Intelligent suture line with synergistic electrical stimulation and drug release and preparation method of intelligent suture line

Abstract

The invention relates to the technical field of medical apparatus and instruments, in particular to an intelligent suture line with electrical stimulation and drug release synergism and a preparation method thereof. The preparation method of the intelligent suture line with synergistic electrical stimulation and drug release comprises the following steps: fully dissolving a high polymer in an organic solvent to obtain a high polymer solution; and mixing the conductive polymer nanoparticles, a stabilizer, a dopant and a micromolecular anti-inflammatory drug to obtain conductive polymer coated drug particles. Uniformly mixing with a high polymer solution to obtain an electrostatic spinning precursor solution; the electrostatic spinning precursor solution and a metal wire are prepared through an electrostatic spinning machine, and then the intelligent suture line is prepared. The prepared intelligent suture line generates inductive charges or alternating current under external stimulation based on a single-electrode mode of a friction nano-generator, realizes control of release of small-molecule drugs and also can generate an alternating electric field to realize electrical stimulation treatment, and can promote rapid healing of wounds under the mutual synergistic effect of the inductive charges and the alternating electric field.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and in particular to an intelligent suture with synergistic electrical stimulation and drug release and a preparation method thereof. Background Art

[0002] With the rapid increase in the number of surgical operations around the world, the market for medical sutures has also grown significantly. Especially in the healthcare and beauty industries, medical sutures have great market potential. Medical sutures have very important application ranges in various fields such as general surgery, plastic surgery, vascular surgery, cosmetic surgery, tissue engineering and dentistry. Medical sutures are a type of medical device that is often used to close wounds, tie and fix tissues in surgical operations. When human tissue is cracked due to incisions or other injuries, medical sutures can be used to treat and suture surgical wounds, thereby promoting and accelerating healing, so that no scars are formed after injury or surgery. Medical sutures, as an indispensable thread material in surgical operations, are usually made of fiber monofilaments, multifilaments, braided or twisted.

[0003] Although there are various types of medical sutures on the market, their functions are relatively simple, mainly used for wound suturing and fixation. In addition, wounds sutured with existing medical sutures are prone to bacterial infection, which is not conducive to wound healing and makes the wounds recover slowly after suture. Summary of the invention

[0004] In order to solve the problem in the prior art that wounds sutured with existing medical sutures are prone to bacterial infection, which is not conducive to wound healing, the present invention provides a method for preparing an intelligent suture with synergistic electrical stimulation and drug release.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is: a method for preparing an intelligent suture with synergistic electrical stimulation and drug release, which comprises the following steps: fully dissolving a polymer in an organic solvent to obtain a polymer solution with a mass fraction of 5% to 10%; subjecting conductive polymer nanoparticles, stabilizers, dopants and small molecule anti-inflammatory drugs to original emulsion polymerization to obtain conductive polymer-coated drug particles; uniformly mixing the conductive polymer-coated drug particles with the polymer solution to obtain an electrospinning precursor solution with a mass fraction of 0.5% to 1%; placing the prepared electrospinning precursor solution in a spray device, placing a metal wire as a nanofiber receiver in an electrospinning machine, and spraying the electrospinning precursor solution through the spray device. The electrospinning precursor liquid is sprayed onto the metal wire to obtain nanofibers loaded with the small molecule anti-inflammatory drug wrapped on the surface of the metal wire, namely the smart suture; the prepared smart suture is based on the single-electrode mode of the friction nanogenerator, and can generate induced charge or alternating current under the stimulation of external mechanical environmental conditions, thereby controlling the release process of the small molecule anti-inflammatory drug loaded on the nanofiber, and the released small molecule anti-inflammatory drug is used to reduce inflammation of the sutured wound; the smart suture can also generate an alternating electric field under the stimulation of external mechanical conditions, which can accelerate cell differentiation, promote fibroblast growth, and realize electrical stimulation therapy; under the synergistic effect of releasing small molecule anti-inflammatory drugs and electrical stimulation therapy, the healing of the wound is accelerated.

[0006] As a further improvement of the above scheme, the small molecule anti-inflammatory drug is one or more of berberine, quaternary ammonium salts, and silver nanoparticles.

[0007] As a further improvement of the above solution, the polymer is one or more of PLA, PLGA, PCL, PGA, and PLLA.

[0008] As a further improvement of the above solution, the conductive polymer nanoparticles are one or more of PANI, PEDOT, and PPy.

