Hydrogel molecule as well as preparation method and application thereof

Abstract

According to the hydrogel molecule, a free radical cross-linked network serves as a main body, a hydrogel monomer shown in the following formula (I) is introduced, under the illumination condition, the free radical cross-linked network is subjected to a free radical cross-linking reaction under the action of a photoinitiator to construct a hydrogel network main body structure, and the hydrogel molecule # imgabs0 is formed, in the formula (I), X is S or O; in the formula, R1 is a carbon chain with the carbon atom number of 0-8 (R1 and R2 do not exist when the number is 0), R2 is-NH2,-COOH or-CHO, L is CR, N, SiR'or # imgabs1 # R, R 'is any organic substituent group, X1 to X3 are the same or different and are respectively and independently CH or N, and L1 is a direct bond or at least one selected from a carbon atom, an alkyl group, an alkynyl group, a ketone group, a carboxyl group, an ester group, an aryl group and an amino group, or a substituted or unsubstituted arylene group.

Description

Technical Field

[0001] The present invention relates to the technical field of biomaterials, and in particular to a hydrogel molecule, a preparation method and application thereof. Background Art

[0002] Hydrogel is a high molecular polymer with water as the main component and a three-dimensional network structure. It can be formed by physical or chemical cross-linking and has good hydrophilicity and biocompatibility. Therefore, it is widely used in many fields such as sensing, driving, drug delivery, wound dressing, etc. Therefore, from a macroscopic perspective, hydrogel material is a type of polymer skeleton with high water retention capacity. It can maintain a three-dimensional network structure in the environment without dissolution, can withstand a certain external force and can restore its original shape after the external force is removed, showing the viscoelasticity of a solid. From a microscopic perspective, due to the high water content inside the hydrogel, the polymer skeleton and water molecules in it penetrate each other without obvious boundaries. Small molecules can move and diffuse freely in it, and it also shows the properties of a liquid.

[0003] However, traditional hydrogel molecules have high water content, which weakens the interaction between polymer chains and has low network cross-linking density, resulting in poor macroscopic mechanical properties. They are affected by the complex physiological environment in the body, such as ion concentration, pH value and proteases, and cannot exist in the body for a long time. This limits the application of hydrogel molecules in tissue engineering, soft robotics and other fields, because hydrogel molecules need to be greatly deformed or need to carry large loads when used, such as replacing tendons and ligaments that bear weight in the body. Therefore, the mechanical properties of hydrogel molecules are very important for the application of hydrogel molecules.

[0004] In view of the shortcomings of the mechanical properties of hydrogel molecules, researchers have also tried to improve the mechanical properties of hydrogel molecules through some methods, such as constructing nanocomposite hydrogels, increasing the cross-linking density of the polymer network by doping nanoparticles, thereby improving the mechanical strength of the hydrogel; for example, improving the toughness of the hydrogel by constructing a double network structure; for example, introducing hydrogel microspheres into the hydrogel network structure, and using the characteristics of the hydrogel microspheres being easily deformed under force to dissipate energy, thereby improving the mechanical strength of the hydrogel molecules.

[0005] However, the above improvement methods can only improve the mechanical properties of hydrogel molecules to a very limited extent, and the functionality is single, because without sacrificing mechanical properties, other properties such as reaction speed and viscosity are difficult to meet the requirements of different application fields at the same time. For example, when hydrogel molecules are used for wound hemostasis, they require fast gelation speed and short gelation time, so as to achieve rapid hemostasis and accelerate wound healing. For another example, clinical photocurable hydrogels are limited by their photocuring speed, comprehensive mechanical properties of the gel and adhesion in application.

[0006] Therefore, for the application of hydrogels, the properties of high stiffness, high toughness and rapid recovery are often contradictory. How to use an effective method to significantly improve the comprehensive performance of hydrogel molecules is a challenging scientific task. Summary of the invention

[0007] In view of the above-mentioned defects of the prior art, the present invention designs the structure of the hydrogel from the molecular level, by increasing the number of teeth of the hydrogel molecules and adjusting the position of dissociation, so that under the action of light, the hydrogel molecules generate active groups to initiate polymerization. As the number of teeth of the hydrogel molecules increases, more active groups are dissociated, which is equivalent to a higher local concentration of active groups participating in the reaction. In this way, at a certain temperature, the number of effective molecular collisions per unit time increases, the reaction rate is accelerated, the gelation time is shortened, and the gelation efficiency is higher. In addition, the number of teeth of the hydrogel molecules increases, and accordingly, the polymer chains connected thereto also increase accordingly. When decomposed by light, the number of dissociated polymer chains is also greater. When entanglement and cross-linking occur, the chain entanglement increases the rigidity of the hydrogel molecules, so that the formed three-dimensional network of the hydrogel will not become brittle, thereby improving the mechanical strength including high rigidity and high toughness.

[0008] An embodiment of the present invention provides a hydrogel molecule, wherein the hydrogel molecule is mainly composed of a free radical cross-linked network, and a hydrogel monomer as described in the following formula (I) is introduced. Under light conditions, the free radical cross-linked network undergoes a free radical cross-linking reaction with the hydrogel monomer under the action of a photoinitiator, and -SH in formula (I) forms a chemical bond with the free radical cross-linked network to construct the main structure of the hydrogel network, thereby forming the hydrogel molecule.

[0009]

[0010] Wherein, in formula (I), X is S or O, R 1 is a carbon chain with 0-8 carbon atoms (when R is 0 1 , R 2 do not exist), R 2 For -NH 2 , -COOH or -CHO, L is CR, N, SiR′ or R and R' are any organic substituent groups. Preferably, R and R' are each independently selected from C1-C18 alkyl, C2-C18 alkenyl or C2-C18 alkynyl. More preferably, R and R' are each independently selected from C1-C6 alkyl, C3-C6 alkenyl or C3-C6 alkynyl. More preferably, R and R' are each independently selected from C1-C4 alkyl.

