Composite hydrogel capable of stopping bleeding, resisting bacteria and promoting alveolar bone repair as well as preparation method and application of composite hydrogel

Abstract

The invention relates to the technical field of hydrogel, in particular to composite hydrogel capable of stopping bleeding, resisting bacteria and promoting alveolar bone repair, a preparation method and application. The composition comprises a polyacrylic acid solution, a calcium chloride solution, a disodium hydrogen phosphate solution, platelet-rich plasma (including plasma, platelet lysis buffer, platelet-rich fibrin and fibrin of high-concentration concentrated growth factors) and nano clay (hectorite). The preparation method has the advantages of simple process, easily available raw materials, environment-friendly production process, safety and short preparation period. The composite hydrogel is good in biocompatibility and injectable, and can be widely applied to the field of biomedical materials.

Description

Technical Field

[0001] The present invention relates to the technical field of hydrogels, and particularly to a composite hydrogel for hemostasis, antibacterial and promoting alveolar bone repair, a preparation method and an application thereof. Background Art

[0002] Periodontitis is an infectious disease initiated by dental plaque. This disease can continuously damage the tooth supporting tissues. Severe periodontitis will lead to tooth loosening and shedding, and further cause alveolar bone loss, resulting in subsequent difficult repair. Clinically, periodontal basic treatments such as supra-gingival scaling, sub-gingival scaling and root planing are mainly used to remove dental plaque to control infection and inflammation. However, affected by periodontal pockets or furcations, simple mechanical therapies often cannot achieve satisfactory results and need to be supplemented with drug treatment. To avoid the adverse reactions of systemic drug use, local drug delivery has become a research hotspot in the treatment of periodontitis. However, common drugs are mostly in the form of ointments, but the ointments cannot penetrate deep into the periodontal pockets, and the local retention time is not long, so the curative effect is limited. It is not sufficient to meet the complex anatomical morphology of the periodontal and oral environments, and the disordered release of antibacterial agents and bone-promoting substances is also not conducive to the natural healing of periodontal tissues. Therefore, it is very important to find a suitable drug carrier. A hydrogel is a three-dimensional polymer network system formed by physical or chemical cross-linking reactions of monomers. It can carry drugs, has good biocompatibility and biodegradability, the preparation process is simple and easy, the performance is adjustable, and it has gradually attracted attention in the treatment of periodontitis. However, there is currently a lack of a systematic summary of relevant research.

[0003] Self-healing is one of the remarkable properties of biological materials such as skin and bone. The ability of natural materials to heal cracks usually involves an energy dissipation mechanism, which is due to the so-called sacrificial bonds breaking and reforming dynamically before the molecular backbone breaks. Currently, the research focus of self-healing hydrogels is to maintain good mechanical properties. If the mechanical strength of self-healing hydrogels is low, it will make them unable to withstand any stress. Therefore, producing self-repairing or stimulus-repairing hydrogels with high mechanical strength is a problem that needs to be solved currently. Polyacrylic acid (PAA) is a high molecular polymer with hydrophilic groups (carboxyl groups), and its molecular weight ranges from several hundred to several million. After polyacrylic acid is dissolved in water, the molecular chains stretch out to form a relatively viscous solution, and its viscosity is about 20 times that of sodium alginate and sodium carboxymethylcellulose, with excellent water retention, safe and non-toxic. Currently, it has been officially approved by the National Health Commission of China as a food-grade thickener. Polyacrylic acid and its derivatives are also commonly used wound dressing matrices, but their weak wet adhesion limits their clinical applications.

