Photo-thermal antibacterial surgical suture and preparation method thereof

Abstract

The invention relates to a photo-thermal antibacterial surgical suture and a preparation method thereof, the photo-thermal antibacterial surgical suture comprises an inorganic-organic hybrid suture with piezoelectric property and photo-thermal property, and the inorganic-organic hybrid suture comprises an organic piezoelectric polymer loaded with photo-thermal nano composite particles, the photo-thermal nano composite particles comprise silicate clay of which the surface is modified with CuS nano particles. The photo-thermal antibacterial surgical suture utilizes an electric signal to make up an endogenous electric field of a damaged wound part, promotes transition of inflammation in the wound, improves collagen arrangement and adjusts collagen remodeling under near-infrared light illumination, so that wound tissue is healed in a regeneration mode instead of a scar mode, the effect of inhibiting / improving scar generation is achieved, and the surgical suture has the advantages of being simple in structure and convenient to use. And the mechanical property of the incision tissue is effectively improved.

Description

Technical Field

[0001] This invention patent relates to the field of medical surgical suture technology, and in particular to a photothermal antibacterial surgical suture and its preparation method. Background Technology

[0002] Surgical sutures are an essential component of wound closure and surgical repair, playing an indispensable role in modern healthcare systems. By holding the wound edges together, surgical sutures reduce the risk of wound dehiscence, decrease tension on the wound bed, and create an environment conducive to tissue regeneration.

[0003] Postoperative scarring is a common problem in surgery. Scar tissue can not only lead to skin dysfunction and damage, but also affect a person's mental health. In severe cases, it can even form pathological scars, which can then cause lesions, itching, burning, and other problems.

[0004] Surgical sutures commonly used in surgery are mostly made of natural materials (such as silk) or synthetic polymers (such as polypropylene). They have reliable tensile strength, good biocompatibility, and provide reliable support for the wound. However, these surgical sutures lack the ability to actively control common wound complications, such as surgical site infection and scar regeneration.

[0005] Therefore, it is of great significance to develop multifunctional surgical sutures that promote wound healing, effectively prevent postoperative infection, and improve or inhibit scar formation. Summary of the Invention

[0006] This invention provides a photothermal antibacterial surgical suture, which is prepared by electrospinning and possesses multifunctional properties including photothermal antibacterial activity, piezoelectricity, and effective scar inhibition. This transforms the traditional suture's "passive" healing promotion into an "active" in-situ electrical stimulation that promotes scarless healing. The photothermal antibacterial surgical suture provided by this invention promotes wound healing, reduces inflammatory responses, improves collagen fiber arrangement, and thus reduces scar formation.

[0007] The present invention provides a photothermal antibacterial surgical suture, comprising an inorganic-organic hybrid suture (CuS-clay suture) with piezoelectric and photothermal properties. The inorganic-organic hybrid suture comprises an organic piezoelectric polymer loaded with photothermal nanocomposite particles (CuS-clay particles), wherein the photothermal nanocomposite particles comprise silicate clay (clay) with CuS nanoparticles modified on its surface.

[0008] Preferably, the photothermal conversion efficiency of the photothermal nanocomposite particles is not less than 30%.

[0009] Specifically, the mass ratio of CuS nanoparticles to acidified silicate clay in the photothermal nanocomposite particles is 1:2.

[0010] Preferably, the silicate clay has a particle size of 200-3000 nm, and the CuS nanoparticles have a particle size of less than 100 nm.

[0011] Preferably, the mass ratio of photothermal nanocomposite particles to organic piezoelectric polymer in the inorganic-organic hybrid suture is 1:10.

[0012] Preferably, the silicate clay is acidified silicate clay.

[0013] Preferably, the silicate clay is selected from natural silicate nanomaterials. The natural silicate nanomaterials include one or more of hollow tubular halloysite (HNT), two-dimensional layered lithium saponite (Lap), two-dimensional sheet-like montmorillonite (MMT), and fibrous rod-shaped attapulgite (PGS).

[0014] Preferably, the organic piezoelectric polymer includes a piezoelectric biomaterial, which may be selected from polyvinylidene fluoride (PVDF).

[0015] Preferably, the inorganic-organic hybrid suture is a surgical suture that reduces skin fibrosis or scarring during wound healing, or the inorganic-organic hybrid suture is a surgical suture that promotes the healing of infected wounds.

