacer. Next, the moulds were irradiated from both sides with UV-A light (365 nm, 100 mW / cm2) for 30 min.

[0338] After the photopolymerization, the obtained films were washed with milliQ overnight, herein referred to as AUP1 -AUP3.

[0339] Table 4 provides an overview of polymer materials prepared according to example 6; ITIPEGAUP is the mass of the corresponding starting material; ITIATIPA is the mass of ATI PA in the reaction mixtures; and UATIPA / nene is the ratio of molar amounts of ATIPA and double bonds from allyl- end group of PEG-AUP.

[0340] Table 4. Specification of reaction mixtures mpEG- / TJATIPA rtATIPA

[0341] Code Starting material

[0342] AUP (9) (mg) / rtene

[0343] AUP1 PEG-AUP 1 .0 40.0 0.036

[0344] AUP2 PEG-AUP 1 .0 80.0 0.072

[0345] AUP3 PEG-AUP 1 .0 160.0 0.145

[0346] Comparative example C

[0347] Polymer material CC1 was prepared according to example 7 by using the PEG-AUP starting materials prepared in example 3b, but without addition of the ATIPA monomer.

[0348] Example 8

[0349] Polycaprolactone based crosslinked polymer materials with I PA monomer were prepared by dissolving the PCL starting material (E-PCL 2300) prepared in example 3a with the IPA monomer prepared in example 4b in DMF (0.45 mL to 1 g of PCL) at 50 °C in a dark glass vial to protect the solution from light. The solution was also sonicated to ensure a proper mixing of all components and bubbled with argon. When all the components were properly dissolved and mixed, the TPO-L initiator (10 mg in each crosslinking solution), and the pentaerythritol tetrakis(3-mercaptopropionate) (1 eq. respectively to the double bonds in the corresponding PCL starting material (E-PCL)) were added to the mixture (exact masses and molar amounts are summarized in Table 2). The resulting solutions were bubbled with argon once more (for 1 min) and injected between two parallel glass plates covered with a thin poly(tetrafluoroethylene) sheet and separated by a 0.5 thick silicone spacer. Next, the molds were irradiated from both sides with UV-A light (365 nm, 100 mW / cm2) for 30 min.

[0350] After the photopolymerization, the obtained films were washed with DMF overnight dried in a desiccator under vacuum for another 3 d to obtain white yellowish films, herein referred to as IPA1 and IPA2. Table 5 provides an overview of polymer materials prepared according to example 8; mpci is the mass of the E-PCL 2300; miPA is the mass of IPA in the reaction mixtures; and UIPA / nene is the ratio of molar amounts of IPA and double bonds from allyl-end groups of selected PCL.

[0351] Table 5. Specification of reaction mixtures mpcL HJIPA

[0352] Code Starting material niPA / nene

[0353] (g) (mg)

[0354] IPA1 E-PCL 2300 1 .0 40.0 0.148

[0355] IPA2 E-PCL 2300 1 .0 80.0 0.294

[0356] Table 6 shows the physico-chemical characteristics of the gelatin-based, PCL-based, and PEG- based crosslinked materials. G’ is the storage modulus; E’ is the Young’s modulus; Iswoiien (in aqueous solvents, note that PCL-based materials do not swell in aqueous solvents) is the iodine content in the crosslinked polymer material by weight; and tgeiis the gelation time (time at which G’ of the reaction mixture exceeds its G”).

[0357] Table 6. Physico-chemical characteristics

[0358] G’ (kPa) for hydrogels;

[0359] Iswoiien tgel

[0360] Code E’ (MPa) for wt. % (s)

