Hydrogel with tissue adhesion as well as preparation method and application thereof

Abstract

The invention relates to the technical field of biomedical materials, in particular to hydrogel with tissue adhesion and a preparation method and application thereof. The preparation raw materials of the hydrogel at least comprise aldehyde polysaccharide and a phenylboronic acid modified polyamino compound; the phenylboronic acid modified polyamino compound is obtained by grafting a phenylboronic acid compound to a polyamino compound; the adhesion strength of the hydrogel to pigskin is greater than or equal to 40kPa. By constructing an aldehyde group-phenylboronic acid-cation ternary synergistic effect system and introducing double dynamic chemical bonds (Schiff base bonds and boric acid ester bonds) to promote the formation of the hydrogel, the prepared hydrogel has triple environmental response capabilities (pH, ROS and blood sugar), can be accurately matched with diabetes wound microenvironments (acidity, high ROS and high blood sugar), reduces the wound infection risk, and has a good application prospect. On-demand release of the medicine is realized, and the treatment efficiency is improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, in particular to a hydrogel with tissue adhesion and a preparation method and application thereof. BACKGROUND

[0002] Diabetes is one of the chronic metabolic diseases with the highest incidence in the world today, which is divided into type I diabetes and type II diabetes: type I diabetes is caused by absolute lack of insulin secretion, and type II diabetes is caused by insulin resistance leading to abnormal glucose metabolism. With the progression of the disease, diabetic patients often have multiple organ system damage, and chronic non-healing wounds are typical complications, including diabetic foot ulcers, lower extremity venous ulcers, and pressure ulcers. Among them, the lower extremity amputation rate of diabetic foot ulcer patients is high, and the mortality rate of such patients is at a high level, and the clinical treatment demand is urgent.

[0003] The core reasons for the slow healing of diabetic wounds include: (1) the wound is in a high-sugar microenvironment for a long time, which is easy to breed bacteria and cause infection; (2) the local macrophage function of the wound is disordered, which cannot effectively remove the invading bacteria, resulting in a continuous inflammatory state of the wound and an increase in reactive oxygen species (ROS) levels; (3) high blood sugar can cause cell membrane hardening and blood vessel contraction, resulting in insufficient blood supply to the local wound and hindering the progress of tissue repair.

[0004] Dressings, as a key consumable for the treatment of diabetic foot ulcers, need to have the following functions: (1) maintain a moist wound environment, promote tissue reconstruction by maintaining temperature, regulating gas exchange, promoting the discharge of exudate and removing necrotic tissue fragments; (2) good biocompatibility, no allergenicity and no immune rejection reaction; (3) high antibacterial performance to prevent or treat secondary infection of the wound; (4) excellent ease of use, without causing secondary damage to the wound when removed. Hydrogel dressings have become an important research direction for diabetic foot ulcer dressings due to their good moisturizing properties and biocompatibility. However, existing hydrogels have problems such as complex preparation process, high equipment dependency, and insufficient precision of drug release, making it difficult to meet the needs of precise treatment of diabetic foot ulcers.

[0005] Chinese patent CN119367275A discloses a hydrogel based on methacrylated gelatin as a substrate, which realizes diabetic wound treatment by adding cyclocarya paliurus extract or cyclocarya paliurus leaf powder, and has certain healing-promoting effect. Chinese patent CN119371683A discloses an oxidized hyaluronic acid-chitosan composite hydrogel, which realizes antibacterial and healing-promoting functions by loading metformin and silver-doped carbon quantum dots. However, these existing technologies do not solve the above technical problems.

[0006] In this context, there is an urgent need to develop a new and efficient hydrogel treatment material to solve the problems of complex preparation process and insufficient tissue adhesion of existing hydrogel dressings. SUMMARY

[0007] In view of the problems of the existing hydrogel dressing, such as complicated preparation process, low drug release accuracy and insufficient tissue adhesion, the application provides a tissue-adhesive hydrogel dressing and a preparation method thereof, which has multiple environmental responsiveness, is easy to prepare and has raw materials available, and can realize efficient repair of diabetic foot ulcer and accurate delivery of drugs, thereby providing a new idea for the research and development of high-quality dressings.