[0009] As a further improvement of the above scheme, the stabilizer is sorbitan monooleate.

[0010] As a further improvement of the above solution, the dopant is sodium dodecylbenzene sulfonate.

[0011] As a further improvement of the above solution, the external mechanical condition stimulation is through mechanical force acting on the smart suture thread or through ultrasonic treatment of the smart suture thread.

[0012] As a further improvement of the above solution, the metal wire is one of magnesium, iron, zinc, a magnesium alloy, an iron alloy or a zinc alloy.

[0013] As a further improvement of the above solution, the length of the metal wire is 20 cm.

[0014] As a further improvement of the above scheme, the parameters of the electrospinning machine in the process of preparing the smart suture thread are: the distance between the needle of the injection device and the metal wire is 15 cm; the flow rate during the spinning process is 0.5 mL / h, and the applied voltage is 15 kV.

[0015] An intelligent suture with synergistic effects of electrical stimulation and drug release is prepared by the above preparation method.

[0016] As a further improvement of the above scheme, the smart suture thread is a skin-core structure, the smart suture thread includes a core layer and a skin layer, the core layer is a metal wire, the skin layer is nanofibers, and the nanofibers are uniformly wrapped on the surface of the metal wire; the nanofibers are formed by the electrospinning precursor solution attaching to the metal wire through the electrospinning machine.

[0017] As a further improvement of the above solution, the nanofibers are loaded with small molecule anti-inflammatory drugs, and the small molecule anti-inflammatory drugs are used to reduce inflammation in wounds after suture.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] (1) The intelligent suture with synergistic electrical stimulation and drug release prepared by the preparation method of the present invention is based on the single-electrode mode of the friction nanogenerator, and can transfer charge under the stimulation of external mechanical conditions, thereby promoting the release of small molecule anti-inflammatory drugs in the nanofibers and realizing the on-demand supply of drugs. The release of small molecule anti-inflammatory drugs can also provide sustained-release anti-inflammatory effects on wounds, and then cooperate with conductive polymer nanoparticles to sterilize bacteria in the wound, thereby promoting rapid wound healing. In addition, the intelligent suture will also generate an alternating electric field under the stimulation of external mechanical conditions, which can accelerate cell differentiation, promote fibroblast growth, realize electrical stimulation therapy, and accelerate wound healing. Therefore, the intelligent suture prepared by the present invention can further accelerate wound healing under the synergistic effect of releasing small molecule anti-inflammatory drugs and electrical stimulation therapy.

[0020] (2) The intelligent suture with synergistic electrical stimulation and drug release prepared by the present invention can generate an alternating electric field under external stimulation, and the generated alternating electric field can stimulate cell differentiation, thereby promoting wound healing and increasing the speed of wound healing.

[0021] (3) The smart suture with synergistic electrical stimulation and drug release prepared by the present invention has the functions of electrically controlled drugs and electrical stimulation. It can transfer charges under the stimulation of external mechanical conditions, thereby promoting the release of drugs in nanofibers and realizing the on-demand supply of drugs; at the same time, the alternating electric field generated can also stimulate cell differentiation and promote the proliferation and migration of fibroblasts. Under the synergistic effect of electrically controlled drugs and electrical stimulation therapy, it can promote rapid healing of wounds.

[0022] (4) The preparation method of the intelligent suture with synergistic electrical stimulation and drug release in the present invention is simple, the structure is novel, and the functions are diverse. It solves the problem of single function of existing products, improves the treatment effect, and has broad application prospects in the field of clinical medicine. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is a schematic diagram of the intelligent suture provided by the present invention.

[0024] Figure 2 This is a cross-sectional schematic diagram of the intelligent suture provided by the present invention.

[0025] Figure 3 This is an electron microscope image of the intelligent suture thread prepared in Example 3 of the present invention.

[0026] Figure 4 This is a schematic diagram of the results of the electrical output performance test of the smart suture prepared in Example 3 of the present invention.

[0027] Figure 5 It is an absorbance curve diagram of dexamethasone sodium phosphate of different concentrations at the 242nm absorption peak in the present invention.

[0028] Figure 6 This is the standard curve for the release of the small molecule drug dexamethasone sodium phosphate in the present invention.

[0029] Figure 7 This is a graph showing the relationship between the release of the drug of the smart suture of Example 3 of the present invention and the change over time when an external force is applied and when no external force is applied.

