The present invention relates to a gel material for regenerative medicine containing a polymer gel having a porous structure consisting of two regions, a dense phase and a dilute phase, of a hydrophilic polymer component, and a kit for producing the gel material. Background technology [0002] In recent years, polymer gels having a network structure have been used for medical purposes such as materials for artificial tissues and regenerative scaffolds, sealing, adhesion prevention, drug delivery, and contact lenses, due to their excellent water retention capacity and biocompatibility. In addition, it is a material that is expected to be applied to various uses such as sensors and surface coatings (for example, Non-Patent Document 1). In particular, for these uses, development of polymeric materials having a porous structure on the order of μm is desired. [0003] However, conventionally, in order to obtain a μm-scale porous structure, a top-down method such as microfabrication by lithography or the like is used for a previously prepared gel or polymer structure, or a solvent-insoluble polymer is used. It was necessary to create a polymeric material using raw materials. On the other hand, in the case of using solvent-philic polymer raw materials, either the material itself dissolves in the solvent in the first place, or only a gel with a porous structure as small as nm scale can be produced. In addition, there have been no reports on the application of gel materials having such a porous structure to the regeneration and repair of living tissue. prior art documents Non-patent literature [0004] Non-Patent Document 1: Sakai et al., Macromolecules, 41, 5379-5384, 2008 SUMMARY OF THE INVENTION Problems to be Solved by the Invention [0005] Accordingly, the present invention provides a gel material composed of a solvent-philic polymer having a micrometer-scale porous structure, and further provides a novel use to which such a gel material can be suitably applied. is the subject. Means to solve problems [0006] As a result of intensive studies aimed at solving the above problems, the present inventors found that a polymer gel obtained by cross-linking a hydrophilic polymer raw material under specific conditions resembles phase separation in a poor solvent polymer. It behaves like a sponge and forms a sponge-like three-dimensional network structure (μm-scale porous structure) consisting of a dense region where the polymer component exists densely and a dilute region where the polymer component exists sparsely, which is not seen in conventional polymer gels. It has been found that it has a unique structure, and furthermore, in the regeneration and repair of living tissue such as bone, by applying a gel material containing such a polymer gel to the affected area, the regeneration and repair of the living tissue can be promoted. . Based on these findings, the present invention has been completed. [0007] That is, in one aspect of the present invention, <1> A gel material for regenerative medicine containing a polymer gel in which hydrophilic polymer units are mutually crosslinked, wherein the polymer gel contains water as a solvent and the polymer units are densely present. It has a three-dimensional network structure having two regions, a first region and a second region in which the polymer units are sparsely present, and the mesh size formed by the first region has a size of 1 to 500 μm. The gel material for regenerative medicine, characterized by It provides [0008] In addition, as a preferred embodiment of the gel material for regenerative medicine of the present invention, <2> The gel material for regenerative medicine according to <1> above, which has a lower transmittance than the polymer unit before gelation; <3> The gel material for regenerative medicine according to <1> or <2> above, which has an osmotic pressure in the range of ⅕ to ½ of the osmotic pressure of the polymer unit before gelation; <4> Any one of <1> to <3> above, wherein the osmotic pressure (Π os) and elastic pressure (Π el) after a certain period of time has elapsed from gelation have a relationship of Π el > Π os The gel material for regenerative medicine described; <5> Any one of <1> to <4> above, wherein the first region has a polymer concentration of 10 to 99% by weight and the second region has a polymer concentration of 0 to 1% by weight. The gel material for regenerative medicine described; <6> The gel material for regenerative medicine according to any one of <1> to <5> above, which has a polymer content of 5% by weight or less; <7> The gel material for regenerative medicine according to any one of <1> to <6> above, wherein the polymer unit is a polymer having a polyethylene glycol skeleton or a polyvinyl skeleton; <8> The polymer units are a first polymer unit having one or more nucleophilic functional groups in side chains or terminals, and a second polymer having one or more electrophilic functional groups in side chains or terminals. The gel material for regenerative medicine according to any one of <1> to <7> above, which