[0361] PCL-based materials

[0362] CA1 7.9 ± 1 .7 0.00 2.33

[0363] M2 13.1 ± 1 .7 0.64 0.09

[0364] M4 14.1 ± 0.8 1 .32 0.03

[0365] M8 18.5 ± 1 .5 1 .63 0.06

[0366] CA2 3.7 ± 0.6 0.00 4.81

[0367] A2 14.8 ± 1 .6 1 .36 0.04

[0368] A4 17.1 ± 0.8 1 .90 0.04

[0369] A8 21 .2 ± 2.3 2.55 0.02

[0370] CA3 5.06 ± 0.3 0.00 2.60

[0371] G70I 6.12 ± 0.2 0.22 1 .18

[0372] G100I 6.57 ± 0.3 0.52 see M2

[0373] GAEMA 6.57 ± 0.3 1 .28 see A2

[0374] CB1 52.8 ± 7.79 0.00 < 1

[0375] P1 - 2.50 < 1 P2 48.2 ± 13.4 3.16 < 1

[0376] P3 64.0 ± 7.65 6.52 < 1

[0377] IPA1 - 3.31 < 1

[0378] IPA2 44.3 ± 7.85 7.81 < 1

[0379] CB2 158 ± 21 .0 0.00 < 1

[0380] P4 - 1 .77 < 1

[0381] P5 130 ± 17.8 3.56 < 1

[0382] P6 143 ± 14.1 7.07 < 1

[0383] CC1 72.8 ± 7.60 0.00 < 1

[0384] AUP1 78.0 ± 12.9 0.81 < 1

[0385] AUP2 66.7 ± 10.3 1 .81 < 1

[0386] AUP3 67.9 ± 13.0 2.30 < 1

[0387] It can be seen from Table 6 that increasing the amount of ATIPA or IPA in the reaction mixture increased the ATIPA or IPA content in the final materials. Therefore, the content of ATIPA or IPA (and, therefore, content of iodine) in the final material can be tuned by the nATiPA or iPA in the reaction mixture. Additionally, it seems that increasing the ATIPA content either improves (chaingrowth polymerization in case of gel-MA / gel-MA-AEMA crosslinking) or does not affect the crosslinking kinetics (combined step-growth and chain growth polymerization in case of PCL crosslinking). The change in the crosslinking kinetics is characterized with the evaluated gelation time, tgei, in Table 6.

[0388] Additionally, the ATIPA or IPA content seems to increase (crosslinked gelatin) or does not affect (crosslinked PCL) the mechanical properties of the final crosslinked materials. The mechanical properties are described by storage moduli (G’, Table 6) for gelatin-based material or Young’s moduli (E’, Table 6) for PCL-based materials.

[0389] Another important mechanical property of the PCL-based crosslinked materials is the exceptionally high elongation at break of over 700 %, which can be seen in Figure 2. The elongation at break is depicted for selected materials P5 and P6 with the highest ATIPA content and compared to the crosslinked E-PCL 4000 without ATIPA monomer (CB2). The results show that at a certain ATIPA concentration (P6, the highest measured nATiPA / nene), the elongation at break decreases.

[0390] Furthermore, the detectability of the cross-linked biomaterials was assessed using pCT in vitro. It can be seen from Figures 3a, 3b, 3c and 3d that all materials could be safely visualized. The gelatin-based crosslinked materials with ATIPA (M2, M4, M8, A2, A4, A8) are compared to crosslinked gelatins without ATIPA monomer (CA1 based on gel-MA-100, and CA2 based on gel-MA-AEMA) in Figure 3a, while PCL-based crosslinked materials with ATIPA or IPA (P1 -P6) are compared to crosslinked PCL without ATIPA or IPA (CB1 based on E-PCL 2300, and CB2 based on E-PCL 4000) in Figures 3b and 3c, respectively, and PEG-based materials (AUP1 - AUP3) are compared to crosslinked PEG-AUP without ATIPA (CC1 ). The radiodensity of the materials in Hounsfield Units (HU) is also depicted in Figures 3a, 3b, 3c and 3d.

[0391] Figure 4 shows the cell seeding study exploiting adipose tissue-derived stem cells seeded on cell-interactive gelatin-based crosslinked polymer material with ATIPA. The results show that even after ATIPA addition the crosslinked gelatin can support cell proliferation, and thus the selected ATIPA content does not alter the cell-interactive properties of gelatin.

[0392] Figure 5 shows the results of the cell viability analysis of selected crosslinked polymer materials with ATIPA (M4, A4) compared to a control. In contrast to gel-MA based polymer materials crosslinked with HEMA, as reported by Dragusin et al., it was surprisingly found that the cell viability of gel-MA based polymer materials crosslinked with ATIPA did not decrease relative to the control.

