An anti-infective pro-healing bifunctional electroactive suture and methods of making and using the same

Abstract

This invention discloses a dual-function electroactive suture for anti-infection and promoting wound healing, its preparation method, and its applications. This invention develops a dual-function electroactive suture that integrates wound closure and piezoelectric functions, possessing both optimized mechanical properties and stable electroactivity under low-intensity pulsed ultrasound. In some embodiments, when treated with low-intensity pulsed ultrasound, the dual-function electroactive suture can generate reactive oxygen species, disrupting bacterial membrane integrity and reducing bacterial activity. In vivo experiments show that this suture can improve inflammatory responses, promote angiogenesis, and enhance tissue repair. Furthermore, the multi-strand structure designed based on the dual-function electroactive suture exhibits superior mechanical properties and wound-healing functions, showing broad application prospects in clinical wound treatment.

Description

Technical Field

[0001] This invention relates to the field of medical materials, specifically to a dual-function electroactive suture for anti-infection and promoting healing, its preparation method, and its application. Background Technology

[0002] Sutures are the most widely used method of wound closure, relying on their own mechanical properties to close the wound and provide support for healing. The history of sutures can be traced back to ancient Egypt around 3000 BC, more than 5000 years ago. Ancient people used natural materials such as flax and horsehair to make sutures, while modern sutures are mainly divided into absorbable sutures made of catgut or polyglycolic acid, and non-absorbable sutures made of polypropylene or nylon. However, from ancient natural materials to modern standardized synthetic polymer materials, the improvement and development of sutures has always focused on improving mechanical properties and biodegradability. No substantial breakthroughs have been made in the function of monofilaments; apart from relying on mechanical strength to achieve the basic function of wound closure, no innovative improvements have been achieved.

[0003] Surgical site infections occur in up to 23% of cases, not only reducing surgical outcomes and prolonging hospital stays, but also potentially leading to serious complications. Traditional single-function sutures struggle to create a long-lasting antibacterial environment and cannot resist the adhesion and invasion of pathogens. As a key instrument for promoting wound closure, researchers have employed various suture modification strategies to enhance their inherent antibacterial properties, such as antibiotic coatings and the incorporation of natural antibacterial agents. However, these strategies have inherent drawbacks, easily inducing antibiotic resistance in bacteria and failing to achieve long-lasting antibacterial effects, thus limiting their clinical application. Currently, there is still a functional gap in achieving localized long-term control of pathogens based on purely physical principles, highlighting the necessity and potential value of developing novel suture systems.

[0004] The information in the background section is merely intended to illustrate the general background of the invention and should not be construed as an admission or implication in any way that such information constitutes prior art known to those skilled in the art. Summary of the Invention

[0005] To address at least some of the technical problems existing in current technologies, such as the current problem of surgical site infection, this invention develops a bifunctional electroactive suture. It utilizes the catalytic effect of a specific organic piezoelectric material, preferably further combined with the local acoustic energy conversion characteristics of on-demand activation by common stress stimulation and low-intensity pulsed ultrasound to achieve bifunctional electroactivity. This invention's bifunctional electroactive suture, designed with a specific organic piezoelectric material as its substrate, not only integrates reactive oxygen species-mediated on-demand antibacterial function and electrically stimulated wound healing promotion, but also possesses excellent mechanical properties. It is operable in both single-strand and multi-strand forms, effectively preventing surgical site infection and accelerating wound healing. This invention pioneers a paradigm shift in sutures from single-function to bioactive, wound-microenvironment-adaptive sutures, providing a scalable platform for next-generation intelligent sutures, thereby driving the biomedical engineering industry's paradigm upgrade from "passive structural support" to "active functional therapy." Specifically, this invention includes the following:

[0006] In a first aspect, the present invention provides a bifunctional electroactive monofilament suture for anti-infection and promoting healing, wherein the suture is made from a raw material comprising an organic piezoelectric material containing a β phase, the suture outputting a voltage of not less than 0.5 V, a breaking strength of not less than 5 N, a nodule strength of not less than 3 N, and a bending stiffness of 1-20 cN·mm. 2 .

[0007] In some embodiments, the anti-infection and healing-promoting bifunctional electroactive monofilament suture according to the present invention has a density of not less than 0.3 pCN. -1 piezoelectric constant d 33 value.

[0008] In some embodiments, the anti-infection and healing-promoting bifunctional electroactive monofilament suture according to the present invention is wherein the frictional force between the suture and the tissue is not higher than 20 cN.

[0009] In some embodiments, the anti-infection and healing-promoting bifunctional electroactive monofilament suture according to the present invention is wherein the suture is made from a raw material comprising an organic piezoelectric material through melt spinning extrusion, stretching, corona polarization and annealing.

[0010] In some embodiments, the anti-infection and healing-promoting bifunctional electroactive monofilament suture according to the present invention is wherein the annealing treatment temperature is less than 120°C and the treatment time is less than 2 hours.

[0011] In some embodiments, the anti-infection and healing-promoting bifunctional electroactive monofilament suture according to the present invention is wherein the suture is not ultrasonically treated.

[0012] In some embodiments, the anti-infection and healing-promoting bifunctional electroactive monofilament suture according to the present invention is wherein the suture is ultrasonically treated, and the parameters of the ultrasonic treatment include at least one of the following: a pulse repetition frequency of 10 Hz to 1 kHz, a frequency of 0.3 MHz to 5 MHz, and an effective sound intensity of 0.10 W / cm². 2 Up to 3.00 W / cm 2 .

[0013] In some embodiments, the anti-infection and healing-promoting bifunctional electroactive monofilament suture according to the present invention has a diameter of 0.05 mm to 0.50 mm.

[0014] A second aspect of the present invention provides an anti-infection and healing-promoting bifunctional electroactive multistrand suture, comprising multiple strands of suture as described in any one of the first aspects.

[0015] In some embodiments, the anti-infection and healing-promoting bifunctional electroactive multistrand suture according to the present invention has a topological structure on its surface along its length, such that there are differences in the potential distribution on its surface.

[0016] A third aspect of the invention provides the use of the sutures according to any one of the foregoing claims in the preparation of medical materials or medical devices for surgical wound closure, prevention or treatment of surgical site infection, and / or promotion of wound healing.

[0017] According to any of the above embodiments of the present invention, the suture contains an organic piezoelectric material that may include at least one of the following: polyvinylidene fluoride, polyvinylidene fluoride-trifluoroethylene copolymer, polyvinylidene fluoride-hexafluoropropylene copolymer, and polyvinylidene fluoride-tetrafluoroethylene copolymer.

[0018] According to any of the above embodiments of the suture, the raw material may further include inorganic piezoelectric materials, such as nanoscale ceramic particles, including at least one of barium titanate, barium strontium titanate, strontium titanate, lithium niobate, and sodium potassium niobate.

