Wound repair material and preparation method thereof

Abstract

The invention provides a wound repair material and a preparation method thereof, and relates to the field of biomedical materials. The preparation method of the wound repair material comprises the following steps: mixing alpha-cyanoacrylate and acetone to obtain an adhesion matrix solution; mixing polyvinyl butyral, quaternized cellulose, dexamethasone and an organic solvent to obtain a functional additive solution; and performing double-needle array electrostatic spinning on the adhesion matrix solution and the functional additive solution to obtain the wound repair material. The wound repair material prepared by the invention has the functions of relatively high adhesion, antibacterial ability, anti-inflammatory ability, biocompatibility and the like, can avoid side effects such as thrombus risk and the like, and can be safely and efficiently adapted to healing environments of different wounds.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedical materials, in particular to a wound repair material and a preparation method thereof. BACKGROUND

[0002] Wound is the damage and loss of normal skin or tissue caused by external injury factors such as surgery, external force, heat, electric current, chemical substances, low temperature and internal factors such as local blood supply disorder.

[0003] Ideal wound repair not only requires epidermal coverage, but also involves complex physiological processes, including hemostasis, granulation tissue formation, angiogenesis and tissue remodeling. Any imbalance in any link may lead to delayed repair or even difficulty in healing, causing great pain and economic burden to patients.

[0004] The traditional dressings (such as gauze, cotton pad, etc.) widely used in clinical practice mainly play a passive covering role. Although they can absorb exudates and isolate external pollution, they have single function and lack active repair function, and have no promoting effect on wound healing process, and are also easy to cause infection and secondary damage. When the gel dressing is used, there is a risk of thrombosis caused by interaction with blood components, which limits its application range. SUMMARY

[0005] The present application aims to provide a wound repair material and a preparation method thereof to solve the above problems.

[0006] To achieve the above purpose, the following technical solutions are adopted in the present application: A preparation method of a wound repair material, comprising: mixing α-cyanoacrylate and acetone to obtain an adhesion matrix solution; mixing polyvinyl butyral, quaternary ammonium cellulose, dexamethasone and an organic solvent to obtain a functional additive solution; carrying out double-needle array electrospinning on the adhesion matrix solution and the functional additive solution to obtain a wound repair material.

[0007] According to the embodiment of the present application, the quaternary ammonium cellulose is prepared by the following method: mixing a mixed solution containing alkali, urea and water with cellulose to dissolve the cellulose and obtain a cellulose solution; mixing quaternary ammonium salt with the cellulose solution, carrying out reaction, neutralizing with acid after reaction is completed, and dialyzing with a dialysis bag to obtain quaternary ammonium cellulose.

[0008] According to the embodiment of the present application, in the mixed solution containing alkali, urea and water, the mass fraction of the alkali is 10-15wt%, and the mass fraction of the urea is 6-10wt%; The alkali comprises NaOH; The mixing of the mixed solution containing alkali, urea and water with cellulose is carried out at a temperature of-10℃ to-4℃; The quaternary ammonium salt comprises 2,3-epoxypropyltrimethylammonium chloride; The molar ratio of the quaternary ammonium salt to the cellulose in the cellulose solution is 10:1 to 12:1; The reaction time of the quaternary ammonium salt with the cellulose solution is 16-24h; The acid comprises hydrochloric acid.

[0009] According to the embodiment of the present application, the adhesion matrix solution comprises 5-15wt% of α-cyanoacrylate and 85-95wt% of acetone.

[0010] According to the embodiment of the present application, the α-cyanoacrylate comprises at least one of n-butyl α-cyanoacrylate and isooctyl α-cyanoacrylate.

[0011] According to the embodiment of the present application, the functional additive solution comprises 1-5wt% of polyvinyl butyral, 1-5wt% of quaternized cellulose, 1-5wt% of dexamethasone, and 85-97wt% of an organic solvent.

[0012] According to the embodiment of the present application, the weight average molecular weight Mw of the polyvinyl butyral is 40000-70000.

[0013] According to the embodiment of the present application, the organic solvent comprises ethanol.

[0014] According to the embodiment of the present application, the double-needle array electrospinning is carried out under the following conditions: a running rate of 10-20ul / min, a voltage of 10-20KV, and a distance from the receiving tissue surface of 5cm-15cm.

[0015] The present application also provides a wound repair material prepared by the preparation method of the wound repair material described above.