[0030] Figure 8 The cell viability of L929 cells in the immersion solution of the blank group, commercial suture and intelligent suture in the present invention was measured by MTT method, and the morphology of the cells was observed by fluorescent fiber microscope.

[0031] Fig. 9 The blank group, commercial suture and intelligent suture in the present invention were respectively measured for the survival rate of L929 cells in the immersion solution by MTT method.

[0032] Fig.10Schematic diagram of the results of antibacterial performance testing of commercial sutures and smart sutures in the present invention on Staphylococcus aureus and Escherichia coli, respectively.

[0033] Fig.11 This is the effect of the electrical signals generated by the blank group, commercial sutures and smart sutures in the present invention on cell growth after being stimulated by external mechanical conditions.

[0034] Fig.12 This is the effect of the electrical signals generated by the blank group, commercial sutures and smart sutures in the present invention on the OD value of cells after being stimulated by external mechanical conditions.

[0035] Fig.13 This is the effect of the electrical signals generated by the blank group, commercial sutures and intelligent sutures in the present invention after being stimulated by external mechanical conditions on the proliferation rate of cells.

[0036] Fig.14 Schematic diagram of wound changes in animal experiments in which wounds were sutured using commercial sutures and the suture of Example 3.

[0037] In the figure: 1. cortex; 11. small molecule anti-inflammatory drug; 2. core layer. DETAILED DESCRIPTION

[0038] The present invention is further described below in conjunction with specific implementation methods. It should be noted that, under the premise of no conflict, the various embodiments or technical features described below can be arbitrarily combined to form a new embodiment.

[0039] In the description of the present invention, it should be noted that for directional words, such as the terms "center", "lateral", "longitudinal", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise" and the like indicating directions and positional relationships are based on the directions or positional relationships shown in the drawings, which are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and cannot be understood as limiting the specific protection scope of the present invention. The terms "first", "second", etc. in the specification and claims of the present invention are used to distinguish similar objects, and are not necessarily used to describe a specific order or sequence. The terms "including" and "having" in the specification and claims of the present invention and any variations thereof are intended to cover non-exclusive inclusions, for example, a process, method, system, product or device including a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or inherent to these processes, methods, products or devices.

[0040] Example 1

[0041] An embodiment of the present invention provides a method for preparing a smart suture with synergistic electrical stimulation and drug release, comprising the following steps:

[0042] (1) Fully dissolving a polymer in an organic solvent to obtain a polymer solution having a mass fraction of 5% to 10%.

[0043] (2) Conductive polymer nanoparticles, stabilizers, dopants and small molecule anti-inflammatory drugs are subjected to raw emulsion polymerization to obtain drug particles coated with conductive polymers.

[0044] (3) The drug particles wrapped by the conductive polymer are uniformly mixed with 5% to 10% by weight of the polymer solution to obtain an electrospinning precursor solution with a weight fraction of 0.5% to 1%.

[0045] (4) placing the prepared electrospinning precursor solution with a mass fraction of 0.5% to 1% in the injection device of the electrospinning machine, placing a metal wire as a nanofiber receiver in the electrospinning machine, and spraying the electrospinning precursor solution onto the metal wire through the injection device to obtain nanofibers loaded with the small molecule anti-inflammatory drug wrapped on the surface of the metal wire, i.e., the smart suture.

[0046] The prepared smart suture is based on the single-electrode mode of the friction nanogenerator, and can transfer charge under the stimulation of external mechanical conditions, thereby controlling the release of the small molecule anti-inflammatory drugs loaded on the nanofibers, and the released small molecule anti-inflammatory drugs are used to reduce inflammation in the wound after suture. In addition, under the stimulation of external mechanical conditions, the smart suture can also generate an alternating electric field, thereby promoting the proliferation and migration of fibroblasts, achieving electrical stimulation therapy, and thus accelerating wound healing. Under the synergistic effect of the released small molecule anti-inflammatory drugs and the generation of the alternating electric field, the rapid healing of the wound can be effectively promoted.

[0047] The smart suture prepared in this embodiment has the functions of controlling drug release, anti-inflammatory and antibacterial, and promoting wound healing. It solves the problem of single function of existing products, adopts electrical stimulation treatment, improves the treatment effect, and has a wide range of application backgrounds in the clinical medical field.

[0048] Nanofibers with smooth and uniform surfaces and loaded with small molecule drugs are prepared through steps (1) to (4) and are uniformly wrapped on the metal wires, thereby forming an intelligent suture with a skin-core structure.