[0008] In a first aspect, the application provides a hydrogel with tissue adhesion, wherein the hydrogel is prepared from at least an aldehyde-based polysaccharide and a phenylboronic acid-modified polyamino compound.

[0009] Optionally, the phenylboronic acid-modified polyamino compound is obtained by grafting a phenylboronic acid compound on a polyamino compound.

[0010] Optionally, the adhesion strength of the hydrogel to pigskin is greater than or equal to 40 kPa.

[0011] Optionally, the adhesion strength of the hydrogel to pigskin is greater than or equal to 60 kPa.

[0012] Optionally, the adhesion strength of the hydrogel to pigskin is greater than or equal to 70 kPa.

[0013] Optionally, the adhesion strength of the hydrogel to pigskin is greater than or equal to 80 kPa.

[0014] Optionally, the aldehyde-based polysaccharide and the phenylboronic acid-modified polyamino compound are crosslinked to form the hydrogel through dynamic chemical bonds. Further optionally, the dynamic chemical bonds include Schiff base bonds and borate ester bonds.

[0015] Dynamic chemical bonds refer to reversible chemical bonds that can be broken and recombined when a chemical reaction reaches equilibrium. Such chemical bonds can undergo dynamic transformation under specific conditions (such as heat, light, pH value, catalyst, etc.), allowing continuous exchange of molecular components and ultimately reaching a thermodynamic minimum state. The core feature is "dynamic reversibility", i.e. the formation and breaking of bonds are in dynamic equilibrium, which endows the material with the ability to respond to environmental changes.

[0016] As an example of dynamic chemical bonds, Schiff base bonds are dynamic covalent bonds containing C=N double bonds (imine bonds) formed by condensation reaction of aldehyde / ketone groups and amino groups.

[0017] As an example of dynamic chemical bonds, borate ester bonds are dynamic covalent bonds formed by esterification reaction of polyols (such as sugars) and boric acid.

[0018] The application significantly improves the tissue adhesion performance of the hydrogel by constructing an "aldehyde group-phenylboronic acid-cation" ternary synergistic system, and the adhesion strength of the obtained hydrogel is ≥40kPa (180℃ peeling test). Specifically, the application introduces two dynamic chemical bonds, Schiff base bond (generated by the reaction of aldehyde group and amino group) and borate bond (formed by the reaction of phenylboronic acid and hydroxyl group), and the synergistic effect of aldehyde group modified polysaccharide and phenylboronic acid modified polyamino compound with a specific concentration enables the hydrogel to have a triple environmental response function to pH, reactive oxygen species (ROS) and blood glucose concentration, and the obtained hydrogel can accurately release drugs according to the microenvironment changes of diabetic wound surface, thereby providing effective protection and treatment for diabetic wound repair.

[0019] Optionally, the polyamino compound comprises a combination of one or more of polylysine or its derivative (such as polylysine hydrochloride), polyethyleneimine or chitosan.

[0020] Further optionally, the polyamino compound comprises polylysine hydrochloride.

[0021] Optionally, the number average molecular weight of the polylysine hydrochloride is 1000-5000Da; further optionally 2000Da.

[0022] Optionally, the polysaccharide comprises a combination of one or more of dextran, cellulose, hyaluronic acid sodium or sodium alginate; further optionally dextran.

[0023] Optionally, the number average molecular weight of the polysaccharide is 50000-100000Da; further optionally 60000-80000Da.

[0024] Optionally, the aldehyde group modified polysaccharide is obtained by at least one of the following two preparation methods: 1) Oxidation method: using an oxidizing agent to modify the polysaccharide by oxidation to obtain an aldehyde group modified polysaccharide; 2) Grafting method: using an aldehyde group modification reagent to modify the polysaccharide by aldehyde group grafting to obtain an aldehyde group modified polysaccharide.

[0025] Oxidation method: Optionally, the oxidizing agent comprises at least one of sodium periodate, potassium periodate, sodium periodate and potassium periodate; further optionally sodium periodate.

[0026] Optionally, the reaction conditions for the oxidation modification are: oxidation reaction temperature 20-25℃, oxidation reaction time 10-14h.

[0027] Optionally, the oxidation modification reaction is carried out in the dark and under ice bath conditions.

