A system for producing a degradable hydrogel

Abstract

The present invention relates to a system for producing a degradable hydrogel, a method for producing a degradable hydrogel, and a kit for producing a degradable hydrogel.

Description

DESCRIPTION A system for producing a degradable hydrogel The present invention relates to a system for producing a degradable hydrogel, a method for producing a degradable hydrogel and a kit for producing a degradable hydrogel. Prostate cancer is the most common cancer in men. The goal of radiation therapy for prostate cancer is to destroy the malignant cells of the cancer. Healthy cells are inevitably damaged in the process. Careful planning of radiation therapy can minimize damage. However, because the wall of the rectum is only a few millimeters from the prostate, inflammatory symptoms (proctitis) often occur (approximately 36%). These can be accompanied by diarrhea, painful hemorrhoids, or bleeding (approximately 12%), and less frequently (1-3%) by chronic bleeding, adhesions, and necrosis. Minimizing the described side effects and simultaneously reducing the number of radiation treatments is achieved through the use of a temporary "spacer." This is placed between the prostate and rectum to create a greater distance between the two organs. This minimizes the radiation dose to the adjacent rectum and drastically reduces potential damage. This also makes it possible to deliver a higher radiation dose. to significantly reduce the number of treatments and thereby improve patients' quality of life. The spacer is broken down and excreted by the body within several months. This eliminates the need for further surgery to remove the spacer. Hydrogels are macromolecular and entropic-elastic networks that can absorb large amounts of water, depending on their cross-linking density and chemical composition. Hydrogels are used for clinical applications such as contact lenses, bandages, and drug delivery systems. In special cases, hydrogels can be injected as liquids and cross-link in situ, adapting their shape to the local structures at the injection site. For example, in vivo cross-linked hydrogels are already being used on a large scale as spacers, tissue adhesives, tissue markers, and hemostatic agents. US 2011 / 0142936 describes biodegradable hydrogel implants containing covalently bound radiopaque substances, which are formed by a cross-linking reaction of a first and a second precursor. Patent application EP 0 436 667 A1 describes a composition for producing biodegradable polymers and in particular the use of such polymers for providing injectable, in-situ moldable, solid, biodegradable implants. US 2008 / 0260802 A1 describes biocompatible cross-linked polymers and processes for their preparation and use, wherein the biocompatible cross-linked polymers are prepared from water-soluble precursors with electrophilic and nucleophilic functional groups are formed that can react and crosslink in situ. WO 00 / 33764 relates generally to biocompatible cross-linked polymers and to processes for their preparation and use. EP 2 233 160 A2 relates to surgical treatments using hydrogels, in particular bio-absorbable, covalently cross-linked hydrogels. WO 2013 / 137736 A1 relates to a biocompatible, covalently cross-linked polymer obtained by reacting nucleophilically activated polyoxazoline (N11-POX) with an electrophilically activated cross-linking agent. EP 1 446 453 A1 describes the use of biomaterials that serve as three-dimensional scaffolds or matrices for wound healing and tissue regeneration. US 2012 / 0027775 A1 relates to absorbable PEG-based hydrogels useful for the sustained release of proteins. W02020 / 227107A1 provides methods for reducing the toxicity of advanced ablative cancer therapies to neighboring organs. The methods provide a distance between individual or multiple tumor sites and neighboring healthy organs. A hyaluronic acid spacer based on a viscoelastic medium that is injected in its viscous form in concentrations between 5 and 100 mg / ml. Commercially available spacers are available on the market. Three-component polyethylene glycol-based spacers (SpaceOAR™ and SpaceOAR VUE™ from Boston Scientific (USA)) are available. A hyaluronic acid spacer (Barrigel® from Palette Life Sciences, Inc. (USA)) is also available on the market. In most clinical hydrogel systems, such as the polyethylene glycol-based spacers SpaceOAR™ and SpaceOAR VUE™, crosslinking between amino groups and N-hydroxysuccinimide esters (NHS esters) occurs through a substitution reaction. The primary disadvantage here is that the NHS ester groups are not stable in water for long periods. Therefore, the polymer in the spacer currently available on the market (SpaceOAR™ and SpaceOAR VUE) must be stored as a powder. This means that the system must consist of a total of three components: a polymer powder (containing NHS ester groups), a liquid to dissolve the powder, and another solution containing the crosslinker. This results in more complex preparation for the actual injection, as an additional dissolution process for the polymer powder is required. Another disadvantage is the low stability of the NHS ester groups, which means that the polymer, after dissolving in the dilution solution, only is stable for a limited period of time. This reduces the treatment window to a maximum of 30 minutes before the precursor becomes unusable. After the components are mixed, hydrogel formation occurs within a short period of a few seconds. This very short time window does not allow for adequate management of complications during the injection. Correct positioning of the spacer by the treating physician is also difficult to achieve in such a short time and places high demands on the physician's skills. The hyaluronic acid spacer (Barrigel® from Palette Life Sciences, Inc. (USA)) is based on a viscoelastic medium that is injected in its viscous form at concentrations between 5 and 100 mg / ml. In the case of Barrigel®, hyaluronic acid (HA) is injected at a concentration of 20 mg / mL in phosphate-buffered saline. The HA gel is pre-prepared in a separate synthesis step. This results in a ready-made, viscoelastic medium that can be injected through a large cannula. The gel is insoluble in water and organic solvents. A disadvantage is that the ready-to-use disposable syringe contains only 3 mL of Barrigel. Therefore, several syringes must be injected consecutively to generate sufficient space. This can be associated with a higher risk of unwanted perforation of the surrounding tissue or bleeding. It is therefore the object of the present invention to overcome the disadvantages of the systems described above. One object of the present invention is to provide ready-to-use compositions, such as for medical devices, wherein no additional dissolution of a polymer powder is required. Furthermore, the ready-to-use medicaments should zin products must be stable and can be stored for a long period of time. A further object of the present invention is to enable simple and single injection of the compositions with sufficient volume. At the same time, the spacer should exhibit sufficient gelation rates, degradation rates, and stiffness. The aim is also to enable the system to be easily adapted for other treatments, such as breast cancer, cervical cancer, etc. Furthermore, it could be advantageous to enable visualization of the spacers throughout the entire treatment period. These objects can be achieved by the subject matter of the following claims. Summary of the invention The following statements summarize some aspects of the present invention. A first aspect of the present invention relates to a system for producing a degradable hydrogel, comprising: (a) a first composition, wherein the first composition (a) is aqueous and contains a first precursor (ai) and a buffer system (a-ii), wherein the first precursor (ai) contains functional groups; and (b) a second composition, wherein the second composition (b) is anhydrous and contains a second precursor (bi), wherein the second precursor (bi) is liquid and contains functional groups and at least one hydrolyzable bond; wherein the functional groups of the first precursor (ai) are functional groups of the second precursor (bi) are reactive; and wherein the first precursor contains at least two functional groups and the second precursor contains at least three functional groups, or the first precursor contains at least three functional groups and the second precursor contains at least two functional groups. A second aspect of the present invention relates to the system according to the first aspect, wherein the first precursor (ai) and the second precursor (bi) each contain at least three functional groups. A third aspect of the present invention relates to the system according to the first aspect or second aspect, wherein the reaction of the functional groups of the first precursor (ai) with the functional groups of the second precursor (bi) is a Michael-type reaction. A fourth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the functional groups of the first precursor (ai) contain conjugated unsaturated functional groups selected from the group containing vinylsulfone, (meth)acrylamide, maleimide, quinone, vinylpyridinium, and combinations thereof, preferably vinylsulfone, maleimide, and combinations thereof, and the functional groups of the second precursor (bi) contain nucleophilic groups selected from the group containing amine, thiol, and combinations thereof, preferably thiol; or the functional groups of the first precursor (ai) contain nucleophilic groups selected from the group containing amine, thiol, and combinations thereof, preferably thiol, and the functional groups of the second precursor (bi) contain conjugated unsaturated functional groups selected from the group containing (meth)acrylate, vinylsulfone, vinylsulfonate, (meth)acrylamide, maleimide, quinone, vinylpyridinium and combinations thereof, preferably (meth)acrylate, vinylsulfone, vinylsulfonate, maleimide, and combinations thereof. A fifth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the functional groups of the first precursor (ai) contain conjugated unsaturated functional groups selected from the group containing vinylsulfone, and the functional groups of the second precursor (bi) contain nucleophilic groups selected from the group containing thiol; or the functional groups of the first precursor (ai) contain nucleophilic groups selected from the group containing thiol and the functional groups of the second precursor (bi) contain conjugated unsaturated functional groups selected from the group containing vinylsulfone A sixth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the functional groups of the first precursor (ai) are located at the end sites of the first precursor (ai). A seventh aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the functional groups of the second precursor (bi) are located at the end sites of the second precursor (bi). An eighth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the first precursor (ai) is polyether, polyacrylic acid, poly(ethylene-co-acrylic acid), polyvinyl acetate, po- lyvinyl alcohol, poly(ethylene-co-vinyl alcohol), polyvinyl acetal, polyvinyl ether, poly(oxazoline), polyvinylpyrrolidone, polyvinylamine, polyvinyl methyl ether, poly(meth)acrylate, polyacrylamide, poly-(N-isopropylacrylamide), poly-(N-ethylacrylamide), polyoxymethylene, polycarbonate or a copolymer thereof, preferably polyether, polyacrylamide, poly-(N-isopropylacrylamide), poly-(N-ethylacrylamide), or a copolymer thereof, more preferably polyether. A ninth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the first precursor (ai) contains polyether, preferably polyethylene oxide, polyglycidol, poly(ethylene oxide-co-propylene oxide), more preferably poly(ethylene oxide-co-propylene oxide). A tenth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the first precursor (ai) comprises random poly(ethylene oxide-co-propylene oxide). An eleventh aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the first precursor (ai) contains a linear, branched, dendritic, circular, or