Macromolecular composite surgical suture with mechanical stability functionalization and preparation process of macromolecular composite surgical suture

Abstract

The invention provides a high-molecular composite surgical suture with mechanical stability functionalization and a preparation process of the high-molecular composite surgical suture, and belongs to the technical field of surgical suture processing. According to the composite suture with the antibacterial function, a skin layer is made of porous polylactic acid fibers loaded with nano-silver particles, and a core layer is made of double-strand poly (p-dioxanone) fibers. In the spinning process, the fiber structure is controlled by controlling the environment humidity, and the PLA fiber membrane with the porous structure is obtained. The porous PLA fiber membrane is used as a woven shell layer, so that the mechanical property of the poly (p-dioxanone) suture line is improved, meanwhile, the specific surface area is increased, and an obtained composite line structure can form a load network structure, can adsorb nano-silver particles more efficiently, improves the antibacterial property and also has a synergistic effect on a subsequent drug slow release behavior.

Description

Technical Field

[0001] The present invention belongs to the technical field of sutures, and in particular relates to a polymer composite suture with mechanical stability functionality and a preparation process thereof. Background Art

[0002] The PPDO sutures used clinically have good toughness and mechanical strength, but often do not have antibacterial function. Therefore, they are prone to infection due to various factors during surgery or surgical suture. Therefore, it is crucial to develop new sutures with antibacterial effects.

[0003] The shell braided yarn produced by Donghua University (CN201711291917.1) has a regular braided structure with an inner core yarn. Each braided yarn in the shell is a bicomponent partially absorbable yarn. The non-absorbable material alleviates the mechanical degradation caused by the degradation of the absorbable material, providing better mechanical support in the early stages of tissue healing. However, the presence of non-absorbable materials in the body can still easily cause inflammatory reactions.

[0004] Shen et al. (CN200510030159.9) used an immersion method to load polymer medical sutures with nanosilver for antibacterial purposes. This method involves immersing the sutures in a prepared nanosilver solution. Because single-strand sutures have a smooth, dense surface, the nanosilver loading capacity is limited, and the loading increases with immersion time. However, immersion in the drug-loaded solution can easily cause hydrolysis of the absorbable sutures, leading to a decrease in mechanical properties.

[0005] How to give sutures antibacterial functionality without affecting their mechanical properties is a challenging task. Summary of the Invention

[0006] The purpose of the present invention is to provide an absorbable polymer composite suture with mechanical stability and antibacterial functionality and a preparation process thereof, so as to solve the problems raised in the above background technology.

[0007] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0008] The present invention provides a process for preparing an absorbable polymer composite suture: nanosilver is first loaded onto a porous PLA fiber membrane, then twisted into fiber strips, and finally composited with PPDO fibers to produce the composite suture. The resulting composite suture has a sheath-core structure, with the sheath being porous PLA fibers loaded with nanosilver particles and the core being polydioxanone fibers.

[0009] Preferably, the preparation process of the polylactic acid fiber membrane is as follows: PLA is dissolved in a chloroform solution, stirred thoroughly, and mixed evenly to obtain a spinning solution with a mass concentration of 8%-10%, and then the PLA fiber membrane is obtained by electrospinning.

[0010] Preferably, the spinning parameters for the polylactic acid fiber membrane are: positive voltage 13-14 kV, negative voltage -1-0 kV; propulsion speed 1.5-2 mL / h; roller receiving device rotation speed 140-150 rpm; nozzle inner diameter 0.5-0.6 mm; distance between nozzle and receiver 20-23 cm; spinning temperature 25-35°C; and during the spinning process, a humidifier with a humidification rate of 300-400 mL / h is used to control the ambient humidity at 40%-80%.

[0011] More preferably, the ambient humidity is controlled to be 70-80%. More preferably, the pore size of the porous PLA nanofibers is 50-350 nm.