[0028] Optionally, the aldehyde group modification reagent comprises para-aldehyde benzoic acid.

[0029] Grafting method: Optionally, the aldehyde group modification process is achieved by coupling reaction of the hydroxyl group of polysaccharide and aldehyde group derivative containing carboxyl group, and an activating agent of carboxyl group is added to promote grafting.

[0030] The activating agent can include 4-dimethylaminopyridine (DMAP), 1-ethyl- (3- dimethylaminopropyl) carbodiimide hydrochloride (EDC), etc.

[0031] Further optionally, the activating agent includes a first activating agent and a second activating agent; the first activating agent is DMAP, and the second activating agent is EDC.

[0032] The aldehyde group derivative containing carboxyl group can include glyoxylic acid, formylacetic acid, p-carboxybenzaldehyde, o-carboxybenzaldehyde, m-carboxybenzaldehyde, etc.

[0033] Optionally, the degree of aldehyde group of the aldehyde group modified polysaccharide is 2-20% (i.e. 2-20 aldehyde groups per 100 glycoside units), and further optionally 5-10%, and further optionally 6%.

[0034] Optionally, the phenylboronic acid modified polyamino compound is formed by chemical grafting of a phenylboronic acid compound and a polyamino compound.

[0035] Optionally, the phenylboronic acid compound includes 2-carboxyphenylboronic acid, 3-carboxyphenylboronic acid, 4-carboxyphenylboronic acid, 3,5-dicarboxyphenylboronic acid, 2,4-dicarboxyphenylboronic acid, etc.

[0036] Optionally, the grafting of the phenylboronic acid compound to the polyamino compound is by amide bond or Schiff base bond to form the phenylboronic acid modified polyamino compound.

[0037] When the phenylboronic acid compound includes 4-carboxyphenylboronic acid, the phenylboronic acid modified polyamino compound is specifically an amide bond modified polyamino compound, and the preparation steps of the phenylboronic acid modified polyamino compound include: dissolving 4-carboxyphenylboronic acid in an organic solvent, adding an amine compound, and activating at 20-30°C for 1-2h; adding an aqueous solution of a polyamino compound, and reacting at 20-30°C for 24-36h; transferring the reaction solution to a dialysis bag with a molecular weight cut-off of 3500Da, and dialyzing in purified water for 48-72h to obtain the phenylboronic acid modified polyamino compound (solution B).

[0038] Optionally, the amine compound includes N-hydroxysuccinimide (NHS) and N,N'- diisopropylcarbodiimide (DIC), and the NHS and DIC can jointly activate the system to promote the formation of amide bond.

[0039] Optionally, the molar ratio of the 4-carboxyphenylboronic acid, the NHS and the DIC is 1:(1.2-1.5):(1.2-1.5).

[0040] Optionally, the molar ratio of the 4-carboxyphenylboronic acid and the polyamino compound is (0.3-0.8):1.

[0041] The organic solvent can be exemplified by dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), acetonitrile, tetrahydrofuran (THF), etc.; and further optionally DMSO.

[0042] In some embodiments, the pH of the hydrogel is 5.5-8.0; the pH response range of the hydrogel in the present application is 5.5-8.0, which meets the application range requirement of wound repair materials.

[0043] Optionally, the raw material for preparing the hydrogel further comprises a drug; the drug can be exemplified by metformin, insulin, silver sulfadiazine, econazole nitrate, dexamethasone, indomethacin, diammonium glycyrrhizinate, epidermal growth factor (EGF), fibroblast growth factor (FGF), etc., which can further improve the wound repair effect.

[0044] The second aspect of the present application provides a preparation method of the hydrogel as described above, and the preparation steps of the hydrogel comprise: preparing an aldehyde-based polysaccharide and dissolving it in water to obtain solution A; preparing a phenylboronic acid-modified polyamino compound to obtain solution B; mixing the solution A and the solution B, and standing to form a hydrogel.

[0045] Optionally, the volume ratio of the solution A and the solution B is (0.5-2):1; and further optionally 1:1.

[0046] Optionally, the standing temperature is 20-30℃, and the standing time is 5-600s.