consists of units; <9> the nucleophilic functional group is selected from the group consisting of a thiol group and an amino group, and the electrophilic functional group is a maleimidyl group, an N-hydroxy-succinimidyl (NHS) group, a sulfosuccinimidyl group; , a phthalimidyl group, an imidazoyl group, an acryloyl group, a nitrophenyl group, and a gel material for regenerative medicine according to <8> above; <10> The gel material for regenerative medicine according to any one of <1> to <9> above, which is used for tissue regeneration; <11> The gel material for regenerative medicine according to <10> above, wherein the tissue is bone, cartilage, skin, or nerve; and <12> A treatment method using the gel material for regenerative medicine according to any one of <1> to <11> above It provides [0009] In another aspect, the present invention also relates to a kit for producing the gel material for regenerative medicine, <13> A kit for producing a gel material for regenerative medicine, characterized in that the following two types of solutions (A) and (B) are stored without being mixed with each other, A) an aqueous solution containing a hydrophilic first raw material polymer having an overlap concentration less than the critical gelling concentration and having a critical gelling concentration or more; (B) an aqueous solution containing a hydrophilic second raw material polymer having an overlapping concentration less than the critical gelling concentration but not less than the critical gelling concentration; The solution of (A) and/or (B) further contains a non-reactive polymer that does not have a functional group capable of undergoing a cross-linking reaction with the raw material polymer in the molecule, and the solution of (A) and (B) above A polymer gel obtained by mixing is a polymer gel obtained by cross-linking the first raw material polymer and the second raw material polymer, and the polymer gel is a polymer derived from the raw material polymer. The kit having a structure composed of two regions: a first region in which the units are densely present and a second region in which the polymer units derived from the raw material polymer are sparsely present; and <14> A kit for producing a gel material for regenerative medicine, characterized in that the following two types of solutions (A') and (B') are stored without being mixed with each other, , (A′) an aqueous solution containing a first gel precursor, wherein the first gel precursor crosslinks a hydrophilic raw material polymer under conditions of less than the overlap concentration and less than the critical gelation concentration. (B') an aqueous solution containing the second gel precursor, , the second gel precursor is obtained by cross-linking a hydrophilic raw material polymer under conditions of less than the overlap concentration and less than the critical gelation concentration, and the storage elastic modulus G′ and the loss elastic modulus The solution having a relationship of G' The kit according to <13> or <14> above, wherein the raw material polymer is a polymer having a polyethylene glycol skeleton or a polyvinyl skeleton; <16> The raw material polymer is a first polymer having one or more nucleophilic functional groups in a side chain or terminal, and a second polymer having one or more electrophilic functional groups in a side chain or terminal. The kit according to any one of <13> to <15> above; <17> the nucleophilic functional group is selected from the group consisting of a thiol group and an amino group, and the electrophilic functional group is a maleimidyl group, an N-hydroxy-succinimidyl (NHS) group, a sulfosuccinimidyl group; , a phthalimidyl group, an imidazoyl group, an acryloyl group, a nitrophenyl group, and a kit according to <16> above; <18> The kit according to <13> above, wherein the non-reactive polymer is polyethylene glycol or cellulose that does not have a crosslinkable group; <19> The first gel precursor and the second gel precursor are both a first polymer having one or more nucleophilic functional groups in side chains or terminals, and one or more in side chains or terminals. wherein the first gel precursor contains more of the first polymer than the second polymer, and the second gel precursor contains is the kit according to <14> above, wherein the content of the second polymer is higher than the content of the first polymer; <20> The kit according to <14> above, wherein the gel precursor has a diameter in the range of 10 to 1000 nm; <21> A method for producing a gel material for regenerative medicine in vivo using the kit according to any one of <13> to <20> above; and <22> Use of the kit according to any one of <13> to <20> above in the treatment of tissue regeneration It provides The invention's effect [0011] The gel material for regenerative medicine of the present invention can promote the regeneration and repair of living tissue such as bone by applying the gel material to the affected area. Specifically, as shown in the Examples, filling the bone defect portion with the gel material