A hydrogel and a preparation method and application thereof

Abstract

This invention belongs to the fields of materials science and clinical medicine, specifically relating to a hydrogel, its preparation method, and its applications. The specific technical solution involves providing a novel polyether-based diolized poly(diolized) fatty acid triol ester, and further preparing a first polymer and a second polymer based on this compound. The mixing of the first and second polymers forms a hydrogel with an extremely short photosensitive curing time, exhibiting broad application prospects.

Description

Technical Field

[0001] This invention belongs to the fields of materials science and clinical medicine, specifically relating to a hydrogel, its preparation method, and its applications. Background Technology

[0002] With the rapid development of modern medical technology, the pharmaceutical industry's requirements for medical materials are constantly increasing. These requirements not only demand good biosafety, but also excellent biomechanical properties, precisely controllable degradation or phase transition properties, and the ability to bind to bioactive factors.

[0003] Photosensitive curable hydrogels have emerged. These materials can be fixed under certain light conditions, thus adapting to complex and ever-changing clinical situations. Polyether-based glycolized poly(diolized fatty acid triol) is a polyester polymer material with excellent biodegradability and biocompatibility, and has a very broad application prospect in the biomedical field. This type of material also has the following advantages: (1) It has a controllable and tunable main chain structure, and compared with polyethylene glycol materials commonly used in the field of biomaterials, it has a lower swelling degree and higher mechanical properties; (2) Compared with traditional biological raw materials such as polylactic acid and polycaprolactone, it contains abundant modifiable side hydroxyl groups, providing the possibility for multifunctional customized modification; (3) Good processability; (4) It can be used as an excellent carrier for bioactive factors, drugs, etc. In summary, polyether-based glycolized poly(diolized fatty acid triol) is a biomedical raw material with great application potential. Studies have found that some polyether-based glycolated polydicarboxylic acid triol esters and their derivatives have the potential to prepare photosensitive curable hydrogels. However, current research is still in its early stages, with limited controllability and drawbacks such as excessively long or uncertain photosensitive curing times, poor biocompatibility after curing, poor mechanical properties after curing leading to easy breakage, and poor tissue adhesion leading to easy detachment.

[0004] Therefore, if a hydrogel with more precise control over curing time, excellent biomechanical properties and good biosafety after curing can be provided, it will greatly expand the range of medical materials available and have important practical value in clinical practice. Summary of the Invention

[0005] The purpose of this invention is to provide a hydrogel that allows for precise control of photosensitive curing in time and space, as well as its preparation method and applications.

[0006] To achieve the above-mentioned objectives, the technical solution adopted by this invention is: a type of polyether-based diolized poly(dicarboxylic acid) fatty triol ester, named a precursor polymer, wherein the general structural formula of the precursor polymer is:

[0007]

[0008] Where z is 1 to 14, n is 1 to 50, m is 3 to 60, and R is -CH3 or H.

[0009] Preferably, the number average molecular weight of the precursor polymer is 5,000 to 100,000 Da.

[0010] Preferably, the molecular weight distribution coefficient of the precursor polymer is 1.0 to 2.0.

[0011] Accordingly, the derivative prepared using the polyether-based diolized polydicarboxylic acid triol ester is named the first polymer, and the general structural formula of the first polymer is:

[0012]

[0013] Where z is 1 to 14, n is 1 to 50, m is 3 to 60, and R is -CH3 or H.

[0014] Preferably, X is independently selected from the following groups: H, CH=CH2, and each structural unit contains an average of at least 0.5 CH=CH2, "CH=CH2" indicates that the double bond is attached to the polyether-based diolized polydicarboxylic acid triol ester derivative through a grafted chain structure.

[0015] Preferably, the side chains of the first polymer include photocrosslinkable molecules with double bonds.

[0016] Preferably, the number average molecular weight of the first polymer is 5,000 to 100,000 Da.

[0017] Accordingly, the derivative prepared using the polyether-based diolized poly(diolized) fatty acid triol ester is named the second polymer, and the general structural formula of the second polymer is:

[0018]

[0019] Where z is 1–14, n is 1–50, m is 3–60, and R is -CH3 or H; Y is independently selected from the following groups: H, CHO, and in a single structural unit, it contains an average of at least 0.5 CHO; "CHO" refers to the aldehyde group being attached to the precursor polymer through a grafted chain structure.