[0393] The photosensitivity of iodine-based compounds is often an issue. It was however found that the crosslinked polymer materials according to the invention can be easily obtained via photopolymerization, such as in 3D printing, without degradation of the iodine-containing groups or moieties. This ensures the attenuation or detectability of the crosslinked polymer materials for X-ray irradiation.

[0394] Example 9

[0395] 3D-printed hydrogel implants were prepared by 2-photon-polymerization of the precursor solution M4 according to example 5a, containing different concentrations (0.1 , 0.5, or 1 .0 mM) of the photo-initiator, as described above. This method enables printing with a resolution down to 100 nm.

[0396] Figure 6 shows 3D printed phantoms prepared according to example 9. It is shown that a concentration of 10 w / v % of the precursor solution, in combination with a low concentration of initiator (I = 1 .0 mM), is sufficient to obtain a CAD-CAM mimicry = 70%). In contrast, Gel-MA- 100 without ATIPA has a long tgei and poor CAD / CAM mimicry with 2PP 3D-printing and can be printed only in concentrated (20 w / v %) solutions as has been described by Van Hoorick, J. et al. Biomacromolecules 2017, 18 (10), 3260-3272. Therefore, adding ATIPA improves the suitability of these inks for 2PP 3D-printing.

[0397] Figure 7 shows the degradation of either porous 3D moulded porous hydrogels (referred to as scaffolds) or grinded injectable gels (referred to as injectables) made from hydrogel films based on example 5b. The examples show that full degradation is achievable with gel-MA based materials within 3 months’ time, which is in agreement with the reported time of degradation for materials based on CA1 and CA3. These results moreover show that even when the cocrosslinker (ATI PA) is added, the degradation does not need to be affected. It is also shown that the degradation can be tuned by selection of the gelatin derivative.

[0398] Figure 8 shows the implantation of P2 and CB1 material, moulded by indirect 3D-printing into porous scaffolds. The CAD design, PLA negative scaffold, and SEM micrograph (Figure 8B), and the in vivo detectability (Figure 8C) of the implanted scaffold can be observed. Only the scaffold containing ATIPA (P2) can be detected in vivo with radiology. The volume of the P2 scaffold was measured with radiology at day 1 , 8, and 173 (Figure 8A). The decrease in volume shows accelerated degradation compared to CB1 , which non-decreasing volume was estimated with ultrasound imaging. It is therefore an advantage of the crosslinked polymer materials as defined herein, that degradation may be drastically shortened compared to CB1 , or commonly used thermoplastic PCL. The degradation of PCL may for instance be drastically shortened from from full degradation between 2-4 years (thermoplastic PCL) to approximately 6-10 months, which is crucial for medical applications.

Claims

CLAIMS1 . A crosslinked polymer material detectable by radiological imaging, comprising: a biocompatible polymeric backbone comprising primary groups; radiodense imaging groups comprising one or more iodine atoms; and linker groups providing a linker between the primary groups and the imaging groups; wherein at least part of the primary groups are covalently bonded to the linker groups; wherein the imaging groups are covalently bonded to each other and / or to one or more of the linker groups; wherein crosslinks connecting two or more of the linker groups comprise one or more imaging groups; and wherein the imaging groups are represented by formula (IV)whereinAr is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;R3 is selected from -H, and -CH3;Xi and X2 are each independently selected from a direct bond, -Ci ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;Rb is selected from -H, and -CH3; andY is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.

2. The crosslinked polymer material as claimed in claim 1 , wherein the biocompatible polymer backbone is a biopolymer selected from polypeptides, proteins, polysaccharides, and polynucleic acids; in particular a biopolymer selected from gelatins, collagens, alginates, dextrans, agarose, glycosaminoglycans, chitosans and carrageenans.

3. The crosslinked polymer material as claimed in claim 1 , wherein the biocompatible polymer backbone is a polymer selected from a polyester, a polyamide, a polyether, and any combination thereof; in particular a polylactone.