[0019] This invention, based on the principle of purely physical antibacterial action, develops a bifunctional electroactive suture that integrates wound closure and piezoelectric functions. This suture combines optimized mechanical properties with stable electroactivity under low-intensity pulsed ultrasound stimulation, achieving a synergistic effect. Under low-intensity pulsed ultrasound stimulation, the bifunctional electroactive suture generates reactive oxygen species, disrupting bacterial membrane integrity and reducing bacterial activity. In vivo experiments show that this suture improves inflammatory responses, promotes angiogenesis, and enhances tissue repair. Furthermore, the multi-strand structure designed based on the bifunctional electroactive suture exhibits superior mechanical properties and healing-promoting functions. This invention establishes a pioneering paradigm for the development of bifunctional sutures that integrate wound closure and long-lasting antibacterial effects, highlighting the potential of piezoelectric materials in advancing clinical wound treatment. Attached Figure Description

[0020] Figure 1 Characterization and electrical properties of bifunctional electroactive sutures are shown. (A) Voltage output of the suture. (B) Representative scanning electron microscope (SEM) images of suture knots. (C) X-ray diffraction (XRD) patterns of sutures with different diameters, with peaks of the polar β phase highlighted in boxes. (D) Surface potential distribution models of sutures with different diameters based on phase field simulation. (E) Representative SKPM images of suture knots with diameters of 0.12, 0.16, and 0.24 mm. (F) UV-Vis absorption spectra of indigo carmine solution treated with low-intensity pulsed ultrasound (LIPUS) using sutures of different diameters. (GH) Free radicals •OH and •O2 driven by low-intensity pulsed ultrasound (LIPUS) in different diameter ranges. - The electron paramagnetic resonance (EPR) spectrum of [the sample / sample] is not significant (in ns). *** p <0.001; **** p <0.0001.

[0021] Figure 2 The voltage output of sutures prepared by different annealing temperatures and times under low-intensity pulsed ultrasound catalysis is shown.

[0022] Figure 3 Different sutures are shown d 33 Quantitative analysis of values.

[0023] Figure 4 The mechanical properties of the sutures are shown. (A) Schematic diagram of suture mechanical property testing. (B) Tensile curve of the suture. (C) Quantitative analysis of breaking force. (D) Quantitative analysis of suture knot strength. (E) Quantitative analysis of bending stiffness. (F) Friction curve between the suture and tissue. (G) Quantitative analysis of the average friction force between the suture and tissue. (ns, no significant; ***) p<0.001; **** p <0.0001.

[0024] Figure 5 A schematic diagram of the suture scratch assay is shown (A). A confocal snapshot of the in vitro scratch assay shows the migration of L929 cells (green) in a culture dish at 0, 12, and 24 hours under low-intensity pulsed ultrasound (LIPUS) stimulation (B). Quantitative analysis of wound closure (C). ns, no significant difference; *** p <0.001; **** p <0.0001.

[0025] Figure 6 The mechanism by which low-intensity pulsed ultrasound catalyzes the anti-Staphylococcus aureus effect of sutures is illustrated. (A) Staphylococcus aureus with sutures and the commercially available suture Prolene. TM Images of live and dead cells after co-culture. (B) Evaluation of Staphylococcus aureus with sutures and commercially available Prolene sutures by DCFH-DA staining. TM Intracellular reactive oxygen species (ROS) levels after co-culture. (C) Staphylococcus aureus with sutures and commercially available Prolene sutures. TM Representative scanning electron microscope (SEM) images after co-culture. Yellow arrows indicate shrinkage and destruction changes in Staphylococcus aureus. (D) Quantitative analysis of antibacterial rate driven by low-intensity pulsed ultrasound, calculated by fluorescence intensity. (E) Quantitative analysis of reactive oxygen species (ROS) intensity driven by low-intensity pulsed ultrasound, calculated by fluorescence intensity. (F) Assessment of Staphylococcus aureus in contrast agents with and without ultrasound, and commercially available Prolene sutures, by crystal violet staining. TM Biofilm formed after co-culturing (with and without ultrasound). ns, no significant difference; *** p <0.001; **** p <0.0001.

[0026] Figure 7 The mechanism by which low-intensity pulsed ultrasound catalyzes the anti-Escherichia coli activity of sutures is illustrated. (A) Escherichia coli with sutures and the commercially available suture Prolene. TM Images of live and dead cells after co-culture. (B) Evaluation of E. coli with sutures and commercial suture Prolene by DCFH-DA staining. TM Intracellular reactive oxygen species (ROS) levels after co-culture. (C) Escherichia coli with sutures and commercially available Prolene sutures. TMRepresentative scanning electron microscope (SEM) images after co-culture with Prolene. Yellow arrows indicate shrinkage and destruction changes in Staphylococcus aureus. (D) Quantitative analysis of antibacterial rate driven by low-intensity pulsed ultrasound, calculated by fluorescence intensity. (E) Quantitative analysis of reactive oxygen species (ROS) intensity driven by low-intensity pulsed ultrasound, calculated by fluorescence intensity. (F) Assessment of Escherichia coli in contrast agents with sutures (with and without ultrasound) and commercially available Prolene sutures, using crystal violet staining. TM Biofilm formed after co-culturing (with and without ultrasound). ns, no significant difference; *** p <0.001; **** p <0.0001.

[0027] Figure 8 This diagram illustrates the mechanism by which low-energy pulsed ultrasound (LIPUS) catalyzes sutures to promote in vivo wound healing and the therapeutic effect of sutures. (A) Establishment of a full-thickness incision model. (B) Representative photographs of wounds from different groups treated with LIPUS at different time points. (C) Representative H&E staining images of wound tissue from different groups treated with LIPUS on days 7 and 14. (D) Representative Masson staining images of wound tissue from different groups treated with LIPUS on days 7 and 14. (E) Quantitative analysis of wound length in different groups driven by low-intensity pulsed ultrasound (LIPUS) on days 7 and 14. (F) The diagram shows the effects of sutures and the commercially available Prolene suture. TM Representative immunofluorescence images of keratin-5 (KRT-5, green), α-smooth muscle actin (α-SMA, red), and interleukin-6 (IL-6, pink) in the wound 14 days after treatment. DAPI-stained cell nuclei (blue). Mean fluorescence intensity was calculated to assess protein expression levels. ns, no significant difference; *** p <0.001; **** p <0.0001.

[0028] Figure 9 The optimized design and functional validation of multi-strand electroactive sutures are shown. (A) Multi-strand sutures woven from three monofilaments. (B) Scanning electron microscopy of the multi-strand sutures. (C) Knot safety test compared to monofilaments. (D) Knot safety test compared to monofilaments. (E) Co-culture of Staphylococcus aureus and Escherichia coli, bacterial viability staining, and ROS detection. (F) Antibacterial rate and ROS quantification of Staphylococcus aureus and Escherichia coli. (G) Cell migration guided by multi-strand sutures (cell scratch assay). (H) Statistical analysis of scratch healing percentage. Detailed Implementation

[0029] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0030] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that the upper and lower limits of the range and each intermediate value between them are specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0031] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to documents cited herein are incorporated by way of citation to disclose and describe methods and / or materials associated with those references.