[0020] Preferably, Y is independently selected from the following group of groups: H, Furthermore, each structural unit contains an average of at least 0.5 to 2

[0021] Accordingly, the application of the polyether-based diolized poly(diolized) fatty triol ester or the derivatives prepared based on the polyether-based diolized poly(diolized) fatty triol ester in the field of hydrogels.

[0022] The present invention has the following beneficial effects: The hydrogel provided by the present invention can precisely control the curing time to the second level, and can be controlled as quickly as 1 to 2 seconds. In clinical or other applications, the hydrogel precursor solution can be applied to the required area first. When curing is required, the area to be cured can be irradiated with light of a specific wavelength for 1 to 2 seconds to complete the curing. Other areas that do not need to be cured immediately can be left unirradiated and can be irradiated with light when needed, thereby precisely achieving the curing time and location; the prepared hydrogel precursor solution can remain in an effective state for more than one month in a light-protected environment.

[0023] The hydrogel precursor provided by this invention possesses abundant grafting sites, exhibiting significant variability in functional modification, including but not limited to: mechanical properties, degradation rate, and grafting of specific groups. This characteristic allows the hydrogel to meet a wide range of mechanical and degradation requirements, thus enabling it to be well-suited for tissues and organs with different mechanical characteristics. The synthetic raw materials and degradation products used in the hydrogel are all native to the human body, ensuring high biocompatibility and minimizing the risk of inflammatory or foreign body reactions. Furthermore, the hydrogel operates under mild reaction conditions during synthesis and phase transition, preventing deformation of bioactive substances and thus effectively loading, protecting, and delivering them.

[0024] Based on the above characteristics, the hydrogel disclosed in this invention can serve as a relatively universal basic material for medical devices, used for the protection, repair, regeneration, and fulfillment of special requirements in different tissues and organs under different environments and conditions. Simultaneously, it can also serve as a basic material for other medical devices, such as medical 3D printing. Attached Figure Description

[0025] Figure 1 Chemical structural formulas and proton NMR spectra of precursor polymers 1-4 prepared in this invention;

[0026] Figure 2 Chemical structural formulas and proton NMR spectra of precursor polymers 5-8 prepared in this invention;

[0027] Figure 3 Fourier transform infrared spectra of precursor polymers 1-4 prepared in this invention;

[0028] Figure 4 Fourier transform infrared spectra of precursor polymers 5-8 prepared for this invention;

[0029] Figure 5 A schematic diagram showing the cell compatibility results of precursor polymers 1-8 prepared in this invention;

[0030] Figure 6 The chemical structural formulas and proton NMR spectra of the first polymers 1-8 prepared in this invention are shown below.

[0031] Figure 7 Fourier transform infrared spectra of the first polymers 1 to 8 prepared in this invention;

[0032] Figure 8 The chemical structural formulas and proton NMR spectra of the second polymers 1-8 prepared in this invention are shown below.

[0033] Figure 9 Fourier transform infrared spectra of the second polymers 1-8 prepared in this invention;

[0034] Figure 10 This is a schematic diagram illustrating the rheological characterization of the various groups of hydrogels prepared in this invention;

[0035] Figure 11 This is a schematic diagram showing the cell compatibility results of the various groups of hydrogels prepared in this invention;

[0036] Figure 12 This is a schematic diagram showing the mechanical characterization results of the various groups of photosensitive hydrogels prepared in this invention;

[0037] Figure 13 This is a schematic diagram showing the tissue adhesion strength results of each group of photosensitive hydrogels prepared in this invention;

[0038] Figure 14 This is a schematic diagram showing the degradation rate results of each group of photosensitive hydrogels prepared in this invention;

[0039] Figure 15 This is a schematic diagram illustrating the properties of hydrogels with different aldehyde grafting rates prepared according to the present invention. Detailed Implementation

[0040] This invention provides a hydrogel. The hydrogel formulation comprises: a first polymer, a second polymer, and a photoinitiator. The mass ratio of the first polymer to the second polymer is 1:6 to 1:1, preferably 1:5 to 1:1, and more preferably 1:4. The mass ratio of the photoinitiator to the first polymer is 0.5% to 2%, preferably 0.5% to 1%.

[0041] The first and second polymers are prepared based on the precursor polymer. The precursor polymer is a novel polyether-based diolized poly(diolized) fatty triol ester with a number-average molecular weight of 5000–100000 Da, preferably 8000–50000 Da, and more preferably 10000–20000 Da. The molecular weight distribution coefficient of the precursor polymer is 1.0–2.0, preferably 1.0–1.5. The structural formula of the precursor polymer is as follows:

[0042]

[0043] z is 1–14, n is 1–50, m is 3–60, and R is -CH3 or H.