star-shaped polymer, preferably a dendritic or star-shaped polymer. A twelfth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the first precursor (ai) contains a star-shaped polymer. A thirteenth aspect of the present invention relates to the system according to the eleventh aspect or the twelfth aspect, wherein the star-shaped polymer has 3 to 12 arms, preferably 3 to 8 arms. A fourteenth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the hydrolyzable bond of the second precursor (bi) comprises ester bonds. A fifteenth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the second precursor (bi) contains polyether, preferably polyethylene oxide, polyglycidol, poly(ethylene oxide-co-propylene oxide), more preferably poly(ethylene oxide-co-propylene oxide). A sixteenth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the second precursor (bi) comprises random poly(ethylene oxide-co-propylene oxide). A seventeenth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the poly(ethylene oxide-co-propylene oxide) contains 50 to 90 wt% ethylene oxide units and 10 to 50 wt% propylene oxide units, more preferably 60 to 90 wt% ethylene oxide units and 10 to 40 wt% propylene oxide units, even more preferably 70 to 90 wt% ethylene oxide units and 10 to 30 wt% propylene oxide units, wherein weight percent is based on the total weight of the ethylene oxide and propylene oxide units of the poly(ethylene oxide-co-propylene oxide). An eighteenth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the second precursor (bi) contains a linear, branched, dendrimary, circular, or star-shaped polymer, preferably a dendrimary or star-shaped polymer. A nineteenth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the second precursor (bi) contains a star-shaped polymer. A twentieth aspect of the present invention relates to the system according to the eighteenth aspect or the nineteenth aspect, wherein the star-shaped polymer has 3 to 12 arms, preferably 3 to 8 arms. A twenty-first aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the first precursor (ai) has a weight-average molecular weight (M w ) from 100 Da to 40 kDa. A twenty-second aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the first precursor (ai) has a weight-average molecular weight (M w ) from 2.5 kDa to 20 kDa. A twenty-third aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the second precursor (bi) has a weight-average molecular weight (M w ) from 100 Da to 40 kDa. A twenty-fourth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the second precursor (bi) has a weight-average molecular weight (M w ) from 2.5 kDa to 20 kDa. A twenty-fifth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the second precursor has a viscosity of up to 4,500 mPa s at room temperature. A twenty-sixth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the second precursor has a viscosity of 5 to 4,000 mPa s at room temperature. A twenty-seventh aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the first composition (a) has a pH of 7 to 10, more preferably 7.4 to 10, even more preferably 7.4 to 9. A twenty-eighth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the system is injectable. A twenty-ninth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the first and / or second composition contains one or more visualization additives. A thirtieth aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the visualization additive comprises lohexol, metrizamide, lopamidol, triiodobenzoate, 2.3.5-triiodobenzoic acid, 2,3,5-triiodobenzoyl chloride, 3,4,5-triiodophenol, erythrosine, rose bengal, 3,5-bis(acetylamino)-2,4,6-triiodobenzoic acid, 3,5-diacetamido-2,4,6-triiodobenzoic acid, meglumine diatrizoate, lopentol, i-opromide, loversol, gadolinium, gadopentetic acid modified zirconium particles, calcium hydroxyapatite, superparamagnetic iron oxide, residues of the foregoing, or a combination thereof. A thirty-first aspect of the present invention relates to the system according to any one of the preceding aspects, wherein the second composition (b) contains a third precursor (b-ii), wherein the third precursor (b-ii) is liquid and contains a functional group and at least one iodine-containing group, wherein the functional group of the third precursor (b-ii) is reactive with the functional groups of the first precursor (ai). A thirty-second aspect of the present invention relates to a method for producing a degradable hydrogel, comprising: providing (i) a system according to the first aspect; and (ii) mixing the first and second compositions. A thirty-third aspect of the present invention relates to the method according to the thirty-second aspect, wherein the (i) system is according to any one of the second to thirty-first aspects. A thirty-fourth aspect of the present invention relates to a kit for producing a degradable hydrogel, comprising: (i) a system according to the first aspect; and (ii) a syringe. A thirty-fifth aspect of the present invention relates to the kit according to the thirty-fourth aspect, wherein the syringe is a double syringe. A thirty-sixth aspect of the present invention relates to the kit according to the thirty-fourth or thirty-fifth aspect, wherein the (i) system is according to any one of the second to thirty-first aspects. Detailed description of the invention The present invention relates to a system for producing a degradable hydrogel. The system contains a first composition (a) and a second composition (b). The first composition (a) is aqueous and contains a first precursor (ai) and a buffer system (a-ii). The first precursor (ai) contains functional groups. The second composition (b) is anhydrous and contains a second precursor (bi). The second precursor (bi) is liquid. The second precursor (bi) contains functional groups and at least one hydrolyzable bond. The functional groups of the first precursor (ai) are reactive with the functional groups of the second precursor (bi). The first precursor (ai) contains at least two functional groups and the second precursor (bi) contains at least three functional groups. Alternatively, the first precursor (ai) contains at least three functional groups and the second precursor (bi) contains at least two functional groups. The term "hydrogel" refers to three-dimensional macromolecular network structures that are capable of absorbing large amounts of water. The term "degradable" refers to a hydrogel that can be degraded in a biological environment either by a biologically assisted mechanism, e.g. an enzyme-catalyzed reaction, or by a chemical mechanism that can take place in a biological medium, e.g.by hydrolysis. Degradation by hydrolysis usually occurs under physiological conditions (at a pH of 7.4 and a temperature of 37 °C). Preferably, the first precursor (ai) and the second precursor (bi) each contain at least three functional groups, wherein the functional groups of the first precursor (ai) are reactive with the functional groups of the second precursor (bi). Reactive groups within the meaning of the invention are those groups that are crosslinkable in a reaction and can form covalent bonds. Preferably, the first precursor (ai) does not contain two different functional groups that are reactive with one another. The first precursor (ai) is preferably not self-crosslinkable. Preferably, the second precursor (bi) does not contain two different functional groups that are reactive with one another. The second precursor (bi) is preferably not self-crosslinkable. The functional groups of the first precursor (ai) can undergo an addition reaction, including a Michael-type reaction, or a substitution reaction with the functional groups of the second precursor (bi). The functional groups of the first precursor (ai) can be electrophilic groups, and the functional groups of the second precursor (bi) can be nucleophilic groups, or the functional groups of the first precursor (ai) can be nucleophilic groups, and the functional groups of the second precursor (bi) can be electrophilic groups. The electrophilic groups can be conjugated unsaturated functional groups selected from the group consisting of (meth)acrylate, vinylsulfone, vinylsulfonate, (meth)acrylamide, maleimide, quinone, vinylpyridinium, oxirane, oxazoline, aldehyde, carboxylic acid, carboxylic acid ester, carboxylic acid anhydride, carboxylic acid halide, sulfonic acid halide, and combinations thereof.As examples of carboxylic acid ester groups, particularly preferred are so-called active ester groups of the formula -C(O)OX, where X represents pentafluorophenyl, pyrrolidin-2,5-dion-1-yl, benzo-1,2,3-triazol-1-yl, or a carboxamidine residue, as well as N-hydroxysuccinimide esters (NHS esters). The nucleophilic groups can be selected from the group consisting of amine, thiol, and combinations thereof. Preferably, the reaction of the functional groups of the first precursor (ai) with the functional groups of the second precursor (bi) is a Michael-type reaction. The term "Michael-type reaction," also called a "Michael-type reaction," refers to a 1,4-addition reaction of a nucleophile to a conjugated unsaturated system. The addition mechanism can be purely polar or proceed via a radical-like intermediate; Lewis acids or appropriately designed hydrogen bonds can serve as catalysts. Reactions are described in detail in US Pat. No. 6,958,212, particularly in column 29, line 36 to column 35, line 20. The functional groups of the first precursor (ai) may contain conjugated unsaturated functional groups selected from the group containing vinylsulfone, (meth)acrylamide, maleimide, quinone, vinylpyridinium, and combinations thereof, preferably vinylsulfone, maleimide, and combinations thereof, and the functional groups of the second precursor (bi) may contain nucleophilic groups selected from the group containing amine, thiol, and combinations thereof, preferably thiol.Alternatively, the functional groups of the first precursor (ai) may contain nucleophilic groups selected from the group containing amine, thiol, and combinations thereof, preferably thiol, and the functional groups of the second precursor may (bi) contain conjugated unsaturated functional groups selected from the group containing (meth)acrylate, vinylsulfone, vinylsulfonate, (meth)acrylamide, maleimide, quinone, vinylpyridinium, and combinations thereof, preferably (meth)acrylate, vinylsulfone, vinylsulfonate, maleimide, and combinations thereof. Preferably, the functional groups of the first precursor (ai) contain conjugated unsaturated functional groups selected from the group containing vinylsulfone, and the functional groups of the second precursor (bi) contain nucleophilic groups selected from the group containing thiol. Alternatively, the functional groups of the first precursor (ai) can contain nucleophilic groups selected from the group containing thiol, and the functional groups of the second precursor (bi) can contain conjugated unsaturated functional groups selected from the group containing vinylsulfone. This combination of functional groups allows rapid The resulting hydrogels exhibited good reaction and gelation times, as well as good stiffness values. Furthermore, unlike active ester groups such as N-hydroxysuccinimide esters (NHS esters), no leaving groups are released. The functional groups of the first precursor (ai) can be located at the terminal positions of the first precursor (ai). The functional groups of the second precursor (bi) can be located at the terminal positions of the second precursor (bi). The reaction of the functional groups of the first precursor (ai) with the functional groups of the second precursor (bi) leads to the gelation of the system and thus to the production of the hydrogel. The reaction of the functional groups of the first precursor (ai) with the functional groups of the second precursor (bi) can take place at room temperature (23 °C) and atmospheric pressure (101.3 kPa). The reaction of the functional groups of the first precursor (ai) with the functional groups of the second precursor (bi) can take place at a pH of 7 to 10. Preferably, the reaction of the functional groups of the first precursor (ai) with the functional groups of the second precursor (bi) takes place in an aqueous composition in the presence of a buffer system. The crosslinking reactions preferably do not release any heat of reaction and do not require any exogenous energy sources to initiate or trigger the reaction. The gelation time, i.e.the time to form a hydrogel may be 7 to 25 seconds, preferably 7 to 23 seconds, more preferably 7 to 20 seconds. According to the present invention, the first composition (a) is aqueous. The term “aqueous” refers to a composition which, at Room temperature (23°C) and atmospheric pressure (101.3 kPa) is liquid and water as the main component of the liquid carrier and less than 50% by weight of organic solvents, such as less than 40% by weight of organic solvents, such as less than 30% by weight of organic solvents, such as less than 20% by weight of organic solvents, such as less than 10% by weight of organic solvents, such as less than 5% by weight of organic solvents, such as less than 2% by weight of water, such as less than 1% by weight of organic solvents, based on the total weight of the liquid carrier, ie the combination of water and organic solvent(s) (if present). The first composition (a) can be substantially free of organic solvents, ie the first composition can contain less than 0.5% by weight of organic solvents, for example less than 0.2% by weight of organic solvents, for example less than 0.1% by weight.