Method for preparing and application of organic-inorganic composite hydrogel with high mechanical adaptability and stable adhesion in wet state

Abstract

The application discloses a preparation method and application of an organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability, and belongs to the technical field of biomedical tissue engineering. The hydrogel comprises calcium phosphate with a mass fraction of 8.125% to 65% and thioctic acid with a mass fraction of 35% to 91.875%. The biomimetic wound dressing is favorable for fibroblast proliferation and migration, and realizes more ideal soft tissue regeneration. Experimental results prove that the hydrogel has good cell compatibility and can quickly promote rat skin defect repair (20±1 mm limit skin damage repair time is shortened to 2 weeks), and the healing effect is more significant compared with traditional suture and gauze which are clinically optimal in repair effect. The prepared organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability has good mechanical properties, and at the same time, has excellent adhesion, and is favorable for soft tissue repair.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biomedical tissue engineering, and specifically relates to a preparation method and application of an organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability. BACKGROUND

[0002] Severe damage to soft tissue can be caused by acute trauma, high temperature, and chemical substances. In clinical practice, most soft tissue injuries (such as oral mucosa injury and skin injury) are in a moist and dynamic physiological environment, and the tissue surface is rich in body fluids and blood. Human soft tissue (such as oral mucosa and skin) is usually soft and fragile, and has the functions of protection, regulation, sensation, and excellent mechanical properties, with an elastic modulus ranging from kilopascals to megapascals. Once severe damage occurs, the body's internal balance will be affected, and open wounds will significantly increase the risk of infection. The process of wound healing includes four stages: hemostasis, inflammation, proliferation, and maturation. Therefore, constructing a new type of bionic wound dressing to quickly close the wound and promote cell proliferation is the key to effectively promoting the repair of soft tissue defects.

[0003] At present, traditional sutures and gauze, bandages and other dressings are the gold standard for wound closure methods in the clinical field. However, these materials have limitations such as single function, difficulty in accurately controlling hemostatic effect, easy bacterial infection during the suturing process, and secondary trauma caused by dressing replacement, which may delay the repair process of soft tissue or even worsen the condition. In emergency medical scenarios, an ideal wound dressing should have the characteristics of convenient application and removal, and should not cause tissue damage. In recent years, a variety of new wound dressings and adhesives (such as porous scaffolds, woven dressings, nanofibers, etc.) have been widely studied, and they have shown certain advantages in terms of antibacterial, moisturizing, and promoting healing. However, there are still deficiencies, such as poor mechanical matching with soft tissue, difficulty in accurately adapting to the irregular shape of the tissue surface, rapid adhesion loss in a wet environment, easy detachment due to tissue swelling or movement, and inability to achieve rapid and tight closure of the wound and effective repair.

[0004] The existing hydrogel materials for soft tissue repair generally have the problem of insufficient mechanical properties. Studies have shown that the mechanical properties of the reinforced hydrogel can be improved by introducing inorganic materials. By introducing inorganic components such as calcium phosphate oligomers, the mechanical stability of the hydrogel can be enhanced through covalent cross-linking between organic and inorganic molecules, thereby improving the mechanical properties and stability thereof. In addition, it has been found that during the soft tissue repair process, cells will spontaneously establish a mechanical balance, thereby tightening the wound during the wound healing process and achieving wound regeneration. Therefore, improving the mechanical adaptability of the material is crucial to improve the repair effect of soft tissue defects. During tissue regeneration, the repair material not only needs to close the wound, but also needs to provide space for the newly generated tissue to support cell growth and functional expression. However, in dynamic physiological activities, if the material and the wound are separated, it will interfere with the natural healing process, and even induce inflammatory reactions and increase the risk of infection. The organic-inorganic composite hydrogel constructed based on calcium phosphate oligomers has high mechanical stability, and is expected to achieve long-term mechanical adaptability in dynamic physiological activities, so that the wound remains closed, which is conducive to promoting tissue repair.

