Method for producing planar, porous hydrogels by means of flow lithography

Abstract

The present invention is in the technical field of additive manufacturing and provides a continuous method for producing planar, porous hydrogels and structures. The present invention also provides an apparatus for the continuous production of hydrogels.

Description

[0001] Method for producing planar, porous hydrogels using flow lithography

[0002] The present invention lies in the technical field of additive manufacturing and provides a continuous process for producing planar, porous hydrogels and structures. The present invention also provides a device for the continuous production of hydrogels.

[0003] Hydrogels are three-dimensional networks of hydrophilic polymers that can absorb large amounts of water, making them flexible and gel-like. They are widely used in medicine, for example in wound dressings and as carrier materials for the controlled release of drugs, as well as in the manufacture of soft contact lenses. In biotechnology, they are used for cell cultures and tissue engineering, while in agriculture they improve water retention in the soil. Furthermore, hydrogels are in demand in the cosmetics industry for moisture retention and in sensors for environmental sensing, highlighting their versatility and biocompatibility.

[0004] These hydrogels are produced by crosslinking hydrophilic polymer chains, creating a three-dimensional network capable of binding water. The polymers can be of natural origin, such as gelatin or alginate, or synthetic, such as polyacrylamide. Crosslinking occurs chemically through covalent bonds or physically through hydrogen bonds and van der Waals forces. This process can be initiated by various methods, such as polymerization in aqueous solution, irradiation, or the use of chemical crosslinkers. The type of crosslinking and the polymers used determine the properties of the resulting hydrogel, such as its strength, porosity, and water absorption capacity. Several methods for producing hydrogels are disclosed in the prior art, and the three-dimensional structures within the hydrogels can be precisely controlled using lithographic techniques.

[0005] The use of two-photon lithography enables targeted microstructuring. Two-photon lithography is a technology for fabricating three-dimensional structures at the nanometer scale. It is based on the principle that two low-energy photons must be absorbed simultaneously by a photosensitive material to trigger a chemical reaction that hardens or modifies the material. Because this absorption occurs only in a tiny volume within the material, extremely precise structures with high resolution can be created.

[0006] A further development of this technology is vertical two-photon lithography, which specifically aims to create structures in the vertical direction (i.e., along the height) with high precision. While traditional two-photon lithography enables the creation of three-dimensional structures through focused light pulses in a photosensitive material, the vertical variant focuses specifically on the growth or patterning of structures along the vertical axis. This technology exploits the property that two-photon absorption occurs only in a very small volume, allowing for the creation of extremely thin and tall structures. Although this technology leads to improved microstructuring and the formation of fine three-dimensional geometries, it cannot be operated continuously on a large scale. The publication "Two-Photon Vertical-Flow Lithography for Microtube Synthesis" (Lölsberg et al.) describes this process., Small 2019, 15, e1901356) describes a two-photon lithography process which enables the fabrication of microtubular structures via a vertical flow, the process using a laser as a light source which rotates point by point for photochemically induced polymerization.

[0007] European patent application EP 3 368 020 A1 discloses a method for producing microparticles and hydrogels of defined size. This involves the use of a microfluidic device in an oxygen-controlled environment. The monomer is polymerized in the device using UV light to form microparticles.

[0008] Furthermore, European patent application EP 3291 971 A1 discloses a method for producing a hydrogel matrix with tunnel-shaped micropores and a 3D structure.

[0009] Korean patent application KR10-2008-0084432 discloses a method for producing microstructured hydrogel membranes. A photomask is used to achieve better pore uniformity.

[0010] European patent application EP 3988 138 A1 discloses a method for manufacturing a multilayer artificial heart muscle.

[0011] The publication “Stop-Flow Lithography for the Continuous Production of Degradable Hydrogel Achiral Crescent Microswimmers” (Xiong et al., DOAJ Vol. 13, No. 5, p. 789) discloses a study in which stop-flow lithography is used to produce degradable hydrogel microswimmers. The method disclosed enables the production of hydrogel particles that also possess magnetic properties and can be used in various biomedical fields. Traditional stop-flow lithography offers precise control over geometry, porosity, and mechanical properties, but is limited by batch processing, which restricts throughput and scalability.

[0012] All publications have in common that they reveal procedures that must be carried out discontinuously and do not reveal any possibilities for a continuous procedure.