[0004] Calcium phosphates such as hydroxyapatite and β-tricalcium phosphate have good biocompatibility. Because they have a chemical composition similar to the inorganic phase in bone, they are widely used as bone substitute materials. This inorganic material has been used as a biological carrier material for application research for a long time. Calcium phosphate can achieve slow drug release, has good biocompatibility and non-immunogenicity to cells and tissues, and also has good biodegradability. However, crystalline calcium phosphate particles are prone to agglomeration and precipitation in water, are difficult to be absorbed by the human body, and cannot be made into injectable drug preparations. Therefore, it is necessary to modify its surface through a certain preparation process to improve its dispersibility and stability and turn it into a biocompatible polymer material.

[0005] Platelet-Rich Plasma (PRP) refers to plasma containing a high concentration of platelets. As an innovative tool in regenerative medicine, PRP can be used for any related diseases involving repair growth and cell protection. These growth factors play an important role in the processes of cell proliferation and tissue healing and are widely used in clinical departments such as oral and maxillofacial surgery, orthopedics, general surgery, burn and plastic dermatology, etc.; in addition, since PRP is prepared from autologous blood, it has the advantages of no immune rejection reaction and risk of disease transmission, short treatment time, reduced infection probability, etc., is safe and reliable, and has broad future development prospects.

[0006] Platelet-rich plasma is a concentrated blood product and is liquid at room temperature. It has disadvantages such as unstable structure, poor biomechanical properties, and too fast release of growth factors. At present, clinically, PRP is mainly used to repair wounds by applying PRP gel on the wound surface. PRP gel is clinically formed by activating liquid PRP by adding a certain proportion of thrombin and calcium gluconate. As an autologous, sterile and non-allergenic regenerative medicine preparation, platelet-rich plasma gel has significant clinical value in the treatment of various wounds. However, the PRP gel prepared by this method faces some problems in practical applications, such as poor mechanical properties, difficulty in adapting to irregular wounds, and short maintenance time of releasing cytokines. Therefore, although PRP gel has great potential in wound healing and regenerative repair, etc., due to its poor function of resisting extrusion or traction and limited utilization rate of growth factors, it affects the application scope of PRP in medicine.

[0007] Nanoclay materials, including montmorillonite, halloysite, palygorskite, saponite, rectorite, etc., are layered silicate nanocrystals composed of silicon-oxygen tetrahedrons and aluminum (magnesium)-oxygen octahedrons. They have the characteristics of rich raw materials, simple process, and low price, and are emerging nanomaterials widely used. Nanoclay materials have unique rheological properties, electrical conductivity, antibacterial properties, and good biocompatibility. In addition, the double-charged surface of nanoclay can attract proteins present in the blood, activate the coagulation cascade reaction, and enhance the adhesion of proteins and cells; it can also quickly absorb the water in the blood and increase the concentration of blood coagulation factors near the wound in a short time. Therefore, it is widely used in the biomedical field.

[0008] Currently, commonly used hemostatic bone repair materials face disadvantages such as component residue, limited effect, increased possibility of secondary bleeding and infection at the wound. Hydrogels are 3D solid structures formed by cross-linking hydrophilic polymer networks. Due to their unique microenvironment, good biocompatibility, ability to maintain a moist wound environment, absorb tissue exudate, regulate the microenvironment, seal important molecules, and promote tissue remodeling, they have currently been used for hemostasis, antibacterial, and bone repair, and are increasingly attracting wide attention in the medical field. According to their different application designs and functions, they can be divided into antibacterial hydrogels, anti-inflammatory hydrogels, antioxidant hydrogels, conductive hydrogels, micro-controlled hydrogels, etc.

[0009] In view of the above defects, the inventors of the present invention finally obtained the present invention through long-term research and practice. Summary of the Invention

[0010] The purpose of the present invention is to solve the problems faced by currently commonly used hemostatic bone repair materials, such as component residue, limited effect, secondary bleeding at the wound, and increased possibility of infection, and to provide a composite hydrogel for hemostasis, antibacterial, and promoting alveolar bone repair, a preparation method, and an application.