[0032] sutures In a first aspect, the present invention provides a bifunctional electroactive monofilament suture for anti-infection and promoting healing, which is prepared from raw materials comprising organic piezoelectric materials. Examples of said organic piezoelectric materials include, but are not limited to, at least one selected from polyvinylidene fluoride, polyvinylidene fluoride-trifluoroethylene copolymer, polyvinylidene fluoride-hexafluoropropylene copolymer, polyvinylidene fluoride-tetrafluoroethylene copolymer, polymethyl methacrylate, polydimethylsiloxane, and polylactic acid (L-lactic acid). The present invention may use one of the above-mentioned organic piezoelectric materials, or a combination of two or more organic piezoelectric materials. When using a combination of two or more organic piezoelectric materials, the ratio between the various organic piezoelectric materials is not particularly limited and can be arbitrary.

[0033] In some embodiments, the raw material of the suture of the present invention may further include inorganic piezoelectric materials, which are generally nanoscale ceramic particles, examples of which include, but are not limited to, barium titanate, barium strontium titanate, strontium titanate, lithium niobate, and sodium potassium niobate. The present invention may use one or more combinations of the above components. In the case of combinations, the proportions of each component are not limited and can be freely set as needed. The particle size of the inorganic piezoelectric material is generally 1 mm. 500 nm, preferably 10 300 nm, more preferably 20 nm 200nm, further optimized to 30 100 nm. When inorganic piezoelectric materials are present, the amount of inorganic piezoelectric materials used in suture raw materials is generally 1 by weight. 20%, preferred 1 15%, more preferably 5 10%.

[0034] In some embodiments, when detected using an electrometer, the voltage output of the single-strand suture of the present invention is not less than 0.5 V, for example -0.5 V to 0.5 V, -1.0 V to 1.0 V, -1.5 V to 1.5 V, or -2.0 V to 2.5 V.

[0035] In some embodiments, the piezoelectric constant of the monofilament suture of the present invention is measured by a piezoelectric coefficient meter. d 33 Generally, it is above 0.3 pC / N, such as 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5 pC / N or above.

[0036] In some embodiments, when using an electronic universal testing machine, with a single knot tied in the middle of the suture, a gauge length of 50 mm, and a tensile speed of 100 mm / min, the breaking strength of the single strand suture of the present invention is not less than 5 N, for example not less than 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50 N.

[0037] In some embodiments, when the suture is knotted on a disc using an electronic universal testing machine with a gauge length of 2 mm and a tensile speed of 100 mm / min, the knot strength of the single-strand suture of the present invention is not less than 3 N, for example not less than 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, or 50 N.

[0038] The monofilament suture of the present invention possesses excellent flexibility suitable for wound closure. In some embodiments, the monofilament suture of the present invention exhibits a bending stiffness of 1-20 cN·mm when measured with a 0.1 G clamp vertical distance. 2 For example, 2-18 cN·mm 2 Such as 2-6, 5-12, 12-18 cN·mm 2 .

[0039] The monofilament suture of this invention has suitable frictional force with tissue. On the one hand, excessive frictional force will significantly increase the difficulty of surgical operation, aggravate tissue damage, and affect the healing effect. On the other hand, insufficient frictional force will cause the knot to loosen on its own (slippage), leading to wound dehiscence. In some embodiments, the frictional force between the monofilament suture of this invention and tissue is not higher than 20 cN, for example, not higher than 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 cN.

[0040] In this invention, the diameter of the single-strand suture is generally 0.05 mm to 0.50 mm, preferably 0.10 mm to 0.30 mm, for example 0.11, 0.12, 0.13, 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.20, 0.21, 0.22, 0.23, 0.24, 0.25, 0.26, 0.27, 0.29, 0.30, etc.

[0041] In this invention, the preparation method of the monofilament suture is not particularly limited. It can be prepared into filaments or fibers from raw materials including organic piezoelectric materials through appropriate pretreatment, and then prepared through appropriate post-treatment. Pretreatment includes, but is not limited to, processes such as melt spinning, solution spinning, or electrospinning. Post-treatment includes, but is not limited to, stretching and heat setting, braiding and twisting, or coating processes. Post-treatment may further include corona polarization and / or annealing. In order to obtain the optimal balance of mechanical and electrical properties suitable for suture applications, thereby giving it excellent mechanical properties, electrical properties, antibacterial properties, and wound healing promotion properties, this invention has conducted in-depth research on annealing temperature. The results show that if the annealing temperature is too high, for example, the excessive increase in certain mechanical properties (such as elastic modulus) is not conducive to suture knotting, and therefore it is not suitable for suture applications. On the other hand, if the annealing temperature is too low, the electrical properties are poor, thereby greatly reducing the antibacterial properties and wound healing promotion properties.

[0042] In this invention, the annealing treatment generally includes placing the monofilament suture at a high temperature for 30 minutes to 1.5 hours, preferably 50 minutes to 1.5 hours, and even more preferably 50 minutes to 1.2 hours. The high temperature generally refers to 80-115°C, preferably 80-110°C, and even more preferably 90-110°C, for example 95-110°C or 95-105°C, such as 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, or 105°C. After the high-temperature standing period, cooling is then performed. Cooling can be natural cooling at room temperature or, for example, at a rate of 0.5-5°C / min, preferably 1-3°C / min, to reduce the temperature to room temperature.

[0043] In this invention, the polarization treatment conditions generally include a polarization medium of air or methyl silicone oil, a polarization voltage of 1 kV-30 kV, more preferably 2 kV-25 kV, and a distance between the electrode tip and the sample of 1 mm-50 mm, such as 5 mm, 10 mm, 15 mm, 20 mm, 25 mm, 30 mm, and 35 mm. The polarization temperature is 20℃-50℃, such as 25, 30, 35, or 40℃. The polarization time is 1 minute-60 minutes, such as 5 minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, and 55 minutes.

[0044] In some non-limiting embodiments, the monofilament suture of the present invention is prepared by melt spinning. The melt spinning temperature is not particularly limited, as long as the piezoelectric polymer is in a molten state. The spinning machine is not particularly limited in the present invention; any melt spinning machine known in the art can be used, as long as the purpose of the present invention is achieved. Alternatively, the filament or fiber can be prepared by solution spinning. In this case, the organic piezoelectric polymer can be dissolved in a suitable solution and further subjected to a solution spinning step. The concentration of the organic piezoelectric polymer is particularly limited and can be adjusted as needed. When using electrospinning, the operating parameters of the electrospinning machine are not particularly limited, as long as the purpose of the present invention is achieved.

[0045] Those skilled in the art will understand that, in the preparation of monofilament sutures, any coated filaments, fibers, or monofilament sutures are also within the scope of protection of this invention, and any coating that can enhance or improve antibacterial, conductive, hydrophobic, hydrophilic, superhydrophilic, flame retardant, high temperature resistant, heat insulating, UV resistant, anti-aging, corrosion resistant, biocompatible, bioactive, drug sustained release, sensor response, or mechanical properties can be used in this invention.