[0013] Therefore, the primary objective of the present invention was to provide a method which enables the implementation of a continuous process for the production of hydrogels with a defined porosity and three-dimensional structure.

[0014] This primary problem was primarily solved by providing a method for producing porous planar hydrogels, comprising or consisting of the steps: i. Providing a solution containing at least two monomer units;

[0015] ii. Introducing the solution provided in step i. as an input current into a photochemical device containing a surface light modulator;

[0016] iii. Initiating and curing the monomer units by means of a light pulse introduced into the solution via the area light modulator, which imparts a predetermined porosity through polymerization of the monomer units;

[0017] iv. Obtaining a planar hydrogel with a predetermined porosity.

[0018] The hydrogels obtained in the present process can have a predefined width by selecting the geometry of the photochemical apparatus.

[0019] The term "sheet hydrogel" includes hydrogels with a predetermined porosity. Preferably, "sheet hydrogels" can also be hydrogels that have a defined thickness determined by the inventive method. Such hydrogels can also be referred to as "three-dimensional hydrogels." The term "three-dimensional" includes the extension of a hydrogel according to the invention along an axis perpendicular to the surface of the hydrogel, as well as the folding of hydrogels obtained according to the invention into desired three-dimensional structures. Such three-dimensional structures can be, for example, tubular structures or wave-like bands.

[0020] The term "porosity" within the context of the present invention defines the arrangement or distribution of pores in a hydrogel. A general distinction is made between different porosities:

[0021] 1. Continuously homogeneous porosity: The entire hydrogel contains the same proportion of polymer with the same degree of swelling. The degree of swelling in hydrogels describes the extent to which a hydrogel can absorb water or other liquids and swell. It indicates the ratio between the amount of liquid absorbed and the original weight or volume of the dry hydrogel. In hydrogels with continuously homogeneous porosity, the degree of swelling is the same throughout the entire hydrogel. 2. Continuously heterogeneous porosity: Due to laterally varying light intensity, differences arise in the degree of cross-linking of the polymers. This causes variable degrees of cross-linking and swelling in both the two-dimensional extent and the thickness of the hydrogel. By creating continuously heterogeneous porosity, hydrogels with variable properties can be achieved across both two-dimensional and three-dimensional dimensions.

[0022] 3. Continuously homogeneous porosity with so-called "defects": Such a hydrogel possesses a porosity as described in 1., but with predefined locations where polymer cross-linking does not occur due to the lack of a light pulse ("defects"). The defects can be present in two-dimensional as well as three-dimensional dimensions.

[0023] 4. Continuously heterogeneous porosity with so-called "defects": Such a hydrogel possesses a porosity as described in section 2, but with predefined locations where polymer crosslinking does not occur due to the lack of a light pulse ("defects"). The defects can be present in both two-dimensional and three-dimensional dimensions.

[0024] The average pore size plays a role in characterizing a hydrogel produced according to the invention. Preferably, within the scope of the present invention, the average diameter of the pore size (dso) is 0.05 to 100 pm, more preferably 0.1 to 75 pm, and most preferably 0.1 to 50 pm.

[0025] Furthermore, the formation of defects also plays a role in characterizing a hydrogel produced according to the invention. Preferably, within the scope of the present invention, the mean diameter of the defects (dso) is more than 50 pm to 500 pm, preferably 50 to 150 pm.

[0026] Preferably, the process according to the invention is a continuous process. Within the framework of a continuous process, planar hydrogels of a theoretically unlimited length can be produced; only the width is defined by the choice of the width of the photochemical apparatus.

[0027] A "continuous process" is one that runs uninterrupted and without interruption. In a continuous process, the solution containing at least two monomer units is continuously fed in, and the resulting hydrogel is continuously withdrawn, thus ensuring a uniform and continuous production. In contrast to batch processes, where specific quantities of material are processed in separate batches, a continuous process ensures a constant flow of both feedstock and product.

[0028] The area light modulator generates a photoinduced polymerization of the solution containing the monomer units by selectively emitting light pulses, preferably in the form of a predefined, area pattern. The solution contains at least two monomers. The porosity of the resulting hydrogels is determined by controlling the light pulse.

[0029] Through such a continuous process in combination with the porosity adjustable by the inventive process, a structure can be achieved that has zones of different porosity and therefore enables the production of complex hydrogel structures compared to structures known from the prior art with the desired mechanical and chemical properties.