[0044] The first polymer is a polyether-based glycolized poly(diolized) fatty triol ester with photocrosslinkable molecules on its side groups; a more preferred embodiment is that the first polymer is obtained by modifying the polyether-based glycolized poly(diolized) fatty triol ester with double bonds, preferably by replacing the side hydroxyl groups on the polyether-based glycolized poly(diolized) fatty triol ester with a double-bonded modifying substance; an even more preferred embodiment is that the double bond grafting rate of the polyether-based glycolized poly(diolized) fatty triol ester derivative with photocrosslinkable molecules on its side groups is 25% to 100%, more preferably 25% to 75%, and even more preferably 25% to 50%.

[0045] In one embodiment, the side chain of the first polymer includes a photocrosslinkable molecule having double bonds, said photocrosslinkable molecule including: acryloyl chloride Cinnamon acid and methacrylic anhydride

[0046] The first polymer comprises the following structural units:

[0047]

[0048] Wherein, z is 1 to 14, preferably 4 to 10; n is 1 to 50, preferably 1 to 20; m is 3 to 60, preferably 5 to 60; and R is -CH3 or H. In one embodiment, X is independently selected from the following groups: H, CH=CH2, and each structural unit contains an average of at least 0.5 CH=CH2. Wherein, "CH=CH2" indicates that the double bond is attached to the precursor polymer through a grafted chain structure.

[0049] The number average molecular weight of the first polymer is 5,000 to 100,000 Da, preferably 8,000 to 50,000 Da, and more preferably 10,000 to 20,000 Da. The molecular weight distribution coefficient is 1.0 to 2.0, preferably 1.0 to 1.5.

[0050] The first polymer can be crosslinked by light irradiation with a wavelength of 300-700 nm under the action of a photoinitiator, preferably 350-450 nm, and more preferably 405 nm.

[0051] The side chains of the second polymer contain molecules with aldehyde groups that can undergo aldehyde-amine reactions, such as 3-carboxybenzaldehyde. and glyoxylic acid

[0052] The structural formula of the second polymer is shown below:

[0053]

[0054] Where z is 1 to 14, n is 1 to 50, m is 3 to 60, and R is -CH3 or H.

[0055] In one embodiment, Y is independently selected from the following groups: H, CHO, and in a single structural unit, it contains an average of at least 0.5 CHO; "CHO" refers to the aldehyde group being attached to the precursor polymer through a grafted chain structure.

[0056] In another implementation, Y is independently selected from the following group groups: H, Furthermore, each structural unit contains an average of at least 0.5 to 2 Preferably, it contains at least 1 to 2 A more preferred approach is to include at least 1.5 to 2

[0057] The number average molecular weight of the second polymer is 5,000 to 500,000 Da, preferably 8,000 to 100,000 Da, more preferably 10,000 to 20,000 Da; the molecular weight distribution coefficient is 1.0 to 2.0, preferably 1.0 to 1.5.

[0058] The aldehyde grafting rate of the second polymer, i.e. the ratio of H to hydroxyl groups in the aldehyde-substituted polyether diolized polydicarboxylic acid triol ester, is 25% to 100%, preferably 50% to 100%, and more preferably 75% to 100%.

[0059] The photoinitiator is one or a combination of the following compounds: lithium phenyl-2,4,6-trimethylbenzoylphosphinate (Lap), 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (Irgacure 2959), phenyl bis(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure 819), 1-hydroxycyclohexylphenyl ketone (Irgacure 184), and 2,2-dimethoxy-2-phenylacetophenone (Irgacure 651).

[0060] The present invention also provides a preparation process for the hydrogel, which specifically includes the following steps:

[0061] 1. Preparation of precursor polymer. Diacid and tetrabutylammonium hydroxide are added to 95% ethanol in a molar ratio of 1:2 and stirred at 40-70°C (preferably 50-55°C) for 20-40 min (preferably 25-35 min). After the reaction is completed, ethanol and water are removed to obtain product 1.

[0062] Subsequently, under a nitrogen atmosphere, diacid, polyether-based glycol diglycidyl ether, and product 1 in a molar ratio of 1:1:0.006 were dissolved in anhydrous N,N-dimethylformamide, and the mixture was stirred and reacted at 80–150°C (preferably 90–120°C) for 48–96 h (preferably 60–84 h) to obtain product 2. Product 2 was purified by dialysis to obtain the desired precursor polymer: polyether-based glycolized poly(diacid) fatty triol ester.