[0005] Thioctic acid is a double sulfur organic matter widely distributed in the cell membranes and cytosol of animals and plants, which has the effects of anti-inflammatory, antioxidant and adhesion enhancement. In the prior art, a tannic acid-thioctic acid (TATA) supramolecular hydrogel is synthesized, which has the characteristics of self-healing, injectability and processability. In addition, the TATA hydrogel also has the properties of antioxidant, antibacterial and adhesion, making it a potential substitute for wound healing sutures. However, the TATA hydrogel still has deficiencies in mechanical matching and wet adhesion, which is easy to separate from the soft tissue during tissue movement, and thus may cause inflammatory reactions and secondary infections.

[0006] In summary, there is still a lack of biomimetic materials with excellent mechanical adaptability and stable wet adhesion in the field of soft tissue repair at present, and the development of such materials has important clinical significance and application value. SUMMARY

[0007] In view of the deficiencies in the prior art, the purpose of the present application is to provide an organic-inorganic composite hydrogel with high mechanical adaptability and wet adhesion stability for soft tissue defect repair, a preparation method and application thereof. The mechanical properties of the material are enhanced by nano-particle (inorganic poly-ion cluster) and thioctic acid organic-inorganic copolymerization cross-linking, and the prepared hydrogel material with high mechanical adaptability and wet adhesion stability can be applied to skin and oral mucosa repair. For a 20±1 mm skin damage model, a good repair effect can be obtained in 2 weeks.

[0008] The organic-inorganic composite hydrogel provided by the present application has good mechanical adaptability and good wet adhesion stability with soft tissue, which has important significance for soft tissue regeneration.

[0009] To achieve the above-mentioned purpose, the specific technical solutions adopted by the present application are as follows:

[0010] The present application provides a kind of high mechanical adaptability and wet state adhesion stability organic-inorganic composite hydrogel, the organic-inorganic composite hydrogel is composed of calcium phosphate nanocluster and thioctic acid, wherein, by mass fraction, 8.125%~65% calcium phosphate and 35%~91.875% thioctic acid are contained.

[0011] The high mechanical adaptability and wet state adhesion stability organic-inorganic composite hydrogel material prepared by the present application shows good mechanical properties, while giving consideration to excellent biocompatibility and antibacterial property, beneficial to soft tissue repair.

[0012] Preferably, the composite hydrogel contains 32.5% calcium phosphate nanoclusters and 67.5% thioctic acid by mass fraction.

[0013] Further, the average size of the calcium phosphate nanoclusters is 1.16±0.14 nm;

[0014] The calcium phosphate nanoclusters are formed by reacting a calcium source, a phosphorus source and a stabilizer in an organic solvent;

[0015] The calcium source is a calcium salt, the phosphorus source is phosphoric acid, and the stabilizer is triethylamine.

[0016] The hydrogel prepared by the present application using ultra-small size calcium phosphate nanoclusters can improve the mechanical properties of the material.

[0017] As preferred, the strain range of the organic-inorganic composite hydrogel is 97%-709%, the maximum tensile strength range is 0.2-1.4 MPa, the elastic modulus range is 0.6-8.4 MPa, and the toughness range is 0.16-6.66 MJ / m 3 , and the hysteresis energy range is 0.02-0.83 MJ / m 3 .

[0018] As preferred, the adhesion strength of the organic-inorganic hydrogel is 0.02-0.16 MPa. The organic-inorganic composite hydrogel prepared by the present application realizes high mechanical strength and high adhesion stability in a wet environment due to the cross-linking between organic and inorganic.

[0019] The present application also provides a preparation method of high mechanical adaptability and wet state adhesion stability organic-inorganic composite hydrogel, the steps are as follows:

[0020] (1) blending calcium phosphate nanocluster solution and thioctic acid solution to form a uniform solution;

[0021] (2) naturally evaporating the solution prepared in step (1) to obtain the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability.

[0022] Preferably, in step (1), the preparation method of the calcium phosphate nanocluster solution is as follows: triethylamine is used as a stabilizer, a calcium salt is used as a calcium source, and phosphoric acid is used as a phosphorus source to generate the calcium phosphate nanocluster solution in an organic solvent; the density of the calcium phosphate nanocluster solution is 12.5±0.5 mg / mL, and the average size of the nanoparticles in the calcium phosphate nanocluster solution is 1.16±0.14 nm.