[0049] The small molecule anti-inflammatory drug can be one or more of berberine, quaternary ammonium salts, and silver nano-ions.

[0050] It is understandable that the small molecule anti-inflammatory drugs are not limited to the drugs mentioned above, but can also be other drugs with antibacterial and anti-inflammatory functions.

[0051] The polymer may be one or more of PLA, PLGA, PCL, PGA, and PLLA.

[0052] It is understandable that the polymer is not limited to the above-mentioned materials, but can also be extended to natural polymer materials with good biocompatibility.

[0053] The conductive polymer nanoparticles may be one or more of PANI, PEDOT, and PPy.

[0054] The stabilizer is sorbitan monooleate.

[0055] The dopant is sodium dodecylbenzene sulfonate.

[0056] The external mechanical condition stimulation can be achieved by acting mechanical force on the smart suture thread, or by performing ultrasonic treatment on the smart suture thread.

[0057] The metal wire is a bioabsorbable conductive metal wire that can be biodegraded. The metal wire can be one of magnesium, iron, zinc, magnesium alloy, iron alloy or zinc alloy.

[0058] The length of the metal wire may be 20 cm.

[0059] The injection device can be a syringe with a steel needle.

[0060] The metal wire is biodegradable.

[0061] The parameters of the electrospinning machine in the process of preparing the intelligent suture are as follows: the distance between the needle of the injection device and the metal wire is 15 cm; the flow rate during the spinning process is 0.5 mL / h, and the applied voltage is 15 kV.

[0062] The smart suture prepared by the above-mentioned preparation method has metal wires and conductive polymer nanoparticles in its raw materials, so that the prepared smart suture is based on the single-electrode mode of the friction nanogenerator, and can transfer charge under the contact stimulation of the external environment, thereby promoting the release of small molecule anti-inflammatory drugs in the nanofibers and realizing the on-demand supply of small molecule anti-inflammatory drugs. The release of small molecule anti-inflammatory drugs can avoid bacterial infection of wounds and promote wound healing. In addition, the alternating electric field can accelerate cell differentiation, promote fibroblast growth, realize electrical stimulation therapy, and promote wound healing. By controlling drug release and generating an alternating electric field to realize electrical stimulation therapy under the stimulation of external mechanical conditions, the wound healing speed can be further accelerated under the synergistic effect of drug release and electrical stimulation therapy. At the same time, the smart suture not only has good biocompatibility, but also controls its degradation cycle to meet application requirements by selecting bioabsorbable materials with different degradation cycles. In general, the preparation method of the smart suture is simple, novel in structure, and diverse in functions. It solves the problem of single function of existing products, improves the treatment effect, and has broad application prospects in the field of clinical medicine.

[0063] Example 2

[0064] A smart suture with synergistic effects of electrical stimulation and drug release is prepared by the method described in Example 1. The prepared smart suture can be Figure 1 shown.

[0065] Please refer to Figure 1 and Figure 2 , a smart suture with synergistic electrical stimulation and drug release, which is a skin-core structure. The smart suture comprises a core layer 2 and a skin layer 1, the core layer 2 is a metal wire, the skin layer 1 is a nanofiber, and the nanofiber is uniformly wrapped on the surface of the metal wire.

[0066] The nanofibers are formed by the electrospinning precursor solution being attached to the metal wire through the electrospinning machine.

[0067] The nanofibers are loaded with small molecule anti-inflammatory drugs 11, and the small molecule anti-inflammatory drugs 11 are used to reduce inflammation in wounds after suture.

[0068] The metal wire is a bioabsorbable conductive metal wire that can be biodegraded. The metal wire can be one of magnesium, iron, zinc, magnesium alloy, iron alloy or zinc alloy.

[0069] The intelligent suture is based on the single-electrode mode of the friction nanogenerator. It can transfer charge under the stimulation of external mechanical conditions, thereby promoting the release of small molecule anti-inflammatory drugs 11 in the nanofibers and realizing the on-demand supply of drugs. The release of small molecule anti-inflammatory drugs 11 can avoid bacterial infection of wounds and promote wound healing. In addition, the alternating electric field can stimulate cell differentiation and promote wound healing. Therefore, the intelligent suture of this embodiment can not only control drug release under the stimulation of external mechanical conditions, but also realize electrical stimulation therapy by generating an alternating electric field. Under the synergistic effect of controlling drug release and electrical stimulation therapy, the healing speed of the wound sutured by the intelligent suture prepared by this embodiment can be improved, so that the intelligent suture prepared by this embodiment can accelerate the healing of wounds. At the same time, the intelligent suture not only has good biocompatibility, but also can control its degradation cycle to meet application requirements by selecting bioabsorbable materials with different degradation cycles.