[0063] 2. Preparation of the first polymer. This polymer is obtained by replacing the side hydroxyl groups on the precursor polymer with a double-bond modifier. Specifically, under a nitrogen atmosphere, the precursor polymer and triethylamine are dissolved in anhydrous N,N-dimethylformamide at a molar ratio of 1:1 to 1:2. Then, 0.5–2 eq of acryloyl chloride is slowly added dropwise, and the mixture is stirred at 0°C for 12 h. After the reaction is complete, the mixture is filtered, precipitated with diethyl ether, and then purified by dialysis to obtain the first polymer.

[0064] 3. Preparation of the second polymer. This is obtained by replacing the side hydroxyl groups on the precursor polymer with an aldehyde-containing modifier. Specifically, under a nitrogen atmosphere, the precursor polymer, p-aldehyde benzoic acid, N,N'-diisopropylcarbodiimide (DIC), and 4-dimethylaminopyridine (DMAP) are dissolved in anhydrous N,N-dimethylformamide in a molar ratio of 1:1:1.5:0.1 to 1:2:1.5:0.1, and the mixture is stirred at room temperature for 24 hours. After the reaction is complete, the second polymer is obtained by dialysis.

[0065] 4. Mix the first polymer, the second polymer, and the photoinitiator to obtain a hydrogel precursor solution. Under light irradiation, a cured hydrogel is obtained. The light wavelength is 300–700 nm, preferably 350–450 nm, and more preferably 405 nm.

[0066] This invention also provides a method for using the hydrogel. Specifically, the area to be bonded is pre-cleaned, a first polymer, a second polymer, and a photoinitiator are mixed in a specific ratio to obtain a hydrogel precursor solution, which is then applied or placed on the area to be bonded. The precursor solution is then irradiated with light of a specific wavelength for ≥0.5 seconds until it solidifies. According to common techniques in the art, the hydrogel can be used for at least: bonding of skin and mucous membrane wounds; wound hemostasis; soft tissue bonding, including but not limited to: blood vessels, nerves, liver, spleen, kidneys, hollow organs of the digestive tract, bladder, ureters, and uterus; bone and cartilage tissue bonding; tissue filling, including but not limited to: facial filling, breast filling, and bone tissue filling; vascular embolization; drug release carrier; medical patches, medical photosensitive 3D printing substrates, and other basic materials for medical devices.

[0067] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art.

[0068] Example 1: Preparation of precursor polymers

[0069] 1. Weigh out different diacids and tetrabutylammonium hydroxide in ethanol at a molar ratio of 1:2, heat and stir at 55°C for 30-60 min, and obtain different diacid di(tetrabutylammonium hydroxide) esters after rotary evaporation and freeze drying. The products are white powders with a yield of 85-95%.

[0070] Under a nitrogen atmosphere, diacid, polyether glycol diglycidyl ether, and the aforementioned white powder were weighed in a molar ratio of 1:1:0.006, dissolved in anhydrous DMF, and heated and stirred at 90–150 °C for 1–3 days to obtain the product. The product was then purified by dialysis and vacuum dried to obtain purified polyether glycol-polydiacid fatty triol ester (i.e., the precursor polymer). The purified precursor polymer was a flowable, pale yellow, transparent polymer at room temperature, with a yield of 80–90%. Table 1 shows the precursor polymers and yields obtained using different diacids and different polyether glycol diglycidyl ethers under different conditions.

[0071] Table 1. Comparison of conditions and results for obtaining different precursor polymers.

[0072] Precursor polymers diacid Polyether diol diglycidyl ether reaction time Yield Precursor polymer 1 adipic acid Polyethylene glycol diglycidyl ether 72h 86％ Precursor polymer 2 Oleic acid Polyethylene glycol diglycidyl ether 72h 87％ Precursor polymer 3 sebacic acid Polyethylene glycol diglycidyl ether 72h 89％ Precursor polymer 4 dodecyldioic acid Polyethylene glycol diglycidyl ether 72h 89％ Precursor polymer 5 adipic acid Polypropylene glycol diglycidyl ether 72h 80％ Precursor polymer 6 Oleic acid Polypropylene glycol diglycidyl ether 72h 82％ Precursor polymer 7 sebacic acid Polypropylene glycol diglycidyl ether 72h 82％ Precursor polymer 8 dodecyldioic acid Polypropylene glycol diglycidyl ether 72h 80％