[0023] Specifically, the preparation method of the calcium phosphate nanocluster is as follows:

[0024] 11.76 g of calcium chloride dihydrate is dissolved in 800 mL of anhydrous ethanol, stirred for 0.5-1 hour, and then a solution containing phosphoric acid (volume percentage 85%) and triethylamine in anhydrous ethanol (i.e. 4.18 mL of 85% phosphoric acid + 221.79 mL of triethylamine + 800 mL of anhydrous ethanol) is added dropwise, and stirred vigorously for 12-24 hours. After standing at room temperature for 12-24 hours, white precipitate accumulates at the bottom of the solution, and the solution above the white precipitate is removed by suction to obtain the calcium phosphate nanocluster solution.

[0025] Preferably, in step (1), the mass ratio of the calcium phosphate nanocluster solution to the lipoic acid solution during blending is 13:7-147.

[0026] The cross-linking method of the hydrogel determines its physical and chemical properties. The strong ionic bond between the small-size calcium phosphate nanoclusters and the lipoic acid molecular chains enables the gel to form a tight network, and the lipoic acid molecules enable the composite hydrogel to have certain adhesion, and the maximum stress during stretching can reach 1.4 MPa.

[0027] Specifically, the blending conditions are as follows: the stirring speed is 600-800 rpm, and the stirring time is 1-2 days.

[0028] Specifically, in step (2), the solution is poured into a polytetrafluoroethylene mold with an inner diameter of 20±1 mm, and naturally evaporated at room temperature (25°C) for 2-3 days, wherein the height of the solution is 5-10 mm.

[0029] Preferably, in step (2), the diameter of the organic-inorganic composite hydrogel, i.e. the biomimetic wound dressing, is 20±1 mm, and the thickness is 1.5±0.5 mm.

[0030] The application also provides the organic-inorganic composite hydrogel prepared by the preparation method and the application of the organic-inorganic composite hydrogel as a biomimetic wound dressing in the preparation of medical materials for repairing soft tissues.

[0031] Preferably, the soft tissue is skin or oral mucosa.

[0032] More preferably, the diameter of the skin damage is 20±1 mm (the size of the extreme skin defect).

[0033] In the embodiment of the present application, the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel is applied to the rat 20±1 mm extreme skin defect model, and the repair effect within 2 weeks is obviously better than that of the traditional suture and dressing.

[0034] The present application also provides a medical material for repairing soft tissue, which comprises an organic-inorganic composite hydrogel prepared by the preparation method or the organic-inorganic composite hydrogel.

[0035] Compared with the prior art, the present application has the following beneficial effects:

[0036] (1) The present application uses lipoic acid as an organic structural unit and calcium phosphate oligomer as an inorganic structural unit, and the two are crosslinked by ionic bonds. Since the size of the calcium phosphate oligomer is small, the bond strength of the ionic bond is increased, the mechanical strength of the material is significantly improved, the organic-inorganic composite hydrogel with good adhesion in a wet environment is obtained, and the obtained material has good biocompatibility. In addition, the material preparation method is simple and controllable, and this simple way has practical significance for industrial application.

[0037] (2) The high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel prepared by the present application is beneficial to fibroblast proliferation and migration, and realizes more ideal soft tissue repair. Experimental results prove that: it has good cell compatibility and can quickly promote rat skin defect repair (the repair time of 20±1 mm extreme skin damage is shortened to 2 weeks), and compared with the traditional suture and dressing which have the best repair effect in clinic, the healing effect is more significant.

[0038] (3) In the prior art, the mechanical matching of the hydrogel material and the soft tissue has problems, and it is easy to separate from the soft tissue during dynamic movement, and even cause inflammation, increase the risk of infection. The high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel prepared by the present application has good mechanical properties, and at the same time, has high wet-state adhesion stability, can effectively tighten the wound, and is beneficial to soft tissue repair. BRIEF DESCRIPTION OF DRAWINGS

[0039] Figure 1 The appearance diagram of the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel obtained in Example 3 of the present application and the appearance diagram of the control group.

