Composite medical suture and preparation method thereof

Abstract

The present invention discloses a composite medical suture and a preparation method thereof, which belong to the field of biomedicine. In view of the problems of poor antibacterial effect and biosafety of existing medical sutures, the present invention provides a composite medical suture, comprising a core layer, a degradation regulating layer, a sustained-release layer and an antibacterial layer arranged in sequence from the inside to the outside; the core layer comprises a blended fiber of polyhydroxybutyrate-valerate copolyester and polycaprolactone-co-glycolide; the degradation regulating layer comprises a mixture of at least two polyethylene glycols of different molecular weights; the sustained-release layer comprises quaternary ammonium salt-loaded graphene oxide nanofibers; the antibacterial layer comprises titanium dioxide loaded with silver nanoparticles. The present invention achieves comprehensive optimization of mechanical properties, degradation rate, drug sustained release and antibacterial function through the synergistic effect between the four layers; achieves the purpose of improving sustained-release antibacterial performance, reducing damage to the human body and reducing the occurrence of inflammation, etc., so that its antibacterial and degradation effects meet recovery requirements.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical materials, and more particularly, relates to a composite medical suture and a preparation method thereof. Background Art

[0002] Medical sutures are key medical materials used for ligation, hemostasis, and tissue closure during surgical procedures. Their types, material properties, and application scenarios are diverse and constantly evolving with technological advancements. Medical sutures are primarily categorized into two types: absorbable and non-absorbable, depending on whether they are absorbable by the body. Absorbable sutures are widely used because they gradually degrade in the body, eliminating the need for suture removal. However, when traditional absorbable sutures, such as polyglycolic acid (PGA) and polylactic acid (PLA), degrade in the body, their degradation products create a localized acidic environment. Studies have shown that this acidic environment can lead to an inflammatory response, impairing normal wound healing. For example, in a clinical study of 100 patients using PGA sutures, over 20% experienced varying degrees of inflammation, manifesting as redness, swelling, increased pain, exudate, and other inflammatory symptoms around the wound. Furthermore, currently commonly used single antimicrobial agents, such as nanosilver, while exhibiting excellent antimicrobial properties, tend to release rapidly during use. Experiments have shown that nanosilver releases over 55% of the total loading within the first 24 hours, resulting in a short antimicrobial effect, typically lasting only 3 to 5 days. Furthermore, excessive nanosilver concentrations can be toxic to cells. Studies have shown that nanosilver concentrations exceeding 10 μg / mL significantly inhibit the activity of human fibroblasts. For example, existing technologies, such as Chinese Patent Publication No. CN115287904A, utilize a PHA / nanosilver composite to prepare sutures. While achieving antimicrobial properties to some extent, this patent fails to effectively address the issue of sudden silver ion release. Simulation experiments with this patented product revealed that silver ion release exceeded 70% within 3 days, resulting in poor antimicrobial efficacy in the later stages. Another example is Chinese Patent Publication No. CN105770978A, which utilizes PHA microspheres for drug delivery but lacks mechanical reinforcement for the suture. When conducting mechanical performance tests on its products, it was found that its tensile strength was only about 100 MPa, which could not meet the requirements of some surgical scenarios that require higher mechanical properties of sutures.

[0003] Corresponding improvements have also been made to address the above-mentioned problems. For example, Chinese patent application number CN202211231418.4, published on November 4, 2022, discloses a method for preparing an absorbable medical suture. First, a core layer (PET / PEG composite fiber) is prepared by a melt spinning method. Then, when the surface temperature of the core layer is 185-200°C, a solution jet spinning method is used to prepare a cortex (chitosan / polylactic acid composite fiber) on the surface of the core layer. Finally, a silk fibroin / berberine composite material coating is applied to the surface of the cortex to prepare an absorbable medical suture. The disadvantage of this patent is that PET is a hydrophobic material, while PEG is hydrophilic. The composite of the two may result in weak interfacial bonding due to poor compatibility, easy delamination or breakage, and poor strength of the suture.

[0004] Another example is Chinese patent application number CN201610156552.0, published on July 20, 2016. This patent discloses a biodegradable medical abdominal surgical suture material. The suture material is a composite biodegradable material consisting of a cylindrical inner core layer, an intermediate layer wrapped around the inner core layer, and an outer skin layer wrapped around the intermediate layer. The material of the inner core layer is selected from polyglycolic acid, polylactic acid, polyvinyl lactone, or their copolymers; the material of the intermediate layer is selected from carboxymethyl chitosan fiber, chitosan fiber, or collagen fiber; and the material of the outer skin layer is selected from polyglycolic acid, polylactic acid, polyvinyl lactone, or their copolymers. The disadvantage of this patent is that chitosan and collagen easily absorb water and swell in body fluids, causing the suture to become brittle or increase in diameter, which may cause tissue compression or difficulty in operation. Summary of the Invention

[0005] 1. Problems to be solved

[0006] To address the poor antimicrobial efficacy and biosafety of existing medical sutures, the present invention provides a composite medical suture and its preparation method. Through the synergistic effect of four layers, the present invention achieves comprehensive optimization of mechanical properties, degradation rate, sustained drug release, and antimicrobial function. This achieves the goal of improving sustained-release antimicrobial performance, reducing damage to the human body, and reducing inflammation, achieving antimicrobial and degradation effects that meet the requirements of postoperative recovery.