[0012] Preferably, the preparation process of the nanosilver-loaded polylactic acid fiber membrane is as follows: silver nitrate is dissolved in deionized water to obtain a 10%-15% silver nitrate solution by mass. A PLA fiber membrane is added and heated to 95-105°C, followed by soaking for 10-15 minutes. The mass ratio of silver nitrate to PLA fiber membrane is 1:4-1:5. A 10g / L sodium citrate solution is then slowly added dropwise. The reaction is allowed to proceed for 1-1.5 hours. The fiber membrane is removed, rinsed three times with deionized water, and then dried in a 100°C oven for 2-3 hours to obtain an in-situ reaction-loaded nanosilver PLA fiber membrane. More preferably, the nanosilver loading is 25-35mg / g.

[0013] The molar ratio of silver nitrate to sodium citrate is 1:5.

[0014] Preferably, the composite fiber preparation process is: composite the nanosilver-loaded PLA fiber membrane with PPDO, that is, twisting the fiber membrane into fiber strips, and coating the double-strand PPDO braided square knot to obtain a composite suture.

[0015] The preferred coating process parameters are: PPDO length of 20-25 cm, coating layer thickness of 0.14±0.05 mm, braiding density of 70±5%, and twist range of 1400-1500 twists / m.

[0016] This invention provides a multi-strand braided composite suture with antibacterial and mechanical stability, made from biodegradable materials PLA and PPDO. While maintaining the mechanical stability of the PPDO monofilament, the invention utilizes a PLA fiber membrane as the braided sheath, and the fibers are perforated to increase the specific surface area. This structure not only forms a load-bearing network but also efficiently adsorbs nanosilver particles, creating a synergistic effect for subsequent sustained-release.

[0017] The PPDO fiber core is the primary load-bearing component of the suture, while the nanosilver-loaded PLA fiber membrane serves as the antibacterial coating. The composite suture exhibits significant antibacterial activity against Staphylococcus aureus (S. aureus) through a 3.39% and 24.6% increase in knotted and unknotted strength, respectively, compared to uncoated PPDO fibers. The sustained-release equilibrium time in PBS buffer is 8 hours. The braided suture exhibits significant antibacterial activity against Staphylococcus aureus. Biocompatibility evaluation with human immortalized keratinocytes (HaCaT) demonstrated its safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 Scanning electron micrographs of the PLA fiber membranes prepared in the present invention. a is from Example 1; b is from Example 4; c is from Example 5;

[0019] Figure 2 The scanning electron microscope images of the PLA fiber membrane loaded with nanosilver of the present invention are shown in Figure 1. Figure a is Example 1; Figure b is Example 6; Figure c is Example 7; Figure d is Comparative Example 2; Figure e is Comparative Example 3.

[0020] Figure 3 A scanning electron microscope image of the composite suture prepared in the present invention;

[0021] Figure 4 The scanning electron microscope images of the PLA fiber membrane prepared in the present invention are shown in Figure 1. a is from Example 2; b is from Example 3.

[0022] Figure 5 This is a scanning electron microscope image of the PLA fiber membrane prepared in Comparative Example 1;

[0023] Figure 6 Scanning electron micrographs of PLA fiber membranes loaded with nanosilver. a is Comparative Example 4; b is Comparative Example 5;

[0024] Figure 7 A diagram showing the mechanical properties of the composite suture prepared according to the present invention;

[0025] Figure 8 This is a graph showing the sustained-release performance of the composite suture prepared in the present invention;

[0026] Figure 9 This is a graph showing the antibacterial properties of the composite suture prepared in the present invention;

[0027] Figure 10 The results of CCK-8 test on the biocompatibility of composite sutures;

[0028] Figure 11 This is a process flow chart of the composite suture prepared by the present invention. DETAILED DESCRIPTION

[0029] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0030] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0031] Example 1

[0032] (1) Preparation of electrospinning membrane: Using chloroform as solvent, a PLA spinning solution with a mass concentration of 8% was prepared. The spinning solution was injected into a 5mL syringe, and a nozzle with an inner diameter of 0.5mm was inserted. By the electrospinning method, the positive voltage was adjusted to 14kV, the negative voltage was -1kV, the propulsion speed was 1.5mL / h, the rotation speed of the roller receiving device was 150r / min, the distance between the nozzle and the receiver was 20cm, and the spinning temperature was 25°C. During the spinning process, a humidifier with a humidification capacity of 300mL / h was used to control the ambient humidity to 80%. The scanning electron microscope image of the obtained PLA fiber membrane is shown in the attached manual. Figure 1 As shown in (a).