[0011] To achieve the above purpose, the present invention discloses a preparation method of a composite hydrogel for hemostasis, antibacterial, and promoting alveolar bone repair, including the following steps:

[0012] S1, uniformly stir and mix polyacrylic acid with a calcium chloride solution to obtain a composite hydrogel matrix, then add a nanoclay solution, and continue to stir evenly to obtain a polyacrylic acid mixed solution;

[0013] S2, ultrasonically treat a disodium hydrogen phosphate solution and platelet-rich plasma. After ultrasonic homogenization, drop it into the polyacrylic acid mixed solution under high-speed stirring. After all are added, continue to stir to fully cross-link and mix evenly, and finally centrifuge to obtain the required composite hydrogel.

[0014] In the step S1, the molecular weight Mw of the polyacrylic acid solution is > 100000, the concentration is 1 - 4 mol / L, and the concentration of the calcium chloride solution is 1 mol / L.

[0015] In the step S1, the nano-clay solution is a laponite solution, and the mass fraction of the laponite solution is 0.2-4 wt%.

[0016] In the step S2, the concentration of the disodium hydrogen phosphate solution is 1 mol / L.

[0017] In the step S2, the molar ratio of the dosage of the disodium hydrogen phosphate solution, the polyacrylic acid solution to the dosage of the calcium chloride solution is 1:4:1-1:1:1.

[0018] In the step S2, the platelet-rich plasma is any one of platelet-rich plasma, platelet lysate, platelet-rich fibrin, and highly concentrated growth factor-rich fibrin.

[0019] In the step S2, the mass fraction of the platelet-rich plasma is 5-20 wt%.

[0020] In the step S2, the mass ratio of the platelet-rich plasma to the composite hydrogel matrix is 19:1-4:1.

[0021] The present invention also discloses a composite hydrogel for hemostasis, antibacterial and promoting alveolar bone repair prepared by the above preparation method, and the application of this composite hydrogel for hemostasis, antibacterial and promoting alveolar bone repair in the preparation of drugs for treating large bleeding, irregular wounds and alveolar bone defects.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0023] 1. The present invention realizes the mechanical improvement of the composite hydrogel by introducing a polyacrylic acid hydrogel with high mechanical properties and excellent rheological properties;

[0024] 2. The present invention introduces amorphous calcium phosphate, which has good biocompatibility and will not cause obvious immune reactions or rejection reactions, which enables it to be compatible with surrounding tissues and promotes the regeneration and repair of bone tissues. It can promote the proliferation and differentiation of osteoblasts and accelerate the regeneration and repair of bone tissues;

[0025] 3. The present invention forms a platelet-rich double-network structure hydrogel by homogeneous mixing of polyacrylic acid hydrogel and platelet-rich plasma, which inhibits the release of growth factors in the platelet-rich plasma to a certain extent and realizes the slow release of growth factors in the platelet-rich plasma-nano-clay composite hydrogel;

[0026] 4. Most of the platelet-rich plasma in the present invention is collected from its own blood, contains a variety of high-concentration growth factors that promote cell proliferation and differentiation, has no risk of immune rejection and disease transmission, and the infection probability is reduced, which is safe and reliable; the laponite adopts the XLG type and has good biocompatibility;

[0027] 5. The present invention improves the injectability of the polyacrylic acid-calcium phosphate composite hydrogel by introducing a lithium saponite solution that increases injectability;

[0028] 6. The PRP preparation technology of the present invention is mature and convenient, and has a good clinical use foundation; the lithium saponite process is simple and low-cost;

[0029] 7. By introducing amorphous calcium phosphate into the polyacrylic acid hydrogel and then adding platelet-rich plasma, the composite hydrogel obtained after activation has improved mechanical properties compared with the biomaterial hydrogels currently used in clinical practice. The amorphous calcium phosphate in the hydrogel promotes bone tissue regeneration and repair, and the growth factors are slowly released by loading platelet-rich plasma in the hydrogel, and it has high biological activity. The introduction of nano-clay significantly improves the injectability of the hydrogel, and can improve the clinical treatment of the hydrogel for large bleeding and irregular wounds and alveolar bone defects. The high biological safety and simple preparation process of the polyacrylic acid hydrogel can achieve the preparation of a new generation of composite hydrogels with high safety and high therapeutic effect at low cost and high efficiency. Description of the Drawings