[0070] In this embodiment, the smart suture thread can also be prepared by a wet spinning method.

[0071] Example 3

[0072] This embodiment uses the preparation method of Example 1 and selects the raw materials in Example 1 to prepare the smart suture. The specific preparation process is as follows:

[0073] (1) 5 g of polymer PCL was fully dissolved in 95 g of organic solvent HFIP to obtain a polymer solution with a mass fraction of 5%.

[0074] (2) Conductive polymer nanoparticles PPy, sorbitan monooleate, sodium dodecylbenzene sulfonate and dexamethasone sodium phosphate are subjected to raw material emulsion polymerization to obtain conductive polymer-coated drug particles.

[0075] (3) 1 g of the drug particles coated with the conductive polymer was mixed evenly with 99 g of the polymer solution to obtain an electrospinning precursor solution with a mass fraction of 1%.

[0076] (4) Take 5 mL of the prepared electrospinning precursor solution with a mass fraction of 1% and place it in a syringe with a steel needle in the electrospinning machine, select an implantable and biodegradable magnesium alloy with a length of 20 cm as a nanofiber receiver and place it in the electrospinning machine, and adjust the experimental parameters of the electrospinning machine as follows: the distance from the steel needle tip to the nanofiber receiver is 15 cm, the spinning flow rate is 0.5 mL / h, and the applied voltage is 15 kV. The electrospinning precursor solution is sprayed onto the magnesium alloy through the syringe to obtain nanofibers loaded with the small molecule anti-inflammatory drug wrapped on the surface of the magnesium alloy, that is, the smart suture.

[0077] The prepared smart suture was placed under a scanning electron microscope for observation. Figure 3 Through observation Figure 3 It can be seen that the prepared nanofibers have a smooth and uniform surface and are loaded with small molecule anti-inflammatory drugs. The nanofibers are uniformly wrapped on the magnesium alloy, thereby forming a skin-core structured intelligent suture.

[0078] The prepared smart suture thread has a skin-core structure with a layer of membrane wrapped around the yarn.

[0079] 1. Study on the electrical response performance of the smart suture prepared in Example 3

[0080] The specific steps are: build a mechatronics test device, which includes a linear motor, an electrometer, an acquisition card, a labview test platform and a sample fixing table. The smart suture prepared in Example 3 is attached to the sample fixing table, and a linear motor with a contact material (such as acrylic, FEP, etc.) is periodically applied to the smart suture under a certain load (5-10N). The electrometer is used to accurately measure the contact and separation process between the contact material and the smart suture. The open circuit voltage, short circuit current, and electrical response performance indicators of the tested smart suture under a certain load or non-contact action are measured, and visualized through the labview program. The following is obtained: Figure 3 The electrical output performance test results.

[0081] pass Figure 4 It can be seen that the prepared smart suture thread has signal feedback in terms of open circuit voltage, short circuit current and transferred charge under the stimulation of external mechanical conditions. The open circuit voltage, short circuit current and transferred charge are indicators of electrical output performance. This shows that the prepared smart suture needle can output electrical signals under the stimulation of external mechanical conditions, thereby providing electrical stimulation therapy.

[0082] 2. Study on the Electroinduced Drug Release of the Smart Suture Prepared in Example 3

[0083] Under the stimulation of external mechanical conditions, the prepared smart suture changes its internal charge due to the coupling effect of electrostatic induction and contact electrification, and the binding strength between its conductive polymer nanoparticles and small molecule anti-inflammatory drugs changes, resulting in the release of small molecule anti-inflammatory drugs. This process can be measured using an ultraviolet spectrophotometer to measure the drug loading of the smart suture and the release behavior of small molecule anti-inflammatory drugs.

[0084] Since the small molecule anti-inflammatory drug used in the smart suture prepared in Example 3 is dexamethasone sodium phosphate, we first prepared dexamethasone sodium phosphate solutions of different concentrations and measured the absorbance at the characteristic absorption peak of 242 nm using an ultraviolet spectrophotometer (e.g. Figure 5 As shown), and draw the release standard curve of dexamethasone sodium phosphate drug (as shown Figure 6 shown).

