Oxygen-releasing antibacterial high-elasticity adhesive composite hydrogel dressing as well as preparation method and application thereof

Abstract

The invention discloses an oxygen-releasing antibacterial high-elasticity adhesive composite hydrogel dressing as well as a preparation method and application thereof, and the preparation method comprises the following steps: dissolving gelatin in PBS (Phosphate Buffer Solution) to obtain a gelatin solution; dropwise adding siloxane into the gelatin solution for full reaction; sequentially adding dopamine hydrochloride, calcium peroxide and metronidazole into the fully reacted gelatin solution to obtain a hydrogel prepolymer; sodium periodate is added into the hydrogel prepolymer, and the oxygen-releasing antibacterial high-elasticity adhesive composite hydrogel dressing is obtained. The technical problem that in the prior art, hydrogel cannot have high pressure resistance, good adhesion, oxygen release and antibiosis at the same time is solved, the hydrogel is simple and convenient in preparation process and short in time consumption, not only has oxygen release and antibiosis performance, but also has high elasticity and good adhesion, is short in gelling time and convenient to use, and the hydrogel is suitable for large-scale popularization and application. The wound healing of the MRONJ model can be effectively promoted, and the application potential in the field of oral medical treatment is great.

Description

Technical Field

[0001] The present application relates to the technical field of biomedical materials, and in particular to an oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing, and a preparation method and application thereof. Background Art

[0002] Medication-related osteonecrosis of the jaw (MRONJ) refers to severe oral and maxillofacial complications caused by the use of bisphosphonates, anti-angiogenic drugs or steroids for osteoporosis, bone metastasis of malignant tumors, and other diseases, resulting in jaw metabolic disorders and osteonecrosis-like diseases. Clinical manifestations include exposure of necrotic bone, severe pain, infection, fistula, etc. As the indications for the use of this type of drug are continuously discovered, the emergence of MRONJ has attracted more and more attention from clinicians and researchers. Although the research on MRONJ has increased in recent years, its specific pathogenic mechanism has not yet been clarified. With the continuous in-depth exploration of drug mechanisms and the increase in clinical understanding, scholars have proposed a variety of potential risk factors for MRONJ, such as changes in bone balance, inhibition of angiogenesis, infection, etc.

[0003] In recent years, hydrogels have become one of the most popular and representative materials in the field of bioengineering due to their good biocompatibility and functionality, as well as their similarity to biological soft tissues. Wound dressings can provide temporary closure and deliver drugs to prevent infection and promote healing. A variety of dressings have been developed to promote wound healing, such as semipermeable membranes, semipermeable foams, hydrocolloids and hydrogels. Among them, hydrogels have become the most competitive candidates among many wound dressings due to their excellent biocompatibility, hydrophilicity and three-dimensional porous structure that simulates the extracellular matrix (ECM). However, most of these dressings do not have oxygen release and antibacterial capabilities. In addition, traditional hydrogel dressings have weak mechanical strength, low adhesion, cannot withstand large stress and are easy to fall off, thus failing to effectively protect wounds. Therefore, it remains a challenge to develop ideal bioactive wound dressings to promote the healing of oral wounds in potential patients. Summary of the invention

[0004] The embodiments of the present application provide an oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing, and a preparation method and application thereof, thereby solving the technical problem that the hydrogel in the prior art cannot simultaneously have strong compressive resistance, good adhesion, oxygen release and antibacterial properties. The hydrogel production process is simple and time-saving. The hydrogel not only has oxygen-releasing and antibacterial properties, but also has strong elasticity and good adhesion, a short gelation time, and is easy to use. It can effectively promote the healing of MRONJ model wounds and has great application potential in the field of oral medicine.

[0005] In a first aspect, an embodiment of the present invention provides a method for preparing an oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing, comprising:

[0006] Dissolve gelatin in PBS to obtain a gelatin solution;

[0007] Adding siloxane dropwise into the gelatin solution and waiting for it to fully react;

[0008] Adding dopamine hydrochloride, calcium peroxide and metronidazole in sequence to the fully reacted gelatin solution to obtain a hydrogel prepolymer;

[0009] Sodium periodate is added to the hydrogel prepolymer to obtain an oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing.