[0016] Compared with the prior art, the present application has the following beneficial effects: The wound repair material prepared in the application has high adhesion, antibacterial ability, anti-inflammatory ability and biocompatibility, etc., and can avoid side effects such as thrombosis risk, can be safely and efficiently adapted to different wound healing environments, and solves the problems of single function, lack of active repair function, easy to cause infection and secondary damage of the wound repair material. In addition, the wound repair material prepared in the application also has the advantages of lightness, good flexibility, good air permeability and the like, and solves the problems of thick and heavy material, insufficient flexibility, air-tightness, easy to cause inflammation and infection of the existing antibacterial material. BRIEF DESCRIPTION OF DRAWINGS

[0017] In order to more clearly illustrate the technical solutions of the embodiments of the application, the following will briefly introduce the drawings needed to be used in the embodiments. It should be understood that the following drawings only show some embodiments of the application, and therefore should not be regarded as limiting the scope of the application.

[0018] Figure 1 SEM image of the material after electrospinning in Example 1; Figure 2 Cumulative drug release curve of the wound repair material of Example 1; Figure 3 is a comparison chart of in vitro bacterial isolation performance evaluation of the control group and the wound repair material of Example 1 on Escherichia coli; Figure 4 is an OD600 comparison chart of the control group and the wound repair material of Example 1 after adding Escherichia coli; Figure 5 is a comparison chart of in vitro bacterial isolation performance evaluation of the control group and the wound repair material of Example 1 on Staphylococcus aureus; Figure 6 is an OD600 comparison chart of the control group and the wound repair material of Example 1 after adding Staphylococcus aureus; Figure 7 is an anti-inflammatory efficiency comparison chart of the control group, the model group and the wound repair material of Example 1. DETAILED DESCRIPTION

[0019] As used herein: “prepared from” is synonymous with “comprising”. The terms “comprising”, “including”, “having” or “containing” or any other variation thereof, as used herein, are intended to cover a non-exclusive inclusion. For example, a composition, step, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but can include other elements not expressly listed or inherent to such composition, step, method, article, or apparatus.

[0020] The conjunctive word "comprising" does not exclude other elements or steps than those listed after it. The word "comprising" is used in the sense of "including" rather than other forms of "comprising" or "comprise" such as "containing" or "holding". The use of any form of "comprising", "including", "containing", "carrying" or "holding", "having" etc. is intended to cover a non-exclusive inclusion such that for a given recitation of these methods or materials any combination of these recited elements can be used unless otherwise specified (e.g., "comprising" should be interpreted as meaning "consisting at least in part of").

[0021] When equivalent, concentration, or other value or parameter is expressed in a range, a preferred range, or a series of upper preferred values and lower preferred values, it is to be understood that all ranges formed by any pair of any stated upper range limit or preferred value and any stated lower range limit or preferred value, even if the ranges themselves are not mentioned, are to be specifically disclosed. For example, where a range of "1-5" is disclosed, it is to be understood that the range "1-4," "1-3," "1-2," "1-2 and 4-5," "1-3 and 5," etc., are to be specifically disclosed. When numerical ranges are disclosed, unless otherwise stated, the range is intended to include all integers and fractions within that range.

[0022] In these embodiments, the parts and percentages described are by mass, unless otherwise indicated.

[0023] "Mass parts" refers to a basic unit of measurement that represents the proportional relationship of the mass of multiple components, 1 part can represent any unit mass, such as 1 g, 2.689 g, etc. If we say that the mass parts of component A is a parts, and the mass parts of component B is b parts, it means that the ratio of the mass of component A to the mass of component B is a:b. Alternatively, it means that the mass of component A is aK, and the mass of component B is bK (K is an arbitrary number, indicating a multiple factor). It should not be misunderstood that, unlike mass parts, the sum of the mass parts of all components is not limited to 100 parts.

[0024] "and / or" is used to indicate one or both of the stated circumstances can occur, for example, A and / or B includes (A and B) and (A or B).

[0025] A method for preparing a wound repair material, comprising: Mixing an alpha-cyanoacrylate and acetone to obtain an adhesion matrix solution; Mixing polyvinyl butyral, quaternized cellulose, dexamethasone, and an organic solvent to obtain a functional additive solution; Carrying out double-needle array electrospinning on the adhesion matrix solution and the functional additive solution to obtain a wound repair material.