[0040] Figure 2 SEM images of the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability obtained in Example 3 of the present application and control group SEM images.

[0041] Figure 3 Inorganic calcium phosphate proportion diagram of the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability obtained in each embodiment of the present application.

[0042] Figure 4 Tensile stress-strain result comparison diagram of the organic-inorganic composite hydrogel obtained in each embodiment of the present application and tensile strength, elastic modulus and toughness result comparison diagram; wherein ns represents p>0.05, * represents p<0.05, *** represents p<0.001, and **** represents p<0.0001.

[0043] Figure 5 Cyclic tensile stress-strain result comparison diagram and hysteresis energy result comparison diagram of the organic-inorganic composite hydrogel obtained in each embodiment of the present application; wherein ns represents p>0.05, ** represents p<0.01, and **** represents p<0.0001.

[0044] Figure 6 Wet environment adhesion stability diagram of the organic-inorganic composite hydrogel obtained in Example 3 of the present application.

[0045] Figure 7 Shear stress-strain result comparison diagram and adhesion strength result comparison diagram of the organic-inorganic composite hydrogel obtained in each embodiment of the present application; wherein ns represents p>0.05, and **** represents p<0.0001.

[0046] Figure 8 Wet environment adhesion stability diagram of the organic-inorganic composite hydrogel obtained in Example 3 of the present application and wet environment adhesion stability diagram of the control group in vivo.

[0047] Figure 9 HE staining diagram after the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability prepared in Example 3 is applied to repair the extreme skin defect of a rat.

[0048] Figure 10 MASSON staining diagram after the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability prepared in Example 3 is applied to repair the extreme skin defect of a rat. DETAILED DESCRIPTION

[0049] The present application is further illustrated below in conjunction with examples.

[0050] Example 1

[0051] 1) Weigh 11.76 g of calcium chloride dihydrate and dissolve in 800 mL of absolute ethanol, stir for 0.5 hours until uniform;

[0052] Mix 221.79 mL of triethylamine solution with 800 mL of absolute ethanol, then add 4.18 mL of phosphoric acid solution (volume percentage 85%), mix for 1 hour until uniform;

[0053] Slowly drop the mixed solution of triethylamine, absolute ethanol and phosphoric acid into the calcium chloride absolute ethanol solution, continue to stir, and the solution gradually changes from transparent and clear to milky white suspension. Continue to stir for 12 hours until uniform.

[0054] 2) Let the solution prepared in step 1) stand at 25°C for 24 hours, so that the white precipitate completely settles to the bottom of the solution, the upper layer is clear solvent, and the upper layer solvent is removed to obtain white ultra-small amorphous calcium phosphate nanoclusters (the average particle size of the nanoparticles therein is 1.16±0.14 nm).

[0055] 3) Weigh 1 g of tris base (tris(hydroxymethyl)aminomethane) and mix with 4 mL of ultrapure water to obtain a tris base solution, then mix 1 g of thioctic acid with 1.8 mL of the tris base solution, stir at 25°C for 10 minutes to fully dissolve and uniform the thioctic acid, to obtain a thioctic acid solution (1.06 g / mL).

[0056] 4) Mix the calcium phosphate nanocluster solution (density 12.5 mg / mL) and the thioctic acid solution at a solute mass fraction of 8.125% and 91.875% respectively, and stir at 25°C for 1-2 days to fully crosslink the ultra-small particle size calcium phosphate and thioctic acid molecules. Pour the mixed solution into a polytetrafluoroethylene mold and evaporate naturally to obtain an organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability.

[0057] Example 2

[0058] The previous steps 1-3 are the same as in Example 1, mix the calcium phosphate nanocluster solution and the thioctic acid solution at a solute mass fraction of 16.25% and 83.75% respectively, and stir at 25°C for 1-2 days to fully crosslink the ultra-small particle size calcium phosphate and thioctic acid molecules. Pour the mixed solution into a polytetrafluoroethylene mold and evaporate naturally to obtain an organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability.