[0016] A method for preparing a photothermal antibacterial surgical suture, the method comprising the following steps: Step (1): CuS nanoparticles are modified onto the surface of silicate clay to obtain the photothermal nanocomposite particles; Step (2): The photothermal nanocomposite particles are uniformly dispersed in an electrospinning solution containing an organic piezoelectric polymer, and the inorganic-organic hybrid suture is prepared under the high-voltage polarization of electrospinning.

[0017] Preferably, step (1) further includes acidification of silicate clay, and the acidified silicate clay and CuS nanoparticles are co-precipitated to obtain the photothermal nanocomposite particles.

[0018] Preferably, the electrospinning parameters in step (2) are: needle size 18 G, voltage 20 KV, pushing speed 0.0030 mm / s, receiving distance 12 cm, receiver rotation speed 150 rpm, and spinning time 20-40 min.

[0019] The present invention relates to the application of photothermal antibacterial surgical sutures in the preparation of wound repair products, wherein the photothermal antibacterial surgical sutures are used to inhibit / improve scar formation.

[0020] The present invention relates to the application of photothermal antibacterial surgical sutures in the preparation of materials that promote wound healing of infections, wherein the photothermal antibacterial surgical sutures are used to reduce inflammatory responses.

[0021] The photothermal antibacterial surgical suture provided by this invention is used in the preparation of photothermal therapy materials. The photothermal antibacterial surgical suture makes the collagen arrangement of wound tissue closer to that of normal tissue through near-infrared response.

[0022] The beneficial effects of the present invention: Based on the concept of electrostimulation and photothermal antibacterial therapy, the present invention designs a photothermal antibacterial surgical suture. The introduction of photothermal nanocomposite particles endows the surgical suture with good photothermal antibacterial properties. Under the action of electrospinning high voltage polarization and stretching, an inorganic-organic hybrid suture with piezoelectric and photothermal properties is successfully prepared.

[0023] The photothermal antibacterial surgical suture provided by this invention has CuS particles dispersed on the surface of silicate clay, which avoids the aggregation of CuS particles, achieves particle refinement, increases the specific surface area of ​​the system, lays the foundation for the efficient application of CuS, and realizes that photothermal nanocomposite particles also have the characteristics of high photothermal conversion efficiency at low concentrations.

[0024] The photothermal antibacterial surgical suture prepared by this invention has good mechanical properties, with a maximum tensile stress of up to 20 MPa and an elastic modulus of about 0.35 MPa, meeting the basic requirements for surgical suturing.

[0025] The photothermal antibacterial surgical suture provided by this invention utilizes electrical signals to compensate for the endogenous electric field at the damaged wound site. Under 808nm near-infrared light irradiation, it promotes the transition of inflammation in the wound, improves collagen arrangement, and regulates collagen remodeling, making the wound tissue more inclined to heal through regeneration rather than scarring, thereby achieving the effect of inhibiting / improving scar formation and effectively enhancing the mechanical properties of the incision tissue. Attached Figure Description

[0026] Figure 1 The image shows the XRD pattern of the particles.

[0027] Figure 2 This is a characterization diagram of the particles. Among them, Figure 2 A in the diagram is a schematic diagram of CuS and CuS-clay particles; Figure 2 B in the image is a SEM-EDS image of CuS-clay particles, with a scale bar of 500 nm. Figure 2 C in the image represents a TEM-EDS image of CuS-clay particles, with a scale bar of 500 nm.

[0028] Figure 3The graph shows the photothermal cycling performance of CuS-clay particles. Figure 3 In the figure, A represents the temperature change curve and photothermal conversion efficiency of CuS-HNT particles; Figure 3 In the figure, B represents the temperature change curve and photothermal conversion efficiency of CuS-Lap particles. Figure 3 In the figure, C represents the temperature change curve and photothermal conversion efficiency of CuS-MMT particles. Figure 3 In the figure, D represents the temperature change curve and photothermal conversion efficiency of CuS-PGS particles.

[0029] Figure 4 SEM images and characterization of the sutures are provided. Figure 4 In the figure, A represents the diameter measurement result of each group of sutures; Figure 4 B in the image represents the SEM images of the P-type suture and the CuS-clay suture, with the upper scale bar at 500 μm and the lower scale bar at 10 μm. Figure 4 In the figure, C represents the infrared spectrum (4000-400 cm⁻¹) of PVDF powder, P suture, and CuS-clay suture. -1 )picture; Figure 4 In the diagram, D represents the XRD patterns of PVDF powder, P suture, and CuS-clay suture.