[0033] (2) Fiber membrane loaded with nanosilver: Prepare a silver nitrate solution with a mass concentration of 13%, add the PLA fiber membrane and heat it to 100℃, and soak it for 10 minutes. The mass ratio of silver nitrate to PLA fiber membrane is 1:4. Then slowly add 10g / L (10mL) of sodium citrate solution, and the molar ratio of silver nitrate to sodium citrate is 1:5. After reacting for 1 hour, take out the fiber membrane and place it in a 100℃ oven for 2 hours to dry, and obtain the PLA fiber membrane loaded with nanosilver by in situ reaction. The scanning electron microscope image of the obtained fiber membrane is shown in the attached manual. Figure 2 As shown in (a).

[0034] (3) Preparation of composite suture: The PLA fiber film loaded with nanosilver was twisted into fiber strips, the PLA fiber strips were composited with PPDO fibers (double strands), and the double strands of PPDO fibers were coated by braiding and twisting to obtain composite suture. The coating process parameters are: PPDO length of 25 cm, average thickness of PLA coating layer of 0.14 mm (longitudinal direction), and diameter of single PPDO core layer of 385 μm. The scanning electron microscope image of the obtained composite suture is attached to the specification. Figure 3 The process flow chart for preparing composite sutures is shown in Figure 10 shown.

[0035] Example 2

[0036] The same as Example 1, except that the mass concentration of PLA in the electrospun membrane preparation process of Example 2 is 9%. The scanning electron microscope image of the obtained PLA fiber membrane is shown in the attached specification. Figure 4 As shown in (a).

[0037] Example 3

[0038] The same as Example 1, except that the mass concentration of PLA in the electrospun membrane preparation process of Example 2 is 10%. The scanning electron microscope image of the obtained PLA fiber membrane is shown in the attached specification. Figure 4 (b) shown.

[0039] By attaching Figure 4 It was found that the morphology of the PLA fiber membrane obtained with spinning solution concentrations of 9% and 10% had no significant difference from that of the fiber membrane with a concentration of 8%. It is believed that this structure has a similar effect on the subsequent nanosilver loading and is feasible.

[0040] Example 4

[0041] The same as Example 1, except that the humidifier controlled the ambient humidity to 60% during the electrospinning membrane preparation process in Example 4. The scanning electron microscope image of the obtained PLA fiber membrane is shown in the attached specification. Figure 1 (b) shown.

[0042] Example 5

[0043] The same as Example 1, except that the humidifier controlled the ambient humidity to 40% during the electrospinning membrane preparation process in Example 5. The scanning electron microscope image of the obtained PLA fiber membrane is shown in the attached specification. Figure 1 (c) shown.

[0044] Attached to the instruction manual Figure 1 It was found that for water-insoluble PLA, the increase in water molecules in the air promotes the phase separation process on the fiber surface. When the ambient humidity is 80%, the PLA fiber membrane exhibits a uniform and clear pore structure (Example 1). As the ambient humidity decreases, the pore structure on the fiber gradually decreases or even disappears (Examples 4 and 5). The rich pore structure on the fiber surface provides an ideal platform for loading nanosilver.

[0045] If the humidity is further increased to above 80%, it was found during the spinning process that the high humidity environment increases the conductivity of the air, weakens the electric field strength, and causes unstable spinning. Therefore, the humidity is no longer increased for subsequent spinning.

[0046] Example 6

[0047] The same as Example 1, except that the mass concentration of silver nitrate in the process of loading nanosilver on the fiber membrane in Example 6 is 10%, and the scanning electron microscope image of the obtained fiber membrane is shown in the attached specification. Figure 2 (b) shown.