-% organic solvents, based on the total weight of the liquid carrier. The first composition (a) may be completely free of organic solvents, i.e., the first composition (a) may contain 0 wt.% organic solvents, based on the total weight of the liquid carrier. Suitable organic solvents should be miscible with water and biocompatible. The term "miscible" means that the solubility of the organic solvent can range from completely miscible to soluble to dispersible in water. Suitable examples of organic solvents can be selected from the group containing N-methyl-2-pyrrolidone, 2-pyrrolidone, ethanol, propylene glycol, acetone, methyl acetate, ethyl acetate, methyl ethyl ketone, dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, caprolactam, decylmethyl sulfoxide, oleic acid, and 1-Dodecylazacycloheptan-2-one and combinations and mixtures thereof. According to the present invention, the first composition (a) contains a buffer system (a-ii). The term "buffer system" or "buffer" for short refers to an acidic or basic aqueous solution consisting of a mixture of a weak acid and its conjugate or corresponding base (or the respective salt) or a weak base and its conjugate or corresponding acid (or the respective salt). Preferably, the first composition (a) contains an alkaline buffer system (a-ii). The buffer system of the present invention can contain a phosphate buffer, a triethanolamine buffer, a borate buffer, a sodium bicarbonate buffer, a HEPES buffer, a HEPPS buffer, a glycine buffer, a glycine / NaOH buffer, a TRIS buffer, or a TRIS / glycine buffer. The first composition (a) may have a pH of at least 7, preferably at least 7.2, more preferably at least 7.4. The first composition (a) may have a pH of less than or equal to 10, preferably less than or equal to 9.5, more preferably less than or equal to 9. The first composition (a) may have a pH of from 7 to 10, preferably from 7.2 to 10, more preferably from 7.4 to 10, even more preferably from 7.4 to 9. According to the present invention, the second composition (b) is anhydrous. The term "anhydrous" refers to a composition to which no water is added and which contains, if any, only traces of water, such as less than 0.05 wt.%, preferably 0.01 wt.%. Contains water, wherein the weight percentage is based on the total weight of the composition. Preferably, the second composition (b) contains 0 wt.% water, wherein the weight percentage is based on the total weight of the composition. The second composition (b) may contain organic solvents. The second composition (b) may contain up to 10 wt.%, such as up to 5 wt.%, or up to 2 wt.%, or up to 1 wt.% of organic solvents, based on the total weight of the second composition (b). The second composition (b) may be substantially free of organic solvents, i.e. the second composition (b) may contain less than 0.5 wt.% of organic solvents, for example less than 0.2 wt.% of organic solvents, for example less than 0.1 wt.% of organic solvents, based on the total weight of the second composition (b). The second composition (b) may be completely free of organic solvents, i.e. the second composition may contain 0 wt.% of organic solvents, based on the total weight of the second composition.Suitable examples of organic solvents are as described above for the first composition (a). According to the present invention, the first precursor (ai) is preferably water-soluble. The term "water-soluble" refers to a substance whose solubility in water is preferably at least 1 wt.% and more preferably 5 wt.% at room temperature (23°C) and atmospheric pressure (101.3 kPa), the weight percentage being based on the weight of water. The first precursor may contain polyether, polyacrylic acid, poly(ethylene-co-acrylic acid), polyvinyl acetate, polyvinyl alcohol, poly(ethylene-co-vinyl alcohol), polyvinyl acetal, polyvinyl ether, poly(oxazoline), polyvinylpyrrolidone, polyvinylamine, polyvinyl methyl ether, poly(meth)acrylate, polyacrylamide, poly-(N-isopropylacrylamide), poly-(N-ethylacrylamide), polyoxymethylene, polycarbonate, or a copolymer thereof. Preferably, the first precursor (ai) may contain polyether, polyacrylamide, poly-(N-isopropylacrylamide), poly-(N-ethylacrylamide), or a copolymer thereof. In particular, the first precursor (ai) may contain polyethers. Suitable examples of polyethers may include polyethylene oxide, polypropylene oxide, polyglycidol, and copolymers thereof, preferably polyethylene oxide, polyglycidol, and poly(ethylene oxide-co-propylene oxide), more preferably poly(ethylene oxide-co-propylene oxide). Polyethers may be prepared by oxyalkylating a polyol with an alkylene oxide, such as ethylene oxide, propylene oxide, and combinations thereof, in the presence of an acidic or basic catalyst. Suitable polyols include, in particular, bisphenol A, trimethylolpropane, pentaerythritol, glycerol, sugar alcohols such as erythritol, xylitol, mannitol, sorbitol, maltitol, isomaltulose, isomalt, and trehalulose, alkylene glycols such as ethylene glycol, propylene glycol, butylene glycol, and 1,6-hexylene glycol, and combinations thereof. The first precursor (ai) may contain polyethylene oxide, polyglycidol, and poly(ethylene oxide-co-propylene oxide), preferably poly(ethylene oxide-co-propylene oxide). Suitable examples of poly(ethylene oxide-co-propylene oxide) may include random poly(ethylene oxide-co-propylene oxide) or poly(ethylene oxide-block-propylene oxide). Preferably, the first Precursor (ai) random poly(ethylene oxide-co-propylene oxide). Random poly(ethylene oxide-co-propylene oxide) can be prepared by alkoxylation of a polyol with a monomer mixture containing ethylene oxide and propylene oxide in the presence of a base, such as potassium hydroxide or sodium hydroxide. The first precursor (ai) may contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which preferably contains no more than 50% by weight of propylene oxide units. The first precursor (ai) may contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains up to 50% by weight, preferably up to 40% by weight, more preferably up to 30% by weight of propylene oxide units. The first precursor (ai) may contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains at least 10% by weight of propylene oxide units. The first precursor (ai) may contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide) containing 10 to 50 wt.%, preferably 10 to 40 wt.%, more preferably 10 to 30 wt.% of propylene oxide units.The weight percent is based on the total weight of the ethylene oxide and propylene oxide units of the poly(ethylene oxide-co-propylene oxide). The first precursor (ai) may contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains at least 50 wt.%, preferably at least 60 wt.%, more preferably 70 wt.% ethylene oxide units. The first precursor (ai) may contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains up to 90 wt.% ethylene oxide. The first precursor (ai) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains 50 to 90 wt.%, preferably 60 to 90 wt.%, more preferably 70 to 90 wt.% ethylene oxide units. The weight percentage is based on the total weight of the ethylene oxide and propylene oxide units of the poly(ethylene oxide-co-propylene oxide). The first precursor (ai) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains 50 to 90 wt.% ethylene oxide units and 10 to 50 wt.% propylene oxide units, preferably 60 to 90 wt.% ethylene oxide units and 10 to 40 wt.% propylene oxide units, more preferably 70 to 90 wt.% ethylene oxide units and 10 to 30 wt.% propylene oxide units. The weight percentages are based on the total weight of the ethylene oxide and propylene oxide units of the poly(ethylene oxide-co-propylene oxide). The functionalization of the precursors can generally be carried out analogously to known state-of-the-art functionalization processes. Starting materials containing OH groups are suitable for functionalization. OH groups can be converted into amino groups, for example, analogously to the method described by Skarzewski, J. et al., Monatsh. Chem. 1983, 114, 1071-1077. Thiol groups can be prepared, for example, analogously to the method described in Houben-Weyl, Methoden der Organischen Chemie, Ed. E. Müller, 4th ed., Vol. 9, p. 749, G. Thieme, Stuttgart 1955, or analogously to the method described in T. Nie, A. Baldwin, N. Yamaguchi and KL Kiick, J. Control Release, 2007, 122, 287-296. The production of precursors with (meth)acrylate groups or (meth)acrylamide groups is achieved, for example, by esterification of prepolymer precursors carrying either OH or NH2 groups with (meth)acrylic acid or by reaction with (meth)acryloyl chloride, or with the anhydrides of (meth)acrylic acid in analogy to known processes (such as Cruise et al. Biomaterials 1998,19, 1287-1294 and Han et al. Macromolecules 1997,30, 6077-6083). Precursors with vinylsulfone groups can be prepared analogously to the procedure described in C. Adelöw, T. Segura, JA Hubbell and P. Frey, Biomaterials, 2008, 29, 314-326 and precursors with vinylsulfonate groups can be prepared analogously to the procedure described in V. Chudasama, RJ Fitzmaurice, JM Ahern and S. Caddick, Chemical Communications, 2010, 46, 133-135. Maleimide functions can be prepared following the procedure described by Coleman et al. JOC, 1959, 24(1), 297-308 and Han et al. Biochem. Pharmacol., 2013, 86(2), 297-308 to prepolymer precursors containing amine groups. The first precursor (ai) may contain a linear, branched, dendritic, circular, or star-shaped polymer, preferably a dendritic or star-shaped polymer. In particular, the first precursor (ai) may contain a star-shaped polymer. The term "star-shaped polymer" refers to a polymer that has several polymer chains bound to a low-molecular-weight central unit, wherein the low-molecular-weight central unit generally has 4 to 100 backbone atoms such as C atoms, O atoms and / or N atoms. The central unit can have both aliphatic and aromatic groups. The central unit comprises, for example, a residue derived from at least 3-hydric alcohol, such as a 3- to 12-hydric alcohol, e.g., glycerol, pentaerythritol, dipentaerythritol, a sugar alcohol such as erythritol, xylitol, mannitol, sorbitol, maltitol, isomaltulose, isomalt, trehalulose, or the like. The residues bound to the low-molecular-weight central unit The polymer chain bound to the cyclic unit is usually referred to as an arm of the star-shaped polymer. The arms of the star-shaped polymer can comprise the polymers of the first precursor described above. The first precursor (ai) may contain a star-shaped polymer having at least 3 arms. The first precursor (ai) may contain a star-shaped polymer having no more than 12, in particular no more than 8, arms. The first precursor (ai) may contain a star-shaped polymer