[0047] In some embodiments, the mass-volume concentration of the aldehyde-based polysaccharide in the solution A is 5-40%, optionally 15-25%; and further optionally 20%.

[0048] In some embodiments, the mass-volume concentration of the phenylboronic acid-modified polyamino compound in the solution B is 5-40%, optionally 15-25%; and further optionally 20%.

[0049] In some embodiments, the aldehyde-based polysaccharide is prepared by an oxidation method, and the preparation steps include: dissolving a polysaccharide solution in a solvent I to obtain a polysaccharide solution I, adding an oxidizing agent to the polysaccharide solution I under ice bath and light shielding conditions, and reacting for 10-14 h under light shielding at 20-25 ℃; after the reaction is completed, the reaction solution is transferred to a dialysis bag with a molecular weight cut-off of 3500 Da, dialyzed in purified water for 48-72 h, and freeze-dried to obtain the aldehyde-based polysaccharide.

[0050] Optionally, the mass-volume concentration of the polysaccharide in the polysaccharide solution is 5-10%.

[0051] Optionally, the mass ratio of the polysaccharide to the oxidizing agent is 1: (0.05-0.2).

[0052] In some embodiments, the dialysis process is performed by replacing the purified water every 8 h.

[0053] The solvent I can be water.

[0054] In some embodiments, the aldehyde-based polysaccharide is prepared by a grafting method, and the preparation steps include: dissolving a polysaccharide in a solvent II to obtain a polysaccharide solution II, adding an aldehyde-based reagent, a first activating agent and a second activating agent to the polysaccharide solution II, wherein the molar ratio of the polysaccharide, the aldehyde-based reagent, the first activating agent and the second activating agent is 1: 0.2-0.5: 0.1-0.3: 0.2-0.5; stirring and reacting for 24-36 h at 25-30 ℃, transferring the reaction solution to a dialysis bag with a molecular weight cut-off of 3500 Da, dialyzing in purified water for 48-72 h, and freeze-drying to obtain the aldehyde-based polysaccharide.

[0055] The solvent II can be dimethyl sulfoxide (DMSO).

[0056] The third aspect of the present application provides an application of the hydrogel as described above, and the hydrogel is applied to biomedical materials. The biomedical materials include wound healing materials or drug delivery materials.

[0057] The hydrogel of the present application can load diabetes wound repair drugs such as metformin and insulin, and is used for wound healing and drug delivery of open wounds.

[0058] Advantages: The present application provides a hydrogel with tissue adhesion, a preparation method and an application thereof, and has the following advantages: (1) The aldehyde group modified polysaccharide and the phenylboric acid modified polyamino compound are used to prepare the hydrogel, the obtained hydrogel has excellent tissue adhesion (>=40kPa), broad-spectrum antibacterial property and biocompatibility (cell survival rate >=90%), the obtained hydrogel can closely adhere to a wound surface, reduces the accumulation of exudate, creates a stable microenvironment conducive to repair for the wound surface, thereby better preventing infection and promoting wound healing; (2) The aldehyde group-phenylboric acid-cation ternary synergistic system is constructed, the double dynamic chemical bonds (Schiff base bond and borate bond) are introduced to promote the formation of the hydrogel, the obtained hydrogel has triple environmental response capability (pH, ROS and blood glucose), can accurately match the diabetic wound microenvironment (acidic, high ROS and high blood glucose), realizes on-demand drug release, improves treatment efficiency and reduces drug side effects; (3) The aldehyde group modified polysaccharide and the phenylboric acid modified polyamino compound are used to prepare the hydrogel, the obtained hydrogel has excellent tissue adhesion (>=40kPa), broad-spectrum antibacterial property and biocompatibility (cell survival rate >=90%), the obtained hydrogel can closely adhere to a wound surface, reduces the accumulation of exudate, creates a stable microenvironment conducive to repair for the wound surface, thereby better preventing infection and promoting wound healing; (4) The raw materials used in the application are medical-grade and easy to obtain, and the cost is low; the preparation process does not require high temperature, high pressure or other special and complex equipment, and the hydrogel can be solidified under room temperature and normal pressure, the reaction conditions are mild, and the requirements of large-scale industrial production can be met; (5) The hydrogel can be widely applied to the treatment of chronic non-healing wounds such as diabetic foot ulcers and lower limb venous ulcers, and has a wide application prospect. BRIEF DESCRIPTION OF DRAWINGS