[0010] In combination with the first aspect, in a possible implementation, the mass fraction of the gelatin solution is 7%-15%; the volume ratio of the siloxane to the gelatin solution is (0.5-1):(7-10); the mass fraction of the dopamine hydrochloride is 2%-5%, the mass fraction of the calcium peroxide is 0.05-0.2%, and the mass fraction of the metronidazole is 0.3%-0.6%; the molar ratio of the sodium periodate to the dopamine hydrochloride is (0.2-0.5):1.

[0011] In combination with the first aspect, in a possible implementation, the condition for dissolving gelatin in PBS is that heating is required for dissolution, and the temperature for heating and dissolving is 50-100°C, and the duration is 1-3h; the temperature condition for fully reacting siloxane with the gelatin solution is 50-100°C, and the duration is 0.2-1h; the temperature condition for sequentially adding dopamine hydrochloride, calcium peroxide, and metronidazole to the fully reacted gelatin solution is 25-100°C, and the duration is 1-5min; the temperature condition for adding sodium periodate to the hydrogel prepolymer is 25-100°C, and the duration is 10-50s.

[0012] In combination with the first aspect, in a possible implementation, the diameter of the calcium peroxide particles is 50-300 mesh; the average molecular weight of the metronidazole is 100-200; and the average molecular weight of the sodium periodate is 100-1000.

[0013] In a second aspect, an embodiment of the present invention provides an oxygen-releasing, antibacterial, highly elastic, adhesive composite hydrogel dressing, which is prepared according to the above-mentioned preparation method.

[0014] In a third aspect, an embodiment of the present invention provides a method for preparing an oxygen-releasing, antibacterial, highly elastic, adhesive composite hydrogel dressing, and application of the hydrogel dressing prepared in the field of biomedicine.

[0015] In conjunction with the third aspect, in a possible implementation, the application in the field of biomedicine is application in drug-related osteonecrosis of the jaw wound.

[0016] One or more technical solutions provided in the embodiments of the present invention have at least the following technical effects or advantages:

[0017] The present invention selects gelatin with good biocompatibility as the basic component for preparing hydrogel. Gelatin is a natural protein derivative material with excellent biocompatibility, biodegradability and non-toxicity. It is widely used in the synthesis of medical hydrogels because of its non-immunogenicity and cell adhesion. Siloxane uses trimethoxysilane (3-glycidyl propoxy) as a silane coupling agent, wherein the hydrogen bond interaction between the amino group on the gelatin and the silanol (Si-OH) of the siloxane, the condensation of the silanol and the hydrophobic effect of the epoxy group promote the gelation of the GT-S hybrid solution, thereby forming a first network. Dopamine (DA) monomer undergoes oxidative polymerization to produce polydopamine (PDA), which contains catechol groups, giving the material good adhesion. Therefore, the gelatin matrix hydrogel with double cross-linking of siloxane and dopamine not only has good biocompatibility, but also has strong mechanical strength and adhesion. On this basis, oxygen-releasing material calcium peroxide and antibacterial drug metronidazole are added to give the hydrogel good oxygen-releasing and antibacterial properties, thereby obtaining an oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing.

[0018] The hydrogel dressing prepared by the method of the present invention demonstrated excellent MRONJ prevention effects in the MRONJ tooth extraction animal model by evaluating the bone formation rate and soft tissue healing rate. At the same time, the loaded calcium peroxide and metronidazole drugs can effectively release oxygen and achieve anti-inflammatory effects under physiological conditions, thereby improving the microenvironment of local hypoxia and infection of MRONJ and promoting tissue healing. In addition, the hydrogel has strong elasticity, i.e. mechanical strength, and has good adhesion, injectability, etc. Therefore, this series of hydrogels has good application prospects in the field of preventing MRONJ.

[0019] Trimethoxysilane (3-glycidylpropoxy) is selected as the siloxane, and as a silane coupling agent, it can cross-link gelatin chemically through the reaction between the epoxy group in its molecule and the amino group on gelatin, and can also cross-link gelatin physically through the interaction of hydrophilic-hydrophobic and hydrogen bonds with gelatin, giving the material strong mechanical strength, so that the material can withstand greater pressure in the oral extraction socket wound model without breaking, maintaining its complete gel structure, and playing a role in protecting and supporting the wound.