for regenerative medicine of the present invention has the effect of improving bone union and new bone growth in the facial bone defect portion. can get. [0012] In addition, by using the kit of the present invention, it is possible to form a gel material for regenerative medicine in situ in vivo, so that it can be used as an injectable gel material into a closed or semi-closed cavity in vivo. . Brief description of the drawing [0013] 1] Fig. 1 is a graph showing the time scale of the gelation reaction in the polymer gel of the present invention produced in Example 2. [Fig. 2] FIG. 2 is a graph showing changes in transmittance in the gelation step of the present invention. [FIG. 3] FIG. 3 is a graph showing changes in transmittance of a comparative gel that does not undergo a gel precursor. [FIG. 4] FIG. 4 is a graph showing time-dependent changes in the degree of swelling of the polymer gel of the present invention. [FIG. 5] FIG. 5 is a graph showing changes in osmotic pressure (Π os) of the polymer gel of the present invention. [FIG. [Fig. 6] Fig. 6 is a fluorescence microscope image of a polymer gel of the present invention (right) and a comparative example gel (left). [Fig. 7] Fig. 7A is micro-CT images of a rat tibia region without polymer gel filling (a to c) and polymer gel filling (d to f) 2, 3, and 4 weeks after bone defect creation. . FIG. 7B shows HE-stained images of rat tibia sites without polymer gel (g and h) and with polymer gel (i and j) 4 weeks after bone defect creation (black bar: 5 mm; (i and j are enlarged views of the broken-line squares in the images of g and h, respectively). [Fig. 8] Fig. 8 shows sham (NTC; negative control), comparative gel filling ("Tetra-PEG gel"), and polymer gel filling of the present invention ( "Tetra-PEG sponge") is a micro-CT image. [Fig. 9] Fig. 9 shows images of the polymer gel of the present invention ("Oligo-TetraPEG gel" and comparative gel (Tetra-PEG gel) implanted subcutaneously in rats. [Fig. MODE FOR CARRYING OUT THE INVENTION [0014] Embodiments of the present invention will be described below. The scope of the present invention is not bound by these descriptions, but rather the following examples. More about this source textSource text required for additional translation information Send feedback Side panels History Saved Contribute 5,000 character limit. Use the arrows to translate more.The outside can also be modified and implemented as appropriate within the scope of the present invention. [0015] 1. Gel material for regenerative medicine of the present invention The gel material for regenerative medicine of the present invention is characterized by containing a polymer gel having a μm-scale sponge-like porous structure. [0016] As used herein, the term “regenerative medicine” broadly refers to the regeneration or repair of biological tissues that have been deficient, damaged, or functionally degraded due to factors such as disease, injury, accident, or aging, and to restore their functions. means cure. Therefore, treatment is not limited to transplantation of somatic stem cells or pluripotent stem cells such as iPS cells collected from oneself or others, or tissues obtained from such cells ("regenerative medicine in a narrow sense"). [0017] Further, in the present specification, the "tissue" that is the target of regenerative medicine is not particularly limited as long as it is a living tissue that needs to be regenerated or repaired. can be mentioned. [0018] Details of the polymer gel, which is the main component of the gel material for regenerative medicine, and the manufacturing method thereof will be described below. [0019] (1) Polymer gel The polymer gel contained in the gel material for regenerative medicine of the present invention is formed by cross-linking hydrophilic polymer units to form a gel, and contains water as a solvent. It is a so-called hydrogel, i) having a three-dimensional network structure having two regions, a first region in which the polymer units are densely present and a second region in which the polymer units are sparsely present; ii) The mesh size formed by the first region has a size of 1 to 500 μm. [0020] That is, although the polymer gel in the present invention is formed from solvent-philic polymer units, it behaves as if a poor-solvent polymer is phase-separated in the solvent, and the polymer in the gel It has a structure in which two regions with different polymer concentrations are formed: a dense phase (first region) in which the components are densely present and a dilute phase (second region) in which the components are sparsely present. Due to this phase separation, the polymer gel forms a sponge-like three-dimensional network/porous structure (hereinafter, such a structure may be referred to as a "sponge-like porous structure"). , and its network size is on the order of μm, which is far larger than the order of nm obtained in conventional gels. Here, the first region is referred to as a "dense phase" in the relative sense that the concentration (density) of the polymer units present