[0073] 2. Fourier transform infrared spectroscopy was obtained using the coating method, and proton nuclear magnetic resonance spectroscopy was obtained using deuterated dimethyl sulfoxide as the deuterating reagent, thereby determining the molecular structure of the polymer. The results are as follows: Figures 1-4 As shown, where, Figure 1 , 2 The chemical structural formulas and 1H NMR spectra of the precursor polymers are shown below. Figure 3 , 4 The Fourier transform infrared spectra of each precursor polymer are shown. Figures 1-4 The numbers in the table represent the corresponding precursor polymers, for example, "1" represents "precursor polymer 1".

[0074] Depend on Figure 1 , 2 As can be seen, peaks a (2.31 ppm), b (1.55 ppm), and c (1.25 ppm) correspond to the methylene peaks of the diacid in the polymers. Since adipic acid only has four methylene groups, precursor polymers 1 and 5 do not have peak c. Peaks d (3.3–3.6 ppm) and e (1.15 ppm) correspond to the methylene and methyl peaks in polypropylene glycol, respectively. This demonstrates the successful preparation of the desired precursor polymers.

[0075] Figure 3 , 4 The peaks from left to right represent the peaks corresponding to hydroxyl, methylene, carbonyl, and ether bonds, respectively. Figure 1 , 2 The proton NMR spectra of each sample further confirm the successful preparation of the desired precursor polymers.

[0076] 3. Biocompatibility Characterization. To evaluate the cytocompatibility of the precursor polymer, the cytotoxicity of mouse fibroblasts (L929) co-cultured with the precursor polymer was investigated at 1, 3, and 7 days. Specifically, each group of precursor polymers was placed in 96-well plates at a concentration of 2 mg per 200 μL of medium. L929 cells were seeded onto the plate surface at a density of 4000 cells / well and then incubated at 37°C in a CO2 incubator. At days 1, 3, and 7, the medium was replaced with Alma blue reagent, and incubation was continued for 2–4 hours. Fluorescence intensity was measured at an excitation wavelength of 540 nm and an emission wavelength of 600 nm. Results are as follows: Figure 5 As shown ( Figure 5 From left to right, these represent the blank group and groups 1 to 8 of the precursor polymers, respectively. All precursor polymers exhibit good cell compatibility.

[0077] Example 2: Preparation of the first polymer

[0078] 1. Preparation of the first polymer: Under a nitrogen atmosphere, the precursor polymer (based on the amount of hydroxyl groups) and triethylamine were dissolved in anhydrous N,N-dimethylformamide at a molar ratio of 1:1.5. The system temperature was maintained at -4℃ to 0℃. Then, 1 eq of acryloyl chloride (relative to the amount of hydroxyl groups in the precursor polymer) was slowly added dropwise through a constant pressure funnel. The reaction was stirred at -4℃ to 0℃ for 12 h. The product obtained by filtration was precipitated with diethyl ether, then purified by dialysis, and freeze-dried to obtain the first polymers. The first polymers were free-flowing, pale yellow, and transparent polymers at room temperature, with yields of 70-85%. The first polymers obtained under different conditions (precursor polymers) and their yields are shown in Table 2.

[0079] Table 2 Comparison of conditions and results for obtaining different first polymers

[0080] First Polymer Precursor polymers reaction time Yield First polymer 1 Precursor polymer 1 12h 80％ First polymer 2 Precursor polymer 2 12h 78％ First polymer 3 Precursor polymer 3 12h 85％ First polymer 4 Precursor polymer 4 12h 80％ First polymer 5 Precursor polymer 5 12h 78％ First Polymer 6 Precursor polymer 6 12h 85％ First Polymer 7 Precursor polymer 7 12h 80％ First Polymer 8 Precursor polymer 8 12h 78％

[0081] 2. The Fourier transform infrared spectra of the products were obtained using the coating method, and the proton nuclear magnetic resonance (NMR) spectra of the products were obtained using deuterated dimethyl sulfoxide as the deuteration reagent, thereby determining the molecular structure of each first polymer. The chemical structural formulas and proton NMR spectra of each first polymer are shown below. Figure 6 As shown. Figure 6 In the diagram, peaks a (2.32 ppm), b (1.52 ppm), and c (1.25 ppm) correspond to the methylene peaks of the diacid in the polymer, peak d (3.51 ppm) is the methylene peak in polyethylene glycol, and peaks g (6.42 ppm), e (6.12 ppm), and f (5.86 ppm) correspond to the hydrogen peaks on the double bonds. The Fourier transform infrared spectra of each first polymer are shown below. Figure 7 As shown. Figure 7The peaks from left to right represent the peaks corresponding to hydroxyl, methylene, carbonyl, double bond, and ether bond, respectively. Figure 7 The numbers in the table represent the corresponding first polymer, for example, "1" represents "first polymer 1".