[0026] The alpha-cyanoacrylate has the effect of polymerizing to adhere to a wound, and has good adhesion to a wound. Specifically, the alpha-cyanoacrylate rapidly polymerizes after contacting the blood on the surface of a wound, thereby effectively enhancing the adhesion of the material to the wound, and enabling the biomaterial to tightly adhere to the surface of the tissue. The polyvinylidene chloride has good biocompatibility, the quaternary ammonium cellulose has antibacterial effect, and the dexamethasone has anti-inflammatory effect. The alpha-cyanoacrylate, the polyvinylidene chloride, the quaternary ammonium cellulose and the dexamethasone can cooperate with each other to enable the wound repair material prepared in the application to simultaneously have the functions of high adhesion, antibacterial ability, anti-inflammatory ability and biocompatibility. In addition, the addition of the polyvinylidene chloride, the quaternary ammonium cellulose and the dexamethasone can increase the spinnability of the material, and can enhance the flexibility, air permeability and tensile properties of the wound repair material.

[0027] According to the embodiment of the application, the quaternary ammonium cellulose is prepared by the following method: a mixed solution containing alkali, urea and water is mixed with cellulose to dissolve the cellulose, thereby obtaining a cellulose solution; a quaternary ammonium salt is mixed with the cellulose solution to perform a reaction, and after the reaction is completed, the reaction product is neutralized with an acid and dialyzed with a dialysis bag, thereby obtaining the quaternary ammonium cellulose.

[0028] According to the embodiment of the application, in the mixed solution containing alkali, urea and water, the mass fraction of the alkali is 10-15wt%, and the mass fraction of the urea is 6-10wt%. For example, the mass fraction of the alkali is 10wt%, 11wt%, 12wt%, 13wt%, 14wt%, 15wt% or any value between 10wt% and 15wt%, and the mass fraction of the urea is 6wt%, 7wt%, 8wt%, 9wt%, 10wt% or any value between 6wt% and 10wt%.

[0029] The alkali includes NaOH. The mixing of the mixed solution containing alkali, urea and water with cellulose is performed at a temperature of-10℃ to-4℃; for example, the temperature of the mixed solution containing alkali, urea and water mixed with cellulose is-10℃, -9℃, -8℃, -7℃, -6℃, -5℃, -4℃ or any value between-10℃ and-4℃.

[0030] The quaternary ammonium salt includes 2,3-epoxypropyltrimethylammonium chloride. The molar ratio of the quaternary ammonium salt to the cellulose in the cellulose solution is 10:1-12:1; for example, the molar ratio of the quaternary ammonium salt to the cellulose in the cellulose solution is 10:1, 11:1, 12:1 or any value between 10:1 and 12:1.

[0031] The quaternary ammonium salt reacts with the cellulose solution for 16-24 hours; for example, the quaternary ammonium salt reacts with the cellulose solution for 16 hours, 18 hours, 20 hours, 22 hours, 24 hours, or any value between 16-24 hours.

[0032] The acid includes hydrochloric acid.

[0033] According to an embodiment of the present application, the adhesion matrix solution includes 5-15 wt% of α-cyanoacrylate, 85-95 wt% of acetone.

[0034] For example, the content of α-cyanoacrylate in the adhesion matrix solution is 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, or any value between 5-15 wt%, and the content of acetone in the adhesion matrix solution is 85 wt%, 86 wt%, 87 wt%, 88 wt%, 89 wt%, 90 wt%, 91 wt%, 92 wt%, 93 wt%, 94 wt%, 95 wt%, or any value between 85-95 wt%.

[0035] According to an embodiment of the present application, the α-cyanoacrylate includes at least one of n-butyl α-cyanoacrylate and isooctyl α-cyanoacrylate, and the α-cyanoacrylate plays an anionic polymerization role on the tissue to increase the adhesion to the wound.

[0036] According to an embodiment of the present application, the functional additive solution includes 1-5 wt% of polyvinyl butyral, 1-5 wt% of quaternized cellulose, 1-5 wt% of dexamethasone, and 85-97 wt% of an organic solvent. The functional additive solution has good antibacterial and anti-inflammatory properties.

[0037] For example, the content of polyvinyl butyral in the functional additive solution is 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, or any value between 1-5 wt%, the content of quaternized cellulose in the functional additive solution is 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, or any value between 1-5 wt%, the content of dexamethasone in the functional additive solution is 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, or any value between 1-5 wt%, and the content of the organic solvent in the functional additive solution is 85 wt%, 86 wt%, 87 wt%, 88 wt%, 89 wt%, 90 wt%, 91 wt%, 92 wt%, 93 wt%, 94 wt%, 95 wt%, 96 wt%, 97 wt%, or any value between 85-97 wt%.