having 3 to 12 arms, and in particular 3 to 8 arms. Some star-shaped precursors are known, e.g., from WO 98 / 20060; US Pat. No. 6,162,862; Götz et al., Macromol. Mater. Eng. 2002, 287, p. 223; Bartelink et al., J. Polymer Science 2000, 38, p. 2555; DE 10216639 and DE 10203937 (polyether star polymers containing different functional groups); Chujo Y. et al., Polym. J. 1992, 24 (11), 1301-1306 (star-shaped polyoxazolines); WO 01 / 55360 (star-shaped polyvinyl alcohols, star-shaped vinylpyrrolidone-containing copolymers), or can be prepared by the methods described therein. The first precursor (ai) can have a weight-average molecular weight (M w ) of at least 100 Da, such as at least 200 Da, or at least 500 Da, or at least 1 kDa, or at least 1.5 kDa, or at least 2 kDa, or at least 2.5 kDa, or at least 2.8 kDa, or at least 3 kDa. The first precursor (ai) may have a weight-average molecular weight (M w) of not more than 40 kDa, such as not more than 35 kDa, or not more than 30 kDa, or not more than 25 kDa, or not more than 20 kDa, or not more than 18 kDa. The first precursor (ai) may have a weight-average molecular cular weight (M w ) in a range of 100 Da to 40 kDa, preferably 1 kDa to 40 kDa, more preferably 1.5 kDa to 30 kDa, even more preferably 2 kDa to 25 kDa, most preferably 2.5 kDa to 20 kDa. The molecular weight, in particular the weight-average molecular weight (M w ), can be determined by gel permeation chromatography using polyethylene glycol standards (PEG standards). According to the present invention, the second precursor (bi) is preferably water-soluble. The second precursor (bi) may contain polyethers. Suitable examples of polyethers include polyethylene oxide, polypropylene oxide, polyglycidol, and copolymers thereof, preferably polyethylene oxide, polyglycidol, and poly(ethylene oxide-co-propylene oxide), more preferably poly(ethylene oxide-co-propylene oxide). The second precursor (bi) may contain polyethylene oxide, polyglycidol, and poly(ethylene oxide-co-propylene oxide), preferably poly(ethylene oxide-co-propylene oxide). Suitable examples of poly(ethylene oxide-co-propylene oxide) may include random poly(ethylene oxide-co-propylene oxide) or poly(ethylene oxide-block-propylene oxide). Preferably, the second precursor (bi) contains random poly(ethylene oxide-co-propylene oxide). The second precursor (bi) may contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which preferably contains no more than 50 wt.% propylene oxide units. The second precursor (bi) may contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains up to 50 wt.%, preferably up to 40 wt.%, more preferably up to 30 wt.% propylene oxide units. The second precursor (bi) may contain po- ly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide) containing at least 10 wt.% propylene oxide units. The second precursor (bi) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), containing 10 to 50 wt.%, preferably 10 to 40 wt.%, more preferably 10 to 30 wt.% propylene oxide units. The weight percentage is based on the total weight of the ethylene oxide and propylene oxide units of the poly(ethylene oxide-co-propylene oxide). The second precursor (bi) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains at least 50% by weight, preferably at least 60% by weight, more preferably 70% by weight of ethylene oxide units. The second precursor (bi) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains up to 90% by weight of ethylene oxide units. The second precursor (bi) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains 50 to 90% by weight, preferably 60 to 90% by weight, more preferably 70 to 90% by weight of ethylene oxide units. The weight percent is based on the total weight of the ethylene oxide and propylene oxide units of the poly(ethylene oxide-co-propylene oxide). The second precursor (bi) may contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains 50 to 90 wt.% ethylene oxide units and 10 to 50 wt.% propylene oxide units, preferably 60 to 90 wt.% ethylene oxide units and 10 to 40 wt.% propylene oxide units, more preferably 70 to 90 wt.% ethylene oxide units and 10 to 30 wt.% propylene oxide units. The weight percentages are based on the total weight of the ethylene oxide and propylene oxide units of the poly(ethylene oxide-co-propylene oxide). According to the present invention, the second precursor (bi) contains at least one hydrolyzable bond. The term "hydrolyzable bond" refers to a covalent bond that is cleavable by reaction with water. The at least one hydrolyzable bond can comprise an ester bond, a carbonate bond, and combinations thereof. Preferably, the at least one hydrolyzable bond comprises an ester bond. Preferably, the first precursor (ai) does not contain a hydrolyzable bond, in particular an ester bond. The at least one hydrolyzable bond of the second precursor enables the degradability of the hydrogel. The hydrogel producible by the present system can be degradable in one day to one year, preferably degradable in two to six months. The second precursor (bi) may contain a linear, branched, dendritic, circular, or star-shaped polymer, preferably a dendritic or star-shaped polymer. In particular, the second precursor (bi) may contain a star-shaped polymer. The second precursor (bi) may contain a star-shaped polymer having at least 3 arms. The second precursor (bi) may contain a star-shaped polymer having no more than 12, in particular no more than 8, arms. The second precursor (bi) may contain a star-shaped polymer having 3 to 12 arms, and in particular 3 to 8 arms. The second precursor (bi) can have a weight-average molecular weight (M w) of at least 100 Da, such as at least 200 Da, or at least 500 Da, or at least 1 kDa, or at least 1.5 kDa, or at least 2 kDa, or at least 2.5 kDa, or at least 2.8 kDa, or at least 3 kDa. The second precursor (bi) may have a weight-average molecular weight (M w ) of not more than 40 kDa, such as not more than 35 kDa, or not more than 30 kDa, or not more than 25 kDa, or not more than 20 kDa, or not more than 18 kDa. The second precursor (bi) may have a weight-average molecular weight (M w ) in a range of 100 Da to 40 kDa, preferably 1 kDa to 40 kDa, more preferably 1.5 kDa to 30 kDa, even more preferably 2 kDa to 25 kDa, most preferably 2.5 kDa to 20 kDa. The molecular weight, in particular the weight-average molecular weight (M w), can be determined by gel permeation chromatography using polyethylene glycol standards (PEG standards). According to the present invention, the second precursor (bi) is liquid. The term "liquid" refers to a precursor that is liquid at room temperature (23°C) and atmospheric pressure (101.3 kPa). The second precursor can have a viscosity of up to 4,500 mPa s, preferably up to 4,000 mPa s, more preferably up to 3,500 mPa s, even more preferably up to 3,000 mPa s at room temperature (23°C). The second precursor can have a viscosity of at least 1 mPa s, preferably at least 2 mPa s, more preferably at least 5 mPa s at room temperature (23°C). The second precursor may have a viscosity of 1 to 4,500 mPa s, preferably 2 to 4,000 mPa s, more preferably 5 to 4,000 mPa s, even more preferably 5 to 3,500 mPa s, most preferably 5 to 3,000 mPa s at room temperature (25 °C). The viscosity can be determined using a rheometer. To determine the viscosity (complex viscosity (Pa s)), the The precursor is analyzed using a DHR 3 rheometer with a 40 mm cone plate geometry from TA Instruments (USA) at 25 °C. For this purpose, 581 pL of the precursor is distributed homogeneously on the rheometer plate using a pipette. The geometry is set to the "Geometry Gap" (57 pm high). The "Flow Sweep" is then performed with a shear rate of 0.1 to 1000 s 1 measured for 5 min. The system according to the present invention may have a precursor concentration of up to 500 mg per 1 mL of solution, such as up to 450 mg per 1 mL of solution, or up to 400 mg per 1 mL of solution, or up to 350 mg per 1 mL of solution, or up to 300 mg per 1 mL of solution, or up to 250 mg per 1 mL of solution, or up to 200 mg per 1 mL of solution. The system according to the present invention can have a precursor concentration of at least 10 mg per 1 mL of solution, such as at least 30 mg per 1 mL of solution, or at least 50 mg per 1 mL of solution, or at least 60 mg per 1 mL of solution, or at least 65 mg per 1 mL of solution, or at least 70 mg per 1 mL of solution, or at least 75 mg per 1 mL of solution, or at least 80 mg per 1 mL of solution, or at least 90 mg per 1 mL of solution. The system according to the present invention can have a precursor concentration in a range of 10 to 500 mg per 1 mL of solution, such asfrom 50 to 500 mg per 1 mL of solution, or from 60 to 400 mg per 1 mL of solution, or from 70 to 300 mg per 1 mL of solution, or from 80 to 200 mg per 1 mL of solution, or from 90 to 200 mg per 1 mL of solution. The precursor concentration is based on the total weight of the precursors used to prepare the hydrogel per total volume of the system's solution. The system of the present invention can be injectable. The term "injectable" refers to a system that can be injected into a human body using a syringe. Preferably, the system of the present invention is a two-component composition. The term "two-component composition" refers to a system in which the two components are stored separately from one another and are only mixed when used. According to the present invention, the first composition (a) and the second composition (b) can be stored separately from one another. The first composition (a) and the second composition (b) can only be mixed immediately before the system is injected. The first composition (a) may contain one or more visualization additives. The second composition (b) may contain one or more visualization additives. The first composition (a) and the second composition (b) may contain one or more visualization additives. The term “visualization additive” refers to a contrast agent for imaging, such as for magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, or combinations thereof. The visualization agent may comprise radiopaque substances. The visualization additives may be free in the first and / or second composition or covalently bound to the first precursor and / or the second precursor. The visualization additives may be covalently bound to a third precursor. The visualization additive can be lohexol, metrizamide, lopamidol, triiodobenzoate, 2,3,5-triiodobenzoic acid, 2,3,5-triiodobenzoyl chloride, 3,4,5-triiodophenol, erythrosine, rose bengal, 3.5-bis(acetylamino)-2,4,6-triiodobenzoic acid, 3,5-diacetamido-2,4,6-triiodobenzoic acid, meglumine diatrizoate, lopentol, i-opromide, loversol, gadolinium, gadopentetic acid modified zirconium particles, calcium hydroxyapatite, superparamagnetic iron oxide, residues of the foregoing, or a combination thereof. According to the present invention, the first precursor (ai) and the second precursor (bi) may contain radiopaque groups, and in particular iodine-containing groups. Preferably, the second precursor (bi) contains radiopaque groups, and in particular iodine-containing groups. Examples of radiopaque groups, and in particular iodine-containing groups, that can be bound to the first precursor (ai) and / or to the second precursor (bi) include iohexol, metrizamide, iohexamidol, triiodobenzoate, 2.3.5-triiodobenzoic acid, 2,3,5-triiodobenzoyl chloride, 3,4,5-triiodophenol, erythrosine, rose bengal, 3,5-bis(acetylamino)-2,4,6-triiodobenzoic acid, 3,5-Diacetamido-2,4,6-triiodobenzoic acid, meglumine diatrizoate, lopentol, iopromide, lovesol, and a combination thereof. The radiopaque groups, and in particular the iodine-containing groups, can be bonded to the first precursor (ai) and / or the second precursor (bi) of the present invention using a variety of methods. Possible methods include the formation of ester bonds, amide bonds, or urethane bonds of the radiopaque groups, and in particular iodine-containing groups, with the first precursor (ai) and / or the second precursor (bi), in particular the second precursor (bi). Some of these methods are described in US 2005 / 0036946 A1 , and in particular in paragraphs