[0046] When a coating is included, the specific composition of the coating is not particularly limited, and includes, but is not limited to, organic materials, inorganic materials, organic-inorganic hybrid materials, metallic materials, carbon materials, or combinations of two or more of the aforementioned materials. Polymer materials include, but are not limited to, thermoplastic polymers, thermosetting polymers, elastomers, conductive polymers, biodegradable polymers, hydrogels, photocurable resins, thermosetting resins, polyurethanes, polyacrylates, polyesters, polyamides, polyimides, polyvinyl alcohol, polyethylene glycol, polylactic acid, polycaprolactone, polyvinylidene fluoride, polytetrafluoroethylene, polystyrene, polypyrrole, polyaniline, polythiophene, or copolymers, blends, or derivatives of the aforementioned substances. Inorganic non-metallic materials include, but are not limited to, metal oxides, metal nitrides, metal carbides, non-metallic oxides, ceramic materials, and glassy materials, such as, but not limited to, silicon dioxide, titanium dioxide, and oxygen. Aluminum oxide, zinc oxide, zirconium oxide, silicon nitride, silicon carbide, graphene oxide, reduced graphene oxide, graphene, carbon nanotubes, fullerenes, carbon quantum dots, clay, zeolite, calcium phosphate, hydroxyapatite; metallic materials including but not limited to gold, silver, copper, aluminum, nickel, titanium, zinc, iron, platinum, palladium, chromium, or alloys of the aforementioned metals, core-shell structured metal nanoparticles, metal nanowires; bioactive materials including but not limited to proteins, peptides, polysaccharides, nucleic acids, growth factors, antibiotics, anti-inflammatory drugs, antimicrobial peptides, enzymes, extracellular matrix components, such as but not limited to collagen, gelatin, chitosan, alginate, hyaluronic acid, heparin; functional materials including but not limited to photocatalysts, photosensitizers, electroactive materials, magnetically responsive materials, phase change materials, flame retardants, UV stabilizers, antioxidants, preservatives, colorants, dyes, pigments, fluorescent markers, quantum dots, self-healing materials.

[0047] In this invention, the formation method of the coating is not particularly limited. A suitable process can be selected based on the properties of the coating material, the characteristics of the fiber substrate, and the final application requirements. This includes, but is not limited to, liquid phase coating, vapor phase deposition, melt or thermal processing, surface chemical modification, and in-situ generation. These processes can be used individually or in combination. For example, surface activation treatment can be performed before coating, or multiple layers of different processes can be used sequentially to form a composite coating. The form of the coating on the fiber surface is not particularly limited. It can be a continuous or discontinuous coating, a single-layer or multi-layer coating, a uniform thickness coating or a gradient thickness / gradient composition coating, a dense or porous coating, a smooth surface coating or a rough surface / micro / nanostructure coating, an encapsulating coating (completely wrapping the fiber), or only covering part of the fiber surface. Furthermore, the coating can also penetrate into the fiber interior to form a surface composite structure.

[0048] In some embodiments, the sutures of the present invention are not ultrasonically treated. In other embodiments, the sutures of the present invention are ultrasonically treated, particularly with low-intensity pulsed ultrasound. Any suitable drive mechanism can be used to provide the desired low-intensity pulsed ultrasound stimulation. The drive mechanism is not particularly limited and can be any low-intensity pulsed ultrasound providing device or unit. Preferably, the effective acoustic intensity of the ultrasound waves generated by the drive mechanism is 0.10 W / cm². 2 Up to 3.00 W / cm 2 Preferably, the concentration is 0.20 to 2.50 W / cm². 2 Furthermore, a preferred value is 0.25 W / cm. 2 The above is preferred, with 2.4 W / cm² being more desirable. 2 The effective sound intensity should not be too high. When the effective sound intensity is higher, the voltage generated by the single-strand suture decreases instead of increasing. When the effective sound intensity is controlled within the above range, it exhibits higher output voltage, antibacterial activity, and wound-healing promotion properties. The frequency of ultrasound is generally 0.3MHz to 5MHz, for example, 0.5-4MHz, such as 1MHz, 2MHz, 3MHz, etc. The frequency of ultrasound should not be too high; as the frequency increases, the output voltage decreases. When the frequency of ultrasound is within the above range, it exhibits higher output voltage, antibacterial activity, and wound-healing promotion properties. Furthermore, the pulse repetition frequency is generally 10Hz to 1kHz, for example, 20-0.5kHz, 50-0.5kHz, etc.

[0049] In some embodiments, the drive mechanism of the present invention is configured to provide ultrasound in a pulsed manner. Pulsed manner refers to providing pulsed ultrasound by outputting ultrasound at fixed and / or variable time intervals, or by outputting different ultrasounds within fixed and / or variable time intervals. The time interval can be, for example, 1-20 ms, preferably 1-10 ms, such as 2 ms, 3 ms, 4 ms, 5 ms, 6 ms, etc. Different ultrasounds refer to, for example, ultrasounds of different frequencies. In an exemplary embodiment, the pulsed manner outputs ultrasound at a fixed time interval of 1 ms. In another exemplary embodiment, the pulsed manner outputs ultrasound at variable time intervals, for example, a first pulse wave followed by an interval of, for example, 1 ms, then a second pulse wave, followed by an interval of, for example, 2 ms. The variable time interval can be regular, for example, gradually increasing or decreasing, or it can be irregular.

[0050] In addition to the drive mechanism, other components or mechanisms connected to the drive mechanism are also within the scope of this invention, such as, but not limited to, microcontrollers, detectors, power supplies, or charging interfaces. It is understood that the microcontroller, detector, and drive mechanism can be communicatively connected.

[0051] In some embodiments, the phase structure was determined by X-ray diffraction (copper target Kα rays, λ=1.5406 Å, 2θ=20°-60°), and the β-phase intensities were as follows: PVDF-0.24: 15746.3456, PVDF-0.16: 13882.5169, PVDF-0.12: 9969.35897, PVDF-N (unannealed and unpolarized PVDF wire): 5620.05747.

[0052] The present invention further provides a dual-function electroactive multistrand suture for anti-infection and wound healing promotion, comprising multiple strands of the single-strand suture as described above. The present invention has found that the multistrand suture exhibits significantly improved electrical properties and certain mechanical properties compared to single-strand sutures, thereby further significantly enhancing its antibacterial and wound healing promoting properties.

[0053] In a preferred embodiment, the multi-strand suture of the present invention has a topological structure on its surface along its length, resulting in a difference in potential distribution on its surface. In some embodiments, the multi-strand suture of the present invention exhibits a non-uniform surface potential distribution in space, wherein the range of the surface potential is greater than 10 mV, preferably greater than 20 mV, more preferably greater than 50 mV, more preferably greater than 70 mV, for example greater than 75, 80, 85, 90, or 100 mV.

[0054] In some embodiments, the surface topology of the multi-strand suture of the present invention is configured to form periodically varying band bends on the surface.

[0055] In some embodiments, the multi-strand suture of the present invention has an uneven structure on its surface, the uneven structure causing the surface to have at least a first region and a second region, the surface potential difference between the first region and the second region being 10-100mV.

[0056] In this invention, the potential distribution difference of multi-strand sutures can be determined using methods known in the art, such as using a Kelvin probe force microscope (KPFM) at room temperature, in an atmospheric environment (or in a vacuum) to measure the contact potential difference (CPD) on the sample surface.

[0057] In a preferred embodiment, the multi-strand suture of the present invention has a breaking strength of not less than 8 N (e.g., 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 N, or greater than 20 N).