[0048] Example 7

[0049] The same as Example 1, except that the mass concentration of silver nitrate in the process of loading nanosilver on the fiber membrane of Example 7 is 15%, and the scanning electron microscope image of the obtained fiber membrane is shown in the attached specification. Figure 2 (c) shown.

[0050] Comparative Example 1

[0051] The same as Example 1, except that the mass concentration of PLA in the electrospun membrane preparation process of Comparative Example 1 is 7%, and the scanning electron microscope image of the obtained PLA fiber membrane is shown in the attached specification. Figure 5 shown.

[0052] When electrospinning low-concentration PLA solutions in high humidity, the moisture in the air increases the wettability of the fiber surface, promoting inter-fiber adhesion and hindering film formation. High-concentration spinning solutions, on the other hand, have high viscosity, poor fluidity, increased crystallinity, and are prone to brittle cracking.

[0053] Comparative Example 2

[0054] The same as Example 1, except that the mass concentration of silver nitrate in the process of loading nanosilver on the fiber membrane of Comparative Example 2 is 8%, and the scanning electron microscope image of the obtained fiber membrane is shown in the attached specification. Figure 2 (d) shown.

[0055] Comparative Example 3

[0056] The same as Example 1, except that the mass concentration of silver nitrate in the process of loading nanosilver on the fiber membrane of Comparative Example 3 is 17%, and the scanning electron microscope image of the obtained fiber membrane is shown in the attached specification. Figure 2 (e) shown.

[0057] From the instruction manual Figure 2 It can be seen that the nanosilver loading on the fiber membrane increases with the increase in the silver nitrate ratio. At an 8% silver nitrate concentration, the nanosilver loading is minimal (Comparative Example 2); at a 17% silver nitrate concentration, the nanosilver aggregates significantly (Comparative Example 3); and at a silver nitrate concentration of 10-15%, the nanosilver loading is more uniform and evenly distributed (Examples 1, 6, and 7).

[0058] Comparative Example 4

[0059] The method is the same as Example 1, except that the nanosilver loading process of the fiber membrane in Comparative Example 4 uses ultrasonic vibration.

[0060] Prepare a 13% silver nitrate solution in deionized water and heat to 100°C. Slowly add 10g / L (10mL) of sodium citrate solution dropwise with rapid stirring at 300 rpm. The reaction lasts for 1 hour to obtain a nanosilver colloidal solution.

[0061] PLA fiber membrane was added to the nanosilver solution, with the feed ratio of silver nitrate to PLA fiber membrane being 1:4. After being placed in an ultrasonic device for 1 hour, the fiber membrane was taken out and placed in a 100℃ oven and dried for 2 hours to obtain a polylactic acid fiber membrane loaded with nanosilver by ultrasound. The scanning electron microscope image of the obtained fiber membrane is shown in the attached manual. Figure 6 As shown in (a).

[0062] Comparative Example 5

[0063] Comparative Example 5 is the same as Example 5, except that the nanosilver loading process of the fiber membrane in Comparative Example 5 uses ultrasonic vibration.

[0064] Prepare a 13% silver nitrate solution in deionized water and heat to 100°C. Slowly add 10g / L (10mL) of sodium citrate solution dropwise with rapid stirring at 300 rpm. The reaction lasts for 1 hour to obtain a nanosilver colloidal solution.

[0065] PLA fiber membrane was added to the nanosilver solution, with the feed ratio of silver nitrate to PLA fiber membrane being 1:4. After being placed in an ultrasonic device for 1 hour, the fiber membrane was taken out and placed in a 100℃ oven and dried for 2 hours to obtain a polylactic acid fiber membrane loaded with nanosilver by ultrasound. The scanning electron microscope image of the obtained fiber membrane is shown in the attached manual. Figure 6 (b) shown.

[0066] According to the instruction manual Figure 6 Because the surface of the PLA fiber membrane has a certain degree of hydrophobicity, it is difficult for the nanosilver dispersed in water to penetrate into the interior of the PLA fiber membrane through ultrasonic vibration, and the loading rate is low.