[0077] until

[0080] ,

[0093] until

[0173] , and

[0215] until

[0364] described. The first precursor (ai) and / or the second precursor (bi), in particular the second precursor (bi), may contain an iodine content of at least 3.0 wt.%, such as at least 3.5 wt.%, or of at least 4.0 wt.%, or of at least 5.0 wt.%, or of at least 6.0 wt.%, or of at least 7.5 wt.%. The first precursor (ai) and / or the second precursor (bi), in particular the second precursor (bi), may contain an iodine content of up to 30.0 wt.%, such as up to 28.0 wt.%, or of up to 27.5 wt.%, or up to 26.0 wt.%, or up to 25.0 wt.%. The first precursor (ai) and / or the second precursor (bi), in particular the second precursor (bi) may have an iodine content of 3.0 to 30.0 wt.%, preferably 3.0 to 27.5 wt.%, more preferably 3.5 to 27.5 wt.%, more preferably from 3.5 to 26.0 wt.%, most preferably from 3.5 to 25.0 wt.%. The iodine content is based on the total weight of the respective precursor. According to the present invention, the second composition (b) may contain a third precursor. The third precursor (b-ii) may be liquid and contain a functional group and a radiopaque group, in particular an iodine-containing group, wherein the functional group of the third precursor (b-ii) is reactive with the functional groups of the first precursor (ai). Examples of radiopaque groups, and in particular iodine-containing groups, that can be bonded to the third precursor (b-ii) include the radiopaque groups, and in particular iodine-containing groups, described for the first and / or second precursors. The third precursor (b-ii) may have an iodine content of at least 3.0 wt.%, such as at least 3.5 wt.%, or at least 4.0 wt.%, or at least 5.0 wt.%, or at least 6.0 wt.%, or at least 7.5 wt.%. The third precursor (b-ii) may have an iodine content of up to 30.0 wt.%, such as up to 28.0 wt.%, or up to 27.5 wt.%, or up to 26.0 wt.%, or up to 25.0 wt.%. The third precursor (b-ii) may contain an iodine content of 3.0 to 30.0 wt.%, preferably 3.0 to 27.5 wt.%, more preferably 3.5 to 27.5 wt.%, even more preferably 3.5 to 26.0 wt.%, most preferably 3.5 to 25.0 wt.%. The iodine content is based on the total weight of the third precursor (b-ii). The functional groups of the third precursor (b-ii) can contain nucleophilic groups selected from the group consisting of amine, thiol, and combinations thereof, preferably thiol. Alternatively, the functional groups of the third precursor (b-ii) can contain conjugated unsaturated functional groups selected from the group consisting of (meth)acrylate, vinylsulfone, vinylsulfonate, (meth)acrylamide, maleimide, quinone, vinylpyridinium, and combinations thereof, preferably (meth)acrylate, vinylsulfone, vinylsulfonate, maleimide, and combinations thereof, more preferably vinylsulfone. The functional groups of the third precursor (b-ii) can be located at the end positions of the second precursor (b-ii). According to the present invention, the third precursor (b-ii) is preferably water-soluble. The third precursor (b-ii) may contain polyethers. The third precursor (b-ii) may contain polyethylene oxide, polyglycidol, and poly(ethylene oxide-co-propylene oxide), preferably poly(ethylene oxide-co-propylene oxide). Preferably, the third precursor (b-ii) contains random poly(ethylene oxide-co-propylene oxide). The third precursor (b-ii) may contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which preferably contains not more than 50 wt.% propylene oxide units. The third precursor (b-ii) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains up to 50 wt.%, preferably up to 40 wt.%, more preferably up to 30 wt.% of propylene oxide units. The third precursor (b-ii) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains at least 10 wt.% of propylene oxide units. The third precursor (b-ii) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains 10 to 50 wt.%, preferably 10 to 40 wt.%, more preferably 10 to 30 wt.% of propylene oxide units. The weight percent is based on the total weight of the ethylene oxide and propylene oxide units of the poly(ethylene oxide-co-propylene oxide). The third precursor (b-ii) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains at least 50 wt.%, preferably at least 60 wt.%, more preferably 70 wt.% ethylene oxide units. The third precursor (b-ii) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains up to 90 wt.% ethylene oxide units. The third precursor (b-ii) can contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains 50 to 90 wt.%, preferably 60 to 90 wt.%, more preferably 70 to 90 wt.% ethylene oxide units. The weight percent is based on the total weight of the ethylene oxide and propylene oxide units of the poly(ethylene oxide-co-propylene oxide). The third precursor (b-ii) may contain poly(ethylene oxide-co-propylene oxide), in particular random poly(ethylene oxide-co-propylene oxide), which contains 50 to Contains 90% by weight of ethylene oxide units and 10 to 50% by weight of propylene oxide units, preferably 60 to 90% by weight of ethylene oxide units and 10 to 40% by weight of propylene oxide units, more preferably 70 to 90% by weight of ethylene oxide units and 10 to 30% by weight of propylene oxide units. The weight percentages are based on the total weight of the ethylene oxide and propylene oxide units of the poly(ethylene oxide-co-propylene oxide). The third precursor (b-ii) can have a weight-average molecular weight (M w ) of at least 100 Da, such as at least 200 Da, or at least 500 Da, or at least 1 kDa, or at least 1.5 kDa, or at least 2 kDa, or at least 2.5 kDa, or at least 2.8 kDa, or at least 3 kDa. The third precursor (b-ii) may have a weight-average molecular weight (M w) of not more than 40 kDa, such as not more than 35 kDa, or not more than 30 kDa, or not more than 25 kDa, or not more than 20 kDa, or not more than 18 kDa. The third precursor (b-ii) may have a weight-average molecular weight (M w ) in a range of 100 Da to 40 kDa, preferably 1 kDa to 40 kDa, more preferably 1.5 kDa to 30 kDa, even more preferably 2 kDa to 25 kDa, most preferably 2.5 kDa to 20 kDa. The molecular weight, in particular the weight-average molecular weight (M w ), can be determined by gel permeation chromatography using polyethylene glycol standards (PEG standards). The present invention further relates to a method for producing a degradable hydrogel. The method of the present invention comprises (i) providing a system of the present invention, and (ii) mixing the first and second compositions. Thus, the method comprises (a) providing a first composition, (b) providing a second composition, and (ii) mixing the first and second compositions. The first composition (a) is aqueous and contains a first precursor (ai) and a buffer system (a-ii). The first precursor (ai) contains functional groups. The second composition (b) is anhydrous and contains a second precursor (bi) and optionally a third precursor (b-ii). The second precursor (bi) is liquid. The second precursor (bi) contains functional groups and at least one hydrolyzable bond. The functional groups of the first precursor (ai) are reactive with the functional groups of the second precursor (bi). The first precursor (ai) contains at least two functional groups and the second precursor (bi) contains at least three functional groups, or the first precursor (ai) contains at least three functional groups and the second precursor (bi) contains at least two functional groups.The third precursor (b-ii) is liquid, contains a functional group and an iodine-containing group, whereby the functional group of the third precursor (b-ii) is reactive with the functional groups of the first precursor (ai). The first composition (a), the second composition (b), the first precursor (ai), the second precursor (bi), the third precursor (b-ii) and the buffer system (a-ii) may comprise the features as described above. The first composition (a) can be provided in a syringe. The second composition (b) can be provided in a syringe. Preferably, the first composition (a) and the second composition (b) are each provided separately in a syringe. For mixing (ii), a mixing attachment, a multi-lumen tube or a Y-connector can be used. Suitable examples of attachments for Mixing includes the adapter systems of Medmix Switzerland AG (Switzerland). The method of the present process may further comprise injecting the first composition (a) and the second composition (b) into an injection site after mixing (ii). A cannula may be used for injection. Furthermore, the present invention relates to a kit for producing a degradable hydrogel. The kit comprises (i) a system according to the present invention and (ii) a syringe. Thus, the kit comprises (a) a first composition, (b) a second composition, and (ii) a syringe. The first composition (a) is aqueous and contains a first precursor (ai) and a buffer system (a-ii). The first precursor (ai) contains functional groups. The second composition (b) is anhydrous and contains a second precursor (bi) and optionally a third precursor (b-ii). The second precursor (bi) is liquid. The second precursor (bi) contains functional groups and at least one hydrolyzable bond. The functional groups of the first precursor (ai) are reactive with the functional groups of the second precursor (bi).The first precursor (ai) contains at least two functional groups and the second precursor (bi) contains at least three functional groups, or the first precursor (ai) contains at least three functional groups and the second precursor (bi) contains at least two functional groups. The third precursor (b-ii) is liquid, contains one functional group and one iodine-containing group, and the functional group of the third precursor (b-ii) is reactive with the functional groups of the first precursor (ai). The first composition (a), the second composition (b), the first precursor (ai), the second precursor (bi), the third precursor (b-ii) and the buffer system (a-ii) may comprise the features as described above. The syringe (ii) may be a double-barreled syringe or a multi-barreled syringe. The kit of the present invention preferably comprises two syringes. The kit may comprise the first composition (a) in one syringe. The kit may comprise the second composition (b) in one syringe. Preferably, the kit comprises the first composition (a) and the second composition (b) in separate syringes or barrels of a double-barreled syringe. The kit may comprise a mixing attachment, a multi-lumen tube or a Y-connector that can be used to mix the first composition (a) with the second composition (b). The kit may include a cannula that can be used to inject the first composition (a) and the second composition (b) after mixing. According to the present invention, this cannula may be a commercially available cannula, such as 18G to 25G cannulas. The following examples serve to illustrate the present invention and should not be construed as limiting the invention. Illustrations Figure 1 shows computed tomography (CT) images of hydrogel discs (as prepared in the examples) prepared from 18 kDa sPEG-VS, 18 kDa sPEG-SH, and 10 wt%, 20 wt%, and 50 wt% of an iodine-containing precursor without a reactive functional group, SPEG-TIB48 (left side), and 3.8 wt%, 7.5 wt%, and 14.6 wt% of an iodine-containing precursor with a reactive functional group, SPEG-TIB48-SH15 (right side). The weight percentages are based on the total weight of the cross-linkable precursors. The upper images show CT images after the hydrogel discs were stored for one day in PBS buffer (pH = 7.4) at 37 °C. The lower images show CT images after the hydrogel discs were stored for 14 days in a PBS buffer (pH = 7.4) at 37 °C. Examples 1 H-NMR and 13 C-NMR measurement methods 1 H-NMR and 13C NMR spectra were recorded using a Bruker Ultrashield 400 FTNMR spectrometer at 400 MHz and at room temperature. Deuterated dimethyl sulfoxide (DMSO, Sigma Aldrich) or chloroform (CDCl3, Sigma Aldrich) were used as solvents for spectroscopy. Gel permeation chromatography (GPC) Gel permeation chromatography (GPC) was performed using dimethylformamide (DMF) as eluent. All experiments were performed using the PSS WinGPC UniChrom software (version 8.1.1) was used for analysis. Measurements were performed using an Agilent 1100 system equipped with a dual RI-A / isco detector (ETA-2020, WGE Dr. Bures GmbH & Co. KG (Germany)). The eluent contained 1 g / L lithium bromide. Distilled water was used as an internal standard in the solvent. A guard column (8 x 50 mm) and four GRAM gel columns (8 x 300 mm, Polymer Standards Service (Germany)) were used at a flow rate of 1.0 mL / min at 40°C. The gel particle diameter was 10 pm, and the nominal pore widths were 30, 100, 1000, and 3000 Å. Polyethylene glycol (PEG) standards (Polymer Standards Service (Germany)) with narrowly distributed molecular weights were used for calibration. Star-shaped polyether polyols (sPEG-OH) Star-shaped 6-arm polyether polyols (sPEG-OH) were used to prepare the first and second precursors. The sPEG-OH is a random poly(ethylene oxide-co-propylene oxide) prepared by anionic ring-opening polymerization from 80 wt.