[0007] 2. Technical solution

[0008] To solve the above problems, the present invention adopts the following technical solutions.

[0009] A composite medical suture comprises a core layer, a degradation regulating layer, a sustained-release layer, and an antibacterial layer, which are sequentially arranged from the inside out; the core layer comprises a blended fiber of polyhydroxybutyrate-valerate copolyester and polycaprolactone-co-polyglycolide; the degradation regulating layer comprises a mixture of at least two polyethylene glycols of different molecular weights; the sustained-release layer comprises quaternary ammonium salt-loaded graphene oxide nanofibers; and the antibacterial layer comprises titanium dioxide loaded with silver nanoparticles; wherein the molecular weights of the mixture of at least two polyethylene glycols of different molecular weights in the degradation regulating layer differ by at least one order of magnitude.

[0010] Furthermore, the core layer further comprises carbon nanotubes, and the mass of the carbon nanotubes accounts for 0.1% to 0.5% of the mass of the entire core layer raw material.

[0011] Furthermore, the mass ratio of polyhydroxybutyrate-valerate copolyester to polycaprolactone-co-polyglycolide in the core layer is (6-8):(2-4); the molecular weight of polyhydroxybutyrate-valerate copolyester is 500,000-800,000; and in the molecular chain of polycaprolactone-co-polyglycolide, the molar ratio of polycaprolactone monomer unit to polyglycolide monomer unit is 80:20.

[0012] Furthermore, the degradation regulating layer includes a mixture of PEG-4000 and PEG-10000; the Mn of PEG-4000 is 3800-4200, and the Mn of PEG-10000 is 9500-10500.

[0013] Furthermore, the mass ratio of PEG-4000 to PEG-10000 is 1:1, and the thickness of the degradation regulating layer is 6-12 μm.

[0014] Furthermore, the quaternary ammonium salt-loaded graphene oxide nanofibers of the sustained-release layer include quaternary ammonium salt, graphene oxide and a substrate polymer, wherein the mass percentage of the quaternary ammonium salt is 2% to 3%, the mass percentage of the graphene oxide is 1% to 2%, and the mass percentage of the substrate polymer is 95% to 97%.

[0015] Furthermore, in the titanium dioxide loaded with silver nanoparticles, the particle size of the silver nanoparticles is 10-20 nm, and the mass percentage of the silver nanoparticles is 1%-2%.

[0016] Furthermore, the antibacterial layer further comprises a photosensitive porphyrin compound, the mass percentage of the photosensitive porphyrin compound is 0.5% to 1%, and the activation wavelength of the photosensitive porphyrin compound is 650±10 nm.

[0017] A method for preparing the composite medical suture as described in any one of the above items specifically comprises the following steps:

[0018] S1: adding the raw materials of the core layer into a twin-screw extruder, and extruding and drawing after melt blending to obtain the core layer;

[0019] S2: dipping the core layer in the degradation regulating layer, drying in an oven to form a film, and coating the outer surface of the core layer with the degradation regulating layer to obtain an intermediate 1;

[0020] S3: obtaining a sustained-release layer by electrospinning, and coating the sustained-release layer on the outer surface of the intermediate 1 to obtain the intermediate 2;

[0021] S4: spraying an antibacterial layer on the outer surface of the intermediate 2 by electrostatic spraying to obtain the final composite medical suture thread.

[0022] 3. Beneficial effects

[0023] (1) The present invention achieves a balance between mechanical properties and biocompatibility and a controllable degradation rate in the core layer through the design of the composite layer; the degradation control layer achieves adjustable degradation rate; the sustained-release layer achieves long-term release of antibacterial substances and biofilm inhibition; the antibacterial layer achieves enhanced bactericidal effect and reduces the amount of AgNPs used to reduce cytotoxicity; through the synergistic effect of the four layers, comprehensive optimization of mechanical properties, degradation rate, drug sustained release and antibacterial function is achieved; the purpose of improving sustained-release antibacterial performance, reducing damage to the human body and reducing inflammation is achieved, so that the antibacterial and degradation effects of the composite medical suture meet the requirements of postoperative recovery of the human body; at the same time, the molecular weights of different polyethylene glycols in the degradation control layer differ by at least one order of magnitude, which can achieve a wide molecular weight range, more scientifically regulate the degradation rate and degradation time of the suture to keep it matching the wound healing time, and improve clinical applicability;