[0058] In a preferred embodiment, the multi-strand suture of the present invention has a nodule strength of not less than 10 N, preferably not less than 15 N, for example not less than 16, 17, 18, 19, 20 N, or greater than 20 N.

[0059] In a preferred embodiment, the bending stiffness of the multi-strand suture of the present invention is 1-20 cN•mm. 2 For example, 2-18 cN•mm 2 Such as 3-8, 8-12, 12-18 cN•mm 2 In some implementations, when measured with a vertical distance of 0.1 G from the clamp, the bending stiffness is 3-7 cN•mm. 2 Within the range. In another embodiment, when measured with a vertical distance of 0.25 G clamp, the bending stiffness is in the range of 8-12 cN•mm. 2 Within the range.

[0060] The multi-strand suture of the present invention has a suitable frictional force with tissue. On the one hand, excessive frictional force of the multi-strand suture will significantly increase the difficulty of surgical operation, aggravate tissue damage, and affect the healing effect. On the other hand, insufficient frictional force of the multi-strand suture will cause the knot to loosen on its own (slippage), leading to wound dehiscence. In some embodiments, the frictional force between the multi-strand suture and the tissue is less than 50 cN, preferably less than 40 cN, and even more preferably less than 38 cN.

[0061] In this invention, the method for preparing multi-strand sutures is not particularly limited. For example, multi-strand sutures as described in this invention can be formed into multi-strand sutures through a suitable process, which is not particularly limited. For example, multi-strand sutures can be formed by weaving or twisting.

[0062] In this invention, the multi-strand suture may include at least two strands, for example, at least three, four, five, six, seven, eight, nine, or ten strands. When two strands are present, for braiding purposes, it can be further compounded with other single-strand fibers, which may or may not have piezoelectric properties. Preferably, the multi-strand electroactive suture is braided from three single-strand sutures with a diameter of 0.12 mm.

[0063] Antibacterial methods In one aspect, the present invention provides an in vitro antibacterial method comprising the step of causing a monofilament or multifilament suture to exhibit enhanced electroresponsiveness under pulsed ultrasound conditions.

[0064] In this invention, antibacterial action is achieved through ultrasound. Ultrasonic antibacterial action not only destroys the structure of bacteria through the sound energy of ultrasound, but more importantly, it achieves antibacterial action by stimulating the piezoelectric activity generated by the ultrasound suture. This antibacterial effect is particularly significant in multi-strand sutures with topological structures. This invention has found that differences in potential distribution significantly improve the antibacterial effect.

[0065] In some embodiments, the antibacterial method of the present invention has a stronger effect, and thus can be understood as a method to improve the antibacterial effect, which not only includes providing ultrasound to the piezoelectric responsive filament, but also further includes providing low-pulse ultrasound to the suture, and more preferably, the target of the low-pulse ultrasound is a multi-strand suture with a surface topology.

[0066] In some embodiments, the antibacterial method of the present invention can be applied to sterilization in the in vitro environment, such as sterilization on the surface of an object.

[0067] application In one aspect, the present invention provides the use of the sutures described in any of the above claims in the preparation of medical materials or medical devices for surgical wound closure, prevention or treatment of surgical site infection, and / or promotion of wound healing.

[0068] In this invention, the medical materials or medical devices are not particularly limited, such as needle sutures, barbed sutures, surgical closure instruments containing said sutures (e.g., but not limited to disposable suture packs, automatic suture devices, laparoscopic suture devices), and wound care devices or systems containing said electroactive sutures (e.g., but not limited to low-intensity pulsed ultrasound therapy devices, etc.).

[0069] Example The following example, using polyvinylidene fluoride as the piezoelectric polymer, illustrates the preparation, characterization, and functional verification of a bifunctional electroactive suture.

[0070] I. Experimental Methods 1. Material preparation Polyvinylidene fluoride was melt-extruded and stretched to obtain suture monofilaments of different diameters. To achieve surface charge polarization, the monofilaments were annealed at 100°C for 1 hour, and then subjected to corona polarization treatment at the same temperature to complete the polarization of the suture and give it a surface charge, thus obtaining a bifunctional electroactive suture.

[0071] Multi-strand electroactive sutures were prepared by mechanical weaving using three strands of 120 μm bifunctional electroactive sutures as raw materials.

[0072] 2. Structural characterization and detection of piezoelectric catalytic effect The microstructure of the suture was characterized using field emission scanning electron microscopy; the surface roughness of the suture was detected using white light interferometry; the phase structure of the polyvinylidene fluoride fiber was determined using X-ray diffraction (copper target Kα rays, λ=1.5406 Å, 2θ=20°-60°); the output voltage of the suture was detected using an electrometer; and the piezoelectric constant was determined using a piezoelectric coefficient meter. d 33Using Rhodamine B as the target degradation product, 50 mg of electroactive suture was dispersed in 50 mL of a 10 mg / L Rhodamine B aqueous solution and treated with low-intensity pulsed ultrasonic vibration (1 W / cm², 1 MHz) for 0, 5, 10, and 15 minutes. At each time point, 3 mL of the suspension was periodically collected, and the concentration of residual Rhodamine B in the supernatant was determined using a UV-Vis spectrophotometer. Electron paramagnetic resonance spectroscopy combined with the spin trapping method of dimethylpyridine N-oxide was used to detect the active substances generated by piezoelectric catalysis: 10 mg of sample was dispersed in 10 mL of deionized water and 10 mL of dimethyl sulfoxide, respectively, to detect hydroxyl radicals and reactive oxygen anions; 200 μL of the above solution was taken, 20 μL of dimethylpyridine N-oxide was added, and the solution was ultrasonicated for 15 minutes before immediately detecting the active substances.

[0073] 3. Characterization of mechanical properties The tensile properties of knotted sutures were tested using an electronic universal testing machine: ① Breaking strength: A single knot was tied in the middle of the suture, with a gauge length of 50 mm and a tensile speed of 100 mm / min; ② Knot strength: The suture was knotted on a disc according to clinical methods, with a gauge length of 2 mm and a tensile speed of 100 mm / min. The frictional properties between the suture and tissue were tested using a self-made friction testing device. A load of 50 cN was applied to the suture, and the crosshead moved at a speed of 75 mm / min. The friction curve and average frictional force were recorded.

[0074] The bending stiffness of the suture was determined by the cantilever method and calculated according to formula (1): A 5 cm long suture was placed horizontally and suspended at 1 cm from one end under 0.1 G conditions. After loading for 15 seconds, the vertical distance between the loaded end and the horizontal plane was measured.

[0075] , In the formula, B is the bending stiffness, F is the force applied to the suture, L is the length of the suture suspended in the air, and X is the deflection of the suture.

[0076] 4. Antibacterial test Staphylococcus aureus and Escherichia coli were diluted to 10. 7 CFU / mL was suspended in LB liquid medium and co-cultured with the sample. The culture was incubated at 37℃ in a 5% CO2 incubator for 24 hours, with optical density measured every 3 hours at 630 nm to plot bacterial growth curves. Bacteria adhering to the material surface were stained using a live / dead bacteria staining kit and observed and photographed using a laser confocal scanning microscope. Field emission scanning electron microscopy was used to observe bacterial adhesion and morphological changes on the material surface. A 10×10⁻⁶ micrometer was used. -6Bacteria were stained with a mol / L dichlorodihydrofluorescein diacetate reactive oxygen species indicator for 15 minutes under light-protected conditions, and then observed by laser confocal scanning microscopy.