[0011] X 1 To X 3 are the same as or different from each other and are each independently CH or N,

[0012] L1 is a direct bond, or at least one selected from a carbon atom, an alkyl group, an alkynyl group, a keto group, a carboxyl group, an ester group, an aryl group, an amine group, or a substituted or unsubstituted arylene group; preferably, L1 is a C6-C30 substituted or unsubstituted arylene group.

[0013] According to one embodiment of the present invention, for example, the free radical cross-linked network includes natural macromolecular monomers modified with unsaturated double bonds and synthetic high molecular polymers containing unsaturated bonds.

[0014] According to one embodiment of the present invention, for example, the free radical cross-linked network includes synthetic polymers modified with hyaluronic acid, chitosan, sodium alginate, heparin, gelatin, chondroitin sulfate, methacrylate, polylactic acid, and fumarate;

[0015] Preferably, the free radical cross-linked network includes at least one of the following seven structures:

[0016]

[0017]

[0018] According to one embodiment of the present invention, for example, the photoinitiator is selected from at least one of the following chemical structures:

[0019]

[0020]

[0021] According to one embodiment of the present invention, for example, in the formula (I), L 1 is selected from at least one of a carbon atom, an alkyl group, an alkynyl group, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; preferably, L 1 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group;

[0022] In the formula (I), L is selected from a nitrogen atom, an alkyl group, a silane group, an aryl group, and a triazine group; preferably, L is selected from a C1-C18 alkyl group, a C1-C18 silane group, and a C6-C18 aryl group;

[0023] In the formula (I), and The positions on the benzene ring are adjacent. It may be located at any substituent position on the benzene ring except L1.

[0024] According to one embodiment of the present invention, for example, the hydrogel monomer has a structure as shown in formula (II):

[0025]

[0026] Among them, in formula (II), L 2 At least one selected from the group consisting of a carbon atom, an alkyl group, an alkyne, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; L 3 At least one selected from the group consisting of a carbon atom, an alkyl group, an alkyne, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; L 4 is selected from at least one of a carbon atom, an alkyl group, an alkyne, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; preferably, L 2 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; L 3 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; L 4 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group;

[0027] In formula (II), L is selected from one of a nitrogen atom, an alkyl group, a silane group, an aryl group, and a heteroaryl group; preferably, L is selected from one of a nitrogen atom, a C1-C18 alkyl group, a C1-C18 silane group, a C6-C18 aryl group, and a C6-C18 heteroaryl group;

[0028] Preferably, the L 2 , L 3 , L 4 Select one of the following structures:

[0029] Carbon atom, -CH2 ,

[0030] Preferably, L is selected from one of the following structures:

[0031] Nitrogen atom, -C-CH 3 、-Si-CH 3 ,

[0032] According to one embodiment of the present invention, for example, the hydrogel monomer has any of the following structures:

[0033]

[0034] An embodiment of the present invention also provides a method for preparing a hydrogel molecule, comprising the following steps: dissolving a hydrogel monomer in a biocompatible medium to obtain a solution A, dissolving the above-mentioned photoinitiator in a biocompatible medium to obtain a photoinitiator solution B, mixing solution A and solution B evenly to obtain a hydrogel precursor solution, and photocrosslinking the hydrogel precursor solution under light to form a hydrogel.

[0035] In the above preparation method, the photoinitiated free radical generating system in solution A generates sulfur-containing active free radicals under light, and undergoes addition polymerization reaction with macromolecules containing double bonds to construct a polymer network. The free radical polymerization reaction relies on a photosensitizer or a photosensitizer system to convert light energy into active free radical fragments to initiate photopolymerization.

[0036] For example, a possible reaction is Figure 1 shown.

[0037] In contrast to the above reaction, the reaction of the monodentate monomer is Figure 2 shown.

[0038] The reaction of bidentate monomers is as follows Figure 3 shown.

[0039] Exemplarily, a hydrogel molecule reaction formula provided in an embodiment of the present invention is as follows (the ligand is tridentate):

[0040]

[0041] In contrast, the monodentate ligand structure is as follows:

[0042]

[0043] The bidentate ligand structure is as follows:

[0044]

[0045] Furthermore, the biocompatible medium is distilled water, physiological saline or buffer.

[0046] The embodiments of the present invention also provide an application of a hydrogel molecule, including the following aspects: postoperative wound closure-skin repair material or drug, postoperative wound closure-postoperative anti-adhesion material or drug, postoperative wound closure-oral ulcer material or drug, tissue fluid leakage blocking-intestinal leakage blocking material or drug, tissue fluid leakage blocking-surgical suture material or drug, hemostatic material-liver hemostatic material or drug, hemostatic material-bone section hemostatic material or drug, hemostatic material-arterial hemostatic material or drug, hemostatic material-heart hemostatic material or drug, tissue engineering scaffold material-cartilage repair material or drug, tissue engineering scaffold material-bone repair material or drug, tissue engineering scaffold material-bone / cartilage composite defect repair material or drug, 3D printing material-bio-ink and cell, protein, drug carrier application.

[0047] Compared with the prior art, the present invention has the following technical effects:

[0048] The structure of the tridentate hydrogel monomer and hydrogel molecule disclosed in the present invention increases the number of teeth of the hydrogel molecule and adjusts the position of dissociation, so that under the action of light, the hydrogel molecule produces active groups to initiate polymerization. Since the number of teeth of the hydrogel molecule increases, the more active groups dissociated are also more, which is equivalent to the higher local concentration of the active groups participating in the reaction. In this way, at a certain temperature, the number of effective molecular collisions per unit time increases accordingly, the reaction rate is accelerated, the gelation time is shortened, and the gel efficiency is higher. In addition, the number of teeth of the hydrogel molecule increases, and accordingly, the polymer chains connected thereto also increase accordingly. When decomposed by light, the number of polymer chains dissociated is also more. When entangled crosslinking occurs, the chain entanglement increases the rigidity of the hydrogel molecule, so that the formed three-dimensional network of the hydrogel will not be brittle, thereby improving the mechanical strength including high rigidity and high toughness.