[0085] By drawing Figure 6 The purpose of the drug release standard curve is to convert the absorbance into concentration and then calculate the amount of drug released.

[0086] Secondly, external force (such as mechanical force or ultrasound) was applied to the smart suture of Example 3 to measure the relationship between the release of the drug and time. Figure 7 shown.

[0087] pass Figure 7 It can be seen that Figure 7 The blue line in the middle is the relationship between the amount of drug released by the smart suture of Example 3 under external mechanical stimulation and time. Figure 7 The red line in the middle is the relationship between the amount of drug released and time without external mechanical stimulation of the smart suture in Example 3. By comparing the two curves, it can be seen that the electrical stimulation generated by the smart suture under external mechanical stimulation can accelerate the release of the drug, thereby achieving regulation of the release of the drug.

[0088] 3. Study on the biocompatibility of the smart suture prepared in Example 3

[0089] In this study, the extract method was mainly used to determine the biocompatibility of the prepared smart suture.

[0090] The specific operation steps are as follows: (11) The smart suture of Example 3 and the commercial suture are sterilized by ultraviolet light respectively, and the sterilization time is at least 4 hours.

[0091] (12) After sterilization, the smart suture and the commercial suture were immersed in culture medium, respectively, and the culture medium was cultured in a biochemical incubator at 37°C for 24 hours to obtain an extract.

[0092] (13) L929 cells were seeded in a 96-well plate, with approximately 5,000 cells per well. After the cells adhered to the plate (approximately 12 hours), the original culture medium was discarded, and the extract from step (12) was added to culture the cells, and the OD value was measured.

[0093] (14) After incubating the cells with the extract of step (12) for 24 hours, the cell viability was assessed using a live / dead cell staining method.

[0094] In the above operation steps, the extract in step (12) can be obtained according to the national standard ISO 10093-12. Specifically, the approximate ratio of the solute to the culture medium is 0.1 g / mL, that is, 0.01 g of the smart suture is immersed in 5 mL of the culture medium.

[0095] Wherein, in step (13), the OD value is determined by the MTT method. The operation of determining the OD value by the MTT method is as follows: add 20 μL of MTT solution to each well (add 10 μL, 5 mg / mL MTT to every 100 μL culture medium, i.e., 0.5% MTT), continue to culture for 4-5 hours, and then remove the supernatant. The blue crystalline formazan cannot be sucked away during the removal of the supernatant. Then add 150 μL of dimethyl sulfoxide to each well and shake for 10 minutes to fully dissolve the crystals. Then use an enzyme-linked immunosorbent assay to measure the absorbance of each well at a wavelength of 490 nm.

[0096] MTT is prepared to a concentration of 5 mg / mL. PBS or saline solution is used as the solvent. During the preparation and storage of MTT solution, the container needs to be wrapped with aluminum foil.

[0097] In addition, when the OD value was determined by the MTT method, a blank control experiment was also conducted and the biocompatibility of commercial sutures was also tested.

[0098] Among them, the principle of live / dead cell staining is as follows: SYTO-9 is a green fluorescent nucleic acid dye that can penetrate the cell membrane and can be used to stain RNA and DNA of live and dead eukaryotic cells, as well as Gram-positive and Gram-negative bacteria. PI is a nuclear stain that can stain DNA and releases red fluorescence after embedding into double-stranded DNA. PI cannot penetrate the intact cell membrane, but it can penetrate the damaged cell membrane of late apoptotic cells and dead cells and stain the cell nucleus red.

[0099] Through the above operation, we can get Figure 8 and Fig. 9 result. Figure 8 The blank group, commercial sutures, and smart sutures were tested for cell viability of L929 cells in the immersion solution using the MTT method, and the cell morphology was observed using a fluorescent fiberscope. In the MTT method, the cytoplasm of live cells is green fluorescent, and the nuclei of dead cells are red fluorescent. Figure 8 It can be seen that the number of live cells in the smart suture experiment is significantly higher than the number of dead cells, and the amount of live cells in the smart suture is higher than that in the commercial suture. Fig. 9 The blank group, commercial sutures, and smart sutures were used to measure the survival rate of L929 cells in the immersion solution using the MTT method. Figure 8It can be seen that the cell survival rate of the smart suture experiment can reach more than 98%, which is comparable to commercial sutures. Figure 8 and Fig. 9 It can be seen that the smart suture prepared in Example 3 has good biocompatibility.