[0020] In the present invention, dopamine cross-linked gelatin is selected as the second network of the hydrogel, and sodium periodate is used as the oxidant of dopamine. The oxidation products of DA, dopaquinone, etc. are covalently cross-linked with the primary amine groups of the gelatin (GT) main chain through Michael addition and Schiff base reaction, and its DA monomer, DA or oligomer grafted onto the GT main chain, etc. are physically assembled into stable polydopamine through hydrogen bonds and π-π stacking bonds to achieve cross-linking. The catechol structure in dopamine can covalently bind to the amino / sulfhydryl groups in the tissue, and cooperate with physical interactions such as hydrogen bonds to produce a strong adhesion effect with the tissue. In addition, due to the presence of a large number of non-covalent bonds from polydopamine in the hydrogel network, it can be given good injectability so as to better adapt to the irregularity of the wound shape. Thereby, the composite gel is better fixed and filled in the tooth extraction socket.

[0021] Calcium peroxide is an oxygen-releasing material. The oxygen it releases in the hypoxic MRONJ local microenvironment can stimulate the proliferation of vascular endothelial cells and promote the formation of granulation tissue, thereby accelerating the repair of bone and soft tissue. In addition, metronidazole, as a commonly used antibiotic in the oral field, can effectively inhibit Streptococcus and Prevotella in the extraction socket, exerting a good antibacterial effect to promote the healing of MRONJ extraction socket wounds.

[0022] It effectively solves the technical problem that hydrogels in the prior art cannot simultaneously have strong compressive resistance, good adhesion, oxygen release and antibacterial properties, and realizes that the hydrogel production process is simple and time-saving. It not only has oxygen-releasing and antibacterial properties, but also has strong elasticity and good adhesion. It has a short gelation time and is easy to use. It can effectively promote the healing of MRONJ model wounds and has great application potential in the field of oral medicine. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments of the present invention or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0024] Figure 1 The rheological properties of the GSDH prepared in Example 1 of the present invention are measured;

[0025] Figure 2 The bending, compression, cutting and rebound experiments of the GSDH prepared in Example 1 of the present invention are as follows;

[0026] Figure 3 The shear strength test of the hydrogels prepared in Example 1 and Example 6 of the present invention;

[0027] Figure 4 The gelation time of the hydrogels prepared in Example 1, Example 2, Example 3 and Example 4 of the present invention is measured;

[0028] Figure 5 The shear strength test of the hydrogels prepared in Example 1, Example 2, Example 3 and Example 4 of the present invention;

[0029] Figure 6 The gelation time of the hydrogel prepared in Example 5 of the present invention is measured;

[0030] Figure 7 This is a Fourier infrared spectrum of GSDH prepared in Example 1 of the present invention;

[0031] Figure 8 The swelling rates of the GSDH, GMC1, GMC3 and GMC5 hydrogels prepared in Examples 1, 8 and 9 of the present invention;

[0032] Fig. 9 The scanning electron microscope microscopic morphology images of the GSDH, GMC1, GMC3 and GMC5 hydrogels prepared in Example 1, Example 8 and Example 9 of the present invention after freeze-drying;

[0033] Fig.10 Evaluation of the in vitro oxygen release behavior of the GMC1 hydrogel prepared in Example 8 of the present invention;

[0034] Fig.11 Evaluation of the in vitro pharmaceutical release behavior of the GMC1 hydrogel prepared in Example 8 of the present invention;

[0035] Fig.12 Evaluation of the hemolysis rate of the GMC1 hydrogel prepared in Example 8 of the present invention;

[0036] Fig.13 This is an evaluation of the cell compatibility of the GSDH, GMC1, GMC3, and GMC5 hydrogels prepared in Example 1, Example 8, and Example 9 of the present invention. DETAILED DESCRIPTION

[0037] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0038] In the description of the embodiments of the present invention, it should be noted that the terms "center", "up", "down", "left", "right", "vertical", "horizontal", "inside", "outside" and the like indicate positions or positional relationships based on the positions or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the embodiments of the present invention and simplifying the description, rather than indicating or implying that the devices or elements referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limitations on the present invention. The terms "first", "second", and "third" are used for descriptive purposes only and cannot be understood as indicating or implying relative importance. In addition, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be an indirect connection through an intermediate medium, or it can be a connection between the two elements. For those of ordinary skill in the art, the specific meanings of the above terms in the embodiments of the present invention can be understood according to the specific circumstances.