[0024] (2) The present invention adds carbon nanotubes to the core layer, and utilizes the high strength and high modulus of carbon nanotubes to significantly improve the tensile strength of the suture; and the elastic modulus of the core layer can be adjusted to make it closer to natural tissue, reducing tissue cutting or inflammatory response caused by stiffness mismatch; at the same time, the content of carbon nanotubes is strictly controlled to avoid excessive carbon nanotubes agglomerating in the matrix to form stress concentration points, resulting in decreased flexibility of the suture; too low a content of carbon nanotubes cannot increase the mechanical properties; its content is limited to a specific range to avoid increased material brittleness, increased processing difficulty, biocompatibility risks and cost-effectiveness imbalance, thereby achieving a balance between cost, safety and performance;

[0025] (3) The present invention limits the proportion of the raw materials of the core layer, because polyhydroxybutyrate-valerate copolyester provides good biocompatibility and degradability; polycaprolactone-co-polyglycolide enhances flexibility and tensile strength; the two together enable the suture to maintain structural integrity during the healing process, avoiding the risk of wound dehiscence caused by rapid degradation of the material; therefore, the mass ratio of the two is limited to achieve a balance of mechanical properties; and the molecular weight of polyhydroxybutyrate-valerate copolyester is limited to further improve the mechanical properties; the molar ratio of polycaprolactone-co-polyglycolide monomer units is limited to achieve precise control of the mechanical properties and degradation rate of the copolymer; ultimately, the core layer can achieve the best effect during use;

[0026] (4) The present invention limits the proportion of substances in the degradation regulating layer. Since the degradation regulating layer forms a gradient of degradation rate, it dynamically matches the different stages of wound healing. Therefore, it is limited within a set range to achieve a balance between optimizing degradation rate and mechanical properties. At the same time, the thickness of the degradation regulating layer is limited. While ensuring sufficient drug load, it avoids the layer being too thick, which leads to a decrease in the overall flexibility of the suture, or being too thin to effectively regulate the degradation rate. The other layers do not need to be specifically limited in thickness because each layer has different functions. The means of achieving the corresponding functions are carried out through other means, which is highly targeted and has significant effects.

[0027] (5) The present invention adds a photosensitive porphyrin compound to the antibacterial layer. The photosensitive porphyrin compound can generate reactive oxygen species, further enhancing the antibacterial effect and promoting tissue repair. It also kills bacteria through a physical mechanism and reduces the risk of recurrence of infection. At the same time, it is taken into account that excessive reactive oxygen species produced by excessive photosensitive porphyrin compounds may damage surrounding fibroblasts, thereby delaying wound healing. The activation wavelength of the photosensitive porphyrin compound is limited to achieve a balance between maximizing tissue penetration depth and minimizing light damage. Ultimately, the multiple considerations of antibacterial efficacy, biocompatibility and clinical feasibility are achieved.

[0028] (6) The preparation method of the composite medical suture of the present invention has simple steps, and each layer is superimposed through different processes to ensure the composite strength between each layer; this not only improves the comprehensive performance of the suture, such as tensile strength, degradation controllability, and drug sustained-release efficiency, but also reduces the preparation cost through process synergy, providing a new solution for the treatment of complex wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 Schematic diagram of the structure of the composite medical suture of the present invention;

[0030] Figure 2 A schematic diagram showing the comparison of the antibacterial performance test results of three different medical sutures against Candida albicans;

[0031] Figure 3 Schematic diagram of the degradation cycle and tensile strength change curve of the composite medical suture thread of the present invention. DETAILED DESCRIPTION

[0032] The present invention is further described below with reference to specific embodiments and accompanying drawings.

[0033] like Figure 1 As shown, a composite medical suture comprises a core layer, a degradation regulating layer, a sustained-release layer and an antibacterial layer arranged in sequence from the inside to the outside; the core layer comprises a blended fiber of polyhydroxybutyrate-valerate copolyester and polycaprolactone-co-polyglycolide; the degradation regulating layer comprises a mixture of at least two polyethylene glycols of different molecular weights; the sustained-release layer comprises quaternary ammonium salt-loaded graphene oxide nanofibers; the antibacterial layer comprises titanium dioxide loaded with silver nanoparticles; wherein the mixture of the at least two polyethylene glycols of different molecular weights in the degradation regulating layer differs by at least one order of magnitude.

[0034] Specifically, in this embodiment:

[0035] Core layer: A fiber blend of PHBV (polyhydroxybutyrate-co-valerate) and PCL-GA (polycaprolactone-co-glycolide) is used. PHBV provides excellent biocompatibility and degradability, while PCL-GA enhances flexibility and tensile strength. This allows the core layer to maintain structural integrity during the healing process, preventing the risk of wound dehiscence caused by rapid material degradation. The blend design of PHBV and PCL-GA controls the degradation rate by adjusting the ratio between the two, avoiding insufficient mechanical support or foreign body reactions caused by excessively fast or slow degradation of a single material.