[0100] 4. Comparison of the antibacterial properties of the smart suture prepared in Example 3 and the commercial suture

[0101] The specific test method is as follows: Gram-negative and Gram-positive representative bacteria Escherichia coli and Staphylococcus aureus were selected to evaluate the antibacterial properties of the samples. 2 cm of the smart suture prepared in Example 3 was decomposed and immersed in a 10% concentration of 5 Escherichia coli and Staphylococcus aureus with CFU / mL were co-cultured at 37°C for 4 h and then diluted 100 times. 100 μL of the bacterial solution after co-culture was spread on an agar plate and then incubated at 37°C for 12 h, and the number of colonies was observed and counted.

[0102] A control group was prepared, and the testing method of the control group was the same as that of the smart suture, except that commercial sutures were used in the control group.

[0103] The experimental results obtained from the above two groups of experiments are as follows Fig.10 shown.

[0104] pass Fig.10 It can be seen that the colony count of the smart suture is significantly reduced compared with the control group. Through calculation, it can be obtained that the bactericidal rate of the smart suture against Staphylococcus aureus is 67.4%, and the bactericidal rate against Escherichia coli is 81.1%. This shows that the smart suture has good antibacterial properties.

[0105] 5. Evaluation and comparison of the therapeutic effects of the smart suture prepared in Example 3 and the commercial suture on wound suture

[0106] L929 cells (from the Cell Bank of the Chinese Academy of Sciences, Shanghai, China) were seeded in a 24-well plate with standard culture medium at a density of 10,000 cells per well and cultured for 4 to 8 hours. After the cells adhered to the wall, 5 smart sutures with a length of 14 mm were placed in parallel in the wells. After 1, 3, and 5 days of co-culture, MTT assay was performed according to the standard protocol. Finally, the OD value was determined. Ultrasonic waste contact was used to stimulate the wound suture for 15 minutes. The smart sutures under external mechanical conditions underwent charge transfer, and the differentiation state of the cells and the healing of the wound were observed.

[0107] At the same time, a blank control group 1 and a commercial suture control group 2 were set up, and the therapeutic effect on the wound was evaluated by comparing the blank control group 1 and the commercial suture control group 2 respectively.

[0108] Through the above three groups of experiments, we can get Figures 11 to 13 The result is Fig.11 The figure shows the differentiation status of cells in three groups of experiments on different days. Fig.12 The OD values ​​of cells grown in three groups of experiments on different days. Fig.13 The cell proliferation rates of three groups of experiments on different days.

[0109] pass Figures 11 to 13 It can be seen that the alternating electric field generated by the smart suture under the action of ultrasound can lead to the largest number of cell proliferation after 5 days; and the cell proliferation rate is about 135%, which is much higher than the cell proliferation rate of commercial sutures. This shows that the smart suture prepared by the present invention can further promote cell proliferation compared with existing commercial sutures, thereby accelerating wound healing. In addition, under the external stimulation of ultrasound, the smart suture undergoes charge transfer, thereby controlling the release of small molecule anti-inflammatory drugs loaded on the nanowire fibers, thereby reducing inflammation of the wound. It can be obtained that the smart suture can control the release of small molecule drugs under external stimulation; and generate an alternating electric field to achieve electrical stimulation therapy, which can effectively promote the proliferation and migration of fibroblasts; under the synergistic effect of the two, it can promote rapid healing of wounds.

[0110] In addition, during the research process, the smart suture of Example 3 and commercial suture were also used for animal experiments. The specific operation of the animal experiment is as follows: two mice were selected, and a linear wound of approximately 2 cm was cut on the back of each mouse, and bacteria were injected into the wound to construct a wound infection model. One of the mice was sutured with commercial sutures, and the other mouse was sutured with smart sutures. The suturing process was controlled to sew 6 stitches, and the wound was ultrasonically stimulated for 15 minutes every day, and then the changes in the wounds of the two mice were observed every day and recorded with photos. The results obtained are as follows: Fig.14 shown.

[0111] The results of the above animal experiments show that the wounds of mice sutured with ordinary commercial sutures have obvious redness from the second day and suppuration on the seventh day. However, the wounds sutured with the smart sutures prepared by the present invention have no redness, swelling or suppuration, and the wounds have healed well since the sixth day. The smart sutures are completely invisible on the eighth day, indicating that the smart sutures have been completely absorbed at this time. This shows that the smart sutures prepared by the present invention can well avoid wound infection and accelerate wound healing.