in that region is greater than the density in the second region. Preferably, the first region has about 100 times the concentration (density) of the second region. [0021] As used herein, the term “gel” generally refers to a high-viscosity polymer dispersion system that has lost fluidity, and has a relationship of G′≧G″ in the storage elastic modulus G′ and the loss elastic modulus G″. refers to the state of having [0022] As described above, the polymer gel in the present invention is characterized by having a micrometer-order porous structure. Specifically, the mesh size formed by the first region can be 1 to 500 μm, preferably 10 to 100 μm. The mesh size means the length of the long side of the mesh unit (that is, the pores) whose perimeter is formed by the dense phase first region. Alternatively, if the mesh unit is substantially circular, it can be the length of its diameter. Inside such a network unit, there is a second region which is a dilute phase and/or a solvent. [0023] Typically, the first region, the dense phase, has a polymer concentration of 10-99% by weight, based on the total solvent-containing gel, and the second region, the lean phase, has a concentration of 0-1% It has a high polymer concentration. Preferably, the first region has a polymer concentration of 40-80 wt% and the second region has a polymer concentration of 0.01-0.1 wt%. [0024] In addition, the polymer content in the entire polymer gel in the present invention is 5% by weight or less, preferably 4% by weight or less, more preferably 1.5 to 3.0% by weight. [0025] As described above, water is used as the solvent contained in the polymer gel in the present invention. In this case, such a polymer gel containing water becomes a hydrogel. However, in some cases, it may further contain an alcohol such as ethanol and an organic solvent such as DMSO. [0026] The following describes the polymer units that constitute the polymer gel used in the gel material for regenerative medicine of the present invention, and the characteristic physical properties exhibited by the polymer gel. [0027] 1-a. Polymer unit　 The polymer unit used to form the polymer gel in the present invention is a solvent-philic polymer, that is, a polymer that is soluble in the solvent contained in the gel. That is, in hydrogels in which the gel contains water as a solvent, the polymer units are hydrophilic polymers. As the polymer unit, as long as it can form a gel by a gelation reaction (crosslinking reaction, etc.) in a solution, a known polymer unit in the technical field may be used according to the final application, shape, etc. of the gel. can be done. More specifically, polymer units that can form a network structure, particularly a three-dimensional network structure, by cross-linking the polymer units with each other in the final gel are preferred. [0028] The hydrophilic polymer used as the polymer unit is preferably a polymer having a polyethylene glycol skeleton or a polyvinyl skeleton. Polymers having a polyethylene glycol backbone typically include polymer species having a plurality of polyethylene glycol backbone branches, and polymer species having four polyethylene glycol backbone branches are particularly preferred. A gel composed of such a four-branched polyethylene glycol skeleton is generally known as Tetra-PEG gel, and each terminal has an electrophilic functional group such as an active ester structure and a nucleophilic functional group such as an amino group. A network structure is constructed by an AB-type cross-end coupling reaction between two tetra-antennary macromolecules having In addition, Tetra-PEG gel can be easily prepared on the spot by simple two-liquid mixing of each polymer solution, and it is also possible to control the gelation time by adjusting the pH and ionic strength during gel preparation. is. And since this gel has PEG as a main component, it is also excellent in biocompatibility. [0029] Polymers other than polyethylene glycol skeletons can also be used as long as they can be crosslinked and gelled. For example, polymers having a polyvinyl skeleton such as methyl methacrylate can also be used. [0030] Although not necessarily limited to these, in order to form a sponge-like porous structure in the final gel, the polymer unit has one or more nucleophilic functional groups on side chains or terminals. A preferred means of cross-linking by reacting two types of polymer species, a first polymer unit and a second polymer unit having one or more electrophilic functional groups on its side chains or terminals. Here, the total number of nucleophilic functional groups and electrophilic functional groups is preferably 5 or more. These functional groups are more preferably present at the ends. In addition, it can be a composition in which the content of the first polymer unit is greater than the content of the second polymer unit, or a composition in which the content of the second polymer unit is greater than the content of the first polymer unit. can also be As will be described later, in a preferred embodiment, once