[0059] Figure 1 . The appearance diagram of the hydrogel prepared in Example 1 after solidification; Figure 2 . The 180° peeling test diagram of the hydrogel prepared in Example 1. DETAILED DESCRIPTION

[0060] The technical solutions of the application will be described in detail below through specific examples, but the protection scope of the application is not limited to the following examples. Unless otherwise specified, the solvent of the solution involved in the application is water; the concentration of the reagent involved is mass / volume concentration (1% represents 100 milliliters of solution); room temperature is 25 DEG C; and the raw materials, equipment and other consumables used in the application can be obtained in the market.

[0061] Example 1 The present embodiment provides a kind of hydrogel with tissue adhesion and preparation method thereof, the preparation raw material of the hydrogel includes aldehyde group modified polysaccharide and phenylboric acid modified polyamino compound;The phenylboric acid modified polyamino compound is obtained by grafting phenylboric acid compound on polyamino compound.

[0062] The aldehyde-based polysaccharide and the phenylboronic acid modified polyamino compound are cross-linked to form a hydrogel through dynamic chemical bonds; the dynamic chemical bonds include a Schiff base bond and a borate ester bond.

[0063] The polysaccharide is dextran, the number average molecular weight of the polysaccharide is 70000 Da, and the polysaccharide is derived from Aladdin.

[0064] The aldehyde-based polysaccharide is prepared by an oxidation method.

[0065] The aldehyde-based polysaccharide has an aldehyde group degree of 6%.

[0066] The phenylboronic acid compound is grafted on the polyamino compound in the following manner: the phenylboronic acid compound is grafted on the molecular chain of the polyamino compound through an amide bond to obtain the phenylboronic acid modified polyamino compound.

[0067] The polyamino compound is polylysine hydrochloride, the number average molecular weight of the polylysine hydrochloride is 2000 Da, and the polylysine hydrochloride is derived from Aladdin.

[0068] The phenylboronic acid compound is 4-carboxyphenylboronic acid.

[0069] The second aspect of the present application provides a preparation method of the hydrogel as described above, and the preparation steps of the hydrogel include: S1. preparing an aldehyde-based polysaccharide and dissolving the aldehyde-based polysaccharide in water to obtain a solution A; the preparation steps specifically include: 1g of dextran is dissolved in 10mL of solvent one (purified water), 0.05g of an oxidizing agent (sodium periodate) is added under the condition of ice bath and light shielding, and an oxidation modification reaction is performed at 25°C for 12h under the condition of light shielding; after the reaction is completed, the reaction liquid is transferred to a dialysis bag with a molecular weight cut-off of 3500 Da, dialysis is performed in purified water for 72h (the purified water is replaced every 8h), and after freeze-drying, an aldehyde-based polysaccharide is obtained; the aldehyde-based polysaccharide is dissolved in purified water to prepare a 20% aldehyde-based polysaccharide solution (solution A).

[0070] S2. preparing a phenylboronic acid modified polyamino compound to obtain a solution B; the preparation steps specifically include: 1g of 4-carboxyphenylboronic acid is dissolved in 10mL of an organic solvent (DMSO), 1g of NHS and 1mL of DIC are added, an activation reaction is performed at 25°C for 1.5h, 10mL of a polylysine hydrochloride aqueous solution (the concentration of the polylysine hydrochloride is 0.2g / mL) is added, a reaction is performed at 25°C for 24h, the reaction liquid is transferred to a dialysis bag with a molecular weight cut-off of 3500 Da, dialysis is performed in purified water for 72h (the purified water is replaced every 8h), the solution after dialysis is freeze-dried, and then the freeze-dried powder is prepared into a 20% phenylboronic acid modified polyamino compound solution (solution B) by using purified water.

[0071] S3. Mix the solution A and the solution B in equal volume, stand for 52 s at 25℃, form a hydrogel.

[0072] Example 2 The present example provides a hydrogel and a preparation method thereof, and the specific embodiment is the same as that of Example 1; the difference lies in that the mass-volume concentration of the phenylboronic acid modified polyamino compound in the solution B is 10%.