[0030] Figure 1 Scanning electron microscope image of the composite material prepared in Example 1;

[0031] Figure 2 Scanning electron microscope image of the composite material prepared in Example 2;

[0032] Figure 3 Scanning electron microscope image of the composite material prepared in Example 3;

[0033] Figure 4 Scanning electron microscope image of the composite material prepared in Example 4;

[0034] Figure 5 Image monitored by energy dispersive X-ray spectrometer of the composite material prepared in Example 1;

[0035] Figure 6 Image monitored by energy dispersive X-ray spectrometer of the composite material prepared in Example 2

[0036] Figure 7 Rheological characterization and frequency scanning results of the composite hydrogels prepared in Examples 1 and 2;

[0037] Figure 8 Rheological characterization and frequency scanning results of the composite hydrogels prepared in Examples 5 and 6;

[0038] Figure 9 Injectability characterization of the composite hydrogels prepared in Example 1 and Example 2;

[0039] Figure 10 Characterization of the injection performance of the composite hydrogels prepared in Example 3 and Example 4;

[0040] Figure 11 Pictures obtained by Fourier transform infrared spectroscopy of the composite hydrogels prepared in Examples 1-6;

[0041] Figure 12 BCI values of the in vitro hemostasis of the composite hydrogel prepared in Example 1 over time;

[0042] Figure 13 OD values of the in vitro hemostasis of the composite hydrogel prepared in Example 1 over time

[0043] Figure 14 SEM images of the composite hydrogel prepared in Example 1 after co-culture with Porphyromonas gingivalis cells. Detailed implementation mode

[0044] The following further elaborates on the above and other technical features and advantages of the present invention in conjunction with the accompanying drawings.

[0045] Example 1

[0046] Dissolve 2 g of lithium saponite powder in 75 mL of deionized water, take 15 mL of 4 mol / L polyacrylic acid solution and stir it evenly with 10 mL of 2 mol / L calcium chloride solution, then add the lithium saponite solution equally in three portions and stir well to obtain a mixed solution A; mix 20 mL of platelet-rich plasma, 10 mL of 2 mol / L disodium hydrogen phosphate solution and 70 mL of deionized water, and stir well to obtain a mixed solution B. Drop the B solution into the vigorously stirred A solution at a rate of 1 mL / min. After full reaction, centrifuge at 5000 rpm for 5 min to obtain a composite hydrogel.

[0047] Example 2

[0048] Dissolve 2 g of lithium saponite powder in 70 mL of deionized water, take 20 mL of 4 mol / L polyacrylic acid solution and stir it evenly with 10 mL of 2 mol / L calcium chloride solution, then add the lithium saponite solution equally in three portions and stir well to obtain a mixed solution A; mix 20 mL of platelet-rich plasma, 10 mL of 2 mol / L disodium hydrogen phosphate solution and 70 mL of deionized water, and stir well to obtain a mixed solution B. Drop the B solution into the vigorously stirred A solution at a rate of 1 mL / min. After full reaction, centrifuge at 5000 rpm for 5 min to obtain a composite hydrogel.

[0049] Example 3

[0050] Dissolve 2 g of hectorite powder in 80 mL of deionized water. Take 10 mL of a 4 mol / L polyacrylic acid solution and stir it evenly with 10 mL of a 2 mol / L calcium chloride solution. Then add the hectorite solution in three equal portions and stir well to obtain mixed solution A. Mix 20 mL of platelet-rich plasma, 10 mL of a 2 mol / L disodium hydrogen phosphate solution, and 70 mL of deionized water evenly to obtain mixed solution B. Slowly drip solution B into solution A under high-speed stirring at a rate of 1 mL / min. After full reaction, centrifuge at 5000 rpm for 5 min to obtain the composite hydrogel.