[0036] Degradation regulation layer: A mixture of at least two PEGs (polyethylene glycol) with different molecular weights, with the two different molecular weights differing by at least one order of magnitude, resulting in a huge difference in molecular weight between different PEGs. Low-molecular-weight PEGs degrade rapidly in the initial stage, releasing degradation products of the inner layer material to avoid inflammation caused by local acid accumulation. High-molecular-weight PEGs degrade slowly, maintaining long-term structural support and preventing tissue collapse. This design can achieve a wide molecular weight range, more scientifically regulating the degradation rate and degradation time of the suture to match the wound healing time, thereby improving clinical applicability. At the same time, the orders of magnitude difference in PEG molecular weights form a mechanical property gradient from the inside to the outside. The low-molecular-weight PEG layer provides a flexible buffer, while the high-molecular-weight PEG layer maintains rigid support, reducing tissue friction and cutting risks.

[0037] Sustained-release layer: Graphene oxide nanofibers loaded with quaternary ammonium salts are used. The high specific surface area of ​​graphene oxide and the cationic properties of quaternary ammonium salts work synergistically: the quaternary ammonium salts bind to the bacterial membrane through electrostatic interaction, and graphene oxide enhances the sustained-release effect of the antibacterial agent, achieving long-term sustained release of antibacterial substances and reducing the risk of postoperative infection.

[0038] Antibacterial layer: Titanium dioxide loaded with silver nanoparticles is used. Silver nanoparticles provide broad-spectrum antibacterial activity. Titanium dioxide produces reactive oxygen species under light, enhancing the bactericidal effect and reducing the amount of AgNPs used to reduce cytotoxicity. Titanium dioxide also photocatalytically decomposes organic pollutants, keeping the suture surface clean and reducing the attachment of infection sources. The coating releases silver ions and reactive oxygen species when it comes into contact with microorganisms, achieving rapid sterilization.

[0039] The first core of this embodiment is: through the synergistic effect of the four layers, the mechanical properties, degradation rate, drug release, antibacterial function and biosafety are fully optimized; the quaternary ammonium salt / graphene oxide sustained release system of the sustained release layer and the antibacterial layer The rapid bactericidal synergistic effect has an antibacterial rate of >99.99%, and a 14-day antibacterial rate of >95% against fungi (Candida albicans); it achieves the purpose of improving sustained-release antibacterial properties, reducing damage to the human body, and reducing inflammation, making the antibacterial and degradation effects of the composite medical suture meet the requirements of human postoperative recovery. At the same time, it avoids the problem of metal antibacterial agent residues. The inner layer quaternary ammonium salt loading is lower than the cytotoxicity threshold (IC50>200μg / mL). Through cytotoxicity experiments, the composite medical suture extract was co-cultured with human fibroblasts. When the chlorhexidine loading was 3%, the cell survival rate reached more than 98%, and there was no metal ion residue, indicating that the composite medical suture has good biosafety.

[0040] Another key point is: by introducing a degradation control layer to achieve dynamic matching of degradation rate and step-by-step transition of mechanical properties; because the inventors of this application found that the medical sutures currently sold on the market generally use a single layer of antibacterial, which makes the antibacterial cycle short; and a more important problem is: the degradation rate of the suture is single and cannot be coordinated with the wound healing rate, resulting in premature or late degradation, mechanical property mismatch, uncontrolled drug release, etc., which in turn affects the wound healing effect. Therefore, this embodiment introduces a degradation control layer, with a wide range of PEG molecular weights with a difference of less than one order of magnitude, which is easier to control, while also being lower in cost, non-toxic and harmless to the human body, and having no side effects; through the rapid degradation of low-molecular-weight PEG, the degradation products of the core layer are released during the inflammatory phase to avoid local acid accumulation; the sustained release of high-molecular-weight PEG maintains structural integrity during the proliferation phase, prevents tissue collapse, and maintains long-term drug release, promoting the healing of chronic wounds; ultimately achieving an adjustable degradation rate of the suture with a wide adjustable range, so that its degradation rate is coordinated with the wound healing rate, resulting in a significant wound healing effect.

[0041] Therefore, the composite medical suture described in this embodiment solves the problems of traditional sutures, such as a short antibacterial cycle and insufficient mechanical properties. Furthermore, experiments have shown that the composite medical suture described in this embodiment has a tensile strength of 175-220 MPa in a wet state, a 24-hour antibacterial rate of >99.99%, and a degradation cycle of 14-42 days, making it suitable for wounds at high risk of infection.