% ethylene oxide and 20 wt.% propylene oxide using sorbitol as the initiator and potassium hydroxide as the catalyst. The weight percentage is based on the total weight of the monomer mixture containing ethylene oxide and propylene oxide. The sPEG-OH used has a weight-average molecular weight (M w ) of 3 kPa, 12 kPa, and 18 kPa. The respective sPEG-OH were functionalized with different groups as described below. Synthesis of star-shaped polyethers with thiol groups (sPEG-SH) The reaction was carried out under an inert gas atmosphere. The sPEG-OH was dried overnight under high vacuum (HV) at 75 °C. sPEG-OH (25 mmol OH functions, 1 eq), 3-mercaptopropionic acid (20.0 eq), p-toluenesulfonic acid (0.2 eq), and dithiothreitol (0.5 eq) were dissolved in toluene (20 mL / g sPEG-OH) at room temperature (RT). The reaction mixture was refluxed for 24 h at 110 °C under nitrogen. All subsequent purification steps were carried out to keep the polymer as cold as possible and minimize the time in air. Therefore, the sample was always cooled and, when possible, treated under a nitrogen atmosphere. The light yellow, clear solution was concentrated under HV at RT. The remaining solution was dissolved in cold DCM (5 mL) and precipitated from pentane (400 mL, technical grade) and diethyl ether (400 mL, technical grade) at 0 °C.After 1.5 h of storage at -80 °C, the precipitant was decanted off, and the polymer was precipitated three more times in the same manner. The product was dissolved in 50 mL of DCM and cooled to 0 °C. This solution was filtered four times through a silica gel-filled filter frit and once through a pleated filter. The product was dissolved in dichloromethane and dried under HV at RT, yielding the sPEG-SH with a yield of 86% and a degree of functionalization of 100% (6-star polymer arms). Functionalization was determined by NMR spectroscopy. The polymer was stored at -20 °C under nitrogen until further use. 1 H NMR (400 MHz, CDCI3): 5 = 5.07-4.88 (1H, m, CH3-CH-O), 4.20-4.05 (2H, m, O-CH2-CH2-O) 3.90-3.11 (m, polymer backbone), 2.72-2.44 (4H, m, -CH2CH2SH), 1.64-1.53 (1 H, m, - SH), 1.14-1.03 (m, polymer backbone -CH2CH(CH3)O-) ppm. Synthesis of star-shaped polyethers with vinylsulfone groups (sPEG-VS) The reaction was carried out under an inert gas atmosphere. The sPEG-OH was dried by azeotropic distillation with toluene under high vacuum at 80 °C. The sPEG-OH (0.45 mmol OH functions, 1 eq) was dissolved in 33 mL of dry DCM. Sodium hydride (7.5 eq) was suspended in 17 mL of dry DCM in a Schlenk flask. The sPEG-OH solution was slowly added dropwise to the NaH solution via a dropping funnel. The mixture was stirred for 30 min. Subsequently, the divinyl sulfone (DVS) (30 eq) was added in one portion, and the mixture was stirred for 72 h. The reaction was quenched by adding acetic acid (7.5 eq), and the solution was stirred again for 30 min. The solution was filtered, washed with THF, and concentrated on a rotary evaporator. The product was purified by dialysis. The crude product was dissolved in 5 mL of technical-grade acetone and dialyzed in 500 mL of technical-grade acetone (Spectra / Por 6 dialysis membrane, MWCO: 1 kDa).The dialysis solvent was changed twice a day. This procedure was repeated until NMR analysis showed no more DVS residues. The product was dissolved in DCM and dried under reduced pressure at room temperature. A yellow, viscous liquid polymer was obtained with a yield of 80% and a degree of functionalization of 100% (6-star polymer arms). 1 H-NMR (400 MHz, CDCI3): 5 = 6.91-6.71 (1 H, m, SO2-CH=CH2), 6.41-6.28 (1 H, m, SO2-CH=CH2), 6.09-5.98 (1 H, m, SO2-CH=CH2), 3.91 (2H, m, CH2-CH2-SO2), 3.78-3.27 (m, polymer backbone), 3.21 (2H, m, CH2-CH2-SO2), 1.11 (3H, m, CH3-CH-O) ppm. Synthesis of star-shaped polyethers with vinylsulfonate groups (sPEG-VS-at) The reaction was carried out under an inert atmosphere. The sPEG-OH (4.712 mmol OH functions, 1 eq) was dried overnight with stirring at 75°C under high vacuum (HV) and dissolved in dichloromethane at a ratio of 50 mL per gram of sPEG-OH. Triethylamine (4 eq) was added with stirring, and the solution was immediately cooled to 0°C. The solution was stirred for 30 minutes, then 2-chloroethane-1-sulfonyl chloride (2 eq) in 10 mL of DCM was added via a dropping funnel over 2 h (approximate dropping rate of 6 drops per minute). After stirring at RT for 24 h, the solvent was removed, and the resulting product was dissolved in 50 mL of tetrahydrofuran (THF). The suspension was cooled in an ice bath and filtered through silica gel (approximate thickness of 0.5 cm). The product was washed with 150 mL of cold THF and concentrated under reduced pressure.This procedure is repeated until no salt residues are detectable by NMR analysis. After successive precipitation steps in 400 mL of pentane and 600 mL of Et2O (technical grade) at -20°C, a yellow viscous liquid polymer was obtained with a yield of 71% and a degree of functionalization of 100% (6-star polymer arms). 1 H-NMR (400 MHz, CDCI3): 6.71-6.49 (1 H, m, SO2-CH=CH2), 6.44-6.26 (1 H, m, SO2-CH=CH2), 6.12-5.97 (1 H, m, SO2-CH=CH2), 4.76-4.59 (1 H, m, CH3-CH-O), 4.31-4.16(2H, m, O-CH2- CH2-O) 3.89-3.05 (m, polymer backbone), 1.40-1.27 (3H, m, CH3-CH-O-SO2), 1.24-1.01 (3H, m, CH3-CH-O) ppm. Synthesis of 1,4-dimethylpyridinium p-toluenesulfonate (DPTS) The reaction was carried out under an inert protective gas atmosphere. 4-Dimethylaminopyridine (1.0 g, 8.19 mmol, 1 eq) was dissolved in 100 mL of dry THF. 1.55 g of p-toluenesulfonic acid monohydrate (8.19 mmol, 1 eq) was added to the stirring solution and stirred at RT for 1 h. The reaction mixture was filtered through a Buchner funnel and washed with THF (pa). The white powder was dried under reduced pressure at RT and stored at -20°C. 1 H-NMR (400 MHz, CDCI3): 5 = 8.20 (2H, d, -CH=NH+-CH=), 7.51 (2H, d, =CH-SO3-=CH- ), 7.14 (2H, d, =CH-C-(CH3)-=CH-), 6.99 (2H, d, -CH=C-(N(CH3)2)-CH=), 3.17 (6H, s, -N-(CH3)2), 2.29 (3H, s, -C-CH3) ppm. Synthesis of 3-((2-vinylsulfonyl)ethyl)thio)propionic acid (mercapto-VS) The reaction was carried out under an inert atmosphere. DVS (2.40 g, 20.3 mmol, 20 eq) was dissolved in DMSO (dry) (2.7 mL / 1 g DVS). 3-Mercaptopropionic acid (1.0 eq) was quickly added to the stirring solution and stirred at RT for 4 h. 1H-NMR (400 MHz, CDCI3): 5 = 6.60-6.51 (1 H, q, SO2-CH=CH2), 6.36-6.30 (1H, d, SO2- CH=CH2), 6.09-6.0 (1 H, d, SO2-CH=CH2), 2.72-2.55 (8H, m, 5-CH2-CH2-S) ppm. 13 C-NMR (400 MHz, CDCI3): 5 = 136.84 (1C, SO2-CH=CH2), 129.75 (1C, SO2-CH=CH2), 37.88 (1C, S-CH2-CH2-S), 19.41 (1C, S-CH2-CH2-S) ppm. Synthese von sternförmigen Polyethern mit Mercapto Vinylsulfon-Gruppen (sPEG-mercapto-VS) The mercapto-VS was dried by azeotropic distillation from toluene in HV at 80°C. The sPEG-OH (0.51 mmol OH functions, 0.5 eq) was dissolved in DMSO (dry) (13.8 mL / 1 g N,N-dicyclohexylcarbodiimide (DCC)). DCC (1.5 eq) and DPTS (0.15 eq) were added to the stirred solution. This solution was slowly added to the mercapto-VS solution. The mixture was stirred for 18 hours at RT. The reaction mixture was filtered through silica gel. The DMSO was evaporated by HV distillation at 60°C. The product was dialyzed five times in 800 mL of technical-grade acetone (prewetted RC tubing MWCO: 1 kDa). The product was then dissolved in 60 mL of cold (0°C) DCM (pa) and filtered through silica gel. This process was repeated until no solid was detectable in the solution. The product was dissolved in 5 mL of DCM (pa) and precipitated in cold (-20°C) Et2O (100 mL) and pentane (100 mL) (technical grade).This procedure was repeated until no DVS residues were detectable. The product was dissolved in DCM and dried under reduced pressure at room temperature. A yellow, viscous liquid polymer was obtained with a yield of 40% and a degree of functionalization of 40% (6-star polymer arms). Synthesis of linear polyethylene glycol with vinylsulfone groups (LPEG-VS) Linear 4 kDa poly(ethylene glycol) (LPEG) (Sigma Aldrich) was dried overnight under HV at 75°C. PEG (1.0 g, 0.5 mmol OH functions, 1 eq) and sodium hydride (0.06 g, 2.5 mmol, 5 eq) were dissolved in THF (65 mL, anhydrous) and stirred for 30 min at room temperature (RT). DVS (1.77 g, 15.0 mmol, 30 eq) was added dropwise, and the reaction mixture was stirred for 96 h at RT. The reaction was quenched by slow addition of acetic acid (0.15 g, 2.5 mmol, 5 eq), and the mixture was stirred for 30 min at RT. The reaction mixture was filtered, washed with THF, and concentrated. The polymer was precipitated from cold (-20°C) diethyl ether (100 mL, technical grade), yielding a colorless solid. This procedure was repeated until no more DVS residues were detectable. The mixture was filtered, and the residues remaining on the filter were dissolved in DCM and dried under HV at room temperature.A white powder was obtained with a yield of 88% and a degree of functionalization of 100% (2 end groups). 1 H-NMR (400 MHz, CDCI3): 5 = 6.86-6.23 (1 H, m, -SO2CH=CH2), 6.39-6.29 (1 H, m, - SO2CH=CH2), 6.10-6.01 (1 H, m, -SO2CH=CH2), 3.85 (2H, m, -CH2- CH2- SO2-), 3.79-3.48 (m, polymer backbone), 3.27 ((2H, m, -CH2- CH2- SO2-) ppm. SpaceOAR™ The SpaceOAR™ (Boston Scientific Corp. (USA)) was prepared according to the enclosed instructions, unless otherwise stated. The SpaceOAR™ prepolymer was dissolved in the enclosed solution (5 mL) and mixed with the SpaceOAR™ crosslinker (5 mL) for further testing. Buffer production Preparation of the salt solution: 0.958 g of sodium tetraborate decahydrate was dissolved in a 100 mL volumetric flask. Buffer preparation: 100 mL of the saline solution was added to a 200 mL volumetric flask. To adjust the desired pH, the appropriate volume of 0.1 M HCl solution was added and the flask was filled with water to obtain 200 mL of buffer (Table 1). Table 1 : Gelation tests The amount of each sPEG polymer was weighed into a separate container (e.g., a 0.5 mL Eppendorf tube). For the experiments, a total precursor concentration of 140 mg (total weight of the first precursor and second precursor) per 1 mL of water of the respective precursor combinations was prepared. The Michael acceptor (1 eq of functions), such as 12 kDa sPEG-VS (3.18 mg, 1 eq of functions), was dissolved in 50 μL of buffer (pH 9.0). The Michael donor (1 eq of functions), such as 18 kDa sPEG-SH (3.82 mg, 1 eq of functions), was used without solvent. The buffer solution was pipetted into the undissolved sPEG-SH. As soon as the two compounds came into contact, the measurement was started. The solution was continuously pipetted up and down, and when the gel had formed (no further pipetting was possible), the measurement was stopped. Each experiment was repeated at least three times. Preliminary tests were conducted with the system according to the invention and a system in which both precursors were dissolved in buffer to investigate whether different gelation times were obtained. For these tests, concentrations of 140 mg (total weight of the first precursor and second precursor) were also adjusted to 1 mL of water. 