[0051] Example 4

[0052] Dissolve 2 g of hectorite powder in 85 mL of deionized water. Take 5 mL of a 4 mol / L polyacrylic acid solution and stir it evenly with 10 mL of a 2 mol / L calcium chloride solution. Then add the hectorite solution in three equal portions and stir well to obtain mixed solution A. Mix 20 mL of platelet-rich plasma, 10 mL of a 2 mol / L disodium hydrogen phosphate solution, and 70 mL of deionized water evenly to obtain mixed solution B. Slowly drip solution B into solution A under high-speed stirring at a rate of 1 mL / min. After full reaction, centrifuge at 5000 rpm for 5 min to obtain the composite hydrogel.

[0053] Example 5

[0054] Dissolve 3 g of hectorite powder in 75 mL of deionized water. Take 15 mL of a 4 mol / L polyacrylic acid solution and stir it evenly with 10 mL of a 2 mol / L calcium chloride solution. Then add the hectorite solution in three equal portions and stir well to obtain mixed solution A. Mix 20 mL of platelet-rich plasma, 10 mL of a 2 mol / L disodium hydrogen phosphate solution, and 70 mL of deionized water evenly to obtain mixed solution B. Slowly drip solution B into solution A under high-speed stirring at a rate of 1 mL / min. After full reaction, centrifuge at 5000 rpm for 5 min to obtain the composite hydrogel.

[0055] Example 6

[0056] Dissolve 1 g of hectorite powder in 75 mL of deionized water. Take 15 mL of a 4 mol / L polyacrylic acid solution and stir it evenly with 10 mL of a 2 mol / L calcium chloride solution. Then add the hectorite solution in three equal portions and stir well to obtain mixed solution A. Mix 20 mL of platelet-rich plasma, 10 mL of a 2 mol / L disodium hydrogen phosphate solution, and 70 mL of deionized water evenly to obtain mixed solution B. Slowly drip solution B into solution A under high-speed stirring at a rate of 1 mL / min. After full reaction, centrifuge at 5000 rpm for 5 min to obtain the composite hydrogel.

[0057] 1. Observe the microstructure of the material using a scanning electron microscope

[0058] After freeze-drying the materials prepared in Examples 1-4 respectively, stick the materials on a metal bracket with conductive double-sided tape. After sputtering with gold, observe the structure of each material under a scanning electron microscope at an accelerating voltage of 10 kV.

[0059] Result analysis: From Figures 1 to 4 it can be seen that the prepared hydrogel presents a three-dimensional porous block structure, and nanoscale calcium phosphate is attached to the surface. The results show that amorphous calcium phosphate is attached to the three-dimensional porous hydrogel structure, and there are flocculates containing protein on the surface.

[0060] 2. Observe the elemental content of the material using an energy dispersive X-ray spectrometer

[0061] After freeze-drying the materials prepared in Example 1 and Example 2 respectively, stick the materials on a metal bracket with conductive double-sided tape. After sputtering with gold, scan the distribution content of various elements contained in the material under a scanning electron microscope at an accelerating voltage of 10 kV.

[0062] Result analysis: From Figure 5 and Figure 6 it can be seen that the elements P, O, Ca, C, and Mg are detected on the surface of the sample, indicating that the sample contains components of nanoclay, calcium phosphate, and polyacrylic acid. The Ca / P ratio of the sample gradually increases with the increase in the content of polyacrylic acid and is between 1.5:1 and 3:1.

[0063] 3. Rheological test

[0064] Take about 2 mL of the material samples of Examples 1, 2, 5, and 6 and lay them flat on the rheometer test bench. At a test temperature of 25 °C and a frequency range of 0.1 - 100 HZ, record the storage modulus G′ (Pa) and loss modulus G″ (Pa). In the flow scanning mode at 25 °C, perform frequency scanning from 100 - 0.1 HZ from high to low.