two or more types of gel precursors having different compositions are formed, such gel precursors can be further crosslinked to obtain a polymer gel. [0031] A thiol group (-SH), an amino group, or the like can be mentioned as the nucleophilic functional group present in the polymer unit, and a person skilled in the art can appropriately use a known nucleophilic functional group. Preferably, the nucleophilic functional group is a -SH group. The nucleophilic functional groups may be the same or different, but are preferably the same. When the functional groups are the same, the reactivity with the electrophilic functional groups that form cross-links becomes uniform, making it easier to obtain a gel with a uniform three-dimensional structure. [0032] An active ester group can be used as the electrophilic functional group present in the polymer unit. Such active ester groups include maleimidyl, N-hydroxy-succinimidyl (NHS), sulfosuccinimidyl, phthalimidyl, imidazoyl, acryloyl, nitrophenyl, —CO 2 PhNO 2 (Ph is o-, m-, or p-phenylene groups), etc., and those skilled in the art can appropriately use other known active ester groups. Preferably, the electrophilic functional group is a maleimidyl group. The electrophilic functional groups may be the same or different, but are preferably the same. When the functional groups are the same, the reactivity with the nucleophilic functional groups that form cross-linked bonds becomes uniform, making it easier to obtain a gel with a uniform three-dimensional structure. [0033] Preferred non-limiting examples of the polymer unit having a terminal nucleophilic functional group include, for example, the following formula (I) having four polyethylene glycol skeleton branches and a terminal thiol group. compound. [Chemical 1] [0034] n11 to n14 may be the same or different. The closer the values of n 11 to n 14 are, the more uniform the steric structure can be and the higher the strength. Therefore, it is preferable that they are the same in order to obtain a high-strength gel. If the values of n 11 to n 14 are too high, the strength of the gel will be weak. Therefore, n 11 to n 14 include integer values of 25 to 250, preferably 35 to 180, more preferably 50 to 115, and particularly preferably 50 to 60. Its molecular weight is 5×10 3 to 5×10 4 Da, preferably 7.5×10 3 to 3×10 4 Da, more preferably 1×10 4 to 2×10 4 Da. [0035] In formula (I) above, R 11 to R 14 are linker moieties that connect the functional group and the core portion. R 11 to R 14 may be the same or different, but are preferably the same in order to produce a high-strength gel having a uniform three-dimensional structure. R 11 to R 14 are a C 1-C 7 alkylene group, a C 2-C 7 alkenylene group, -NH-R 15-, -CO-R 15-, -R 16-OR 17-, -R 16 -NH-R 17-, -R 16-CO 2-R 17-, -R 16-CO 2-NH-R 17-, -R 16-CO-R 17-, R 16-NH-CO-R 17 - or -R 16-CO-NH-R 17-. Here, R 15 represents a C 1-C 7 alkylene group. R 16 represents a C 1-C 3 alkylene group. R 17 represents a C 1-C 5 alkylene group. [0036] Here, the “C 1-C 7 alkylene group” means an alkylene group having 1 or more and 7 or less carbon atoms which may be branched, and is a linear C 1-C 7 alkylene group or one or two It means a C2-C7 alkylene group having one or more branches (2 or more and 7 or less carbon atoms including branches). Examples of C 1 -C 7 alkylene groups are methylene, ethylene, propylene, butylene groups. Examples of C1-C7 alkylene groups are -CH2-, -(CH2)2-, -(CH2)3-, -CH(CH3)-, -(CH2)3-, -( CH(CH3))2-, -(CH2)2-CH(CH3)-, -(CH2)3-CH(CH3)-, -(CH2)2-CH(C2H5) -, -(CH 2) 6-, -(CH 2) 2-C(C 2H 5) 2-, and -(CH 2) 3C(CH 3) More about this source textSource text required for additional translation information Send feedback Side panels History Saved Contribute 5,000 character limit. Use the arrows to translate more.2CH 2- and the like. [0037] The “C 2-C 7 alkenylene group” is a branched or branched alkenylene group having 2 to 7 carbon atoms and having one or more double bonds in the chain. A divalent group having a double bond formed by removing 2 to 5 hydrogen atoms of adjacent carbon atoms from an alkylene group can be mentioned. [0038] On the other hand, preferred non-limiting examples of the polymer unit having an electrophilic functional group at its terminal include, for example, the following formula (II) having four polyethylene glycol skeleton branches and a maleimidyl group at its terminal. compounds that are [Chemical 2] [0039] In the above formula (II), n21 to n24 may be the same or different. The closer the values of n 21 to n 24 are, the more the gel can have a uniform three-dimensional structure and the higher the strength. If the values of n 21 to n 24 are too high, the strength of the gel will be weak, and if the values of n 21 to n 24 are too low, gel formation will be difficult due to steric hindrance of the compound. Therefore, n 21 to n 24 include integer values of 5 to 300, preferably 20 to 250, more preferably 30 to 180, even more preferably 45 to 115, and even more preferably 45 to 55. The molecular weight of the second four-branching