[0077] 5. Cytotoxicity test L929 fibroblasts were seeded in 48-well plates at a density of 1.2 × 10⁶ cells per well. 4 Cells were cultured in a constant temperature incubator for 24 hours. After removing the culture medium, the suture was cut into 1 cm segments and added to different wells. After 1, 2, and 3 days of culture, the cell counting kit CCK-8 reagent was added to the test wells, and the cells were incubated at 37°C for 1 hour. The absorbance was measured at 450 nm, and cell viability was evaluated based on the optical density. Simultaneously, the biocompatibility of the suture to L929 fibroblasts was assessed using a live / dead bacteria staining method: at the above time points, live / dead bacteria staining solution was added to the samples, and after incubation for 15 minutes, the samples were observed using a laser confocal scanning microscope.

[0078] 6. Scratch test With a concentration of 1×10 5 Fibroblasts were seeded at a density of 10 cells / mL in culture dishes. After cell confluence, a 250 μm incision was made using a cell scraper. The cells were gently washed three times with phosphate-buffered saline (PBS) to remove cell debris. Sutures were then placed at the incision sites. The culture medium was replaced with serum-free DMEM, and the cells were sonicated for 10 minutes at 1 W / cm². 2 (1 MHz); Scratch images were captured using a laser confocal scanning microscope at 0, 12, and 24 hours. The pixel coverage of the scratch area at different time points was compared using ImageJ software to quantitatively analyze cell migration rate.

[0079] 7. Thermal Imaging Experiment Coupling agent was applied to the ultrasound probe, and the suture was fixed to the probe. A thermal imager was used to photograph and record the temperature change of the suture before and after ultrasound treatment.

[0080] 8. Animal models This experimental protocol was approved by the Laboratory Animal Welfare and Ethics Committee of Peking University (ethics number: LA2023523). Six-week-old male SD rats weighing 180-200 g were selected to evaluate suture performance. After anesthetizing the rats, the hair on their backs was shaved, and 1 cm long full-thickness skin incisions were made on both sides of the midline of the back. The wounds were closed using bifunctional electroactive sutures and Proline sutures, respectively. The rats were housed separately, with half of them receiving 10 minutes of low-intensity pulsed ultrasound activation every two days throughout the experimental period. Rats were sacrificed on days 3, 7, and 14 post-surgery, and subcutaneous regenerated tissue was harvested for analysis. The newly formed epithelial tissue samples were fixed in 4% paraformaldehyde, dehydrated, and embedded in paraffin. The samples were cut into 5 μm thick sections and stained with hematoxylin-eosin, Masson's stain, and immunofluorescence, respectively. Interleukin-6, α-smooth muscle actin, and keratin 5 antibodies were used to evaluate the inflammatory response, neocapillary formation, and neoepithelial formation, respectively.

[0081] 9. Statistical Analysis All statistical data are expressed as mean ± standard deviation. One-way ANOVA was used to test differences between groups, with * indicating the mean ± standard deviation. p <0.05、** p <0.01、*** p <0.001、**** p <0.0001 indicates a statistically significant difference.

[0082] II. Results 1. Design, fabrication and characterization of low-intensity pulsed ultrasound-driven bifunctional electroactive sutures Existing non-absorbable sutures essentially rely solely on mechanical action to achieve wound closure. Therefore, this embodiment designs a bifunctional suture based on polyvinylidene fluoride (PVDF), overcoming this fundamental functional limitation. This design not only meets standard suturing requirements but also utilizes the piezoelectric effect to provide on-demand antibacterial and wound-healing effects. This invention confirms that mechanical stretching, annealing, and corona polarization synergistically promote the directional alignment of piezoelectric β-phase crystal planes, while low-intensity pulsed ultrasound stimulation can achieve dynamic charge redistribution. To ensure the suture possesses both surgical flexibility and excellent piezoelectric responsiveness, this embodiment employs a multi-step fabrication process involving melt spinning extrusion, continuous mechanical stretching, corona polarization, and thermal annealing to prepare bifunctional electroactive sutures with diameters of 0.12 mm (PVDF-0.12), 0.16 mm (PVDF-0.16), and 0.24 mm (PVDF-0.24), respectively. Optimization experiments show that the piezoelectric response performance of the suture reaches its optimal level after annealing at 100°C. Figure 1 A, Figure 2Scanning electron microscopy images and surface roughness test results showed that the bifunctional electroactive suture had a smooth, defect-free surface, comparable in performance to Prolyne polypropylene sutures, and exhibited no burrs or cracks even after knotting. Figure 1 B).

[0083] X-ray diffraction analysis showed that a higher β-phase content was detected in the larger diameter bifunctional electroactive sutures. Figure 1 C). It is worth noting the β-phase ratio and piezoelectric constant of the suture. d 33 The piezoelectric properties increase with increasing diameter, indicating that their piezoelectric properties exhibit a diameter-dependent enhancement characteristic. Figure 3 To visually represent the surface potential distribution, this embodiment constructs a theoretical model based on phase-field simulation. Phase-field simulation results, verified by scanning Kelvin probe microscopy, show that there is localized electric field concentration in the suture nodule region, with its surface potential higher than that of the monofilament segment. Figure 1 (D, E) This phenomenon originates from the differential stress distribution generated by the nodules. Furthermore, under low-intensity pulsed ultrasound-driven piezoelectric catalysis, bifunctional electroactive sutures can induce significant, time-dependent degradation of Rhodamine B, while Proline sutures have minimal degradation effect on Rhodamine B. Figure 1 F). Catalytic efficiency is positively correlated with suture diameter and with β-phase content and piezoelectric constant. d 33 The trend was consistent. Spin-trapped electron paramagnetic resonance spectroscopy of dimethylpyridine N-oxide confirmed that the suture could generate reactive oxygen anions and hydroxyl radicals, and the radical signal intensity increased with increasing suture diameter. Figure 1 G, H).

[0084] The mechanical properties of surgical sutures are crucial for ensuring stable wound healing and providing sufficient mechanical support and operability for surgical procedures. Therefore, this embodiment comprehensively tested the mechanical properties of bifunctional electroactive sutures. Figure 4 A). Breaking strength is a core performance indicator of sutures. Mechanical test results show that the strength of the bifunctional electroactive suture exceeds the value specified in the national standards for "Non-absorbable Monofilament Sutures" (GB / T1.1-2009, YY 0167-2020). Figure 4 B), among which PVDF-0.24 has the highest strength. Moisture is commonly present in wound environments; therefore, this embodiment also simulates the breaking force and knot strength of the suture under physiological conditions. Figure 4CD), the results showed that its breaking force and nodule firmness were still higher than the national standard values, confirming the stability of the bifunctional electroactive suture in clinical settings. Compared with 4-0 Proling suture, PVDF-0.24 showed a significant improvement in flexural stiffness, while PVDF-0.12 and PVDF-0.16 had lower flexural stiffness due to their smaller diameter. Figure 4 E). Excessive friction between sutures and soft tissue can affect wound healing. The coefficient of friction of bifunctional electroactive sutures is significantly lower than that of 5-0 and 4-0 Prolyne sutures. This is due to their optimized surface roughness, which reduces traction on soft tissue and makes it easier for the sutures to pass through the tissue. Figure 4 FG).