[0038] According to the embodiments of the present application, the weight average molecular weight Mw of the polyvinyl butyral is 40000-70000. If the weight average molecular weight Mw of the polyvinyl butyral is too small, the viscosity of the functional additive solution is too low, and the solution cannot be spun; if the weight average molecular weight Mw of the polyvinyl butyral is too large, the viscosity of the functional additive solution is too high, and the spinning effect is poor.

[0039] According to the embodiments of the present application, the organic solvent comprises ethanol.

[0040] In some embodiments, the double-needle array electrospinning of the adhesive matrix solution and the functional additive solution comprises: using a double-needle array electrospinning device, feeding the adhesive matrix solution and the functional additive solution into two needles respectively, giving a double-needle array after blending and then electrospinning to obtain the wound repair material.

[0041] According to the embodiments of the present application, the double-needle array electrospinning is performed under the following conditions: the running rate is 10-20ul / min, the voltage is 10-20KV, and the distance from the receiving tissue surface is 5cm-15cm.

[0042] For example, the double-needle array electrospinning is performed under the following conditions: the running rate is 10ul / min, 15ul / min, 20ul / min, or any value between 10-20ul / min, the voltage is 10KV, 15KV, 20KV, or any value between 10-20KV, and the distance from the receiving tissue surface is 5cm, 10cm, 15cm, or any value between 5-15cm.

[0043] In some embodiments, the specific conditions for electrospinning of the two needles are the same.

[0044] The present application also provides a wound repair material prepared by the preparation method of the wound repair material described above.

[0045] The embodiments of the present application will be described in detail below with specific examples, but those skilled in the art will understand that the following examples are only for illustration of the present application, and should not be regarded as limiting the scope of the present application. If the specific conditions are not specified in the examples, the conventional conditions or the conditions recommended by the manufacturer are used. If the reagents or instruments used are not specified by the manufacturer, they are all conventional products that can be purchased on the market.

[0046] Preparation of quaternary ammonium cellulose: A mixed solution of 190 g of NaOH, urea and water was prepared, wherein the mass fraction of NaOH in the mixed solution was 12 wt%, and the mass fraction of urea was 8.5 wt%; the mixed solution of NaOH, urea and water was cooled in a -5℃ ice-salt bath, and then 10 g of cellulose (polymerization degree 500) was added and stirred rapidly to obtain a transparent cellulose solution. The ultracentrifuge was operated at 10000 r / min and 15℃ for 30 min. The cellulose solution did not change before and after centrifugation, and there was no micellar precipitation and fiber.

[0047] Quaternary ammonium salt reaction: 2,3-epoxypropyl trimethylammonium chloride and cellulose solution were reacted at a molar ratio of 12:1 for 16h, the reactants were neutralized with hydrochloric acid, and dialysis bags were used for dialysis (8000) to obtain quaternized cellulose.

[0048] The synthesis route of quaternized cellulose is as follows: .

[0049] Example 1 Example 1 provides a wound repair material, and the preparation method thereof comprises: 10 wt% of n-butyl α-cyanoacrylate, 90 wt% of acetone were mixed to obtain an adhesion matrix solution; 5 wt% of polyvinyl butyral (weight average molecular weight Mw is 40000~70000), 1 wt% of quaternized cellulose, 1 wt% of dexamethasone, 93 wt% of ethanol were mixed to obtain a functional additive solution; An electrospinning device with double needle array was used to deliver the adhesion matrix solution and the functional additive solution into two needles, and then electrospinning was carried out after blending of the double needle array. The specific conditions of electrospinning were as follows: the running rate was 16ul / min, the voltage was 15KV, and the distance from the receiving tissue surface was 10cm. The specific conditions of electrospinning of the two needles were the same. After electrospinning, the material was placed at room temperature for 10min.

[0050] Figure 1 a in the figure is the SEM image of the spinning of the adhesion matrix solution, Figure 1 b in the figure is the SEM image of the spinning of the functional additive solution, Figure 1 c in the figure is the SEM image of the wound repair material prepared in Example 1, which is Figure 1 It can be seen that the materials prepared by the adhesion matrix solution, the functional additive solution and the double needle solution of Example 1 all have good fiber morphology.