[0030] A "digital mirror device" (DMD) is a microelectromechanical system (MEMS) consisting of an array of tiny, movable mirrors. These mirrors are mounted on a semiconductor chip and can be individually controlled to reflect or block light. By rapidly tilting the mirrors between different positions (e.g., "on" and "off"), they can precisely direct light pulses and thus generate planar patterns for polymerization. Modulating the light pulse into a planar pattern via the mirrors enables simultaneous, precise emission to initiate the photochemical reaction and, consequently, to create a desired, predetermined porosity.

[0031] Hydrogels produced according to the inventive method are particularly suitable for replicating heterogeneous cell tissues, since the use of the area light modulator allows for the simultaneous production of different porosities and, through a continuous process, theoretically unlimited lengths of the desired hydrogels. Other applications of the hydrogels produced according to the invention, such as synthetic membranes, are also possible and obvious to those skilled in the art. The monomer units contained in the solution react with each other via a photochemical reaction and form the hydrogel through polymerization. In photochemical polymerization, a photosensitive initiator is activated by irradiation with light of a specific wavelength, causing it to decompose into reactive species such as free radicals or ions.These species react with monomers and break their double bonds, triggering a chain reaction in which monomer units are linked to form long polymer chains. The process ends when two reactive species meet and neutralize each other, or when a radical is stabilized so that no further monomers are added to the chain. Thus, a solid polymer is formed from liquid monomers, the polymerization of which can be precisely controlled by the area light modulator used within the scope of the present invention.

[0032] The advantage of the present invention is that the flow conditions during lithographic polymerization are optimized in such a way that the effective polymerization area is extended beyond the limits of a single focal point. By using an area light modulator to synchronize the parameters of the light pulse with the flow rate of the solution containing the monomer units, the present invention provides a method for the continuous production of porous hydrogels. This approach increases the throughput and flexibility of the manufacturing process.By adjusting the composition of the solution containing the monomer units and by using non-reactive or reactive species, the method of the present invention also offers more differentiated control over the physical and chemical properties of the hydrogel obtained and enables the production of porous hydrogels with a predefined width through the geometry of the photochemical device used and of infinite length, which are suitable for a variety of applications.

[0033] Preferably, within the scope of the present invention, at least one photoinitiator selected from the group consisting of compounds with benzoin methyl ether residues, benzoin ethyl ester, benzildimethyl ketal, cyclo-bis(acyl)phospin oxide, diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide, camphorquinone or lithium phenyl 2,4,6-trimethylbenzoylphosphinate is present in the solution provided in step i.

[0034] Preferably, the photoinitiator provided in the present process is lithium phenyl 2,4,6-trimethylbenzoylphosphinate. Furthermore, photoinitiators or crosslinkers that impart chemical modifications to the hydrogels obtained are preferred in the context of the present invention.Such photoinitiators are sold, for example, by TCI Chemicals and are selected from the group consisting of 4-azido-2,3,5,6-tetrafluorobenzoic acid, 4-(N-maleimido)benzophenone, N-succinimidyl 4-benzoyl benzoate, 4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzoic acid, 4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzylamine hydrochloride, bis[2-(4-azidosalicylamido)ethyl]disulfide, N-succinimidyl-5-azido-2-nitrobenzoate, N-succinimidyl-4-azido-2,3,5,6-tetrafluorobenzoate, 4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl alcohol, N-succinimidyl 6-(4-azido-2-nitroanilino)hexanoate, N-hydroxysuccinimide 4-azidobenzoate, 4-nitrophenyl [2-[3-[(Prop-2-yn-1-yloxy)methyl]-3H-diazirin-3-yl]ethyl] carbonate, and 2,5-Dioxopyrrolidin-1-yl-3-[[2-[3-(3-Methyl-3H-diazirin-3-yl)propanamido]ethyl]disulfaneyl]propanoate.Chemical modifications in the resulting hydrogels can, for example, influence the electrical conductivity of the hydrogel and thus adapt the hydrogels to the requirements for a variety of uses.

[0035] Furthermore, preferably the solution provided in step i. contains at least two monomer units selected from the group consisting of N-isopropylacrylamide (NIPAM), poly(N-isopropylacrylamide) (PNIPAM), N,N'-methylenebisacrylamide), polyethylene glycol)diacrylate (PEGDA), agarose, polyacrylamide, cellulose acetate, poly(2-hydroxyethyl methacrylate) (pHEMA), poly(N-isopropylacrylamide) (pNIPAM), polyhyaluronic acid, polyethylene glycol (PEG), poly(lactic acid) (PLA) or poly(L-lysine) (PLL).