[0039] The present invention discloses a method for preparing an oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing, which specifically comprises the following steps:

[0040] Step 1) Dissolve gelatin (derived from pig skin) in PBS to obtain a gelatin solution.

[0041] Step 2) Add siloxane dropwise into the gelatin solution and wait for it to fully react.

[0042] Step 3) dopamine hydrochloride, calcium peroxide and metronidazole are sequentially added to the gelatin solution after the above reaction to obtain a hydrogel prepolymer.

[0043] Step 4) sodium periodate is added to the hydrogel prepolymer to obtain an oxygen-releasing, antibacterial, highly elastic, adhesive composite hydrogel dressing.

[0044] The oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing prepared by the present invention can be used in preventing MRONJ, such as wound dressing.

[0045] Embodiment 1

[0046] Step 1), fully dissolve 1.5g gelatin (from pig skin) in 10ml PBS at 55°C for 1 hour.

[0047] Step 2), slowly add 0.75 ml of siloxane to the solution obtained in step 1), and allow it to react for 0.5 h.

[0048] Step 3), add 0.4 g dopamine hydrochloride to the solution obtained in step 2) and wait for it to fully dissolve.

[0049] Step 4), when the temperature of the solution obtained in step 3) is reduced to 37°C, 0.169g of sodium periodate is added to the solution, and the molar ratio of sodium periodate to dopamine hydrochloride is 0.375:1, a highly elastic adhesion composite hydrogel can be obtained, which is named GT150-S-40DA, i.e. GSDH.

[0050] Embodiment 2

[0051] Step 1), fully dissolve 1.5g gelatin (from pig skin) in 10ml PBS at 55°C for 1 hour.

[0052] Step 2), slowly add 0.75 ml of siloxane to the solution obtained in step 1), and allow it to react for 0.5 h.

[0053] Step 3), add 0.3g or 0.2g dopamine hydrochloride to the solution obtained in step 2), and wait for it to fully dissolve.

[0054] Step 4), when the temperature of the solution obtained in step 3) is reduced to 37°C, 0.169g of sodium periodate is added to the solution, and the molar ratio of sodium periodate to dopamine hydrochloride is 0.375:1, a highly elastic adhesion composite hydrogel can be obtained, which is named GT150-S-30DA, GT150-S-20DA, i.e. GSDH.

[0055] Embodiment 3

[0056] Step 1), fully dissolve 1g gelatin (derived from pig skin) in 10ml PBS at 55°C for 1 hour.

[0057] Step 2), slowly add 0.75 ml of siloxane to the solution obtained in step 1), and allow it to react for 0.5 h.

[0058] Step 3), add 0.4 g dopamine hydrochloride to the solution obtained in step 2) and wait for it to fully dissolve.

[0059] Step 4), when the temperature of the solution obtained in step 3) is reduced to 37°C, 0.169g of sodium periodate is added to the solution, and the molar ratio of sodium periodate to dopamine hydrochloride is 0.375:1, a highly elastic adhesive composite hydrogel can be obtained, which is named GT100-S-40DA, i.e. GSDH.

[0060] Embodiment 4

[0061] Step 1), fully dissolve 1g gelatin (derived from pig skin) in 10ml PBS at 55°C for 1 hour.

[0062] Step 2), slowly add 0.75 ml of siloxane to the solution obtained in step 1), and allow it to react for 0.5 h.

[0063] Step 3), add 0.3g or 0.2g dopamine hydrochloride to the solution obtained in step 2), and wait for it to fully dissolve.