[0082] Example 3: Preparation of the second polymer

[0083] 1. Preparation of the second polymer: Under a nitrogen atmosphere, the precursor polymer, p-aldehyde benzoic acid, N,N'-diisopropylcarbodiimide (DIC), and 4-dimethylaminopyridine (DMAP) were dissolved in anhydrous N,N-dimethylformamide at a molar ratio of 1:1.5:1.5:0.1, and the mixture was stirred at room temperature for 24 h. The product obtained by dialyzing was then dried under vacuum to obtain the second polymer. The second polymer is a flowable, pale yellow, transparent polymer at room temperature, with a yield of 75–85%. The second polymers obtained under different conditions (precursor polymers) and their yields are shown in Table 3.

[0084] Table 3. Comparison of conditions and results for obtaining different second polymers.

[0085]

[0086]

[0087] 2. The Fourier transform infrared spectra of the products were obtained using the coating method, and the proton nuclear magnetic resonance (NMR) spectra were obtained using chloroform as a deuteration reagent, thus determining the molecular structure of each second polymer. The chemical structural formulas and proton NMR spectra of each second polymer are shown below. Figure 8 As shown. Figure 8 In the diagram, peaks a (2.32 ppm), b (1.52 ppm), and c (1.25 ppm) correspond to the methylene peaks of the diacid in the polymer; peak d (3.51 ppm) is the methylene peak in polyethylene glycol; and peaks e (8.12 ppm), g (8.03 ppm), and f (10.11 ppm) correspond to the peaks of the benzene ring and aldehyde group, respectively. The Fourier transform infrared spectra of each second polymer are shown below. Figure 9 As shown. Figure 9 The peaks from left to right represent the peaks corresponding to hydroxyl, methylene, carbonyl, double bond, and ether bond, respectively. Figure 9 The numbers in the text represent the corresponding second polymers; for example, "1" represents "second polymer 1".

[0088] Example 4: Preparation and Performance Demonstration of Hydrogels

[0089] Weigh the first polymer, the second polymer, ultrapure water, and the photoinitiator (in this embodiment, the photoinitiator is lithium phenyl-2,4,6-trimethylbenzoyl phosphite) according to a mass ratio of 1:4:1.5:0.04. Mix the above substances thoroughly to obtain a test sample, and perform the various tests of this embodiment. Using different first and second polymers prepared in Examples 2 and 3, mix them separately and test to obtain multiple treatment groups. The settings for each treatment group are shown in Table 4.

[0090] Table 4. Comparison of conditions and results for obtaining different first polymers

[0091] Processing group First Polymer Second polymer Group 1 First polymer 1 Second polymer 1 Group 2 First polymer 2 Second polymer 2 Group 3 First polymer 3 Second polymer 3 Group 4 First polymer 4 Second polymer 4 Group 5 First polymer 5 Second polymer 5 Group 6 First Polymer 6 Second polymer 6 Group 7 First Polymer 7 Second polymer 7 Group 8 First Polymer 8 Second polymer 8

[0092] 1. Rheological Characterization of Photosensitive Hydrogels. To evaluate the injectability of mixtures used to prepare photocurable tissue-adhesive hydrogels, the changes in storage modulus and loss modulus during hydrogel formation, as well as the gelation time, were investigated using a rotational rheometer. The test temperature was 37℃, the frequency was fixed at 10Hz, the strain was fixed at 5%, and the test time was 10 min. The mixtures prepared in each treatment group were transferred to the test platform. Sufficient irradiation with 405nm blue light was applied, and the data were recorded to obtain the curves of storage modulus and loss modulus versus time during hydrogel formation. The gelation time and the stabilized storage modulus of the hydrogel were analyzed and calculated, where the gelation time is the time when the storage modulus and loss modulus intersect. The results are as follows: Figure 10 As shown, all eight groups of hydrogels can gel within 30 seconds, exhibiting a relatively fast gelation time. Among them, groups 3 and 4 can solidify rapidly within 1 to 2 seconds, achieving second-level solidification.