[0049] In addition, when the tridentate hydrogel monomers and hydrogel molecules disclosed in the present invention break bonds under light to generate active free radicals, three molecular fragments can be formed, all of which can participate in gelation, and the fragments can be used for tissue adhesion, occlusion, hemostasis, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] Figure 1 A possible reaction diagram of the present invention is shown in FIG. 1 , wherein X is S, R 1 -CH 2 -CH 2 ,R 2 For -NH 2 .

[0051] Figure 2 Schematic diagram of the monodentate monomer reaction process.

[0052] Figure 3 Schematic diagram of the bidentate monomer reaction process. DETAILED DESCRIPTION

[0053] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0054] For the convenience of describing the following examples, the chemical structures in this application are referred to in the following table:

[0055]

[0056]

[0057] In the present specification, unless specifically described to the contrary, a description that a part “includes” certain constituent elements means that other constituent elements can also be included, and other constituent elements are not excluded.

[0058] In this specification, the term "substituted" means that a hydrogen atom bonded to a carbon atom of a compound is changed into another substituent. The position of substitution is not limited as long as it is a position where a hydrogen atom is substituted, i.e., a position where a substituent can be substituted, and when two or more substituents are substituted, the two or more substituents may be the same or different from each other.

[0059] Throughout the specification of the present application, the term “combination thereof” included in a Markush-type expression means a mixture or combination of one or more selected from the constituent elements described in the Markush-type expression, and means including one or more selected from the constituent elements.

[0060] In the present specification, the alkyl group may be linear or branched, and although not particularly limited thereto, the number of carbon atoms is preferably 1 to 50. Specific examples thereof may include methyl, ethyl, propyl, n-propyl, isopropyl, butyl, n-butyl, isobutyl, tert-butyl, sec-butyl, 1-methyl-butyl, 1-ethyl-butyl, pentyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methyl-2-pentyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, n-heptyl, 1-methylhexyl, cyclopropyl, cyclobutyl, cyclopentyl, 3-methylcyclopentyl, 2,3 -dimethylcyclopentyl, cyclohexyl, 3-methylcyclohexyl, 4-methylcyclohexyl, 2,3-dimethylcyclohexyl, 3,4,5-trimethylcyclohexyl, 4-tert-butylcyclohexyl, cycloheptyl, cyclooctyl, octyl, n-octyl, tert-octyl, 1-methylheptyl, 2-ethylhexyl, 2-propylpentyl, n-nonyl, 2,2-dimethylheptyl, 1-ethyl-propyl, 1,1-dimethyl-propyl, isohexyl, 2-methylpentyl, 4-methylhexyl, 5-methylhexyl, etc., but are not limited thereto.

[0061] In the present specification, the alkynyl group may be linear or branched, and although not particularly limited thereto, the number of carbon atoms is preferably 2 to 30. Specific examples thereof may include ethynyl, propynyl, 2-methyl-2-propynyl, 2-butynyl, 2-pentynyl and the like, but are not limited thereto.

[0062] In the present specification, the aryl group is not particularly limited, but preferably has 6 to 60 carbon atoms, and may be a monocyclic aryl group or a polycyclic aryl group. According to one embodiment, the number of carbon atoms of the aryl group is 6 to 30. According to one embodiment, the number of carbon atoms of the aryl group is 6 to 20. When the aryl group is a monocyclic aryl group, examples thereof may include phenyl, biphenyl, terphenyl, etc., but are not limited thereto. Examples of polycyclic aryl groups may include naphthyl, anthracenyl, phenanthrenyl, pyrenyl, perylenyl, pyrenyl, fluorenyl, etc., but are not limited thereto.

[0063] In this specification, heteroaryl is a group containing one or more non-carbon atoms, i.e. heteroatoms, and specifically, heteroatoms can include one or more atoms selected from O, N, Si, Se, S, etc. The number of carbon atoms of heteroaryl is not particularly limited, but preferably 2 to 30, and heteroaryl can be monocyclic or polycyclic. The example of heteroaryl can include xanthene, thioxanthene, thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, diazolyl, pyridyl, pyrimidyl, triazine, triazolyl, quinolyl, quinazolinyl, carbazolyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzocarbazolyl, benzothienyl, dibenzothienyl, benzofuranyl, phenanthroline, isoxazolyl, thiadiazolyl, dibenzofuranyl, etc., but is not limited thereto.

[0064] In the structural formulae in the present specification, Ph means a phenyl group, and Me means a methyl group.

[0065] The compound according to one embodiment of the present application can be prepared using a preparation method described later.

[0066] Hereinafter, this specification will be described in detail with reference to embodiments. However, embodiments according to this specification can be modified into various other forms, and the scope of this application should not be interpreted as being limited to the embodiments described below. The embodiments of this application are provided to more fully describe this specification to those of ordinary skill in the art.

[0067] Example 1 Preparation of Monomer 1

[0068] The preparation method of monomer 1 is as follows:

[0069]

[0070] First, triphenylethane is added to a 53% nitric acid solution to react to obtain structure 1, the compound of structure 1 is added to a carbon tetrachloride solution, AIBN (Azobisisobutyronitrile) and NBS (N-Bromosuccinimide) are added thereto, and the mixture is refluxed for 1.5 h under light conditions to obtain a compound of structure 2, the compound of structure 2 and thiourea are reacted in acetonitrile (ACN) at 40°C for 16 h, and then K is added. 2 CO 3 and Na 2 S 2 O 5 The mixed solution was reacted for 45 minutes, and then washed with DMF and water to separate the organic layer. The organic layer was purified by column chromatography to obtain a compound of structure 3, i.e., monomer 1, with a yield of 68%.