[0059] Example 3

[0060] The steps 1-3 are the same as those in Example 1. The calcium phosphate nanocluster solution and the lipoic acid solution are mixed at a solute mass fraction of 32.5% and 67.5%, respectively, and stirred at 25°C for 1-2 days to allow the ultra-small particle size calcium phosphate and lipoic acid molecules to be fully cross-linked. The mixed solution is poured into a polytetrafluoroethylene mold and naturally evaporated to obtain the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability.

[0061] Example 4

[0062] The steps 1-3 are the same as those in Example 1. The calcium phosphate nanocluster solution and the lipoic acid solution are mixed at a solute mass fraction of 32.5% and 67.5%, respectively, and stirred at 25°C for 1-2 days to allow the ultra-small particle size calcium phosphate and lipoic acid molecules to be fully cross-linked. The mixed solution is poured into a polytetrafluoroethylene mold and naturally evaporated to obtain the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability.

[0063] Example 5 Evaluation and characterization of the mechanical properties of the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability

[0064] A control group is set up. The calcium phosphate nanocluster solution is not mixed in the control group to prepare the lipoic acid hydrogel.

[0065] The appearance of the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability prepared in Example 3 and the appearance of the control group are shown in Figure 1 The mixing of the calcium phosphate nanocluster solution makes the appearance of the hydrogel of the present application more transparent. Meanwhile, SEM observation shows that the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability obtained in Example 3 has a porous structure, and the control group also has a porous structure Figure 2 ).

[0066] Then, the proportion of inorganic calcium phosphate in the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability prepared in each example of the present application is tested. The test results are shown in Figure 3 The proportion of inorganic calcium phosphate in the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability prepared in Examples 1-4 is 11%, 14%, 20%, and 36%, respectively. Overall, the proportion of inorganic calcium phosphate in the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability prepared in the present application is between 11% and 36% Figure 3 ).

[0067] In addition, the tensile test is performed on the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability to evaluate the mechanical properties of the material. The comparison of the tensile stress and strain results, the comparison of the tensile strength, the elastic modulus, and the toughness of the organic-inorganic composite hydrogel with high mechanical adaptability and wet-state adhesion stability obtained in each example of the present application are shown in Figure 4As shown in FIG. 6, it can be seen that the strain range of the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel prepared in the application is 97%-709%, the maximum tensile strength range is 0.2-1.4 MPa, the elastic modulus range is 0.6-8.4 MPa, and the toughness range is 0.16-6.66 MJ / m 3 .

[0068] In order to further explore the fatigue resistance of the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel, a cyclic tensile test was performed. The cyclic tensile stress-strain result comparison and hysteresis energy result comparison chart of the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel obtained in each embodiment of the application are as shown in FIG. 7. Figure 5 As shown in FIG. 7, it can be seen that the hysteresis energy range of the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel prepared in the application is 0.02-0.83 MJ / m 3 .

[0069] Example 6 Wet adhesion stability of the biomimetic soft tissue repair hydrogel

[0070] The high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel was respectively adhered to the surface of plastic, metal, glass, teeth, bones, muscles, hearts and kidneys and soaked in a beaker containing water to evaluate the wet environment adhesion stability of the material. The wet environment adhesion stability of the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel obtained in Example 3 of the application is as shown in FIG. 8. Figure 6 As shown in FIG. 8, it can be seen that the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel prepared in the application has good adhesion stability in a wet environment.

[0071] The high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel was subjected to pig skin shear test to evaluate the adhesion performance of the material. The stress-strain result comparison and adhesion strength result comparison chart of the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel obtained in each embodiment of the application are as shown in FIG. 9. Figure 7 As shown in FIG. 9, it can be seen that the adhesion strength of the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel prepared in the application is 0.02-0.16 MPa.

[0072] The high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel was adhered to the surface of cheeks, tongues, palates, gums and teeth and the wet environment adhesion stability performance of the material in the cheek mucosa of New Zealand rabbits was observed. The in vivo wet environment adhesion stability of the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel obtained in Example 3 of the application and the in vivo wet environment adhesion stability of the control group (Picosulfate hydrogel) are as shown in FIG. 10. Figure 8As shown, it can be seen that the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel prepared by the application has good adhesion stability in the in-vivo wet environment.