[0036] The choice of at least one photoinitiator and at least two monomer units can, as described above, influence the chemical and physical properties of the hydrogel.

[0037] Within the scope of the present invention, it is particularly preferred that the resulting hydrogel preferably possesses electrical conductivity and is thus especially suitable for replicating cardiac structures. The property of electrical conductivity can be introduced into the hydrogel via various methods: 1. Mixing a solution of PEDOT:PSS (poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOTPSS)) with the at least two monomers, followed by simultaneous polymerization and crosslinking.

[0038] 2. Treating the obtained hydrogels with a solution containing 3,4-ethylenedioxythiophene (EDOT monomers) and subsequent repolymerization and cross-linking of the monomer solution by means of a light pulse on the hydrogels.

[0039] 3. Mixing the solution containing the at least two monomers with a solution containing carbon nanotubes (CNTs, multi- or single-wall nanotubes) and subsequent simultaneous crosslinking so that the CNTs are incorporated into the structure of the hydrogel.

[0040] 4. Simultaneous crosslinking of the polymer scaffolds to obtain the hydrogels with EDOT without additional photoinitiators.

[0041] The use of the described materials adds new functionalities to hydrogels. For example, the use of PEDOTPSS enables the targeted cultivation of cells (e.g., cardiac muscle cells) on or in the resulting hydrogel to form artificial, biomimetic heart structures. The use of PEDOTPSS as a material for cell culture is described in Rauer et al., "Porous PEDOTPSS Particles and their Application as Tunable Cell Culture Substrate," Advanced Materials Technologies, volume 7, issue 1, 2021. In this context, in addition to electrical conductivity, the elasticity of such a hydrogel achieved through the use of PEDOTPSS is also crucial. Furthermore, the formation of hydrogels using other electrically conductive polymers is also advantageous. The article Sury ef a / 2021 J. Phys.: Conf Ser.1788 012004 “Synthesis of Conducting Polyaniline with Photopolymerization Method and Characterization” describes, for example, polyanilines as electrically conductive materials that are used in photopolymerization.

[0042] Preferably, the light source used is a UV light source. "UV light" (ultraviolet light) is a form of electromagnetic radiation that lies in the spectrum between visible light and X-rays. It has shorter wavelengths than visible light and is therefore not perceived by the human eye. UV light is divided into three main types: UV-A (320-400 nm), UV-B (280-320 nm), and UV-C (100-280 nm), with UV-C being the most energetic and potentially most dangerous form. Preferably, the light pulse has a wavelength between 315 and 400 nm.

[0043] Preferably, in the present method, the flow rate of the solution provided in step i. is synchronized with the area light modulator at the point of entry into the photochemical apparatus. "Synchronization" means that the flow rate of the solution provided in step i. into the photochemical apparatus is matched with the irradiation pattern and / or the irradiation duration emitted by the area light modulator.

[0044] Preferably within the framework of the present method, the area light modulator generates a dynamic pattern of light pulses.

[0045] Preferably, the width of the hydrogel is determined by the width of the photochemical apparatus. Preferably, the photochemical apparatus also includes a shaping element that defines the shape of the resulting hydrogel.

[0046] The device is designed such that, following the photochemical reaction zone where polymerization takes place, it includes a shaping element that allows the outflow stream to be shaped, resulting in the formation of specific forms such as tubular structures or wavy loops. Enlarging the flow channel in the device according to the invention can lead to folding due to the resulting reduction in flow velocity. The dimension of such folds is determined either by the height of the enlarged flow channel or by exposure effects in the form of fold lines. A spiral shape results when the planar hydrogel flows into an enlarged flow channel at an angle. The spiral shape is determined by the inlet angle to the flow channel and the cross-section of the enlarged flow channel.Furthermore, the combination of fold lines and shaping elements can lead to further three-dimensional structures of the hydrogels obtained according to the invention.

[0047] Preferably within the scope of the present invention and as described herein, the obtained planar hydrogel has its dimension by the width of the photochemical device and / or its porosity by adjusting the light pulse via the planar light modulator.