[0071] Comparative Example 1-1 (single tooth)

[0072] The synthesis method is shown in Example 1, and the synthesis route is as follows:

[0073]

[0074] Comparative Example 2-1 (double teeth)

[0075] The synthesis method is shown in Example 1, and the synthesis route is as follows:

[0076]

[0077] Example 2 Preparation of Monomer 2

[0078] The preparation method of monomer 2 is as follows:

[0079]

[0080] Compound C 8 H 8 BrNO 2 and C 6 H 9 B 3 O 6 Add to a mixed solution of acetone and water (volume ratio 3:1), and then add PdCl 2 and K 2 CO 3 , where the catalyst PdCl 2 The amount of the compound was 1.69 mol%, and the mixture was stirred at room temperature for 24 h to obtain a compound of structure 1 with a yield of 97%. Then, the compound of structure 1 in this example was added to a carbon tetrachloride solution, and AIBN (Azobisisobutyronitrile) and NBS (N-Bromosuccinimide) were added thereto, and the mixture was refluxed for 1.5 h under light conditions to obtain a compound of structure 2. The compound of structure 2 and thiourea were reacted in acetonitrile (ACN) at 40°C for 16 h, and then K was added. 2 CO 3 and Na 2 S 2 O 5 The mixed solution was reacted for 45 minutes, and then washed with DMF (dimethylformamide) to obtain a compound of structure 3, i.e., monomer 2, with a yield of 72%.

[0081] Comparative Example 1-2 (single tooth)

[0082] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0083]

[0084] Comparative Example 2-2 (double teeth)

[0085] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0086]

[0087] Example 3 Preparation of Monomer 3

[0088] The preparation method of monomer 3 is as follows:

[0089] 1,3,5-Benzenetricarboxylic acid chloride and 4-nitro-3-(trifluoromethyl)phenol were added to a mixed solvent of THF and pyridine, and the reaction was carried out at 0° C. for 18 h. The monomer 3 was purified and the yield was 89%.

[0090] Comparative Example 1-3 (single tooth)

[0091] The synthesis method is shown in Example 3, and the synthesis route is as follows:

[0092]

[0093] Comparative Example 2-3 (double teeth)

[0094] The synthesis method is shown in Example 3, and the synthesis route is as follows:

[0095]

[0096] Example 4 Preparation of Monomer 4

[0097] The preparation method of monomer 4 is as follows:

[0098]

[0099] 1,3,5-tribromotoluene, 5-hydroxy-2-nitrobenzoic acid methyl ester and K 2 CO 3 Add to DMF solution, react for 3h to obtain the intermediate product in the preparation method of this embodiment, and then react the intermediate product with Na 2 S 2 O 5 Reaction, in H 2 O and CH 2 Cl 2 The mixed solution was refluxed for 12 hours to obtain a crude product, which was then purified to obtain monomer 4.

[0100] Comparative Example 1-4 (single tooth)

[0101] The synthesis method is shown in Example 4, and the synthesis route is as follows:

[0102]

[0103] Comparative Example 2-4 (double teeth)

[0104] The synthesis method is shown in Example 4, and the synthesis route is as follows:

[0105]

[0106] Example 5 Preparation of Monomer 5

[0107] The preparation method of monomer 5 is as follows:

[0108]

[0109] 1,3,5-Triiodobenzene and (3-methyl-4-nitrophenyl)boric acid were added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 5 with a yield of 67%.

[0110] Comparative Example 1-5 (single tooth)

[0111] The synthesis method is shown in Example 5, and the synthesis route is as follows:

[0112]

[0113] Comparative Example 2-5 (double teeth)

[0114] The synthesis method is shown in Example 5, and the synthesis route is as follows:

[0115]

[0116] Example 6 Preparation of Monomer 6

[0117] The preparation method of monomer 6 is as follows:

[0118]

[0119] 1,3,6-triethynylbenzene, C 7 H 6 BrNO 2 S and CuI (5 mol%) were added to a solvent of toluene and triethylamine, and then a catalyst PdCl was added thereto. 2 (PPh 3 ) 2 After reacting for 24 h, a crude product was obtained, which was purified to obtain monomer 6 with a yield of 92%.

[0120] Comparative Example 1-6 (single tooth)

[0121] The synthesis method is shown in Example 6, and the synthesis route is as follows:

[0122]

[0123] Comparative Example 2-6 (double teeth)

[0124] The synthesis method is shown in Example 6, and the synthesis route is as follows:

[0125]

[0126] Example 7 Preparation of Monomer 7

[0127] The preparation method of monomer 7 is as follows:

[0128]

[0129] 1,3,5-tribromobenzene, C 7 H 6 BrNO 2 S and K 2 CO 3 Introduce into a round-bottom flask and dissolve in methylpyrrolidone (NMP) (0.3 M), add CuI (5 mol%) and ferric acetylacetonate (10 mol%) under a nitrogen atmosphere, and stir at 150°C for 4 h. After the reaction, the reaction solution is cooled to room temperature, washed and purified by column chromatography to obtain monomer 7.

[0130] Comparative Example 1-7 (single tooth)

[0131] See Example 7 for the synthesis method. The synthesis route is as follows:

[0132]

[0133] Comparative Example 2-7 (double teeth)

[0134] See Example 7 for the synthesis method. The synthesis route is as follows:

[0135]

[0136] Example 8 Preparation of Monomer 8

[0137] The preparation method of monomer 8 is as follows:

[0138]

[0139] 1,3,5-aminobenzene and C 7 H 6 BrNO 2S and sodium tert-butoxide were introduced into the round-bottomed biscuit and dissolved in anhydrous toluene. Then, the mixed solution was stirred at room temperature for 10 min under a nitrogen atmosphere, and the oil container was heated from room temperature to 110°C. When the internal temperature became 60°C, 2,3-tert-butylphosphine palladium (9 mol%) was added dropwise thereto, and the resultant was stirred overnight. After the reaction, the obtained crude product was precipitated with CH 2 Cl 2 / H 2 O was washed and separated, and the monomer 8 was purified by column chromatography with a yield of 87%.

[0140] Comparative Example 1-8 (single tooth)

[0141] The synthesis method is shown in Example 8, and the synthesis route is as follows:

[0142]

[0143] Comparative Example 2-8 (double teeth)

[0144] The synthesis method is shown in Example 8, and the synthesis route is as follows:

[0145]

[0146] Example 9 Preparation of Monomer 9

[0147] The preparation method of monomer 9 is as follows:

[0148]

[0149] The synthesis method of monomer 9 can be found in Example 7. 10 H 15 F 3 , C 7 H 6 BrNO 2 S and K 2 CO 3 Introduce into a round-bottom flask and dissolve in methylpyrrolidone (NMP) (0.3M), add CuI (5 mol%) and ferric acetylacetonate (10 mol%) under a nitrogen atmosphere, and stir at 150°C for 4 hours. After the reaction, the reaction solution is cooled to room temperature, washed and purified by column chromatography to obtain monomer 9 with a yield of 94%.