[0073] Example 7 Effect experiment of high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel in soft tissue defect repair

[0074] Application of high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel: The rats were anesthetized with 3% sodium pentobarbital, anesthetized and analgesized with 4% atikaine (bisan) injection, iodophor was used for skin disinfection, the skin of the back of the rat was cut to form a 20 mm diameter skin defect. The high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel prepared in Example 3 was applied to the 20 mm limit skin defect model of the rat as an experimental group, and the repair effect was obviously better than that of the traditional suture and gauze covered blank group and the polysulfated hydrogel treated control group within 2 weeks. Figure 9 、 Figure 10 From the HE staining results, compared with the blank group, the high mechanical adaptability and wet-state adhesion stability organic-inorganic composite hydrogel prepared in Example 3 can obviously promote the repair of skin defects, the skin defect range is obviously reduced, and new blood vessels appear in the center of the defect within 2 weeks, and the number of new blood vessels reaches a level better than that of traditional suture and gauze.

[0075] The above-described embodiments are only a preferred scheme of the present application, and are not intended to limit the present application. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the present application. Therefore, any technical scheme obtained by equivalent replacement or equivalent transformation falls within the protection scope of the present application.

Claims

1. An organic-inorganic composite hydrogel with high mechanical adaptability and wet adhesion stability, characterized in that, The organic-inorganic composite hydrogel was formed by blending calcium phosphate nanoclusters solution and lipoic acid solution at mass fractions of solute of 8.125% and 91.875%, 16.25% and 83.75%, 32.5% and 67.5%, or 65% and 35%, respectively. The density of the calcium phosphate nanoclusters solution is 12.5 mg / mL, and the density of the lipoic acid solution is 1.06 g / mL.

2. The organic-inorganic composite hydrogel according to claim 1, characterized in that, The average size of the calcium phosphate nanoclusters is 1.16 ± 0.14 nm; The calcium phosphate nanoclusters are formed by the reaction of a calcium source, a phosphorus source, and a stabilizer in an organic solvent; The calcium source is a calcium salt, the phosphorus source is phosphoric acid, and the stabilizer is triethylamine.

3. A method for preparing the organic-inorganic composite hydrogel as described in claim 1 or 2, characterized in that, The steps are as follows: The organic-inorganic composite hydrogel was formed by blending calcium phosphate nanoclusters solution with thioctic acid solution.

4. The method for preparing the organic-inorganic composite hydrogel according to claim 3, characterized in that, The calcium phosphate nanocluster solution is prepared by adding triethylamine as a stabilizer, calcium salt as a calcium source, and phosphoric acid as a phosphorus source to an organic solvent to generate the calcium phosphate nanocluster solution. The density of the calcium phosphate nanocluster solution is 12.5 mg / mL, and the average size of the nanoparticles in the calcium phosphate nanocluster solution is 1.16 ± 0.14 nm. The blending conditions are: a stirring speed of 600-800 rpm and a stirring time of 1-2 days.

5. The method for preparing the organic-inorganic composite hydrogel according to claim 3, characterized in that, After blending, a homogeneous solution is formed. The solution is poured into a polytetrafluoroethylene mold with an inner diameter of 20±1 mm and allowed to evaporate naturally at room temperature for 2-3 days, with the height of the solution being 5-10 mm. The organic-inorganic composite hydrogel has a diameter of 20±1 mm and a thickness of 1.5±0.5 mm.

6. The application of the organic-inorganic composite hydrogel according to claim 1 or 2 as a biomimetic wound dressing in the preparation of medical materials for repairing soft tissue.

7. The application according to claim 6, characterized in that, The soft tissue is skin or oral mucosa.

8. The application according to claim 7, characterized in that, The maximum diameter of the skin injury is 20 ± 1 mm.

9. A medical material for repairing soft tissue, characterized in that, The medical material for repairing soft tissue comprises the organic-inorganic composite hydrogel as described in claim 1 or 2.

Images