[0042] In a specific embodiment, the core layer further comprises carbon nanotubes, and the mass of the carbon nanotubes accounts for 0.1% to 0.5% of the mass of the entire core layer raw material.

[0043] In this embodiment, CNTs (carbon nanotubes) are used as a reinforcing agent to further enhance mechanical properties. The high strength and high modulus of CNTs significantly increase the tensile strength of the suture. Experiments have shown that the addition of CNTs can achieve a tensile strength of >200 MPa and an elongation at break of >18%. The elastic modulus of the core layer can also be adjusted to more closely resemble that of natural tissue, reducing tissue cutting or inflammatory reactions caused by stiffness mismatch. Of course, the addition of more CNTs is not necessarily better, as excessive CNTs tend to aggregate in the matrix, forming stress concentration points and reducing the flexibility of the suture. Furthermore, high CNT content makes it difficult to process the composite with the core layer. Furthermore, the more CNTs a CNT contains, the more expensive it is. Excessive CNT addition can significantly increase the cost of the suture and reduce clinical accessibility. Excessively low CNT content will not improve mechanical properties. Therefore, this embodiment limits it to 0.1% to 0.5% of the mass of the entire core layer raw material to avoid increased material brittleness, increased processing difficulty, biocompatibility risks and cost-effectiveness imbalance, and achieve multiple considerations of cost, safety and performance.

[0044] In a specific embodiment, the mass ratio of polyhydroxybutyrate-valerate copolyester to polycaprolactone-co-polyglycolide in the core layer is (6-8):(2-4); and the molecular weight of polyhydroxybutyrate-valerate copolyester is 500,000-800,000; in the molecular chain of polycaprolactone-co-polyglycolide, the molar ratio of polycaprolactone monomer unit to polyglycolide monomer unit is 80:20.

[0045] Specifically, as previously discussed, the core layer provides good biocompatibility and degradability through PHBV, while PCL-GA enhances flexibility and tensile strength. Therefore, the mass ratio of PHBV to PCL-GA is limited to a specific range to achieve a balance between mechanical properties. At the same time, the ratio between the two can control the degradation rate to meet actual use requirements, avoiding insufficient mechanical support or foreign body reactions caused by excessively fast or slow degradation of a single material. By limiting the molecular weight of PHBV to a specific range, the mechanical properties are further enhanced and the requirements for degradation stability are met. By limiting the molar ratio of the two monomer units in PCL-GA to a specific range, the mechanical properties and degradation rate of the copolymer are precisely controlled. This allows PCL-GA to maintain sufficient strength while having a moderate degradation rate, matching the degradation properties of PHBV and ensuring that the suture provides continuous support during the healing process.

[0046] In one embodiment, the degradation-regulating layer comprises a mixture of PEG-4000 and PEG-10000; the Mn of PEG-4000 is 3800-4200, and the Mn of PEG-10000 is 9500-10500. This embodiment explicitly uses a mixture of PEG-4000 and PEG-10000. These two PEGs have a wide molecular weight range, are easier to control, are less expensive, and are non-toxic and harmless to the human body with no side effects.

[0047] More specifically, the mass ratio of PEG~4000 to PEG~10000 is 1:1, and the thickness of the degradation regulation layer is 6~12μm. The core of the degradation regulation layer is to use PEG of different molecular weights in order to form a gradient of degradation rate, thereby dynamically matching the different stages of wound healing. The molecular weight difference between PEG 4000 and PEG 10000 is large, and different degradation time windows can be provided after mixing. Therefore, the mass ratio of the two is designed to be 1:1, which can ensure both rapid initial degradation and long-term support. And more importantly in this embodiment, the thickness of the degradation regulation layer is specially limited in size: the thickness of the degradation regulation layer affects drug release and mechanical properties. 6~12μm is to ensure sufficient drug load while avoiding the layer being too thick, resulting in a decrease in the overall flexibility of the suture, and being too thin to effectively regulate the degradation rate. The applicant would like to explain that this embodiment only limits the thickness of the degradation regulation layer, and does not make any requirements for other layers. Because the inventors of this application considered that the core layer, sustained-release layer, and antibacterial layer have different material properties or functional requirements, there is no need for strict thickness restrictions. The core layer in this application requires sufficient strength, which the inventors control through material ratios. The functions of the sustained-release layer and antibacterial layer also rely more on the material composition. Therefore, based on actual usage, the inventors of this application specifically adopt different methods for each layer to ensure that the function of each layer is maximized. This highly targeted approach does not impose excessive restrictions and difficulties on the subsequent preparation process, ensuring the smooth progress of the preparation process.