[0150] Comparative Example 1-9 (single tooth)

[0151] See Example 9 for the synthesis method. The synthesis route is as follows:

[0152]

[0153] Comparative Example 2-9 (double teeth)

[0154] See Example 9 for the synthesis method. The synthesis route is as follows:

[0155]

[0156] Example 10 Preparation of Monomer 10

[0157] The preparation method of monomer 10 is as follows:

[0158]

[0159] The preparation process of monomer 10 can be referred to Example 5, except that 1,3,5-triiodobenzene in Example 5 is replaced by C 18 H 12 I 3 N, specifically, C 18 H 12 I 3 N and (3-methyl-4-nitrophenyl)boric acid were added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 10 with a yield of 71%.

[0160] Comparative Example 1-10 (single tooth)

[0161] See Example 10 for the synthesis method. The synthesis route is as follows:

[0162]

[0163] Comparative Example 2-10 (double teeth)

[0164] See Example 10 for the synthesis method. The synthesis route is as follows:

[0165]

[0166] Example 11 Preparation of Monomer 11

[0167] The preparation method of monomer 11 is as follows:

[0168]

[0169] The preparation process of monomer 11 can refer to Example 5, except that the (3-methyl-4-nitrophenyl)boric acid in Example 5 is replaced by (2-nitrophenyl-3-methyl)boric acid. Specifically, 1,3,5-triiodobenzene and (2-nitrophenyl-3-methyl)boric acid are added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) is added thereto. 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 11 with a yield of 69%.

[0170] Comparative Example 1-11 (single tooth)

[0171] The synthesis method is shown in Example 11, and the synthesis route is as follows:

[0172]

[0173] Comparative Example 2-11 (double teeth)

[0174] The synthesis method is shown in Example 11, and the synthesis route is as follows:

[0175]

[0176] Example 12 Preparation of Monomer 12

[0177] The preparation method of monomer 12 is as follows:

[0178]

[0179] The synthesis method of monomer 12 can refer to Example 5, except that 1,3,5-triiodobenzene is replaced by C 19 H 15 I 3 Si, specifically, C 19 H 15 I 3Si and (3-methyl-4-nitrophenyl)boric acid were added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 12 with a yield of 68%.

[0180] Comparative Example 1-12 (single tooth)

[0181] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0182]

[0183] Comparative Example 2-12 (double teeth)

[0184] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0185]

[0186] Example 13 Preparation of Monomer 13

[0187] The preparation method of monomer 13 is as follows:

[0188]

[0189] The synthesis method of monomer 14 is similar to that of Example 5, except that 1,3,5-triiodobenzene is replaced by C 21 H 12 I 3 N 3 , specifically, C 21 H 12 I 3 N 3 and (3-methyl-4-nitrophenyl)boric acid were added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 13 with a yield of 71.2%.

[0190] Comparative Example 1-13 (single tooth)

[0191] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0192]

[0193] Comparative Example 2-13 (double teeth)

[0194] The synthesis method is shown in Example 2, and the synthesis route is as follows:

[0195]

[0196] Example 14 Preparation of Monomer 14

[0197] The preparation method of monomer 14 is as follows:

[0198]

[0199] The synthesis method of monomer 14 can refer to Example 5, except that (3-methyl-4-nitrophenyl)boric acid is replaced with (3-nitro-4-methyl)boric acid. Specifically, 1,3,5-triiodobenzene and (3-nitro-4-methyl)boric acid are added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) is added thereto. 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 14 with a yield of 67%.

[0200] Comparative Example 1-14 (single tooth)

[0201] See Example 14 for the synthesis method. The synthesis route is as follows:

[0202]

[0203] Comparative Example 2-14 (double teeth)

[0204] See Example 14 for the synthesis method. The synthesis route is as follows:

[0205]

[0206] Example 15 Preparation of Monomer 15

[0207] The preparation method of monomer 15 is as follows:

[0208]

[0209] The synthesis method of monomer 15 is similar to that of Example 5, except that (3-methyl-4-nitrophenyl)boric acid is replaced with (2-methyl-3-nitro)boric acid. Specifically, 1,3,5-triiodobenzene and (2-methyl-3-nitro)boric acid are added to a mixed solvent of water and ethylene glycol dimethyl ether, and Ba(OH) is added thereto. 2 , react for 15 h, and then add catalyst Pd(PPh 3 ) 4 Reflux reaction for 12h, add NBS and AIBN to the reaction solution, 4 The reaction was carried out in a solvent for 36 hours to obtain an intermediate product, and then thiourea and Na 2 S 2 O 5 , reacted in acetonitrile at 40°C for 16 h, and finally K 2 CO 3 The solvent was a mixed solution of water and DMF in a volume ratio of 1:1. The reaction was carried out for 45 minutes to obtain a crude product. The crude product was purified to obtain monomer 15 with a yield of 68%.

[0210] Comparative Example 1-15 (single tooth)

[0211] See Example 15 for the synthesis method. The synthesis route is as follows:

[0212]

[0213] Comparative Example 2-15 (double teeth)

[0214] See Example 15 for the synthesis method. The synthesis route is as follows:

[0215]

[0216] Example 16 Preparation of hyaluronic acid molecules modified with hydrogel monomers

[0217] Sodium hyaluronate is dissolved in deionized water to form a uniform, transparent solution, the hydrogel monomer and 1-hydroxybenzotriazole synthesized in Example 1-Example 15 are dissolved in dimethyl sulfoxide respectively, and added dropwise in the reaction bottle, after the reaction mixture is stirred at room temperature for 5min, the pH value of the reaction solution is adjusted to 4.5, and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) is dissolved in dimethyl sulfoxide, and added dropwise to the reaction system. After the reaction mixture is stirred at room temperature for 48 hours, the reaction solution is loaded into a dialysis bag, and it is placed in a deionized water solution containing 0.1M NaCl at pH 3.5 and dialyzed for 2 days. Subsequently, it is placed in deionized water and continues to be dialyzed for 2 days, and the dialysate is changed every 3 hours during the dialysis process. After dialysis is completed, the mixed solution in the dialysis bag is placed in a 50mL centrifuge tube, freeze-dried for 3 days under a dark state, and a white flocculent product is collected.