[0064] Step 4), when the temperature of the solution obtained in step 3) is reduced to 37°C, 0.169g of sodium periodate is added to the solution, and the molar ratio of sodium periodate to dopamine hydrochloride is 0.375:1, and a highly elastic adhesion composite hydrogel is obtained, which is named GT100-S-30DA, GT100-S-20DA, i.e. GSDH.

[0065] Embodiment 5

[0066] Step 1), fully dissolve 1.5g gelatin (from pig skin) in 10ml PBS at 55°C for 1 hour.

[0067] Step 2), slowly add 0.75 ml of siloxane to the solution obtained in step 1), and allow it to react for 0.5 h.

[0068] Step 3), add 0.4 g dopamine hydrochloride to the solution obtained in step 2) and wait for it to fully dissolve.

[0069] Step 4), when the temperature of the solution obtained in step 3) is reduced to 37°C, 0.169g of sodium periodate is added to the solution, and the molar ratio of sodium periodate to dopamine hydrochloride is (0.300:1), (0.350:1), (0.375:1), or (0.400:1), to obtain a highly elastic adhesion composite hydrogel, namely GSDH1, GSDG2, GSDH3, and GSDH4.

[0070] Embodiment 6

[0071] Step 1), fully dissolve 1.5g gelatin (from pig skin) in 10ml PBS at 55°C for 1 hour.

[0072] Step 2), slowly add 0.75 ml of siloxane to the solution obtained in step 1), and allow it to react for 0.5 h.

[0073] Step 3), placing the mixed solution obtained in step 2) in an oven at 37°C overnight to obtain GT150-S, which is named GTS.

[0074] Embodiment 7

[0075] Dissolve 1.5 g of gelatin solution in 10 ml of PBS at 55°C for 1 hour, and leave the mixed solution to solidify naturally at room temperature.

[0076] The following experimental treatments were specifically performed in the examples of this application:

[0077] The rheological properties of the hydrogel prepared in Example 1 were measured. Figure 1 As shown, it can be observed that the storage modulus is greater than the dissipation modulus, suggesting that the object is indeed a solid colloidal state.

[0078] The hydrogel prepared in Example 1 was subjected to compression, bending and cutting experiments. Figure 2 As shown, it can be observed that after the gel is cured, it has strong mechanical strength and good resilience, and can withstand various stresses given by the outside world, such as pressure, bending force, etc. In the oral field, this ability enables the material to resist various stresses caused by factors such as the tongue, food, and gums during speaking and chewing, thereby maintaining its shape without breaking, and enabling it to effectively perform other functions such as oxygen release.

[0079] The gelling time of the gels prepared in the above-mentioned examples 1, 2, 3 and 4 was measured, referring to Figure 3 , Figure 4 It can be observed that with the increase of gelatin concentration, the gelation time of the gel is greatly shortened, among which the gelation time of GT150-S-40DA is only 3-4 minutes. The shorter gelation time means faster curing and retention, which is more conducive to clinical application.

[0080] The shear strength of the gels prepared in the above-mentioned Examples 1, 2, 3, 4 and 6 was measured, referring to Figure 5 It can be observed that when the gelatin component is determined, as the dopamine hydrochloride content increases, the adhesion of the gel also increases. This strong adhesion ability ensures that the gel has strong chemical adhesion in addition to the physical retention brought by its shape filling, thereby greatly enhancing the retention ability of the gel.

[0081] The gelation time of the hydrogel prepared in Example 5 was also measured. Figure 6 It can be seen that the different molar ratios of sodium periodate and dopamine hydrochloride greatly affect the gelation time of the gel. The experimental results show that when the molar ratio of sodium periodate to dopamine hydrochloride is 0.375, the gelation time is about 3.5 minutes, which can better meet the needs of clinical applications.

[0082] Fourier transform infrared spectroscopy analysis was performed on the above-mentioned embodiment 1, embodiment 6 and embodiment 7. Figure 7 , the occurrence of silicon-oxygen bonds and Schiff base reactions in Example 1 can be observed, thereby confirming that the cross-linking agent in the gel successfully cross-linked the gel.