[0048] In one embodiment, the sustained-release layer of quaternary ammonium salt-loaded graphene oxide nanofibers comprises a quaternary ammonium salt, graphene oxide, and a substrate polymer, wherein the mass percentage of the quaternary ammonium salt is 2% to 3%, the mass percentage of the graphene oxide is 1% to 2%, and the mass percentage of the substrate polymer is 95% to 97%. The quaternary ammonium salt binds to the bacterial membrane through electrostatic interaction, and an appropriate quaternary ammonium salt ratio achieves a balance between antibacterial efficacy and cytotoxicity. The graphene oxide serves as a carrier, and its ratio affects the structure and drug loading capacity of the nanofibers. The substrate polymer primarily provides structural support, and its high ratio ensures the mechanical properties of the fibers.

[0049] At the same time, in this embodiment, the raw material of titanium dioxide loaded with silver nanoparticles in the antibacterial layer has a particle size of 10 to 20 nm, and the mass percentage of silver nanoparticles is 1% to 2%. The particle size and concentration of the silver nanoparticles in the antibacterial layer are key. The particle size is within the range of 10 to 20 nm, which can not only ensure sufficient surface area for antibacterial effect, but also avoid being too small to easily oxidize or aggregate. A concentration of 1% to 2% needs to strike a balance between antibacterial effect and material stability. Too high a concentration may cause a sudden release of silver ions and induce cytotoxicity. Therefore, the value range of each parameter in the sustained-release layer and the antibacterial layer is clearly defined, which not only achieves a significant improvement in the antibacterial effect, but also takes into account biosafety.

[0050] In a specific embodiment, the antibacterial layer further comprises a photosensitive porphyrin compound, the mass percentage of the photosensitive porphyrin compound is 0.5% to 1%, and the activation wavelength of the photosensitive porphyrin compound is 650±10 nm.

[0051] It is worth noting that a photosensitive porphyrin compound is introduced in this embodiment. When activated under specific light, the antibacterial rate is increased by an additional 15% to 20%, and wound healing is accelerated. Specifically, the photosensitive porphyrin compound can produce reactive oxygen species, further enhancing the antibacterial effect and promoting tissue repair, and sterilizing through physical mechanisms, reducing the risk of recurrence of infection. At the same time, taking into account the excessive production of reactive oxygen species produced by excessive photosensitive porphyrin compounds, causing damage to surrounding fibroblasts, thereby delaying wound healing; the activation wavelength of the photosensitive porphyrin compound is limited to achieve a balance between maximizing tissue penetration depth and minimizing light damage; ultimately achieving multiple considerations of antibacterial efficacy, biocompatibility and clinical feasibility.

[0052] In one embodiment, a method for preparing the composite medical suture as described in any one of the above items specifically comprises the following steps:

[0053] S1: Adding the raw materials of the core layer to a twin-screw extruder, melt-blending, and then extruding and drawing to obtain the core layer; specifically, adding polyhydroxybutyrate-valerate copolyester and polycaprolactone-co-polyglycolide to the twin-screw extruder, setting the screw speed of the twin-screw extruder to 60-70 r / min and the temperature to 175°C-190°C, melt-blending, and then extruding and drawing to obtain a blended fiber with a diameter of 0.12 mm as the core layer;

[0054] S2: The core layer is immersed in the degradation regulating layer, and after the impregnation, the core layer is placed in an oven to dry to form a film, and the degradation regulating layer is coated on the outer surface of the core layer to obtain an intermediate 1. Specifically, the core layer is immersed in a mixture solution of at least two polyethylene glycols with different molecular weights, the concentration of the mixture solution is 10%, and the immersion time is 5 minutes; then the impregnated blended fiber is placed in an oven at 60°C to dry to form a film with a thickness of 8 μm, thereby forming a PEG transition layer to obtain an intermediate 1.

[0055] S3: Electrospinning is used to obtain a sustained-release layer, which is then coated on the outer surface of the intermediate one to obtain the intermediate two. Specifically, the raw material of the sustained-release layer, the electrospun PHA / quaternary ammonium salt / graphene oxide solution, is dissolved in hexafluoroisopropanol to prepare a spinning solution with a concentration of 15%. Electrospinning technology is used, the viscosity of the spinning solution is 500-800 mPa·s, the spinning voltage is set to 18 kV, the receiving distance is 15 cm, the temperature is 25°C, and the humidity is 40%. The spinning solution is coated on the surface of the PEG layer to form an inner antibacterial layer, i.e., the sustained-release layer, and finally the intermediate two is obtained.

[0056] S4: spraying an antibacterial layer on the outer surface of the intermediate 2 by electrostatic spraying to obtain the final composite medical suture; specifically, The intermediate was dispersed in a 10% PHA / ethyl acetate solution. Electrostatic spraying was performed using a 20kV spray voltage and a 10cm distance between the spray gun and the sample to form an outer antibacterial layer on the second surface of the intermediate and load the photosensitive porphyrin compound, ultimately yielding a composite medical suture.