[0218] The general reaction formula of the preparation process is as follows:

[0219]

[0220] Comparative Example 3-1

[0221] The preparation method is the same as that of Example 16, except that the monomer 1 in Example 1-15 is replaced by the corresponding monodentate compound prepared in Comparative Examples 1-1 to 1-15, and the structure is as follows:

[0222]

[0223] Comparative Example 4-1

[0224] The preparation method is the same as that of Example 16, except that the monomer 1 in Example 1-15 is replaced by the corresponding bidentate compound prepared in Comparative Examples 2-1 to 2-15, and the structure is as follows:

[0225]

[0226] Example 17 Preparation of hydrogel monomer-modified gelatin molecules

[0227] Add gelatin and CB buffer to a 250mL three-necked flask, heat at 50°C to dissolve and form a uniform transparent solution. Add the monomers prepared in Examples 1 to 15 dropwise to the reaction flask, and stir the reaction mixture at 50°C for 3 hours. After the reaction is completed, transfer the reaction mixture to a dialysis bag and dialyze in deionized water for 3 days. After dialysis, transfer the solution in the dialysis bag to a 50mL centrifuge tube and freeze-dry for 3 days in the dark to obtain a white foamy product.

[0228] The general reaction formula of the preparation process is as follows:

[0229]

[0230] Comparative Example 3-2

[0231] The preparation method is the same as that of Example 17, except that the monomer 1 in Example 1-15 is replaced by the corresponding monodentate compound prepared in Comparative Examples 1-1 to 1-15, and the structure is as follows:

[0232]

[0233] Comparative Example 4-2

[0234] The preparation method is the same as that of Example 17, except that the monomer 1 in Example 1-15 is replaced by the corresponding bidentate compound prepared in Comparative Examples 2-1 to 2-15, and the structure is as follows:

[0235]

[0236] Example 18 Preparation of chitosan modified with hydrogel monomers

[0237]

[0238] Comparative Example 3-3

[0239] The preparation method is the same as that of Example 18, except that the monomer 1 in Example 1-15 is replaced by the corresponding monodentate compound prepared in Comparative Examples 1-1 to 1-15, and the structure is as follows:

[0240]

[0241] Comparative Example 4-3

[0242] The preparation method is the same as that of Example 18, except that the monomer 1 in Example 1-15 is replaced by the corresponding bidentate compound prepared in Comparative Examples 2-1 to 2-15, and the structure is as follows:

[0243]

[0244] Example 19 Preparation of hydrogel monomer modified heparin

[0245]

[0246] Comparative Examples 3-4

[0247] The preparation method is the same as that of Example 19, except that the monomer 1 in Example 1-15 is replaced by the corresponding monodentate compound prepared in Comparative Examples 1-1 to 1-15, and the structure is as follows:

[0248]

[0249] Comparative Example 4-4

[0250] The preparation method is the same as that of Example 19, except that the monomer 1 in Example 1-15 is replaced by the corresponding bidentate compound prepared in Comparative Examples 2-1 to 2-15, and the structure is as follows:

[0251]

[0252] Example 20 Preparation of Chondroitin Sulfate Modified with Hydrogel Monomer

[0253]

[0254] Comparative Examples 3-5

[0255] The preparation method is the same as that of Example 20, except that the monomer 1 in Example 1-15 is replaced by the corresponding monodentate compound prepared in Comparative Examples 1-1 to Comparative Examples 1-15, and the structure is as follows:

[0256]

[0257] Comparative Examples 4-5

[0258] The preparation method is the same as that of Example 20, except that the monomer 1 in Example 1-15 is replaced by the corresponding bidentate compound prepared in Comparative Examples 2-1 to 2-15, and the structure is as follows:

[0259]

[0260] Example 21 Preparation of Sodium Alginate Modified with Hydrogel Monomer

[0261]

[0262] Comparative Examples 3-6

[0263] The preparation method is the same as that of Example 21, except that the monomer 1 in Example 1-15 is replaced by the corresponding monodentate compound prepared in Comparative Examples 1-1 to Comparative Examples 1-15, and the structure is as follows:

[0264]

[0265] Comparative Examples 4-6

[0266] The preparation method is the same as that of Example 21, except that the monomer 1 in Example 1-15 is replaced by the corresponding bidentate compound prepared in Comparative Examples 2-1 to 2-15, and the structure is as follows:

[0267]

[0268] Example 22 Preparation of polylactic acid modified with hydrogel monomer

[0269]

[0270] Comparative Examples 3-7

[0271] The preparation method is the same as that of Example 22, except that the monomer 1 in Example 1-15 is replaced by the corresponding monodentate compound prepared in Comparative Examples 1-1 to Comparative Examples 1-15, and the structure is as follows:

[0272]

[0273] Comparative Examples 4-7

[0274] The preparation method is the same as that of Example 22, except that the monomer 1 in Example 1-15 is replaced by the corresponding bidentate compound prepared in Comparative Examples 2-1 to 2-15, and the structure is as follows:

[0275]

[0276] Example 23 Preparation of hydrogel molecules

[0277] The hydrogel monomer-modified products prepared in Examples 16 to 22 and LAP were dissolved in PBS solution respectively, and ultrasonically heated and dissolved at 50° C. to form a uniform and transparent solution. The two solutions were mixed together and stirred to mix them evenly. The mixed solution was placed under an ultraviolet lamp to solidify into a gel to obtain a hydrogel.