[0093] 2. Biocompatibility Characterization of Photocurable Hydrogels. To evaluate the cytocompatibility of photocurable tissue-adhesive hydrogels, the cytotoxicity of mouse fibroblasts (L929) co-cultured with the hydrogels was investigated at 1, 3, and 7 days. Specifically, after photocuring each group of hydrogels, 1 mm discs (diameter sufficient to completely cover a 96-well plate) were prepared and placed in 96-well plates. L929 cells were seeded onto the material surface at a density of 4000 cells / well, and then incubated in a 37°C CO2 incubator. At days 1, 3, and 7, the culture medium was replaced with Alma Blue reagent, and incubation continued for 2–4 hours. Fluorescence intensity was measured at an excitation wavelength of 540 nm and an emission wavelength of 600 nm. Results are as follows: Figure 11 As shown, all groups of hydrogels exhibited good cell compatibility. Figure 11 In the middle, from left to right, are the blank group and the precursor polymers of groups 1 to 8, respectively.

[0094] 3. Mechanical Characterization of Photosensitive Hydrogels. The tensile properties of the cured hydrogels prepared in each treatment group were tested using a universal tensile testing machine, with commercially available PEG hydrogel used as a control. The mixed solutions of each treatment group were poured into a rectangular PTFE mold measuring 2.5 cm long, 1 cm wide, and 0.15 cm thick, and irradiated with 405 nm blue light for 10 s. The resulting hydrogels were then fixed in the fixture of the universal tensile testing machine, and the tensile curves were measured at a tensile rate of 10 mm / min. The results are shown below. Figure 12 As shown, the tensile strength of each group of photocurable hydrogels ranged from 0.18 to 0.68 MPa, while the tensile strength of the PEG control group was approximately 0.20 MPa. This indicates that the photocurable hydrogels in this study have mechanical properties equivalent to or far superior to those of commercially available PEG products.

[0095] 4. Characterization of the tissue adhesion strength of the photocurable hydrogel. To evaluate the adhesion performance of the photocurable tissue adhesion hydrogel to moist tissue (pigskin soaked in PBS), the adhesion strength of the hydrogel was investigated using an overlap-shear tensile test. A single piece of pigskin was 6 cm long and 2.5 cm wide, with an overlap of 2.5 × 1 cm. The pigskin was soaked in PBS before being bonded with the hydrogel to simulate a moist physiological environment in vivo. The tensile rate was 50 mm / min. The results are as follows: Figure 13 As shown, the adhesive strength of the hydrogel can reach up to 43 kPa, which is higher than that of cyanoacrylate, and even the lowest adhesive strength group exceeds that of commercial fibroin glue.

[0096] 5. Degradation rate of photosensitive hydrogels. Phosphate-buffered saline (PBS) was used to simulate the body fluid environment, and porcine liver lipase was added at a concentration of 0.625 units / mg hydrogel to simulate the in vivo physiological environment. Circular hydrogel discs with a diameter of 1 cm and a height of 0.35 cm were prepared, and their lyophilized mass was recorded as W0. Each group of hydrogel discs was immersed in PBS and placed in a constant-temperature shaking incubator at 37°C with shaking at 80 rpm. At a preset time point t, the hydrogels were removed, lyophilized, and weighed, which was recorded as Wt.

[0097] The formula for calculating the degradation rate is: The results are as follows Figure 14 As shown, the complete degradation time of the photocurable hydrogel is 42–56 days, which meets the requirements for in vitro and in vivo use.

[0098] 6. The tunability of photosensitive hydrogel properties. This includes tensile properties, compressive properties, degradation properties, and adhesive strength. Hydrogels prepared in group 3 of Table 4 (made from polymer 3 and polymer 3) were used for related experiments.

[0099] (1) In the synthesis of the first polymer 3, the feed ratio of the precursor polymer (calculated according to the theoretical hydroxyl content) and acryloyl chloride was 1:0.5, 1:1, and 1:2, respectively, thus obtaining three sets of first polymer 3 with different double bond grafting rates; in the synthesis of the second polymer, the feed ratio of the precursor polymer and p-aldehyde benzoic acid was maintained at 1:1.5. Three sets of hydrogels were prepared accordingly for tensile properties, compressive properties, and degradation rate experiments.