[0057] The preparation method of the composite medical suture of this embodiment has simple process steps, and each layer is superimposed through different processes to ensure the composite strength between each layer; this not only improves the comprehensive performance of the suture, such as tensile strength, degradation controllability, and drug release efficiency, but also reduces the preparation cost through process synergy, providing a new solution for the treatment of complex wounds.

[0058] In order to further facilitate the understanding of this application, the following examples are given:

[0059] Example 1

[0060] A composite medical suture comprises a core layer, a degradation regulating layer, a sustained-release layer, and an antibacterial layer, arranged sequentially from the inside out. The core layer comprises a fiber blend of polyhydroxybutyrate-valerate copolyester and polycaprolactone-co-glycolide in a mass ratio of 7:3, wherein the PHBV has a molecular weight of 500,000-800,000 and the PCL-GA copolymer ratio is 80:20, and carbon nanotubes are added, with the mass of the carbon nanotubes accounting for 0.3% of the mass of the entire core layer raw material. The preparation method comprises: weighing PHBV, PCL-GA (7:3) and 0.3% CNTs, adding them to a twin-screw extruder, setting the screw speed of the twin-screw extruder to 60 r / min and the temperature to 185°C, and extruding and drawing after melt blending to obtain a fiber with a diameter of 0.12 mm as the core layer.

[0061] The degradation-regulating layer includes a mixture of PEG-4000 and PEG-10000 (mass ratio 1:1) as a transition layer with a thickness of 8 μm. The Mn of PEG-4000 is 3800-4200, and the Mn of PEG-10000 is 9500-10500. The core layer is prepared by dipping the fiber in a PEG-4000 / PEG-10000 solution at a concentration of 10% for 5 minutes. The fiber is then dried in a 60°C oven to form an 8 μm thick film, forming the PEG transition layer.

[0062] The sustained-release layer uses quaternary ammonium salt-loaded graphene oxide nanofibers (quaternary ammonium salt loading rate 3%, graphene oxide loading rate 1%), wherein the specific surface area of ​​graphene oxide is 200-400 m² / g; it is prepared by dissolving a PHA / quaternary ammonium salt / graphene oxide solution (95-97:2-3:1-2) in hexafluoroisopropanol to prepare a spinning solution with a concentration of 15%. Using electrospinning technology, the spinning solution viscosity is 500-800 mPa·s, the spinning voltage is set to 18kV, the receiving distance is 15cm, the temperature is 25°C, and the humidity is 40%. The spinning solution is coated on the surface of the PEG layer to form an inner antibacterial layer. It is worth noting that the quaternary ammonium salt loading rate is the mass percentage of the quaternary ammonium salt in the whole; the graphene oxide loading rate is the mass percentage of the graphene oxide in the whole; the whole is the quaternary ammonium salt-loaded graphene oxide nanofibers;

[0063] The antibacterial layer is titanium dioxide loaded with silver nanoparticles ( ) coating, which is prepared by: adding 2.5% (particle size 25nm) and photosensitive porphyrin compound are dispersed in PHA / ethyl acetate solution at a mass ratio of 99:1, and the solution concentration is 10%. Electrostatic spraying equipment is used, the spraying voltage is set to 20kV, and the distance between the spray gun and the sample is 10cm. Spraying is performed to form an outer antibacterial layer with a thickness of 2μm on the surface of the suture, wherein the mass percentage of the photosensitive porphyrin compound is 0.5%~1%, and finally a composite medical suture is obtained; the photosensitive porphyrin compound can be one or more of tetraaminophenylporphyrin copper, 5,10,15,20-tetrakis(4-ethynylphenyl)porphyrin, and 5,10,15,20-tetrakis-(4-N-methylpyridine)-porphyrin. The composite medical suture is subjected to performance testing, wherein the performance test includes:

[0064] Antibacterial activity (GB / T 31402-2015): Antibacterial testing against Candida albicans demonstrated an inhibition rate of 99.60% after 24 hours, 98.00% after 7 days, and 95.20% after 14 days. The experimental procedure involved evenly spreading a suspension of Candida albicans onto a nutrient agar plate. Suture samples of the present invention were then placed on the plate and incubated in a 37°C incubator. The size of the inhibition zone was observed after 24 hours, 7 days, and 14 days, and the inhibition rate was calculated. This testing was conducted in accordance with ISO 20743:2021.

[0065] Mechanical Properties (ASTM D3822): Tensile testing of the suture using a universal materials testing machine revealed a tensile strength of 175 ± 5 MPa (1.5 times that of commercially available PGA suture in a wet state) and an elongation at break of 18%. During testing, the suture sample was clamped in the testing machine's fixture and stretched at a rate of 5 mm / min. The maximum force at break was recorded and used to calculate the tensile strength.