[0112] The above describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The above embodiments and descriptions only describe the principles of the present invention. The present invention may be subject to various changes and improvements without departing from the spirit and scope of the present invention. These changes and improvements fall within the scope of the present invention to be protected. The scope of protection claimed by the present invention is defined by the attached claims and their equivalents.

Claims

1. A method for preparing an intelligent suture with synergistic electrical stimulation and drug release, characterized in that: It includes the following steps: Fully dissolving the polymer in an organic solvent to obtain a polymer solution with a mass fraction of 5% to 10%; Conductive polymer nanoparticles, stabilizers, dopants and small molecule anti-inflammatory drugs are subjected to raw material emulsion polymerization to obtain conductive polymer-coated drug particles; The conductive polymer-coated drug particles are uniformly mixed with the polymer solution to obtain an electrospinning precursor solution with a mass fraction of 0.5% to 1%; The prepared electrospinning precursor solution is placed in a spray device, a metal wire is placed in an electrospinning machine as a nanofiber receiver, and the electrospinning precursor solution is sprayed onto the metal wire through the spray device to obtain nanofibers loaded with the small molecule anti-inflammatory drug wrapped on the surface of the metal wire, i.e., the smart suture; The metal wire in the prepared smart suture is based on the single-electrode mode of the friction nanogenerator, and can generate induced charge or alternating current under the stimulation of external mechanical environmental conditions, thereby controlling the release process of the small molecule anti-inflammatory drug loaded on the nanofiber, and the released small molecule anti-inflammatory drug is used to reduce inflammation of the sutured wound; the smart suture can also generate an alternating electric field under the stimulation of external mechanical conditions, which can accelerate cell differentiation, promote fibroblast growth, and realize electrical stimulation therapy; under the synergistic effect of releasing small molecule anti-inflammatory drugs and electrical stimulation therapy, the healing of the wound is accelerated.

2. The method for preparing the intelligent suture with synergistic electrical stimulation and drug release according to claim 1, characterized in that: The small molecule anti-inflammatory drug is one or more of berberine, quaternary ammonium salts, and silver nanoparticles.

3. The method for preparing the intelligent suture with synergistic electrical stimulation and drug release according to claim 1, characterized in that: The polymer is one or more of PLA, PLGA, PCL, PGA, and PLLA; And / or, the conductive polymer nanoparticles are one or more of PANI, PEDOT, and PPy.

4. The method for preparing the intelligent suture according to claim 1, characterized in that: The stabilizer is sorbitan monooleate; And / or, the dopant is sodium dodecylbenzene sulfonate.

5. The method for preparing the intelligent suture with synergistic electrical stimulation and drug release according to claim 1, characterized in that: The external mechanical condition stimulation is through mechanical force acting on the smart suture thread or through ultrasonic treatment of the smart suture thread.

6. The method for preparing the intelligent suture with synergistic electrical stimulation and drug release according to claim 1, characterized in that: The metal wire is one of magnesium, iron, zinc, magnesium alloy, iron alloy or zinc alloy; And / or, the length of the metal wire is 20 cm.

7. The method for preparing the intelligent suture with synergistic electrical stimulation and drug release according to claim 1, characterized in that: The parameters of the electrospinning machine in the process of preparing the intelligent suture are as follows: the distance between the needle of the injection device and the metal wire is 15 cm; the flow rate during the spinning process is 0.5 mL / h, and the applied voltage is 15 kV.

8. An intelligent suture with synergistic electrical stimulation and drug release, characterized in that: It is prepared by the preparation method of the smart suture according to any one of claims 1 to 7.

9. The intelligent suture with synergistic electrical stimulation and drug release as claimed in claim 8, characterized in that: The smart suture thread is a skin-core structure; the smart suture thread comprises a core layer (2) and a skin layer (1), the core layer (2) is a metal wire, the skin layer (1) is nanofibers, and the nanofibers are uniformly wrapped on the surface of the metal wire; the nanofibers are formed by the electrospinning precursor solution being attached to the metal wire through the electrospinning machine.

10. The intelligent suture with synergistic electrical stimulation and drug release as claimed in claim 9, characterized in that: The nanofibers are loaded with small molecule anti-inflammatory drugs (11), and the small molecule anti-inflammatory drugs (11) are used to reduce inflammation in wounds after suturing.

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