compound of the present invention is 5×10 3 to 5×10 4 Da, preferably 7.5×10 3 to 3×10 4 Da, and 1×10 4 to 2×10 4 Da. is more preferred. [0040] In the above formula (II), R 21 to R 24 are linker moieties that connect the functional group and the core portion. R 21 to R 24 may be the same or different, but are preferably the same in order to produce a high-strength gel having a uniform three-dimensional structure. In formula (II), R 21 to R 24 are each the same or different, a C 1-C 7 alkylene group, a C 2-C 7 alkenylene group, -NH-R 25-, -CO-R 25-, -R 26-OR 27-, -R 26-NH-R 27-, -R 26-CO 2-R 27-, -R 26-CO 2-NH-R 27-, -R 26-CO-R 27 -, -R 26-NH-CO-R 27-, or -R 26-CO-NH-R 27-. Here, R 25 represents a C 1-C 7 alkylene group. R 26 represents a C 1-C 3 alkylene group. R 27 represents a C 1-C 5 alkylene group. [0041] In the present specification, the alkylene group and alkenylene group may have one or more arbitrary substituents. The substituents include, for example, an alkoxy group, a halogen atom (which may be a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), an amino group, a mono- or di-substituted amino group, a substituted silyl group, an acyl groups, or aryl groups, etc., but are not limited to these. When an alkyl group has more than one substituent, they may be the same or different. The same applies to the alkyl moieties of other substituents containing alkyl moieties (for example, alkyloxy groups and aralkyl groups). [0042] Further, in the present specification, when a certain functional group is defined as "optionally having a substituent", the type of substituent, the substitution position, and the number of substituents are not particularly limited, When having two or more substituents, they may be the same or different. Examples of substituents include, but are not limited to, alkyl groups, alkoxy groups, hydroxyl groups, carboxyl groups, halogen atoms, sulfo groups, amino groups, alkoxycarbonyl groups, and oxo groups. These substituents may further have a substituent. [0043] 1-b. Physical properties of polymer gel As described above, the polymer gel used in the gel material for regenerative medicine of the present invention has micrometer-order, sponge-like pores formed by a dense phase (first region) and a dilute phase (second region) in the gel. It has a body structure, and due to such a structure, it has characteristic properties in terms of various physical properties. [0044] The polymer gel in the present invention has a lower transmittance than the polymer unit before gelation. This is because the polymer gel has two regions with different polymer concentrations: a dense phase (first region) and a dilute phase (second region). This is due to the fact that it behaves like a phase-separated state, so that it is cloudy rather than completely transparent. Preferably, the polymeric gel has a transmittance in the range of 90-96%. In terms of such transmittance, it exhibits properties that are completely different from those of ordinary polymer gels that are almost transparent. [0045] The polymer gel in the present invention has an osmotic pressure in the range of 1/5 to 1/2 of the osmotic pressure of the polymer unit before gelation. It also has a lower osmotic pressure than a single-phase polymer gel formed from the same polymer units. [0046] In addition, in the polymer gel of the present invention, the osmotic pressure (Π os) and the elastic pressure (Π el) after a certain period of time from gelation have a relationship of Π el > Π os. This relationship that Π el is greater than Π os indicates that the gel is contracted. In contrast to ordinary polymer gels, which generally have a relationship of Π el < Π os and tend to swell. [0047] Although not necessarily bound by theory, the polymer gel used in the gel material for regenerative medicine of the present invention has a structure that resembles a two-phase separation of a dense phase and a dilute phase. It is understood that the osmotic pressure (Π os) is reduced compared to normal single-phase polymeric gels, while the increased elastic pressure causes the gel to tend to shrink. In these respects, it can be said that the polymer gel of the present invention has characteristic properties that are significantly different from those of conventional polymer gels. [0048] Furthermore, as described above, since the polymer units have different polymer densities in the dense phase and the dilute phase, the polymer gel in the present invention can also have different water contents in these two regions. Specifically, in the polymer gel of the present invention, the water content of the first region (dense phase) is in the range of 10 to 99%, and the water content of the second region (dilute phase) is 99 to 100%. is in the range of [0049] The polymer gel in the present invention can be processed into various shapes such as a thin film depending on its use. Such processing can employ any technique known in the art. For example, in the case of a thin film, the thin film can be obtained by a method such as coating a flat substrate such