[0067] Comparative Example 6

[0068] The same as Example 1, except that the PLA fiber of Comparative Example 6 is obtained by melt spinning.

[0069] PLA pellets were oven-dried at 110°C for 24 hours and then placed in the feed chamber of a melt spinning machine. Preheated at 190°C, the pellets were melt-extruded through a screw extruder at a speed of 100 mm / min and a spinneret diameter of 1 mm to produce pre-stretched fibers. The pre-stretched fibers were then stretched and oriented using low-speed and high-speed rollers at a draw ratio of 1:3 before being wound to yield PLA fibers.

[0070] PLA fibers obtained by melt spinning are dense, single-strand fibers with a diameter of 0.55 mm. Due to their small surface area, efficient loading of silver nanoparticles is difficult, and the load is primarily distributed on the fiber surface, making sustained release difficult. This suggests that the complex network structure of the porous nanofiber membrane can significantly facilitate the loading and sustained release of silver nanoparticles.

[0071] Specific applications

[0072] The mechanical properties of the composite suture obtained in Example 1 were measured by an electronic single yarn strength tester. The length of the sample was 20 cm and the tensile speed was set to 200 mm / min. The test results of the unknotted strength and knotted strength are shown in the attached manual. Figure 7 The knotted and unknotted strengths of the composite suture were 51.8 N and 65.4 N, respectively, which were 3.39% and 24.6% higher than those of PPDO without a coating layer, indicating that the braided coating of PLA film can effectively improve the mechanical properties of surgical sutures.

[0073] The composite suture obtained in Example 1 was tested for the sustained release of nanosilver using an inductively coupled plasma mass spectrometer. The sustained release solution consisted of deionized water and a PBS buffer solution with a pH of 7.4. The test results are shown in the attached manual. Figure 8 As shown. Due to the strong permeability of water molecules, the antimicrobial agent can be quickly released in H2O, and the release amount at 3h is 0.87mg / g. As time increases, the release amount of the antimicrobial agent reaches equilibrium at 78h (1.68mg / g). In the PBS buffer solution, the release amount of AgNPs of the composite yarn is only 0.02mg / g at 0.5h. The equilibrium sustained release amount of the antimicrobial agent of the composite yarn is 0.84mg / g, and the sustained release equilibrium is reached in 8h. The slow controlled release of the antimicrobial agent in PBS buffer can not only avoid the drug poisoning reaction caused by the rapid release of the loaded drug in a short time, but also prolong the duration of drug action.

[0074] The composite suture obtained in Example 1 was tested with Staphylococcus aureus and Escherichia coli as the test bacteria, and the antibacterial effect of the sample was tested using the agar plate diffusion method. A 4 cm sample was placed on a plate coated with 1×10 3 The sample was placed in the center of the agar medium containing the bacterial solution, ensuring that the sample and the agar medium remained in contact during the entire incubation period. After culturing in a 37°C constant temperature incubator for 24 hours, the sample was observed to see if there was an inhibition zone around it, i.e., an area where no bacteria grew, and the outer diameter of the inhibition zone was measured. All instruments used in the antibacterial experiment, such as test tubes, culture dishes, and pipette tips, were sterilized. The test results are shown in the attached instructions. Figure 9 As shown, the antibacterial effect on Staphylococcus aureus is better than that on Escherichia coli. The width of the antibacterial zone of the sample against Staphylococcus aureus is 1.3 mm, and the bacteria do not reproduce. The composite wire has a certain antibacterial effect.