[0278] Comparative Example 5-1

[0279] The preparation method is the same as that of Example 23, except that the hydrogel monomer-modified products prepared in Examples 16 to 22 are replaced by the monodentate products in Comparative Examples 3-1 to 3-7.

[0280] Comparative Example 6-1

[0281] The preparation method is the same as that of Example 23, except that the hydrogel monomer-modified products prepared in Examples 16 to 22 are replaced by the bidentate products in Comparative Examples 4-1 to 4-7.

[0282] In the present application, not only hydrogel monomers and their corresponding hydrogel molecules are prepared, comparative examples are constructed for verification, but also the prepared hydrogel molecules (tridentate) and the monodentate hydrogel molecules and bidentate hydrogel molecules of the comparative examples are tested, and the test method is as follows:

[0283] Rheological analysis: The rheological dynamics experiment was carried out under a UV light source (365 nm, 40 mW / cm 2 ) on a rheometer. Use a pipette to transfer 400 μL of the hydrogel precursor solution and spread it on the lower plate of the rheometer. A time scanning oscillation test was performed under ultraviolet light. Under controlled strain conditions, the oscillation amplitude was set to x, the test frequency was set to y, the plate spacing was set to 0.8 mm, and the test temperature was set to 25°C. The gel point was determined as the intersection of the storage modulus (G′) and the loss modulus (G″), and the final modulus was the average modulus when the storage modulus reached equilibrium.

[0284] It should be noted here that rheology mainly studies the phenomena of creep and stress relaxation of various materials, which are specifically manifested in changes in material viscosity and modulus. Storage modulus (G′): also known as the elastic modulus, refers to the amount of energy stored in the material due to elastic (reversible) deformation when the material is deformed, reflecting the elasticity of the material. Loss modulus (G″): also known as the viscous modulus, refers to the amount of energy lost due to viscous deformation (irreversible) when the material is deformed, reflecting the viscosity of the material. When G' is less than G”, the system mainly undergoes viscous deformation and the material is in liquid state; when G' is greater than G”, the system mainly undergoes elastic deformation and the material is in solid state; and when G' is equal to G”, the material is in a gel state, so the intersection of the G' and G” curves is defined as the gel point.

[0285] Mechanical property evaluation: When the compressive strain was 50%, the compressive strength of the hydrogels of the embodiments and comparative examples was tested. In addition, when a certain load was applied to the hydrogels of the embodiments and comparative examples under the condition of fixed strain, the corresponding stress during the loading and unloading process of the hydrogel was recorded.

[0286] Photocuring time: The in-situ gelation process of the hydrogel precursor solution prepared in the examples and comparative examples under ultraviolet light was tested, and the time from the start of light irradiation to the gelation of the hydrogel precursor solution was recorded. It should be noted that the gelation time generally refers to the time required for the gel solution to transform from a flowable liquid state to a gel state under a certain light.

[0287] There are two general definitions of gel time. One is the initial gel time, which is the time from when the hydrogel solution starts to crosslink until the gel system does not deform due to its own weight after inversion. The other is the stable gel time, which is the time required for the gel solution to be completely crosslinked. The macroscopic gel time is used here, which can be understood as the moment when the sol-gel transformation is observed macroscopically as the intermediate state of the whole process. At this time, the gel network has a certain strength but has not reached a stable state.

[0288] In order to facilitate the recording of the experimental performance obtained in the examples and comparative examples, the hydrogel molecules prepared in the examples, i.e., the tridentate hydrogel, are marked as TD-Gel (Tridentate Gel), the monodentate hydrogel in the comparative example is marked as MD-Gel (monodentate Gel), and the bidentate hydrogel in the comparative example is marked as BD-Gel (Bidentate Gel). The test results are shown in the following table:

[0289]

[0290]

[0291]

[0292]

[0293]

[0294]

[0295]

[0296]

[0297] The above experimental results prove that the mechanical properties of tridentate gel molecules are significantly improved compared with their corresponding bidentate gel molecules and monodentate gel molecules, and the gel time is significantly shortened. The main reason may be the effective dissipation of energy by the dynamic covalent cross-linking points dispersed inside the tridentate hydrogel. This dissipation process enables the hydrogel to maintain good recovery performance when subjected to large external mechanical forces, and still maintain structural integrity and high elasticity of the gel under large deformation.

[0298] The hydrogel molecules in this application can be used for photothermal therapy. The hydrogel precursor solution is injected into the mouse through intratumoral injection and solidified into gel in situ under ultraviolet light. The mouse tumor site is irradiated with an 808nm laser to heat the photothermal material in the tumor, and the temperature of the tumor site is monitored with a thermal imager. The results show that the hydrogel in the embodiment of the present application has good response performance to the temperature during photothermal therapy, and can effectively amplify the afterglow luminescence at high temperature (60°C) for monitoring and warning of high temperature thresholds.

[0299] The hydrogel molecules in this application can also be used for in-situ minimally invasive occlusion of puncture needle tracts. After the hydrogel contacts the biological tissue, the two gradually bond in the form of chemical bonds, thereby firmly anchoring the hydrogel to the tissue surface and providing long-term adhesion. The characteristics of fast but weak physical adhesion are combined with the characteristics of slow but strong chemical adhesion to construct a photo-crosslinked adhesive with instantaneous and firm adhesion. The results show that under CT guidance, in-situ, accurate and rapid hemostasis of pig kidney puncture wounds can be achieved. This is due to the physical and chemical interactions between the hydrogel and the surface of the biological tissue, which enables it to have good adhesion and quickly and firmly bond to the surface of the needle tract. This property enhances the ability of the hydrogel to resist the impact of blood flow at the wound site, avoids the risk of being washed away by high-pressure blood flow during the occlusion process, and thus improves the hemostatic effect.