[0048] Another aspect of the present invention relates to a device for the continuous production of hydrogels with predetermined porosity comprising at least one pump, at least one inlet, at least one photochemical reaction chamber, at least one area light modulator and at least one outlet.

[0049] As described herein, the width of the photochemical reaction chamber, or the width of the inlet, defines the width of the resulting planar hydrogel.

[0050] The device may also include a shaping element downstream of the photochemical reaction chamber, which additionally defines the three-dimensional structure of the resulting hydrogel.

[0051] Furthermore, the device can also include a controller that controls the area light modulator by inputting a desired structure and porosity. Such a controller can be a computer. An area pattern can be set via the digital, computer-based control system so that precise exposure is achieved by synchronizing the flow rate with the pattern movement in the area light modulator. Dynamic exposure patterns that do not occur synchronously with the flow rate may also be desired. These result in more complex exposure patterns and corresponding structural formations and can be pre-programmed via simulations.

[0052] Preferably, the pump and the area light modulator are synchronized so that the flow rate of the input current is synchronized with the light pulses emitted by the area light modulator. Synchronization can be achieved via a controller that controls both the flow rates of the input current and the associated emission of light pulses.

[0053] The hydrogels obtained within the scope of the present invention can be used in a variety of applications, such as for the production of biomimetic structures for tissue engineering, as filters or as membranes with defined permeability and mechanical stability.

[0054] The invention is described in more detail below by means of illustrative examples. List of figures

[0055] Figure 1: Electron micrograph (FESEM) of a preserved hydrogel showing folding and porosities.

[0056] Figure 2: Series of hydrogel patches with an induced third porosity level (3 rd ) due to the absence of irradiation spots within a regular hexagonal spot arrangement of circular spots with a diameter of 7 pm on the patches (first- and second-degree porosity (1 st and 2 nd From left to right: without additional induced porosity, induced 44 pm porous areas due to individual missing irradiation spots, induced 95 pm pores due to the absence of an array of seven spots. Visualization of the spots by (a) mask schemes and corresponding brightfield images of the spots and (b) FESEM images indicating the porosity grades. The scales (a: 100 pm, b: 50 pm) apply to all micrographs.

[0057] Figure 3: Microscopic image of a cell culture (L929 mouse fibroblasts) on a circular field with 95 pm defects and highly cross-linked regions of 7 pm diameter in a hexagonal arrangement, regularly interrupted by through pores of 95 pm diameter after four days. Examples

[0058] Example 1: Production of a hydrogel according to the invention

[0059] a) Preparation of the monomer solution or the material base

[0060] Two material systems were used to produce the hydrogels according to the invention. The first is based on the monomer poly(ethylene glycol) diacrylate (PEGDA) (average molecular weight of Mn = 575 Da, with 400–600 ppm MEHQ as an inhibitor, Sigma-Aldrich). The other contains the monomer N-isopropylacrylamide (NIPAM) (98%, Acros Organics, recrystallized to hexane (99%, VWR)) and the crosslinker N,N'-methylenebisacrylamide (BIS) (99%, Sigma-Aldrich). Both material systems were initiated with UV light (365 nm) and the photoinitiator lithium phenyl 2,4,6-trimethylbenzoylphosphinate (LAP) (>95%, Sigma-Aldrich). Water (HiPerSolv CHROMANORM, VWR) was used as the solvent. To prepare the reaction solutions, depending on the material system, the monomer NIPAM or the prepolymer PEGDA (each 20 wt%) was weighed into a container (1.5 mL, Eppendorf) and water (77 wt% for NIPAM and 79 wt% for PEGDA) was added. The initiator LAP (1 wt%) was then added.The monomer solution (-%) was weighed into a separate, light-protected brown container (1.5 mL, Eppendorf). In the case of the NIPAM material system, the crosslinker BIS (2 wt%) was also weighed and added to the initiator vessel. The monomer solutions were then added to the initiator-crosslinker vessel. This mixture was homogenized using a vortex mixer (Vortex Genie 2 Digital, Scientific Industries) (3000 rpm, 20 s). As the final preparation step for the reaction solution before hydrogel synthesis, the vessel was then centrifuged (Mini Star Silverline, VWR) (6000 rpm, 3 minutes).