12 kDa sPEG-VS and 12 kDa sPEG-SH were used. In the example according to the invention, only the 12 kDa sPEG-VS was dissolved in 50 pL of buffer (pH = 9.0) as described above, and the buffer solution was pipetted into the undissolved 12 kDa sPEG-SH. For comparison, the 12 kDa sPEG-VS and the 12 kDa sPEG-SH were each dissolved in 25 pL of buffer (pH = 9.0) and the buffer solution containing the 12 kDa sPEG-VS was pipetted into the buffer solution containing 12 kDa sPEG-SH. The system according to the invention exhibited a gel time of 10.43 s (±1.01), while the comparative example exhibited a gel time of 10.89 s (±1.05). It is evident that both systems exhibit comparable gel times, which indicates homogeneous and rapid mixing and thus rapid reactivity of the precursors in the system according to the invention. Thus, swellability, stiffness, and degradability are also expected to exhibit comparable values. Mining attempts As an example, experiments were prepared with a concentration of 140 mg (total weight of the first precursor and second precursor) per 1 mL of water of the respective precursor combinations. Freshly prepared precursor solutions were used. The Michael donor (1 eq of functional groups), such as 12 kDa sPEG-SH (66.63 mg, 1 eq of functional groups), was dissolved in 2 mL of buffer (pH = 9). The 2 mL Michael acceptor solution was prepared with the same number of functional groups (1 eq of functional groups), such as 12 kDa sPEG-VS (73.37 mg, 1 eq of functional groups). The solutions were pipetted into a double syringe (volume ratio 1:1, 2.5 mL per chamber, ADCHEM, K-System) and pressed into a flexible mold (2.0 cm x 2.0 cm x 1.5 cm) through a mixing adapter (ADCHEM, K-System, MKH 02-12S). After gelation, the hydrogel was removed and cut into four pieces. The hydrogel disc was stored in 4.0 mL of PBS buffer (AccuGENE PBS Buffer, pH = 7.4) at RT or 37°C (Cultura© M mini-incubator, 4 L). Degradability was examined by removing the medium, weighing the sample, and comparing it with the original weight of the hydrogel. After the measurement, new buffer was added to maintain constant degradation conditions. This process was repeated at specific time intervals until the hydrogel had completely dissolved. Swelling tests The amount of each precursor (see Table 2) was weighed into a separate vessel. The polymers were dissolved in pH 9.0 borax / HCl buffer. The precursor solutions were mixed on a shaker for 10 minutes. The sPEG-SH solution was always used immediately. The solutions were pipetted into a double syringe (volume ratio 1:1, 2.5 mL per chamber, ADCHEM, K-System) and injected into a cylindrical mold (diameter = 1.7 cm) through a two-component mixing attachment (ADCHEM, K-System, MKH 02-12S). Table 2: The hydrogel sample was removed from the mold and transferred to a 20 mL vial. The mass of the vial was determined empty and with hydrogel. 4.0 mL of PBS buffer (pH = 7.4) was added to the hydrogel. To ensure reproducibility, three of these samples were stored at 37°C and one at RT. The solvent (PBS buffer) was changed every four hours for the first 24 hours and then daily. For each condition, the wet hydrogel was weighed without buffer to determine the change in swelling and water content. The degree of swelling of the hydrogel was calculated using the formula: Measurement of the stiffness (storage modulus G') of the hydrogel To determine the mechanical properties of the hydrogel (storage modulus G'), both polymer components (total volume: 74 pL) were dissolved separately in borax / HCl buffer at a concentration of 140 mg (total weight of the first and second precursor) to 1 mL of solution and measured on a rheometer at 37 °C. Fresh precursor solutions were used. The Michael donor (1 eq of functional groups), such as 18 kDa sPEG-SH (6.07 mg, 1 eq of functional groups), was dissolved in 37 pL of buffer (pH = 9). The 37 pL Michael acceptor solution was prepared with the same Number of functions (1 eq of functions), such as 12 kDa sPEG-VS (4.29 mg, 1 eq of functions). Rheological characterization was performed using a DHR 3 rheometer with a 20 mm cone plate geometry from TA Instruments (USA). All samples were prepared directly onto the heated (37 °C) plate of the rheometer. 74 μl of the prepolymer solution, a volume ratio of 1:1 between sPEG-SH and the VS compound, both dissolved in a buffer solution with a pH of 9, were gelled into the punched PDMS film with a diameter of 20 mm, corresponding to the diameter of the geometry (δ = 20 mm), with the punched hole of the film placed exactly below the geometry. After the gel had formed, the PDMS film was removed, and the geometry was adjusted to the "geometry gap" (51 μm high). The following three measurements were then started: 300 s time sweeps, which were always followed by a frequency sweep (0.1 - 100 Hz, 0.5% strain) and an amplitude sweep (0.1 - 1000% strain, 1.0 Hz). The obtained values ​​of the gelling, degradation, swelling and stiffness tests of the precursor combinations are shown in Table 3. Table 3: Synthesis of star-shaped polyethers functionalized with iodine-containing groups (SPEG-TIB48) 3 kDa sPEG-OH (10.560 g, 21.12 mmol OH functions, 1.0 eq) was prepared via Dried overnight at 50 °C under high vacuum and stored in dry DCM (50 mL) dissolved. Subsequently, dry triethylamine (1.0 eq) was added, and the solution was cooled to 0 °C in an ice bath. In a separate Schlenk flask, 2,3,5-triiodobenzoyl chloride (TIB-Cl) (0.67 eq.) was dissolved in dry dichloromethane (30 mL) and then slowly added dropwise to the sPEG-OH solution at 0 °C over 30 minutes. After the addition was complete, the reaction was stirred for 20 h at room temperature. The DCM was evaporated off, and the crude product was taken up in unstabilized THF (50 mL) and filtered through a glass frit with a thin silica layer (approx. 2 cm high) to separate the insoluble triethylamine hydrochloride. The solvent was then removed using a rotary evaporator. The product was dissolved in THF and further purified by precipitation in a 1:1 mixture of diethyl ether and pentane at 0 °C. This procedure was repeated twice. The sPEG-TIB was obtained with a degree of functionalization of 48% (3 star polymer arms).The functionalization was determined by NMR spectroscopy. The SPEG-TIB48 has an iodine content of 26 wt.%, with the iodine content based on the total weight of the SPEG-TIB48. 1 H-NMR (400 MHz, CDCI3): 5 = 8.25-8.21 (1 H, m, OC(O)-C-CH), 7.71-7.65 (CI-CH-CI), 4.45-4.32 (2H, m, O-CH2-CH2-OC(O)-C) 3.95-3.05 (m, polymer backbone), 2.72-2.44 (4H, m, -CH2CH2SH), 1.64-1.53 ​​(1H, m, -SH), 1.10-1.02 (m, polymer backbone -CH2CH(CH3)O-) ppm. Synthesis of star-shaped polyethers with thiol groups and functionalized with iodine-containing groups (SPEG-TIB48-SH15) The SPEG-TIB48 (1.007 g, 0.674 mmol OH functions, 1eq) was dissolved in 20 mL of dry toluene in a Schlenk flask and dithiothreitol (0.5 eq) and p-toluenesulfonic acid (0.2 eq) were added. Subsequently, 3-mercaptopropionic acid (0.33 eq) was added, and the reaction mixture was refluxed for 24 h at 110 °C under protective gas. After the reaction time, the solvent was removed using a rotary evaporator, and the crude product was redissolved in dichloromethane and precipitated in a 1:1 mixture of diethyl ether and pentane. After storage at -80 °C for 1.5 h, the precipitant was decanted off, and the polymer was dried under vacuum. This step was repeated twice. The product was then dissolved in 50 mL of THF (unstabilized), cooled to 0 °C, and then filtered through silica gel to remove residues of p-toluenesulfonic acid. Finally, the polymer was subjected to a final precipitation in diethyl ether:pentane (1:1). One arm of SPEG-TIB48 could be modified with thiol groups, which corresponds to a degree of functionalization of 15%.The functionalization was determined by NMR spectroscopy. The SPEG-TIB48-SH15 has an iodine content of 25 wt%, with the iodine content based on the total weight of the SPEG-TIB48-SH15. 1 H NMR (400 MHz, CDCI3): 5 = 8.27-8.20 (1 H, m, OC(O)-C-CH), 7.72-7.65 (CI-CH-CI), 5.14-4.96 (1 H, m, CH2-C(H)CH3-OC(O)-CH2), 4.45-4.32 (2H, m, O-CH2-CH2-OC(O)-C), 4.24-4.14 (2H, m, O-CH2-CH2-OC(O)-CH2-), 3.95-3.05 (m, polymer backbone), 2.77-2.51 (4H, m, -CH2CH2SH), 1.67-1.58 (1 H, m, CH2-SH), 1.22-1.15 (3H, m, CH2-CH(CH3)OC(O)-), 1.13-0.99 (m, polymer backbone -CH2CH(CH3)O-) ppm. Gelation experiments were conducted with the iodine-containing star-shaped polyethers SPEG-TIB48 and SPEG-TIB48-SH15. Total precursor concentrations of 140 mg per 1 mL of water of the respective precursor combinations were used. The same conditions were used. as described above for the gelation experiments. 18 kDa sPEG-VS and 18 kDa sPEG-SH were used. In addition, 5 wt%, 10 wt%, 20 wt%, or 50 wt% of SPEG-TIB48 or 3.8 wt%, 7.5 wt%, or 14.6 wt% of SPEG-TIB48-SH15 were added, with the weight percent of the iodine-containing components being based on the total weight of the cross-linkable precursors. For all examples, 1 eq of VS functions and 1 eq of SH functions of the precursors were used. The 18 kDa sPEG-VS was dissolved in 50 μL of buffer (pH 9.0). The 18 kDa sPEG-SH was mixed with SPEG-TIB48 or SPEG-TIB48-SH15 and used without solvent. The following weights of the respective components were used (see Table 4). Table 4: The solutions have the following gelation times, which are shown in Table 5. Table 5: Visualization attempts using computed tomography (CT) Hydrogel discs were prepared as described for the degradation tests. 5. 18 kDa sPEG-VS and 18 kDa sPEG-SH were used. As described for the gelation experiments, 5 wt%, 10 wt%, 20 wt%, or 50 wt% of SPEG-TIB48 or 3.8 wt%, 7.5 wt%, or 14.6 wt% of SPEG-TIB48-SH15 were added, whereby the Weight percentage of iodine-containing components based on the total weight of the crosslinkable precursors. For the visualization experiments, the hydrogel discs were stored in PBS buffer (pH = 7.4) for 1 day and for 14 days. CT images were acquired on both days (Brilliance Big from Philips (Netherlands)) with a scan parameter of 184 mAs, a scan time of 13 see, and a CTDIvol of 13 mGy (radiation intensity). The hydrogel discs were immersed in water during the CT scans to achieve better contrast. The CT images are shown in Figure 1. It is clearly evident that the hydrogel discs with higher iodine concentrations allow for good CT visualization. The hydrogel discs containing 50% SPEG-TIB48 and 14.6% SPEG-TIB48-SH15 show sufficient CT visualization even after 14 days. The hydrogels containing SPEG-TIB48-SH15 show the best CT visualization, even over a longer period.