[0300] In addition, the hydrogel of the present application can also be used for postoperative wound closure-skin repair materials or drugs, postoperative wound closure-postoperative anti-adhesion materials or drugs, postoperative wound closure-oral ulcer materials or drugs, tissue fluid leakage blocking-intestinal leakage blocking materials or drugs, tissue fluid leakage blocking-surgical suture materials or drugs, hemostatic materials-liver hemostatic materials or drugs, hemostatic materials-bone section hemostatic materials or drugs, hemostatic materials-arterial hemostatic materials or drugs, hemostatic materials-heart hemostatic materials or drugs, tissue engineering scaffold materials-cartilage repair materials or drugs, tissue engineering scaffold materials-bone repair materials or drugs, tissue engineering scaffold materials-bone / cartilage composite defect repair materials or drugs, 3D printing materials-bio-ink and cells, proteins, drug carriers.

Claims

1. A hydrogel molecule, It is characterized in that The hydrogel molecule is mainly composed of a free radical cross-linking network, and a hydrogel monomer as described in the following formula (I) is introduced. Under light conditions, the free radical cross-linking network undergoes a free radical cross-linking reaction with the hydrogel monomer under the action of a photoinitiator, and the -SH in formula (I) forms a chemical bond with the free radical cross-linking network to construct the main structure of the hydrogel network, thereby forming the hydrogel molecule. Wherein, in formula (I), X is S or O, R 1 is a carbon chain with 0-8 carbon atoms (when R is 0 1 , R 2 do not exist), R 2 For -NH 2 , -COOH or -CHO, L is CR, N, SiR′ or R and R' are any organic substituent groups. Preferably, R and R' are each independently selected from C1-C18 alkyl, C2-C18 alkenyl or C2-C18 alkynyl. More preferably, R and R' are each independently selected from C1-C6 alkyl, C3-C6 alkenyl or C3-C6 alkynyl. More preferably, R and R' are each independently selected from C1-C4 alkyl. X 1 To X 3 are the same as or different from each other and are each independently CH or N, L1 is a direct bond, or at least one selected from a carbon atom, an alkyl group, an alkynyl group, a keto group, a carboxyl group, an ester group, an aryl group, an amine group, or a substituted or unsubstituted arylene group; preferably, L1 is a C6-C30 substituted or unsubstituted arylene group.

2. The hydrogel molecule according to claim 1, It is characterized in that The free radical cross-linking network includes natural macromolecular monomers modified with unsaturated double bonds and synthetic high molecular polymers containing unsaturated bonds.

3. The hydrogel molecule according to claim 1, It is characterized in that The free radical cross-linked network includes synthetic polymers modified with hyaluronic acid, chitosan, sodium alginate, heparin, gelatin, chondroitin sulfate, methacrylate, polylactic acid, and fumarate; Preferably, the free radical cross-linked network includes at least one of the following seven structures:

4. The hydrogel molecule according to any one of claims 1 to 3, It is characterized in that The photoinitiator is selected from at least one of the following chemical structures:

5. The hydrogel molecule according to claim 1, It is characterized in that In the formula (I), L 1 is selected from at least one of a carbon atom, an alkyl group, an alkynyl group, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; preferably, L 1 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; In the formula (I), L is selected from a nitrogen atom, an alkyl group, a silane group, an aryl group, and a triazine group; preferably, L is selected from a C1-C18 alkyl group, a C1-C18 silane group, and a C6-C18 aryl group; In the formula (I), The positions on the benzene ring are adjacent. It may be located at any substituent position on the benzene ring except L1.

6. The hydrogel molecule according to claim 1, It is characterized in that The hydrogel monomer has a structure as shown in formula (II): Among them, in formula (II), L 2 At least one selected from the group consisting of a carbon atom, an alkyl group, an alkyne, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; L 3 At least one selected from the group consisting of a carbon atom, an alkyl group, an alkyne, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; L 4 is selected from at least one of a carbon atom, an alkyl group, an alkyne, a keto group, a carboxyl group, an ester group, an aromatic group, and an amine group; preferably, L 2 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; L 3 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; L 4 At least one selected from a carbon atom, a C1-C18 alkyl group, a C2-C18 alkynyl group, a C3-C18 keto group, a C1-C18 carboxyl group, a C3-C18 ester group, a C6-C18 aryl group, and a C1-C18 amine group; In formula (II), L is selected from one of a nitrogen atom, an alkyl group, a silane group, an aryl group, and a heteroaryl group; preferably, L is selected from one of a nitrogen atom, a C1-C18 alkyl group, a C1-C18 silane group, a C6-C18 aryl group, and a C6-C18 heteroaryl group; Preferably, the L 2 , L 3 , L 4 Select one of the following structures: Carbon atom, -CH 2 , Preferably, L is selected from one of the following structures: Nitrogen atom, -C-CH 3 、-Si-CH 3 , 7. A hydrogel monomer according to claim 6, It is characterized in that The hydrogel monomer has any of the following structures:

8. The method for preparing a hydrogel molecule according to any one of claims 1 to 7, comprising the following steps: dissolving a hydrogel monomer in a biocompatible medium to obtain a solution A, dissolving a photoinitiator in a biocompatible medium to obtain a photoinitiator solution B, uniformly mixing solution A and solution B to obtain a hydrogel precursor solution, and subjecting the hydrogel precursor solution to a photocrosslinking reaction under light to form a hydrogel.

9. A method for preparing a hydrogel molecule according to claim 8, It is characterized in that The biocompatible medium is distilled water, physiological saline or buffer.

10. The use of the hydrogel molecules according to any one of claims 1 to 7, comprising using the hydrogel molecules as postoperative wound closure-skin repair materials or drugs, postoperative wound closure-postoperative anti-adhesion materials or drugs, postoperative wound closure-oral ulcer materials or drugs, tissue fluid leakage blocking-intestinal leakage blocking materials or drugs, tissue fluid leakage blocking-surgical suture materials or drugs, hemostatic materials-liver hemostatic materials or drugs, hemostatic materials-bone section hemostatic materials or drugs, hemostatic materials-arterial hemostatic materials or drugs, hemostatic materials-heart hemostatic materials or drugs, tissue engineering scaffold materials-cartilage repair materials or drugs, tissue engineering scaffold materials-bone repair materials or drugs, tissue engineering scaffold materials-bone / cartilage composite defect repair materials or drugs, 3D printing materials-bio-ink and cells, proteins, drug carriers.

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