[0085] 2. Dual-function electroactive sutures promote cell migration and achieve in vitro antibacterial properties. Cell compatibility is a primary indicator for evaluating the biocompatibility of sutures; therefore, this embodiment utilized the L929 cell line to conduct a comprehensive biocompatibility assessment. Qualitative and quantitative analyses both showed that the bifunctional electroactive suture exhibited excellent in vitro cell compatibility within a 3-day cell culture period, with no cytotoxicity. Furthermore, there was no significant difference in L929 cell proliferation among the experimental groups. To investigate whether low-intensity pulsed ultrasound caused changes in the local microenvironment temperature, this embodiment examined the thermal effect induced by ultrasound treatment. Thermal imaging analysis showed that after 10 minutes of low-intensity pulsed ultrasound treatment, the suture surface temperature remained below 37°C, confirming that increased local temperature did not affect cell viability. Within 24-48 hours after injury, fibroblasts migrate to the wound site by expressing matrix metalloproteinases to degrade fibrin clots and replace them with collagen fibers. Therefore, this embodiment used a scratch assay to observe the migration of L929 cells co-cultured with the suture under low-intensity pulsed ultrasound. The results showed that, compared with the Pro-Lysyl suture group, the migration rate of L929 cells towards the scratch center region was significantly accelerated in the bifunctional electroactive suture group, which was attributed to the electric field gradient generated by the bifunctional electroactive suture. Figure 5 ).

[0086] This study evaluated the antibacterial properties of electroactive sutures against Staphylococcus aureus and Escherichia coli, common bacteria in wound infections. Results showed that the bifunctional electroactive sutures exhibited significant antibacterial activity against both bacteria. The bifunctional electroactive sutures without low-intensity pulsed ultrasound activation showed a 39.72% higher antibacterial rate against Staphylococcus aureus compared to the Proline suture group. Scanning electron microscopy revealed severe membrane damage and cytoplasmic shrinkage in this group of bacteria. Figure 6C), while the bacterial cell structure of the Pro-Lin suture group remained intact. Increasing the level of reactive oxygen species (ROS) within bacteria is one of the effective strategies for inhibiting pathogenic bacteria; therefore, this study used dichlorodihydrofluorescein diacetate fluorescence staining to detect the level of ROS within bacteria. The bactericidal rate of the bifunctional electroactive suture activated by low-intensity pulsed ultrasound was further increased by 56.46%, which was positively correlated with the increase in the level of ROS within bacteria. Figure 6 Among the groups (AB, DE), the PVDF-0.24 group showed the most significant reactive oxygen species induction effect. Figure 6 E). Similarly, the bifunctional electroactive suture showed a 58.78% higher antibacterial rate against E. coli compared to the Proline suture group (E). Figure 7 In Escherichia coli (AE), extensive damage to the bacterial membrane structure was observed. Biofilm formation is an important mechanism for bacteria to resist harsh environments and develop drug resistance; therefore, this embodiment uses crystal violet staining to detect bacterial biofilm formation. Figure 6 (F, 7F). The results showed that the piezoelectric effect driven by low-intensity pulsed ultrasound could significantly increase the mortality rate of Staphylococcus aureus and Escherichia coli in biofilms. The above results confirm that the bifunctional electroactive suture achieves a dose-dependent antibacterial mechanism through the generation of reactive oxygen species. The synergistic effect of the material itself and ultrasound activation can enhance the bactericidal effect through a dual pathway of oxidative stress and structural destruction.

[0087] 3. Bifunctional electroactive sutures promote wound healing in animal models. To further explore the clinical application value of electroactive sutures, this embodiment evaluates their efficacy in the treatment of skin wounds. Figure 8 A). Using SD rats as an animal model, a full-thickness skin incision of about 1 cm was made on their backs, and after suturing with bifunctional electroactive sutures, low-intensity pulsed ultrasound was performed for 10 minutes every 2 days. Figure 8 B shows the gross observation results of wound repair at 0, 3, 7 and 14 days postoperatively. The results show that at almost all time points, the wound healing effect of the bifunctional electroactive suture group was significantly better than that of the Prolyne suture group, and the wound closure speed was faster.

[0088] Wound healing was evaluated at 7 and 14 days post-surgery using hematoxylin-eosin staining. The results showed that at 7 days post-surgery, the degree of inflammatory cell infiltration with the bifunctional electroactive suture was significantly lower than in other groups. Figure 8C) indicates that the electric field-mediated approach can effectively inhibit the acute inflammatory response. Collagen formation plays a crucial role in wound healing; during the proliferative phase of wound healing, collagen promotes cell migration and is the basis for extracellular matrix deposition. At 14 days post-surgery, the bifunctional electroactive suture group showed more significant collagen remodeling, characterized by denser collagen deposition, regular fiber arrangement, and intact epidermal barrier formation; while other groups exhibited incomplete wound healing, sparse matrix distribution, and persistent inflammation. Figure 8 D). The wound healing speed of bifunctional electroactive sutures was significantly accelerated, achieving complete closure within 14 days post-surgery, while wounds sutured with Pro-Ling sutures did not heal completely. Figure 8 E). Further hematoxylin-eosin staining results showed that the hair follicle density in the Prolin suture group was significantly reduced, collagen fiber deposition was disordered, the reticular structure was broken, and the epidermal continuity was damaged; while the wound in the bifunctional electroactive suture group showed obvious hair follicle regeneration, collagen bundles were polarized, and the fiber structure was intact. Figure 8 F).

[0089] Studies have confirmed that electrical stimulation can significantly improve wound healing by promoting cell proliferation, directional migration, and extracellular matrix synthesis. The bifunctional electroactive suture group prepared in this embodiment can continuously release an electric field (-1.55 to 1.55 V), effectively converting mechanical energy into bioelectric signals. Keratin 5 is a protein associated with cell migration and skin cell differentiation, often used to evaluate skin regeneration potential; α-smooth muscle actin is a marker of functional blood vessels; and interleukin 6 is a classic inflammatory cytokine protein. Therefore, in this embodiment, the expression levels of keratin 5, α-smooth muscle actin, and interleukin 6 were detected by immunofluorescence staining 14 days postoperatively. The results showed that the bifunctional electroactive suture group can regulate wound healing through dual molecular pathways: upregulation of keratin 5 and α-smooth muscle actin expression indicates enhanced epidermal re-epithelialization and reduced fibrotic scar formation; downregulation of interleukin 6 expression indicates inhibition of pro-inflammatory signals. Comprehensive analysis results show that the bifunctional electroactive suture group can regulate the spatiotemporally specific synergistic response at the wound site, accelerating wound healing while alleviating pathological fibrosis and inflammatory responses, thus achieving mature wound closure. Figure 8 The above results confirm that low-intensity pulsed ultrasound-driven electroactive sutures are most conducive to wound healing.