[0051] Example 2 Referring to the method of Example 1, other than Example 1, the difference is that the content of n-butyl α-cyanoacrylate in the adhesion matrix solution is 5wt%, and the content of acetone is 95wt%. The content of polyvinyl butyral in the functional additive solution is 1wt%, the content of quaternized cellulose is 1wt%, the content of dexamethasone is 1wt%, and the content of ethanol is 97wt%.

[0052] Example 3 Referring to the method of Example 1, other than Example 1, the difference is that the content of n-butyl α-cyanoacrylate in the adhesion matrix solution is 15wt%, and the content of acetone is 85wt%. The content of polyvinyl butyral in the functional additive solution is 5wt%, the content of quaternized cellulose is 5wt%, the content of dexamethasone is 5wt%, and the content of ethanol is 85wt%.

[0053] Example 4 Referring to the method of Example 1, other than Example 1, the difference is that the content of polyvinyl butyral in the functional additive solution is 3wt%, the content of quaternized cellulose is 3wt%, the content of dexamethasone is 3wt%, and the content of ethanol is 91wt%.

[0054] Example 5 Referring to the method of Example 1, other than Example 1, the difference is that the specific conditions of electrospinning are as follows: the running rate is 10ul / min, the voltage is 10KV, and the distance from the receiving tissue surface is 5cm.

[0055] Example 6 Referring to the method of Example 1, other than Example 1, the difference is that the specific conditions of electrospinning are as follows: the running rate is 20ul / min, the voltage is 20KV, and the distance from the receiving tissue surface is 15cm.

[0056] Example 7 Referring to the method of Example 1, other than Example 1, the difference is that the specific conditions of electrospinning are as follows: the running rate is 15ul / min, the voltage is 15KV, and the distance from the receiving tissue surface is 10cm.

[0057] Comparative Example 1 The same formula as Example 1 is used to prepare the adhesion matrix solution and the functional additive solution. The adhesion matrix solution and the functional additive solution are mixed to directly undergo a polymerization curing reaction, which cannot be spun.

[0058] Performance test (1) In vitro drug release efficiency test The in vitro drug release performance of the wound repair materials prepared in Examples 1-7 was evaluated.

[0059] The films in the middle part of the wound repair materials prepared in Examples 1-7 with a size of 1x3 cm were respectively placed in 50 ml of PBS, and 3 ml of PBS was respectively taken at 1 h, 2 h, 3 h, 6 h, 12 h, 24 h, 48 h and 96 h, and 3 ml of PBS was timely supplemented after each sampling. After the sampling points were completed, the remaining residual material was completely dissolved, the drug concentration of dexamethasone in the solution was determined, and the drug release curve was plotted after accumulation.

[0060] Figure 2 The drug cumulative release curve of the wound repair material of Example 1 is as follows: Figure 2 It can be seen that the wound repair material of Example 1 can achieve a large amount of drug release (about 78%) within 50 h, and can quickly achieve anti-inflammatory effect.

[0061] The wound repair materials of Examples 2-7 can also achieve a large amount of drug release in a short time, and have excellent anti-inflammatory effect.

[0062] (2) In vitro bacteria isolation and antibacterial performance test The in vitro bacteria isolation and antibacterial performance of the wound repair materials of Examples 1-7 were evaluated.

[0063] The in vitro bacteria isolation and antibacterial performance of the wound repair materials of Examples 1-7 were evaluated.

[0064] Blood plate bacteriostatic ring method: the concentration of the bacterial solution was 1x10 6 CFU / mL, and the culture was carried out at 37°C for 24 hours, and whether a ring fell was observed; The bacteriostatic rate was calculated by the OD600 method (determined by a spectrophotometer), and the formula was (the OD600 value of the control group-the OD600 value of the experimental group) / the OD600 value of the control groupx100%.

[0065] All operations need to be completed aseptically in a biological safety cabinet, the concentration of the bacterial solution needs to be accurately controlled, each group has 3 biological repeats, the data is expressed as mean±standard deviation, and t test is used for analysis.