[0065] Result analysis: From Figure 7 and Figure 8 it can be seen that the storage modulus G′ and loss modulus G″ are measured in the frequency scan. The storage modulus measures the ability of the material to store energy and reflects the network cross-linking density. The higher the cross-linking degree, the greater the storage modulus; while the loss modulus measures the dissipation of energy in the material, that is, the energy lost as heat. The value of G′ provides information on the gel strength. G′ higher than G″ indicates that the gel is more elastic and solid-like. Figure 4 and Figure 5 ​The frequency sweep test curves of the hydrogel are shown. This indicates that the formulation exhibits the typical viscoelastic behavior of a hydrogel with G′ higher than G″. As the shear frequency gradually increases, G′>G″ proves that the hydrogel is stable and has good mechanical properties.

[0066] 4. Injectability Test

[0067] To study the injectability of the hydrogel, Examples 1-4 were used to measure the force required to inject the hydrogel through a 25G needle from a 1 mL syringe at a set flow rate (1.0 mL / min) using a mechanical tester.

[0068] The results show that from Figure 9 and Figure 10 it can be seen that as the input amount of the polyacrylic acid solution increases, the injection force required for the sample gradually increases, but the sample still has good injectability and can be injected in situ into the wound to achieve complete filling of the wound area with the polyacrylic acid-calcium phosphate composite material.

[0069] 5. Fourier Transform Infrared Spectroscopy Test

[0070] After the prepared Examples 1-6 were freeze-dried respectively, about 0.1 mL of the freeze-dried sample powder was taken and scanned from 500 - 4000 cm-1 wavenumber to observe the transmittance of the material, so as to analyze the structural composition and chemical groups of the sample.

[0071] The results show that from Figure 11 it can be seen that the Fourier Transform Infrared (FT-IR) spectrum clearly shows the characteristic absorption peaks of amorphous phosphate of CaP (1053 and 575 cm-1, P-O vibration of PO43-). The broad peak at 575 cm-1 is a single peak rather than split into a doublet, indicating that the inorganic component is amorphous CaP. The peaks between 1310 and 1630 cm-1 are the stretching motions of the carboxyl groups (C=O) in the carboxyl groups of the PAA molecules. Proteins in plasma show amide I and II peaks between about 1650 and 1700 cm-1. It shows that the material contains amorphous calcium phosphate, polyacrylic acid and protein components in plasma.

[0072] 6. In Vitro Blood Coagulation Index (BCI) Test

[0073] The hemostatic ability of the hydrogel was evaluated by the blood coagulation index (BCI) of the composite hydrogel. Material group: Anticoagulated pig blood was mixed with 0.1 M calcium chloride solution in a ratio of 9:1 to activate the pig blood. The material was placed in the wells of a 6-well plate. 200 μL of the activated pig blood was added dropwise onto the surface of the material. At predetermined time points (5 s, 30 s, 60 s, 90 s, 120 s, 150 s), 5 mL of deionized water was added to wash and dissolve the uncoagulated blood. 200 μL of the liquid in the well was added into the wells of a 96-well plate, and the OD value at 540 nm was measured using a microplate reader. Blank group: At the predetermined time points, 200 μL of calcified blood was added to 5 mL of deionized water. 200 μL of the mixed liquid was added into the wells of a 96-well plate, and the OD value at 540 nm was measured using a microplate reader.

[0074] The blood coagulation index was calculated by the formula:

[0075] where OD Sample is the absorbance of the material group, and ODcontrol is the absorbance of the blank group. It can be seen that Figure 12 after the calcified blood was added dropwise onto the material, it was quickly absorbed into the material. By 150 s, the coagulation index of the material group reached 31.5%. This indicates that after the material contacts the blood, it can quickly promote blood coagulation. Figure 13 In [reference], the transmittance of the composite hydrogel was significantly lower than that of the blank control group, indicating that it has the ability of rapid hemostasis.