[0083] Embodiment 8

[0084] Step 1), fully dissolve 1.5g gelatin (from pig skin) in 10ml PBS at 55°C for 1 hour.

[0085] Step 2), slowly add 0.75 ml of siloxane to the solution obtained in step 1), and allow it to react for 0.5 h.

[0086] Step 3), add 0.4 g dopamine hydrochloride to the solution obtained in step 2) and wait for it to fully dissolve.

[0087] Step 4), when the temperature of the solution obtained in step 3) drops to 37°C, 10 mg of calcium peroxide and 50 mg of metronidazole are added in sequence to make them fully react, and then 0.169 g of sodium periodate is added. GSDH@CaO2&MDZ is obtained, which is named GMC1.

[0088] Embodiment 9

[0089] Step 1), fully dissolve 1.5g gelatin (from pig skin) in 10ml PBS at 55°C for 1 hour.

[0090] Step 2), slowly add 0.75 ml of siloxane to the solution obtained in step 1), and allow it to react for 0.5 h.

[0091] Step 3), add 0.4 g dopamine hydrochloride to the solution obtained in step 2) and wait for it to fully dissolve.

[0092] Step 4), when the temperature of the solution obtained in step 3) drops to 37°C, 30mg or 50mg of calcium peroxide and 50mg of metronidazole are added in sequence to make them fully react, and then 0.169g of sodium periodate is added. GSDH@CaO2&MDZ loaded with different concentrations of calcium peroxide can be obtained, which are named GMC3 and GMC5.

[0093] The following experiments were further performed in the examples of this application:

[0094] The gels obtained in Example 1, Example 8 and Example 9 were subjected to swelling experiments. Figure 8 , it can be observed that GSDH has the lowest swelling rate, with a 24-hour swelling rate of only about 40%. As the calcium peroxide content in the hydrogel increases, the swelling rate of the hydrogel also increases, and GMC5 has reached nearly 100%. Therefore, we can assume that the swelling rates of the GSDH group and the GMC1 group are lower. A lower swelling rate means a smaller volume expansion. In clinical applications, due to the limited space in the extraction socket, lower swelling also means that it can better fill the irregular extraction socket and will not protrude above the wound to increase the risk of stress.

[0095] The gels obtained in Example 1, Example 8 and Example 9 were subjected to electron microscope microscopic morphology analysis. Fig. 9It can be observed that the hydrogel dressing exhibits a porous structure with pore diameters ranging from 20 to 150 μm. This result indicates that the hydrogel dressing prepared by the present invention has a good pore structure.

[0096] The oxygen release rate of the GMC1 hydrogel prepared in Example 8 was evaluated. Fig.10 As shown, the composite gel has good oxygen release within 5 days, indicating that the hydrogel dressing sample prepared by the present invention exhibits good oxygen release behavior.

[0097] The in vitro pharmacological release behavior of the GMC1 hydrogel prepared in Example 8 was evaluated. Fig.11 As shown, it can be observed that within 24 hours, the drug can be continuously released with a release rate of about 60%, indicating that the hydrogel dressing samples prepared by the present invention all exhibit good drug release behavior.

[0098] The hemolysis rate of the GMC1 hydrogel prepared in Example 8 was measured using rat blood cells. Fig.12 As shown, the red blood cells in the rat blood were separated and incubated with freeze-dried gel dispersions of different concentrations at 37°C for 1 hour. After centrifugation, the absorbance of the supernatant was tested and the hemolysis rate was calculated. 0.1% Triton X-100 was used as a positive control and PBS was used as a negative control. As shown in the figure, the GMC1 hydrogel prepared above showed a hemolysis rate of less than 5%. This shows that the hydrogel dressing samples prepared by the preparation method of the present invention all showed good blood compatibility.

[0099] The cell compatibility of the GMC1 hydrogel prepared in the above Example 8 was tested using rat bone marrow mesenchymal stem cells. After the hydrogel was freeze-dried, it was sterilized at 55°C for at least 24 hours. The sterilized sample was soaked in a complete medium without FBS at 37°C for 24 hours, centrifuged and filtered to remove solids and bacteria, and an extract was prepared with concentrations of 0.625 mg / ml, 1.25 mg / ml, and 2.5 mg / ml, respectively. Bovine serum albumin was then added to the extract, and after culturing with cells for 24 hours, the cell viability was tested. As shown in the figure, the GMC1 hydrogel exhibited higher cell viability. This shows that the hydrogel dressing samples prepared by the present invention all showed good cell compatibility.