[0061] b) Formation of the hydrogel

[0062] The solution obtained in step a) was introduced into a microfluidic setup with a surface light modulator and a UV light source (wavelength 365 nm, LZ1-00UV00, LED Engin.) and photochemically induced polymerization was initiated by irradiation. The exposure patterns were set using a computer.

[0063] After preparation, the reaction solution surrounding the hydrogels was replaced by dialysis with deionized water (Zellutrans, MWCO: 12-14 kDa, 25 mm flat width, 20 pm wall thickness, Carl Roth GmbH) in a water bath (deionized, 10 L, 2 x 24 hours). The resulting hydrogels were then optionally folded into three-dimensional structures.

[0064] c) Characterization of the hydrogels obtained

[0065] Figures 1 to 3 show various hydrogel structures obtained.

[0066] A hydrogel produced according to the invention in a three-dimensional configuration is shown in Figure 1. This shows an image taken using field emission scanning electron microscopy (FESEM), on which both the different porosities within the hydrogel and the structure achieved by folding the hydrogel can be seen.

[0067] Figure 2 shows different porosities of the hydrogel. In addition to the formation of first- and second-degree porosity by using a planar irradiation pattern of the hydrogel, further porosities (so-called third-degree pores) can be formed through additional irradiation patterns or the absence of irradiation. Figure 2a shows the irradiation pattern and the corresponding bright-field image. Figure 2b shows FESEM images with information on the achieved porosity grades.

[0068] Figure 3 shows the cultivation of L929 mouse fibroblasts on a hydrogel according to the invention with through pores of 95 pm diameter. Furthermore, the hydrogel has a core structure with continuous circular, highly cross-linked regions with a diameter of 7 pmm. The cultivation time was four days. The hydrogel is based on polymerized PEGDA monomers with added GMA to enable coating with fibronectin for cell culture. The hydrogel structure influences cell morphology. The cells arrange themselves around the through pores, allowing these to serve as channels for cell migration in three-dimensional configurations.

Claims

Claims 1. A method for producing porous planar hydrogels, comprising or consisting of the steps: i. Providing a solution containing at least two monomer units; ii. Introducing the solution obtained in step i. as an input current into a photochemical device containing a surface light modulator; iii. Initiation and polymerization of the monomer units by a light pulse introduced into the solution via the area light modulator, which imparts a predetermined porosity through polymerization of the solution; iv. Obtaining a hydrogel with a predetermined porosity.

2. The method of claim 1, wherein the method is a continuous method.

3. A method according to claim 1 or 2, wherein the solution provided in step i. contains at least one photoinitiator, preferably selected from the group consisting of compounds with benzoin methyl ether residues, benzoin ethyl ester, benzildimethyl ketal, cyclo-bis(acyl)phospin oxide, diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide, camphorquinone or lithium phenyl 2,4,6-trimethylbenzoylphosphinate. and / or Contains at least two monomer units selected from the group consisting of N-isopropylacrylamide (NIPAM), poly(N-isopropylacrylamide) (PNIPAM), N,N'-methylenebisacrylamide), polyethylene glycol)diacrylate (PEGDA), agarose, polyacrylamide, cellulose acetate, poly(2-hydroxyethyl methacrylate) (pHEMA), poly(N-isopropylacrylamide) (pNIPAM), polyhyaluronic acid, polyethylene glycol (PEG), poly(lactic acid) (PLA) or poly(L-lysine) (PLL).

4. Method according to one of the preceding claims, wherein the light pulse has a wavelength of between 315 and 400 nm.

5. Method according to one of the preceding claims, wherein the flow rate of the solution provided in step i. is synchronized with the area light modulator at the entry point into the photochemical device.

6. Method according to one of the preceding claims, wherein the area light modulator generates a dynamic pattern of light pulses.

7. Method according to one of the preceding claims, preferably claim 5 or 6, wherein the hydrogel obtained is given a predetermined porosity by adjusting the light pulse.

8. Device for the continuous production of hydrogels with predetermined porosity comprising at least one pump, at least one inlet, at least one photochemical reaction chamber, at least one area light modulator and at least one outlet.

9. Device according to claim 8, wherein a further area for forming three-dimensional structures of the obtained hydrogels is located downstream of the photochemical reaction chamber.

10. Device according to claim 8 or 9, wherein the pump and the area light modulator are synchronized so that the flow rate at the input current is synchronized with the light pulses emitted by the area light modulator, and preferably the synchronization is carried out via a controller.

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