as glass while the gel is in a fluid state before it is completely solidified. [0050] (2) Method for producing polymer gel Next, the method for producing the polymer gel (gelation step) used in the gel material for regenerative medicine of the present invention will be described. The polymer gel in the present invention can be produced, for example, by the steps shown in the following first and second aspects. It can be manufactured by By carrying out the gelling step under such conditions, a polymer gel having a micrometer-order porous structure, which has been difficult in the past, can be produced from a solvent-philic polymer. [0051] 2-a. First aspect of method for producing polymer gel In the first aspect, the method for producing a polymer gel according to the present invention is characterized by comprising the following steps: a) cross-linking a solvophilic starting polymer under conditions below the overlap concentration and below the critical gelling concentration to form a gel precursor; b) a step of cross-linking the gel precursors with each other with a cross-linking agent to obtain a polymer gel as the final product; [0052] In step a), the raw material polymer (polymer unit) that will eventually constitute the polymer gel is reacted in a state just before gelation, and has a structure that has not yet reached gel formation, that is, in a sol state. is a step of forming a gel precursor (polymer cluster). Then, in step b), if desired, an appropriate cross-linking agent is added, and these gel precursors are further reacted with each other to three-dimensionally cross-link each other to obtain a polymer gel as the final product. Here, the gel precursor is not limited to a single kind having the same composition as described later, and a plurality of gel precursors having different compositions can be used. Thus, the manufacturing method of the first aspect is based on the concept of using the gel precursor as a so-called final gel intermediate. [0053] In step a), conditions are used in which the initial concentration of the raw material polymer is less than the overlapping concentration and less than the critical gelation concentration. By using such an initial concentration of the starting polymer, it is possible to form a gel precursor that has a sol state that does not lead to gelation, preferably a structure that is on the verge of gelation. [0054] The initial concentration of the raw material polymer in step a) is less than the overlap concentration C*, preferably less than ⅓ C*. Here, the “overlap concentration” (also referred to as “overlap concentration”) is the concentration at which the macromolecules in the solvent begin to come into spatial contact with each other. expressed. [Number 1] (wherein Mw is the weight average molecular weight of the polymer; α is the specific gravity of the solvent; NA is the Avogadro constant; Rg is the radius of gyration of the polymer). [0055] For the calculation method of the overlapping concentration C*, for example, Polymer Physics (authored by M. Rubinstein and R. Colby) can be referred to. Specifically, for example, it can be obtained by measuring the viscosity of a dilute solution and using the Flory-Fox equation. [0056] Also, in step a), the initial concentration of the raw material polymer is set below the critical gelation concentration. Here, the "critical gelation concentration" means the minimum concentration of the raw material polymer required to achieve the gelation in a system that builds a gel with a three-dimensional structure by cross-linking the raw material polymer. Also called concentration. In the present invention, the term critical gelling concentration includes, for example, in a system in which two or more raw material polymers are used, in addition to the case where the total concentration does not reach the concentration at which gelation occurs, one raw material polymer The case where only the concentration of is low, that is, the case where the ratio of each raw material polymer is non-equivalent and does not cause gelation is also included. [0057] In general, the critical gelation concentration (minimum gelation concentration) depends on the type of raw material polymer used, but such concentrations are known in the art or can be easily ascertained experimentally by those skilled in the art. can be done. Typically, it is 0.5 to 5% by weight, and the lower limit is about 1/5 of the overlapping concentration. [0058] As a method for adjusting the initial concentration of the raw material polymer to be less than the critical gelation concentration, for example, when using two types of polymer units having a nucleophilic functional group or an electrophilic functional group as described above, or conditions that do not cause gelation by making the concentration of one type of polymer unit low, i.e., non-equivalent. can be used. [0059] Step a) can typically be performed by mixing or stimulating a solution containing two types of raw material polymers. It can also be carried out by radical polymerization of