[0076] 7. Scanning electron microscopy test of Porphyromonas gingivalis cells

[0077] After co-culturing for 48 h, we observed the bacteria using scanning electron microscopy. The results showed that when Porphyromonas gingivalis was co-cultured with the composite hydrogel, the number of bacteria decreased significantly, and all the bacteria were dead bacteria, and the bacteria were significantly damaged. While the bacteria in the blank control were intact and viable without being damaged. ( Figure 14 )

[0078] The above are only the preferred embodiments of the present invention, which are illustrative rather than restrictive to the present invention. Those skilled in the art understand that many changes, modifications, and even equivalents can be made within the spirit and scope defined by the claims of the present invention, but all will fall within the protection scope of the present invention.

Claims

1. A method for preparing a composite hydrogel that stops bleeding and has antibacterial properties and promotes alveolar bone repair, characterized in that: The following steps are involved: S1, uniformly stirring and mixing polyacrylic acid and calcium chloride solution to obtain a composite hydrogel matrix, then adding the nanoclay solution, and continuing to stir uniformly to obtain a polyacrylic acid mixed solution; S2, ultrasonically treating the disodium hydrogen phosphate solution and platelet-rich plasma, and then dropping them into the high-speed stirred polyacrylic acid mixed solution after they are all added, and continuing to stir to fully cross-link and mix, and finally renewing to obtain the desired composite hydrogel.

2. The method for preparing the hemostatic, antibacterial and alveolar bone repair-promoting composite hydrogel according to claim 1, characterized in that: In the step S1, the molecular weight Mw of the polyacrylic acid solution is greater than 100000, the concentration is 1-4 mol / L, and the concentration of the calcium chloride solution is 1 mol / L.

3. The method for preparing the hemostatic, antibacterial and alveolar bone repair-promoting composite hydrogel according to claim 1, characterized in that: In the step S1, the nanoclay solution is a hectorite solution, and the mass fraction of the hectorite solution is 0.2-4 wt%.

4. The method for preparing the hemostatic, antibacterial and alveolar bone repair-promoting composite hydrogel according to claim 1, characterized in that: In step S2, the concentration of the disodium hydrogen phosphate solution is 1 mol / L.

5. The method for preparing the hemostatic, antibacterial and alveolar bone repair-promoting composite hydrogel according to claim 1, characterized in that: In step S2, the molar ratio of the amount of the disodium hydrogen phosphate solution and the polyacrylic acid solution to the amount of the calcium chloride solution is 1:4:1 to 1:1:

1.

6. The method for preparing the hemostatic, antibacterial and alveolar bone repair-promoting composite hydrogel according to claim 1, characterized in that: In step S2, the platelet-rich plasma is any one of platelet-rich plasma, platelet lysate, platelet-rich fibrin, and fibrin with high concentration of concentrated growth factors.

7. The method for preparing the hemostatic, antibacterial and alveolar bone repair-promoting composite hydrogel according to claim 1, characterized in that: In the step S2, the mass fraction of platelet-rich plasma is 5-20 wt%.

8. The method for preparing the hemostatic, antibacterial and alveolar bone repair-promoting composite hydrogel according to claim 1, characterized in that: The mass ratio of platelet-rich plasma to the composite hydrogel matrix in step S2 is 19:1 to 4:

1.

9. A composite hydrogel for promoting alveolar bone repair and having hemostasis and antibacterial properties obtained by the preparation method according to any one of claims 1 to 8.

10. Use of the hemostatic, antibacterial and alveolar bone repair-promoting composite hydrogel according to claim 9 in the preparation of a drug for treating large bleeding and irregular wounds and alveolar bone defects.

Images