[0066] Figure 3 is a comparison chart of the in vitro bacteria isolation performance of the wound repair material of Example 1 (experimental group) and the control group on Escherichia coli, Figure 3 The left side is a chart of the in vitro bacteria isolation performance of the wound repair material of Example 1 on Escherichia coli, Figure 3 The right side is a chart of the in vitro bacteria isolation performance of the control group on Escherichia coli. FromFigure 3 It can be seen that no bacterial colonies grew after adding the wound repair material of Example 1. This shows that the wound repair material of Example 1 exhibited good bacteria isolation performance on E. coli.

[0067] Bacterial colonies grew after adding the wound repair materials of Examples 2-7, and the wound repair materials of Examples 2-7 had good bacteria isolation performance on E. coli.

[0068] Figure 4 is a comparison chart of OD600 of the control group and the wound repair material of Example 1 (experimental group) after adding E. coli, from which Figure 4 It can be seen that the bacteriostatic rate of the wound repair material of Example 1 on E. coli was 93.75%.

[0069] The wound repair materials of Examples 2-7 had a high bacteriostatic rate on E. coli.

[0070] Figure 5 is a comparison chart of the in vitro bacteria isolation performance evaluation of the control group and the wound repair material of Example 1 (experimental group) on S. aureus, Figure 5 the left side is a chart of the in vitro bacteria isolation performance evaluation of the wound repair material of Example 1 (experimental group) on S. aureus, Figure 5 and the right side is a chart of the in vitro bacteria isolation performance evaluation of the control group on S. aureus. From which Figure 5 It can be seen that no bacterial colonies grew after adding the wound repair material of Example 1. This shows that the wound repair material of Example 1 exhibited good bacteria isolation performance on S. aureus.

[0071] Bacterial colonies grew after adding the wound repair materials of Examples 2-7, and the wound repair materials of Examples 2-7 had good bacteria isolation performance on S. aureus.

[0072] Figure 6 is a comparison chart of OD600 of the control group and the wound repair material of Example 1 (experimental group) after adding S. aureus, from which Figure 6 It can be seen that the bacteriostatic rate of the wound repair material of Example 1 on S. aureus was 90.15%.

[0073] The wound repair materials of Examples 2-7 had a high bacteriostatic rate on S. aureus.

[0074] (3) Adhesion test The adhesion of the wound repair materials of Examples 1-7 and traditional spun materials (polyvinyl butyral, Mw 4-7W) was evaluated.

[0075] The test was performed according to the following standard: YYT 0729.1-2009 Adhesion performance test method for tissue adhesives Part 1: lap-shear tensile load bearing strength.

[0076] The test results are shown in Table 1.

[0077] Table 1. Comparison of Adhesion Strength Tests between Wound Repair Material and Traditional Spinning Material in Example 1

[0078] As can be seen from Table 1, the wound repair material of Example 1 has higher adhesion than the traditional spinning material polyvinyl butyral.

[0079] The wound repair materials in Examples 2-7 have high adhesive strength.

[0080] (4) Anti-inflammatory efficacy test The wound repair materials from Examples 1-7 were applied to a rat model of full-layer dermal injury and infection to test their anti-inflammatory effects.

[0081] Experimental Procedure: SPF-grade male SD rats (200-250 g) were acclimatized for 7 days, then anesthetized with 10% chloral hydrate (3 mL / kg) via intraperitoneal injection. The back was shaved and disinfected three times with alternating iodine and alcohol. A full-thickness skin defect (reaching the fascia layer) was created beside the spine using a scalpel (10 mm in diameter, error ≤0.1 mm). After hemostasis with sterile cotton swabs, 100 μL of Staphylococcus aureus solution (1×10⁻⁶) was injected. 7 CFU (Cellular Fuel) was evenly applied to the wound; patients were housed individually after surgery. Group interventions were initiated on postoperative day 3: the control group had sterile gauze covering the infected wound (changed daily), the model group had no treatment for the infected wound, and the experimental group had the wound repair material from Examples 1-7 covered on the infected wound (changed daily). On day 14, serum levels of inflammatory factors such as IL-6, IL-1β, TNF-α, and IL-10 were measured using ELISA. Figure 7 In the figure, 'a' is a comparison of serum TNF-α, a inflammatory factor, in rats of the control group, model group, and experimental group (using the wound repair material from Example 1) after full-dermal infection and injury. Figure 7 Figure b in the figure is a comparison of serum anti-inflammatory factor IL-10 in rats after full-dermal infection and injury in the control group, model group, and wound repair material (experimental group) of Example 1. Figure 7 In the figure, 'c' is a comparison of serum inflammatory factor IL-6 in rats of the control group, model group, and experimental group (using the wound repair material from Example 1) after full-layer dermal infection and injury. Figure 7 In the figure, 'd' represents a comparison of serum inflammatory factor IL-1β in rats of the control group, model group, and experimental group (using the wound repair material from Example 1) after full-scale dermal infection and injury. Figure 7It can be seen that, compared with the control group and the model group, the wound repair material of Example 1 significantly reduces the levels of inflammatory factors IL-6, IL-1β and TNF-α, and increases the level of anti-inflammatory factor IL-10, showing excellent anti-inflammatory efficacy.