monomers using a radical initiator. The concentration, addition speed, mixing speed, and mixing ratio of each solution are not particularly limited, and can be appropriately adjusted by those skilled in the art. Also, even when three or more kinds of starting polymers are used, it is obviously possible to similarly prepare a solution containing the corresponding starting polymers and mix them appropriately. As a solvent for the solution containing the starting polymer, water, alcohols such as ethanol, DMSO, and the like can be used. If the solution is an aqueous solution, a suitable pH buffer such as phosphate buffer can be used. [0060] As a means of mixing, for example, international publication WO2007/083522 More about this source textSource text required for additional translation information Send feedback Side panels History Saved Contribute 5,000 character limit. Use the arrows to translate more.t can be carried out using a two-liquid mixing syringe as disclosed in the publication. The temperature of the two liquids at the time of mixing is not particularly limited as long as the precursor units are dissolved and the liquids have fluidity. For example, the temperature of the solution during mixing may be in the range of 1°C to 100°C. Although the two liquids may have different temperatures, it is preferable that the two liquids have the same temperature because the two liquids are easily mixed. [0061] The gel precursor obtained in step a) has a structure in which the precursor units are mutually bonded or crosslinked, but is formed under conditions that do not yet result in gelation. Therefore, the gel precursor has a relationship of G' Π os. material. [Claim 5] The gel for regenerative medicine according to any one of claims 1 to 4, wherein the first region has a polymer concentration of 10 to 99% by weight, and the second region has a polymer concentration of 0 to 1% by weight. material. [Claim 6] The gel material for regenerative medicine according to any one of claims 1 to 5, which has a polymer content of 5% by weight or less. [Claim 7] The gel material for regenerative medicine according to any one of claims 1 to 6, wherein the polymer unit is a polymer having a polyethylene glycol skeleton or a polyvinyl skeleton. [Claim 8] The polymer unit consists of a first polymer unit having one or more nucleophilic functional groups in a side chain or terminal, and a second polymer unit having one or more electrophilic functional groups in a side chain or terminal. , The gel material for regenerative medicine according to any one of claims 1 to 7. [Claim 9] The nucleophilic functional group is selected from the group consisting of thiol groups and amino groups, and the electrophilic functional group is maleimidyl group, N-hydroxy-succinimidyl (NHS) group, sulfosuccinimidyl group, phthalimidyl group. , imidazoyl group, acryloyl group, nitrophenyl group, and —CO 2 PhNO 2 . [Claim 10] The regenerative medical gel material according to any one of claims 1 to 9, which is used for tissue regeneration. [Claim 11] The regenerative medicine gel material according to claim 10, wherein the tissue is bone, cartilage, skin, or nerve. [Claim 12] A treatment method using the gel material for regenerative medicine according to any one of claims 1 to 11. [Claim 13] A kit for producing a gel material for regenerative medicine, characterized in that the following two types of solutions (A) and (B) are contained without being mixed with each other, (A) an aqueous solution containing a hydrophilic first raw material polymer having a concentration less than the overlapping concentration and equal to or higher than the critical gelling concentration; (B) an aqueous solution containing a hydrophilic second raw material polymer having a concentration less than the overlap concentration and equal to or higher than the critical gelling concentration; The solution of (A) and/or (B) above further contains a non-reactive polymer that does not have a functional group in its molecule that can undergo a cross-linking reaction with the raw material polymer, The polymer gel obtained by mixing the solutions of (A) and (B) above is a polymer gel obtained by cross-linking the first raw material polymer and the second raw material polymer, The polymer gel has a structure composed of two regions: a first region in which the polymer units derived from the raw material polymer exist densely, and a second region in which the polymer units derived from the raw material polymer exist sparsely. have "The kit." [Claim 14] A kit for producing a gel material for regenerative medicine, characterized in that the following two types of solutions (A') and (B') are contained without being mixed with each other, (A′) an aqueous solution containing a first gel precursor, wherein the first gel precursor is obtained by cross-linking a hydrophilic raw material polymer under conditions of less than the overlap concentration and less than the critical gelation concentration; wherein the storage modulus G′ and the loss modulus G″ have a relationship of G′