[0090] 4. Optimized design and functional verification of multi-strand electroactive sutures To synergistically optimize the mechanical support, electroactive output, and biological function of the suture, this embodiment further designed a multi-strand electroactive suture based on the bifunctional electroactive suture, and completed the fabrication of the multi-strand structure. Figure 9A). Scanning electron microscopy images first confirmed the successful preparation of the multi-strand electroactive suture, noting its smooth surface and the absence of burrs or cracks after knotting. Figure 9 B). Multi-strand braiding strategies significantly improve the mechanical properties of the sutures. Figure 9 CD analysis showed that multi-strand electroactive sutures exhibited higher breaking strength and nodule stability compared to bifunctional electroactive sutures. This performance improvement stems from the superior stress dispersion capability resulting from the interaction between monofilaments, better meeting the reliable mechanical performance requirements of surgical sutures.

[0091] Furthermore, this structural design also significantly enhances biological function. In vitro experiments against Staphylococcus aureus and Escherichia coli demonstrate that the low-intensity pulsed ultrasound-driven multi-strand electroactive suture exhibits stronger broad-spectrum antibacterial activity. Figure 9 This is due to the fact that the multi-stranded structure can integrate more functional units, generating stronger endogenous electrical stimulation, and interfering with bacterial metabolic processes through an electrochemical synergistic mechanism. Simultaneously, the enhanced electroactivity brought about by the multi-stranded structure directly translates into a positive regulatory effect on tissue repair-related cells. Cell scratch assay results showed that under stimulation with the multi-stranded electroactive suture group, fibroblasts exhibited significantly better migration speed and scratch closure rate within 24 hours compared to the bifunctional electroactive suture group. This result strongly confirms that the multi-stranded design, by optimizing electrical signal output, can more effectively guide cell migration in a directional manner. Figure 9 In summary, structural optimization from monofilament to multi-strand is an effective technical approach to synergistically enhance the mechanical strength, antibacterial activity, and healing-promoting biological functions of sutures. Simultaneously, fibers with multi-layered or multi-material structures can generate therapeutic electrical stimulation during movement through triboelectric or piezoelectric effects, further effectively regulating cell behavior and promoting tissue regeneration.

[0092] In summary, this invention, based on the principle of purely physical antibacterial action, successfully designed and fabricated a bifunctional electroactive suture activated by low-intensity pulsed ultrasound, demonstrating its significant effects in combating bacterial infection and promoting wound healing. Evaluation of the antibacterial activity of the electroactive suture against Staphylococcus aureus and Escherichia coli verified the excellent antibacterial efficacy imparted to the bifunctional electroactive suture by the piezoelectric effect driven by low-intensity pulsed ultrasound. Further research revealed that the piezoelectric effect induced by low-intensity pulsed ultrasound in the bifunctional electroactive suture can stimulate the generation of reactive oxygen species, thereby disrupting bacterial membrane structure and inhibiting bacterial activity. Biocompatibility evaluation results showed that the bifunctional electroactive suture exhibited extremely low cytotoxicity; mechanical performance evaluation results indicated that its mechanical strength exceeded the national standard, confirming the safety and applicability of this suture as a ligation material. In vivo experiments in rats confirmed that the bifunctional electroactive suture group can be used as a flexible suture to effectively repair full-thickness skin defects. Furthermore, the multi-strand electroactive suture group achieved a dual enhancement of mechanical properties and biological function. This invention redefines surgical sutures as active bioelectric interfaces that combine real-time infection control and matrix adaptability regeneration, thus solving the balance problem between antibacterial intervention and wound healing in injury treatment.

[0093] Although the invention has been described with reference to exemplary embodiments, it should be understood that the invention is not limited to the disclosed exemplary embodiments. Various adjustments or changes may be made to the exemplary embodiments described in this specification without departing from the scope or spirit of the invention. The scope of the claims should be interpreted in the broadest possible sense to cover all modifications and equivalent structures and functions.

Claims

1. A dual-function electroactive monofilament suture for anti-infection and promoting healing, characterized in that, The suture is made from raw materials including organic piezoelectric materials containing a β phase, wherein the suture outputs a voltage of not less than 0.5 V, a breaking strength of not less than 5 N, a nodule strength of not less than 3 N, and a bending stiffness of 1-20 cN·mm. 2 .

2. The anti-infection and healing-promoting dual-function electroactive monofilament suture according to claim 1, characterized in that, The suture has a density of not less than 0.3 pCN. -1 piezoelectric constant d 33 value.

3. The anti-infection and healing-promoting dual-function electroactive monofilament suture according to claim 1, characterized in that, The frictional force between the suture and the tissue is no higher than 20 cN.

4. The anti-infection and healing-promoting dual-function electroactive monofilament suture according to claim 1, characterized in that, The suture is prepared from raw materials including organic piezoelectric materials containing β phase through appropriate pretreatment to form filaments or fibers, and then through appropriate posttreatment. The pretreatment includes melt spinning, solution spinning, or electrospinning; The post-treatment includes stretching and heat setting, weaving twisting, or coating; The post-processing includes at least one of corona polarization, annealing and ultrasonic treatment; The organic piezoelectric material includes at least one of the following: polyvinylidene fluoride, polyvinylidene fluoride-trifluoroethylene copolymer, polyvinylidene fluoride-hexafluoropropylene copolymer, and polyvinylidene fluoride-tetrafluoroethylene copolymer; Optionally, the raw material further includes inorganic piezoelectric materials, such as nanoscale ceramic particles, including at least one of barium titanate, barium strontium titanate, strontium titanate, lithium niobate, and sodium potassium niobate.

5. The anti-infection and healing-promoting dual-function electroactive monofilament suture according to claim 1, characterized in that, The annealing temperature is less than 120°C and the processing time is less than 2 hours.

6. The anti-infection and healing-promoting dual-function electroactive monofilament suture according to claim 1, characterized in that, The sutures were not ultrasonically treated.

7. The anti-infection and healing-promoting dual-function electroactive monofilament suture according to claim 1, characterized in that, The suture is ultrasonically treated, and the ultrasonic treatment parameters include at least one of the following: a pulse repetition frequency of 10 Hz to 1 kHz, a frequency of 0.3 MHz to 5 MHz, and an effective sound intensity of 0.10 W / cm². 2 Up to 3.00 W / cm 2 .

8. The anti-infection and healing-promoting dual-function electroactive monofilament suture according to claim 1, characterized in that, The diameter of the single-strand suture is from 0.05 mm to 0.50 mm.

9. A dual-function electroactive multistrand suture for anti-infection and promoting healing, characterized in that, It includes multiple strands of suture as described in any one of claims 1-8; Preferably, the multi-strand suture has a topological structure on its surface along its length, resulting in a difference in potential distribution on its surface.

10. The use of the suture according to any one of claims 1-9 in the preparation of medical materials or medical devices for surgical wound closure, prevention or treatment of surgical site infection, and / or promotion of wound healing.

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