[0082] Compared with the control group and the model group, the wound repair material of Example 2-7 can significantly reduce the levels of inflammatory factors IL-6, IL-1β and TNF-α, and increase the level of anti-inflammatory factor IL-10, and the wound repair material of Example 2-7 has excellent anti-inflammatory efficacy.

[0083] Finally, it should be noted that: the above examples are only used to illustrate the technical solutions of the present application, but not to limit them; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that: it can still modify the technical solutions recorded in the foregoing examples, or make equivalent replacement for part or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application.

[0084] In addition, those skilled in the art can understand that, although some embodiments herein include certain features rather than other features included in other embodiments, the combination of features of different embodiments means to be within the scope of the present application and form different embodiments. For example, in the above claims, any one of the claimed embodiments can be used in any combination. The information disclosed in the background section is only intended to deepen the understanding of the general background of the present application, and should not be regarded as acknowledging or implying in any form that the information constitutes prior art known to those skilled in the art.

Claims

1. A method for preparing a wound repair material, characterized by, The application relates to a wound repair material and a preparation method thereof. An alpha-cyanoacrylate and acetone are mixed to obtain an adhesion matrix solution; Polyvinyl butyral, quaternary ammonium cellulose, dexamethasone and an organic solvent are mixed to obtain a functional additive solution; The adhesion matrix solution and the functional additive solution are subjected to double-needle array electrospinning to obtain the wound repair material.

2. The method for producing a wound repair material according to claim 1, wherein The quaternary ammonium cellulose is prepared by the following steps: A mixed solution containing alkali, urea and water is mixed with cellulose to dissolve the cellulose and obtain a cellulose solution; A quaternary ammonium salt is mixed with the cellulose solution to react, and after the reaction is completed, the reaction product is neutralized with acid and dialyzed with a dialysis bag to obtain the quaternary ammonium cellulose.

3. The method for producing a wound repair material according to claim 2, characterized by, In the mixed solution containing alkali, urea and water, the mass fraction of the alkali is 10-15 wt%, and the mass fraction of the urea is 6-10 wt%; The alkali comprises NaOH; The mixed solution containing alkali, urea and water is mixed with cellulose at a temperature of-10 DEG C to-4 DEG C; The quaternary ammonium salt comprises 2,3-epoxypropyltrimethylammonium chloride; The molar ratio of the quaternary ammonium salt to cellulose in the cellulose solution is 10:1-12:1; The quaternary ammonium salt is reacted with the cellulose solution for 16-24 hours; The acid comprises hydrochloric acid.

4. The method for producing a wound repair material according to claim 1, wherein The adhesion matrix solution comprises 5-15 wt% of alpha-cyanoacrylate and 85-95 wt% of acetone.

5. The method for producing a wound repair material according to claim 4, wherein The alpha-cyanoacrylate comprises at least one of n-butyl alpha-cyanoacrylate and isooctyl alpha-cyanoacrylate.

6. The method of preparing a wound repair material according to claim 1, wherein The functional additive solution comprises 1-5 wt% of polyvinyl butyral, 1-5 wt% of quaternary ammonium cellulose, 1-5 wt% of dexamethasone and 85-97 wt% of an organic solvent.

7. The method for producing a wound repair material according to claim 6, wherein The weight average molecular weight Mw of the polyvinyl butyral is 40000-70000.

8. The method for producing a wound repair material according to claim 6, wherein The organic solvent comprises ethanol.

9. The method of producing a wound repair material according to any one of claims 1 to 8, characterized in that, The double-needle array electrospinning is carried out under the following conditions: a running rate of 10-20 ul / min, a voltage of 10-20 KV and a distance from the receiving tissue surface of 5 cm-15 cm.

10. A wound repair material, characterized by, The wound repair material is prepared by the preparation method of the wound repair material according to any one of claims 1-9.

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