[0100] In summary, the oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing prepared by the present invention has good adhesion and resilience, wherein siloxane cross-linked gelatin is used as the first network of the hydrogel. It can promote gelatinization through the hydrophobic effect of silanol, hydrogen bond and epoxy group, and the hydrophobic effect of epoxy group can give the hydrogel controllable low swelling performance. Dopamine cross-linked gelatin is selected as the second network of the hydrogel, and sodium periodate is used as the oxidant of dopamine. The catechol structure in dopamine can covalently bind to the amino / sulfhydryl group in the tissue, and cooperate with the physical interaction such as hydrogen bond to produce a strong adhesion effect with the tissue. This hydrogel can protect the wound, is not easy to fall off, break and can adapt to irregular wounds; it has oxygen release characteristics, which can improve the local hypoxia state in the initial stage of MRONJ tooth extraction socket; it has antibacterial properties and can prevent wound infection. Therefore, the hydrogel dressing prepared by the present invention can be used in the clinical application field of preventing MRONJ, especially in the tooth extraction socket.

[0101] The various embodiments in this specification are described in a progressive manner, and the same or similar parts between the various embodiments can be referenced to each other. Each embodiment focuses on the differences from other embodiments.

[0102] The above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit the present application. Although the present application has been described in detail with reference to the aforementioned embodiments, a person of ordinary skill in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some or all of the technical features thereof may be replaced by equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the present application.

Claims

1. A method for preparing an oxygen-releasing, antibacterial, highly elastic, adhesive composite hydrogel dressing, characterized in that: include: Dissolve gelatin in PBS to obtain a gelatin solution; Adding siloxane dropwise into the gelatin solution and waiting for it to fully react; Adding dopamine hydrochloride, calcium peroxide and metronidazole in sequence to the fully reacted gelatin solution to obtain a hydrogel prepolymer; Sodium periodate is added to the hydrogel prepolymer to obtain an oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing.

2. The method for preparing the oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing according to claim 1, characterized in that: The mass fraction of the gelatin solution is 7%-15%; the volume ratio of the siloxane to the gelatin solution is (0.5-1):(7-10); the mass fraction of the dopamine hydrochloride is 2%-5%, the mass fraction of the calcium peroxide is 0.05-0.2%, and the mass fraction of the metronidazole is 0.3%-0.6%; the molar ratio of the sodium periodate to the dopamine hydrochloride is (0.2-0.5):

1.

3. The method for preparing the oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing according to claim 1, characterized in that: The condition for dissolving gelatin in PBS is that heating is required for dissolution, and the temperature for heating and dissolution is 50-100°C, and the duration is 1-3h; the temperature condition for fully reacting siloxane with the gelatin solution is 50-100°C, and the duration is 0.2-1h; the temperature condition for sequentially adding dopamine hydrochloride, calcium peroxide, and metronidazole to the fully reacted gelatin solution is 25-100°C, and the duration is 1-5min; the temperature condition for adding sodium periodate to the hydrogel prepolymer is 25-100°C, and the duration is 10-50s.

4. The method for preparing the oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing according to claim 1, characterized in that: The diameter of the calcium peroxide particles is 50-300 mesh; the average molecular weight of the metronidazole is 100-200; and the average molecular weight of the sodium periodate is 100-1000.

5. An oxygen-releasing and antibacterial high-elastic adhesive composite hydrogel dressing, characterized in that: Prepared according to the preparation method according to any one of claims 1 to 4.

6. Use of the hydrogel dressing prepared by the method for preparing the oxygen-releasing, antibacterial, highly elastic and adhesive composite hydrogel dressing according to any one of claims 1 to 4 in the preparation of biomedicine.

7. The use according to claim 6, characterized in that: The application in the field of biomedicine is application in drug-related osteonecrosis of the jaw wound.

Images