[0073] The curing time (the standing time of the step S3) of the hydrogel is 374 s.

[0074] Example 3 The present example provides a hydrogel and a preparation method thereof, and the specific embodiment is the same as that of Example 1; the difference lies in that the mass-volume concentration of the phenylboronic acid modified polyamino compound in the solution B is 5%.

[0075] The curing time (the standing time of the step S3) of the hydrogel is 545 s.

[0076] Example 4 The specific embodiment of the present example is the same as that of Example 1; the difference lies in that the mass-volume concentration of the aldehyde group modified polysaccharide solution in the solution A is 10%, and the mass-volume concentration of the phenylboronic acid modified polyamino compound in the solution B is 10%.

[0077] The solution A and the solution B are mixed in equal volume in the step S3, and no curing occurs after standing at 25℃, so that the hydrogel cannot be formed.

[0078] Example 5 The present example provides a hydrogel and a preparation method thereof, and the specific embodiment is the same as that of Example 1; the difference lies in that the amount of the oxidant (sodium periodate) added in the step S1 is 0.2 g, the degree of aldehyde group modification of the aldehyde group modified polysaccharide prepared is 23.76%, and the mass-volume concentration of the aldehyde group modified dextran in the solution A is 10%.

[0079] The curing time (the standing time of the step S3) of the hydrogel is 31 s.

[0080] Comparative Example 1 The present comparative example provides a hydrogel and a preparation method thereof, and the specific embodiment is the same as that of Example 1; the difference lies in that the raw materials for preparing the hydrogel include an aldehyde group modified polysaccharide and a polyamino compound (not modified by phenylboronic acid); the step S2 is: dissolving the polylysine hydrochloride in purified water to prepare a polylysine hydrochloride solution (solution B) with a mass-volume concentration of 20%.

[0081] The curing time (the standing time of the step S3) of the hydrogel is 404 s.

[0082] Comparative Example 2 This comparative example provides a hydrogel and a preparation method thereof, the raw materials for preparing the hydrogel comprising an aldehyde-based polysaccharide and a polyamino compound; wherein the aldehyde-based polysaccharide is prepared as in Example 5 (the degree of aldehyde-based of the aldehyde-based polysaccharide is 23.76%, and the mass-volume concentration of the aldehyde-based dextran in solution A is 10%), and the polyamino compound is as in Comparative Example 1 (no modification by phenylboronic acid, and the mass-volume concentration of the polylysine hydrochloride in solution B is 20%).

[0083] The curing time (the standing time in step S3) of the hydrogel is 15 s.

[0084] Performance test 1. The appearance of the hydrogel of Example 1 after curing is shown in Figure 1 ; it can be seen from Figure 1 that the product after mixing solution A and solution B and curing is in the form of a transparent gel, without stratification or bubble phenomenon, and the appearance meets the basic requirements of medical dressings.

[0085] 2. The hydrogels prepared in Examples 1-5 and Comparative Examples 1-2 are subjected to adhesion strength and pH tests; the test results are shown in Table 1; and the 180° peeling test of Example 1 is shown in Figure 2 .

[0086] Among them, the test substrate for adhesion strength is pigskin, and the test instrument is a universal material testing machine.

[0087] Table 1

[0088] The test results of Table 1 show that the hydrogel formed by the cross-linking of the specific aldehyde-based polysaccharide and the phenylboronic acid-modified polyamino compound through dynamic chemical bonds can have high adhesive strength and a pH value within the application range of a wound surface. The pH values of the hydrogels of Examples 1-3, Example 5 and Comparative Examples 1-2 are all within the application range of a wound surface. However, in Example 2, the concentration of the phenylboronic acid-modified polylysine is reduced, and the cross-linking density is decreased. In Example 3, the concentration of the phenylboronic acid-modified polylysine is too low, and the synergistic effect is weakened. In Example 5, the polysaccharide is excessively oxidized, and the degree of aldehyde group of the aldehyde-based polysaccharide is beyond the preferred range. In Comparative Examples 1 and 2, the polyamino compound is not modified by phenylboronic acid, and the adhesive strength of the resulting hydrogel is significantly decreased. In Example 4, the concentrations of the aldehyde-based polysaccharide and the phenylboronic acid-modified polylysine are both too low, and the cross-linking density of the system is insufficient, so that a stable gel structure cannot be formed. The results of Comparative Examples 1 and 2 show that increasing the degree of aldehyde group of the aldehyde-based polysaccharide can improve the adhesive strength of the hydrogel to a certain extent, but the adhesive strength of the hydrogel obtained by using the polyamino compound without phenylboronic acid modification cannot reach a level of ≥40 kPa. This further proves that only the preferred phenylboronic acid-modified polyamino compound and the polysaccharide with a suitable degree of aldehyde group can maximize the synergistic effect and significantly improve the adhesive strength of the hydrogel, so as to meet the application requirements of the dressing for the repair of diabetic foot ulcers and other application scenarios.