Claims

CLAIMS 1. A system for producing a degradable hydrogel comprising: (a) a first composition, wherein the first composition (a) is aqueous and contains a first precursor (ai) and a buffer system (a-ii), wherein the first precursor (ai) contains functional groups; and (b) a second composition, wherein the second composition (b) is anhydrous and contains a second precursor (bi), wherein the second precursor (bi) is liquid and contains functional groups and at least one hydrolyzable bond; wherein the functional groups of the first precursor (ai) are reactive with the functional groups of the second precursor (bi); and wherein the first precursor contains at least two functional groups and the second precursor contains at least three functional groups, or the first precursor contains at least three functional groups and the second precursor contains at least two functional groups.

2. The system according to claim 1, wherein the first and second precursors contain at least three functional groups; and / or wherein the reaction of the functional groups of the first precursor (ai) with the functional groups of the second precursor (bi) is a Michael-type reaction.

3. The system according to one of claims 1 or 2, wherein the functional groups of the first precursor (ai) contain conjugated unsaturated functional groups selected from the group containing vinylsulfone, (meth)acrylamide, maleimide, quinone, vinylpyridinium, and combinations thereof, preferably vinylsulfone, maleimide, and combinations thereof, preferably vinylsulfone, and the functional groups of the second precursor (bi) nucleophilic groups selected from the group containing amine, thiol, and combinations thereof, preferably thiol; or the functional groups of the first precursor (ai) contain nucleophilic groups selected from the group containing amine, thiol, and combinations thereof, preferably thiol, and the functional groups of the second precursor (bi) contain conjugated unsaturated functional groups selected from the group containing (meth)acrylate, vinylsulfone, vinylsulfonate, (meth)acrylamide, maleimide, quinone, vinylpyridinium, and combinations thereof, preferably (meth)acrylate, vinylsulfone, vinylsulfonate, maleimide, and combinations thereof, more preferably vinylsulfone; and / or wherein the hydrolyzable bond of the second precursor (bi) comprises ester bonds.

4. The system according to any one of claims 1 to 3, wherein the functional groups of the first precursor (ai) are located at the end sites of the first precursor (ai); and / or wherein the functional groups of the second precursor (bi) are located at the end sites of the second precursor (bi).

5. The system according to any one of claims 1 to 4, wherein the first precursor (ai) contains polyether, polyacrylic acid, poly(ethylene-co-acrylic acid), polyvinyl acetate, polyvinyl alcohol, poly(ethylene-co-vinyl alcohol), polyvinyl acetal, polyvinyl ether, poly(oxazoline), polyvinylpyrrolidone, polyvinylamine, polyvinyl methyl ether, poly(meth)acrylate, polyacrylamide, poly-(N-isopropylacrylamide), poly-(N-ethylacrylamide), polyoxymethylene, polycarbonate or a copolymer thereof, preferably polyether, polyacrylamide, poly-(N-isopropylacrylamide), poly-(N-ethylacrylamide), or a copolymer thereof, more preferably polyether.

6. The system according to any one of claims 1 to 5, wherein the first precursor (ai) contains polyether, preferably polyethylene oxide, polyglycidol, poly(ethylene oxide-co-propylene oxide), more preferably poly(ethylene oxide-co-propylene oxide), even more preferably random poly(ethylene oxide-co-propylene oxide); and / or wherein the second precursor (bi) contains polyether, preferably polyethylene oxide, polyglycidol, poly(ethylene oxide-co-propylene oxide), more preferably poly(ethylene oxide-co-propylene oxide), even more preferably random poly(ethylene oxide-co-propylene oxide); wherein the poly(ethylene oxide-co-propylene oxide) preferably contains 50 to 90 wt.% ethylene oxide units and 10 to 50 wt.% propylene oxide units, more preferably 60 to 90 wt.% ethylene oxide units and 10 to 40 wt% propylene oxide units, more preferably 70 to 90 wt% ethylene oxide units and 10 to 30 wt% propylene oxide units, wherein the weight percent is based on the total weight of the ethylene oxide and propylene oxide units of the poly(ethylene oxide-co-propylene oxide).

7. The system according to any one of claims 1 to 6, wherein the first precursor (ai) contains a linear, branched, dendritic, circular, or star-shaped polymer, preferably a dendritic or star-shaped polymer, more preferably a star-shaped polymer; and / or wherein the second precursor (bi) contains a linear, branched, dendritic, circular, or star-shaped polymer, preferably a dendritic or star-shaped polymer, more preferably a star-shaped polymer; wherein the star-shaped polymer preferably has 3 to 12 arms, preferably 3 to 8 arms.

8. The system according to any one of claims 1 to 7, wherein the first precursor (ai) has a molecular weight of 100 Da to 40 kDa, preferably 2.5 kDa to 20 kDa; and / or wherein the second precursor (bi) has a molecular weight of 100 Da to 40 kDa, preferably 2.5 kDa to 20 kDa.

9. The system according to any one of claims 1 to 8, wherein the first composition has a pH of 7 to 10, more preferably 7.4 to 10, even more preferably 7.4 to 9; and / or wherein the second precursor has a viscosity of up to 4,500 mPa s at room temperature; and / or wherein the system is injectable.

10. The system according to any one of claims 1 to 9, wherein the second composition (b) contains a third precursor (b-ii), wherein the third precursor (b-ii) is liquid and contains a functional group and at least one iodine-containing group, wherein the functional group of the third precursor (b-ii) is reactive with the functional groups of the first precursor (ai).

11. A method for producing a degradable hydrogel, comprising: (i) providing a system according to claim 1; and (ii) mixing the first and second compositions.

12. A kit for producing a degradable hydrogel, comprising: (i) a system according to claim 1; and (ii) a syringe, preferably a double syringe.

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