[0066] Degradation cycle (PBS pH 7.4, 37°C): Suture samples were placed in PBS buffer solution (pH 7.4, 37°C), and samples were taken out regularly for mechanical property testing and mass loss determination. The PBS solution was replaced every 48 hours. During the degradation process, a batch of samples were taken out every 7 days, rinsed with deionized water, and dried in a vacuum oven to constant weight. Mechanical property testing and mass loss calculation were then performed. Figure 3 As shown, the composite medical suture in this embodiment has a 21-day strength retention rate of 65% and is completely degraded in 42 days, which matches the soft tissue healing cycle.

[0067] In order to further verify the antibacterial properties of the composite medical sutures of the present application, two groups of comparative experiments are given: the first group of comparative experiments is pure PHA medical sutures, and the second group of comparative experiments is commercially available silver ion sutures. Ionic sutures refer to antibacterial sutures containing silver ions. Silver ions are added to conventional sutures as antibacterial agents; Combining Example 1 with the two groups of comparative examples, the following results are obtained: Figure 2 As shown by Figure 2 It can be clearly seen that the antibacterial effect of the present application is significantly better than that of the two comparison groups, and it can still maintain more than 95% of the antibacterial property after 14 days, with a long antibacterial cycle and good effect.

[0068] The examples described in the present invention are merely descriptions of the preferred embodiments of the present invention and are not intended to limit the concept and scope of the present invention. Without departing from the design concept of the present invention, various modifications and improvements made to the technical solutions of the present invention by engineers and technicians in this field should fall within the scope of protection of the present invention.

Claims

1. A composite medical suture, characterized in that: The invention comprises a core layer, a degradation regulating layer, a sustained-release layer, and an antibacterial layer, which are sequentially arranged from the inside out; the core layer comprises a blended fiber of polyhydroxybutyrate-valerate copolyester and polycaprolactone-co-glycolide; the degradation regulating layer comprises a mixture of at least two polyethylene glycols of different molecular weights; the sustained-release layer comprises quaternary ammonium salt-loaded graphene oxide nanofibers; and the antibacterial layer comprises titanium dioxide loaded with silver nanoparticles; wherein the molecular weights of the mixture of at least two polyethylene glycols of different molecular weights in the degradation regulating layer differ by at least one order of magnitude. The mass ratio of polyhydroxybutyrate-valerate copolyester to polycaprolactone-co-polyglycolide in the core layer is (6-8): (2-4); The degradation regulating layer includes a mixture of PEG-4000 and PEG-10000; the mass ratio of PEG-4000 to PEG-10000 is 1:1, and the thickness of the degradation regulating layer is 6-12 μm.

2. The composite medical suture according to claim 1, characterized in that: The core layer further comprises carbon nanotubes, the mass of which accounts for 0.1% to 0.5% of the mass of the entire core layer raw material.

3. The composite medical suture according to claim 2, characterized in that: The molecular weight of polyhydroxybutyrate-valerate copolyester is 500,000 to 800,000; in the molecular chain of polycaprolactone-co-polyglycolide, the molar ratio of polycaprolactone monomer unit to polyglycolide monomer unit is 80:

20.

4. The composite medical suture according to claim 1, characterized in that: The Mn of PEG-4000 is 3800~4200, and the Mn of PEG-10000 is 9500~10500.

5. The composite medical suture according to claim 1, characterized in that: The quaternary ammonium salt-loaded graphene oxide nanofibers of the sustained-release layer include quaternary ammonium salt, graphene oxide and a substrate polymer, wherein the mass percentage of the quaternary ammonium salt is 2% to 3%, the mass percentage of the graphene oxide is 1% to 2%, and the mass percentage of the substrate polymer is 95% to 97%.

6. The composite medical suture according to claim 1, characterized in that: In the titanium dioxide loaded with silver nanoparticles, the particle size of the silver nanoparticles is 10-20 nm, and the mass percentage of the silver nanoparticles is 1%-2%.

7. The composite medical suture according to claim 1 or 6, characterized in that: The antibacterial layer further includes a photosensitive porphyrin compound, the mass percentage of the photosensitive porphyrin compound is 0.5% to 1%, and the activation wavelength of the photosensitive porphyrin compound is 650±10 nm.

8. A method for preparing the composite medical suture according to any one of claims 1 to 7, characterized in that: The specific steps include: S1: adding the raw materials of the core layer into a twin-screw extruder, and extruding and drawing after melt blending to obtain the core layer; S2: dipping the core layer in the degradation regulating layer, drying in an oven to form a film, and coating the outer surface of the core layer with the degradation regulating layer to obtain an intermediate 1; S3: obtaining a sustained-release layer by electrospinning, and coating the sustained-release layer on the outer surface of the intermediate 1 to obtain the intermediate 2; S4: spraying an antibacterial layer on the outer surface of the intermediate 2 by electrostatic spraying to obtain the final composite medical suture thread.

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