[0089] The detailed descriptions listed in the present application are only specific descriptions of the feasible embodiments of the present application, and they are not intended to limit the protection scope of the present application. Any equivalent embodiments or changes made without departing from the spirit of the present application should be included in the protection scope of the present application. In addition, the relational terms (such as S1, S2 steps) in the present application are only used to distinguish one entity / operation from another entity / operation, and do not necessarily require or imply an actual relationship or sequence between the entities / operations; in specific implementation, the operation can be performed according to the actual use requirements.

Claims

1. A hydrogel with tissue adhesion properties, characterized in that, The raw materials for preparing the hydrogel include at least aldehyde-modified polysaccharides and polyamino compounds modified with phenylboronic acid; The phenylboronic acid-modified polyamino compound is obtained by grafting a phenylboronic acid compound onto a polyamino compound; The adhesion strength of the hydrogel to pigskin is ≥40 kPa.

2. The hydrogel according to claim 1, characterized in that, The aldehyde-modified polysaccharide and the phenylboronic acid-modified polyamino compound cross-link through dynamic chemical bonds to form a hydrogel; The dynamic chemical bonds include Schiff base bonds and borate ester bonds.

3. The hydrogel according to claim 1, characterized in that, The polyamino compound includes one or more combinations of polylysine or its derivatives, polyethyleneimine, and chitosan.

4. The hydrogel according to claim 3, characterized in that, The polyamino compound includes polylysine hydrochloride; the number average molecular weight of the polylysine hydrochloride is 1000-5000 Da.

5. The hydrogel according to claim 1, characterized in that, The method of grafting phenylboronic acid compounds onto polyamino compounds is as follows: phenylboronic acid compounds are grafted onto the molecular chain of polyamino compounds via amide bonds or Schiff base bonds to obtain phenylboronic acid-modified polyamino compounds.

6. The hydrogel according to claim 1, characterized in that, The aldehyde-modified polysaccharide is obtained by at least one of the following two preparation methods: 1) Oxidation method: Polysaccharides are oxidized and modified using an oxidizing agent to obtain aldehyde-modified polysaccharides; 2) Grafting method: Aldehyde-modified polysaccharides are modified by aldehyde grafting using aldehyde-modifying reagents to obtain aldehyde-modified polysaccharides.

7. The hydrogel according to claim 6, characterized in that, The degree of aldehyde alkylation of the aldehyde-modified polysaccharide is 2-20%.

8. The hydrogel according to claim 6, characterized in that, The polysaccharide includes one or more of dextran, cellulose, sodium hyaluronate, or sodium alginate; the number average molecular weight of the polysaccharide is 50,000-100,000 Da.

9. The method for preparing the hydrogel according to any one of claims 1-8, characterized in that, The preparation steps of the hydrogel include: Aldehyde-modified polysaccharides were prepared and dissolved in water to obtain solution A; A phenylboronic acid-modified polyamino compound was prepared to obtain solution B; Solution A and solution B are mixed and allowed to stand to form a hydrogel. The mass-volume concentration of the aldehyde-modified polysaccharide in solution A is 15-25%. The mass-volume concentration of the phenylboronic acid-modified polyamino compound in solution B is 15-25%.

10. An application of the hydrogel according to any one of claims 1-8, characterized in that, The hydrogel is used in biomedical materials; The biomedical materials include wound healing materials or drug delivery materials.

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