[0075] The cytotoxicity of the composite suture obtained in Example 1 was determined using a CCK-8 assay in human immortalized keratinocytes. The sample was washed twice with PBS buffer, immersed in 70% ethanol, and sterilized by ultraviolet irradiation. The sample was immersed in DMEM culture medium containing 10% fetal bovine serum, 100 U / mL penicillin, and 1% streptomycin for 24 hours. The cells were seeded in a 96-well plate (1×10 4 cells / well) and incubated at 37°C for 24 hours. The culture medium in the 96-well plate was then replaced with the extraction medium. The plates were placed in an incubator for 1, 3, and 5 days, respectively. Subsequently, 10 μL of CCK-8 was introduced into each well, and the plates were incubated for 3 hours. After incubation, the absorbance value of each sample was measured at 450 nm. The cells were stained with the live / dead staining working solution, and the cell status was observed under a fluorescence microscope. The cell viability formula is:

[0076]

[0077] As is the absorbance value of the experimental well, A; Ab is the absorbance value of the blank well, A; Ac is the absorbance value of the control well, A.

[0078] The test results are as shown in the attached manual. Figure 10 As shown. The cell survival rate decreased with the increase in culture days: the cell survival rates at 1 day, 3 days and 5 days of culture were 95%, 90% and 82%, respectively, and the sample showed low cytotoxicity. Fluorescence microscope photos of cells at different culture days also showed the presence of large areas of green fluorescence, indicating that a large number of cells survived. Although, as the culture time increased, the red area in the fluorescence photos increased. However, even after 5 days of culture, there were still very few red fluorescent spots, indicating that the cell mortality rate was low and the composite suture had good biosafety.

[0079] While the embodiments of the present invention have been shown and described, it will be apparent to those skilled in the art that various changes, modifications, substitutions, and alterations can be made to the embodiments without departing from the principles and spirit of the invention.

Claims

1. A mechanically stable functionalized polymer composite surgical suture, characterized by: The composite suture has a skin-core structure, the skin layer is porous polylactic acid fiber loaded with nano-silver particles, and the core layer is polydioxanone fiber.

2. The mechanically stable functionalized polymer composite surgical suture according to claim 1, characterized in that: First, a porous polylactic acid fiber membrane loaded with nanosilver particles is prepared, the porous polylactic acid fiber membrane is twisted into fiber strips, and then coated with polydioxanone fiber by weaving a flat knot to obtain a composite suture; the average thickness of the cortex is 0.14±0.05mm.

3. A process for preparing the mechanically stable functionalized polymer composite surgical suture according to claim 1, characterized in that: The preparation steps are: (1) PLA was dissolved in chloroform solution, stirred and mixed thoroughly to obtain a spinning solution, and then electrospinning was performed. During the spinning process, the ambient humidity was controlled at 40%-80% to obtain a porous PLA fiber membrane; (2) dissolving silver nitrate in deionized water to obtain a silver nitrate solution, adding the porous PLA fiber membrane and heating it to 95-105° C. for soaking, then adding a reducing agent dropwise for reaction, and after the reaction, taking out the fiber membrane, washing it, and drying it to obtain an in-situ reaction-loaded PLA fiber membrane with nanosilver; (3) The PLA fiber membrane loaded with nanosilver was twisted into fiber strips, and the composite suture was obtained by coating the PPDO braided flat knot.

4. The process for preparing the mechanically stable functionalized polymer composite surgical suture according to claim 3, characterized in that: In step (1), the mass concentration of the spinning solution is 8%-10%.

5. The process for preparing the mechanically stable functionalized polymer composite surgical suture according to claim 3, characterized in that: In step (1), the electrospinning parameters are: positive voltage 13-14 kV, negative voltage -1-0 kV, propulsion speed 1.5-2 mL / h, roller receiving device speed 140-150 r / min, nozzle inner diameter 0.5-0.6 mm, distance between nozzle and receiver 20-23 cm, and spinning temperature 25-35 ° C.

6. The process for preparing the mechanically stable functionalized polymer composite surgical suture according to claim 3, characterized in that: In step (1), the ambient humidity is controlled to be 70-80%.

7. The process for preparing the mechanically stable functionalized polymer composite surgical suture according to claim 3, characterized in that: In step (2), the reducing agent is sodium citrate.

8. The process for preparing the mechanically stable functionalized polymer composite surgical suture according to claim 3, characterized in that: In step (2), the mass fraction of the silver nitrate solution is 10%-15%; the mass ratio of silver nitrate to PLA fiber membrane is 1:4-1:5.

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