4. The crosslinked polymer material as claimed in any one of claims 1 to 3, wherein the primary groups comprise amine groups and / or hydroxyl groups and / or carboxylic acid groups.

5. The crosslinked polymer material as claimed in any one of claims 1 to 4, wherein the linker groups comprise propanoic and / or 2-methylpropanoic moieties.

6. The crosslinked polymer material as claimed in any one of claims 1 to 5, wherein the imaging groups are represented by formula (IVa)whereinAr is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents; andR3 is selected from -H, and -CH3.

7. The crosslinked polymer material as claimed in any one of claims 1 to 5, wherein the imaging groups are represented by formula (IVb)whereinAr is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of Ri is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;R3 is selected from -H, and -CH3; andRb is selected from -H, and -CH3.

8. The crosslinked polymer material as claimed in any one of claims 1 to 5, wherein the imaging groups are represented by formula (V)wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;Ri and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;R3 is selected from -H, and -CH3;Xi and X2 are each independently selected from a direct bond, -Ci ealkylene-, -NRt>-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;Rb is selected from -H, and -CH3; andY is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.

9. The crosslinked polymer material as claimed in any one of claims 1 to 5, wherein the imaging groups are represented by formula (Vb)wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;R1 and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;R3 is selected from -H, and -CH3; andRb is selected from -H, and -CH3.

10. A method to prepare the crosslinked polymer material as claimed in any one of claims 1 to 9, the method comprising the steps of: a) providing a biocompatible polymeric backbone comprising primary groups; b) reacting at least part of the primary groups with a pre-linker group introducing agent to covalently bind pre-linker groups comprising at least one C-C double bond with the primary groups; and c) crosslinking at least part of the pre-linker groups with monomers comprising at least one C-C double bond by free radical chain-growth polymerization and / or step-growth polymerization, wherein at least part of the monomers are radiodense imaging monomers comprising one or more iodine atoms; wherein the imaging monomers are represented by formula (VII)whereinAr is aryl; n is an integer selected from 1 , 2, 3, 4, and 5; m is an integer selected from 0, 1 , 2, 3, and 4; each instance of R1 is independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa- R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;R3 is selected from -H, and -CH3;Xi and X2 are each independently selected from a direct bond, -Ci ealkylene-, -NRb-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;Rb is selected from -H, and -CH3; andY is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.1 1 . The method as claimed in claim 10, wherein the primary groups comprise amine groups and / or hydroxyl groups and / or carboxylic acid groups.

12. The method as claimed in claim 10 or 1 1 , wherein the pre-linker group introducing agent in step b) is an acrylating agent, a methacrylating agent, or any combination thereof, thereby providing pre-linker groups comprising acrylic moieties, methacrylic moieties, or any combination thereof.

13. The method as claimed in any one of claims 10 to 12, wherein the imaging monomers are represented by formula (VIII)wherein each instance of Z is independently selected from -H, and -I, wherein at least one instance of Z is -I;R1 and Rr are each independently selected from -COOH, -NRa-C(O)-R2, and -C(O)-NRa-R2; each instance of Rais independently selected from -H, and -CH3; each instance of R2 is independently -Ci ealkyl; wherein said -Ci ealkyl optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally and independently substituted with one or more -OH substituents;R3 is selected from -H, and -CH3;Xi and X2 are each independently selected from a direct bond, -Ci ealkylene-, -NRb-, -O-, - C(O)O-, -OC(O)-, -S-, -C(O)NRb-, and -NRbC(O)-; wherein said -Ci ealkylene- optionally comprises one or more heteroatoms selected from N, O and S and / or is optionally andindependently substituted with one or more -OH substituents;Rb is selected from -H, and -CH3; andY is selected from a direct bond, -Ci ealkylene-, and a polyether moiety.

14. The crosslinked polymer material as claimed in any one of claims 1 to 9, or as prepared according to the method as claimed in any one of claims 10 to 13, for use in human and / or veterinary medicine, in particular for use in tissue engineering or biofabrication.

15. A medical device comprising the crosslinked polymer material as claimed in any one of claims 1 to 9, or as prepared according to the method as claimed in any one of claims 10 to 13.

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