[0100] (2) In the synthesis of the second polymer 3, the feed ratio of the precursor polymer and p-aldehyde benzoic acid was 1:1, 1:1.5, and 1:2, respectively, thus obtaining three sets of second polymers 3 with different aldehyde grafting rates; in the synthesis of the first polymer, the feed ratio of the precursor polymer and acryloyl chloride was kept at 1:1. Three sets of hydrogels were prepared for adhesive strength experiments.

[0101] Tensile properties: The tensile properties of the cured hydrogels prepared by each treatment group were tested using a universal tensile testing machine. The mixed solutions of each treatment group were poured into a rectangular PTFE mold measuring 2.5 cm long, 1 cm wide, and 0.15 cm thick, and irradiated with 405 nm blue light for 10 s. The resulting hydrogels were then fixed in the fixture of the universal tensile testing machine, and the tensile curves were measured at a tensile rate of 10 mm / min.

[0102] Compression performance: The hydrogel was prepared into a cylinder with a diameter of 10 mm and a height of 7 mm, and the test was conducted using a universal tensile testing machine at a compression rate of 10 mm / min.

[0103] Degradation performance: Phosphate-buffered saline (PBS) was used to simulate the body fluid environment, and porcine liver lipase was added at a concentration of 0.625 units / mg hydrogel to simulate the in vivo physiological environment. Circular hydrogel discs with a diameter of 1 cm and a height of 0.35 cm were prepared, and their lyophilized mass was recorded as W0. Each group of hydrogel discs was immersed in PBS and placed in a constant-temperature shaking incubator at 37°C with shaking at 80 rpm. At a preset time point t, the hydrogels were removed, lyophilized, and weighed, which was recorded as Wt.

[0104] The formula for calculating the degradation rate is:

[0105] Adhesive strength: The adhesive strength of the hydrogel was investigated using an overlap-shear tensile test. A single piece of pigskin was 6 cm long and 2.5 cm wide, with an overlap of 2.5 × 1 cm. The pigskin was soaked in PBS before being bonded with the hydrogel to simulate a moist physiological environment in the body. The tensile rate was 50 mm / min. Results are as follows: Figure 15 As shown, Figure 15In the diagram, A represents the tensile stress-strain curve; B represents the compressive stress-strain curve; C represents in vitro degradation performance; and D represents the overlap-shear strength. A, B, and C all use the synthesis of the first polymer 3 as a variable; D uses the synthesis of the second polymer 3 as a variable. Figure 15 It was found that the tensile strength of the photocurable hydrogel was adjustable from 0.42 to 0.80 MPa, the compressive strength from 0.10 to 0.15 MPa, the degradation rate from 4 to 13 weeks, and the adhesive strength from 18 to 60 kPa. The results indicate that the photosensitive hydrogel in this study exhibits adjustable properties, with its tensile, compressive, degradation, and adhesive strength properties adjustable by changing the mass ratio of the first and second polymers.

[0106] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Any modifications, alterations, substitutions, or variations made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention shall fall within the protection scope defined by the claims of the present invention.

Claims

1. A hydrogel, characterized by: The formulation includes a first polymer, a second polymer, and a photoinitiator; The general structure of the first polymer is: , z is 1 to 14, n is 10 to 50, m is 3 to 60, R is -CH3or H, X is each independently selected from the following group of radicals: H, and in one structural unit, on average, at least 0.5 , " means that the double bond is attached to the precursor polymer via the grafted chain structure; The general structural formula of the second polymer is: ， wherein z is 1 to 14, n is 10 to 50, m is 3 to 60, R is -CH3or H; each Y is independently selected from the following group of radicals: and in one structural unit, on average, at least 0.5 ;" " means that the aldehyde group is attached to the precursor polymer through the grafted chain structure; The general structural formula of the precursor polymer is: ， z is 1–14, n is 10–50, m is 3–60, and R is -CH3 or H.

2. The hydrogel of claim 1, wherein: The number-average molecular weight of the first polymer is 5,000 to 100,000 Da.

3. The hydrogel according to claim 1, characterized in that: The structural formula of the first polymer is any one of the following chemical structural formulas: in each structural formula, m is 3 to 60; ， ， ， ， ， ， ， 。 4. The hydrogel according to claim 1, characterized in that: The second polymer has the following structural formulas: in each formula, m is 3 to 60. ， ， ， ， ， ， ， 。 5. The hydrogel according to claim 1, characterized in that: The mass ratio of the first polymer to the second polymer is 1:6 to 1:

1.

6. The hydrogel according to claim 1, characterized in that: The mass ratio of photoinitiator to first polymer is 0.5:100 to 2:100.

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