[0030] Figure 5 The results of the mechanical property tests for each group of sutures are presented. Figure 5 In this context, A represents the stress-strain statistical results from the tensile test; Figure 5 In this context, B represents the statistical result of the maximum tensile stress. Figure 5 In this context, C represents the statistical result of the elastic modulus from the tensile test.

[0031] Figure 6 Each group of sutures was subjected to 808 nm near-infrared laser (1.5 W / cm²) 2 Temperature change image after 10 minutes of irradiation.

[0032] Figure 7 The image shows the results of the in vitro antibacterial performance test of CuS-clay sutures. All scale bars are 2cm. Figure 7 In the image, A represents a colony plate image of Staphylococcus aureus treated with CuS-clay sutures in an antibacterial experiment. Figure 7 In this context, B represents CuS-clay sutures exposed to an 808 nm near-infrared laser (1.5 W / cm²). 2 Colony plate images of Staphylococcus aureus treated with irradiation for 10 min in an antibacterial experiment; Figure 7 C in the image represents a colony plate image of Escherichia coli treated with CuS-clay sutures in an antibacterial experiment. Figure 7In this context, D represents the CuS-clay suture irradiated by an 808 nm near-infrared laser (1.5 W / cm²). 2 Colony plate images of Escherichia coli treated with irradiation for 10 min for antibacterial purposes.

[0033] Figure 8 The graph shows the piezoelectric performance test results for each group of sutures. Among them, Figure 8 In the diagram, A represents a schematic representation of the piezoelectric performance test. Figure 8 In the image, B represents the voltage change of the P suture. Figure 8 C in the image represents the voltage change of the CuH@P suture. Figure 8 In the image, D represents the voltage change of the CuL@P suture. Figure 8 E in the image represents the voltage change of the CuM@P suture. Figure 8 F in the figure represents the voltage change image of the CuP@P suture.

[0034] Figure 9 This is a diagram showing the results of an animal experiment. Among them, Figure 9 In the diagram, A represents a schematic diagram of the animal experiment process; Figure 9 Image B in the image shows the healing of full-thickness skin incisions infected with rats on days -2, 0, 3, 7, 10, and 14.

[0035] Figure 10 CuH@P and CuM@P sutures were used on day 0 after a full-thickness skin incision in rats, followed by the application of an 808 nm near-infrared laser (1.5 W / cm²). 2 A line graph showing the temperature change after 10 minutes of irradiation.

[0036] Figure 11 The image shows the in vivo antibacterial results of each group of sutures, with a scale bar of 2cm.

[0037] Figure 12 Images show the H&E staining results for each group of suture-treated infected incisions. Figure 12 Image A in the image represents a representative image of H&E staining of skin tissue on day 7, with a scale bar of 200 μm. Figure 12 B in the image represents a representative image of H&E staining of skin tissue on day 14, with a scale bar of 200 μm.

[0038] Figure 13 Masson's trichrome staining results for each group of suture-treated infected incisions. Among them, Figure 13 In the image, A represents a representative image of skin tissue stained with Masson's trichrome on day 7, with a scale bar of 200 μm. Figure 13 B in the image represents a representative image of Masson trichrome staining of skin tissue on day 14, with a scale bar of 200 μm.

[0039] Figure 14 The results of Sirius red staining after suture treatment of infected incisions in each group. Figure 14 A in the image is a representative image of Sirius red staining of skin tissue on day 7, with a scale bar of 200 μm; Figure 14 B in the image represents a representative image of Sirius red staining of skin tissue on day 14, with a scale bar of 200 μm.

[0040] Figure 15 The statistical results of skin tissue collagen fiber orientation on day 14 after suture treatment of infected incisions in each group.

[0041] Figure 16 Immunohistochemical staining results of keratin in skin tissue after suture treatment of infected incisions in each group are shown. Scale bar: 200 μm. Figure 16 Image A in the image represents a typical image of skin tissue keratin immunohistochemical staining on day 7. Figure 16 Image B in the image represents a typical image of skin tissue keratin immunohistochemical staining on day 14.

[0042] Figure 17 Immunofluorescence staining results of skin tissue on day 7 after suture treatment of infected incisions in each group. Scale bar: 50 μm. Figure 17 In the image, A represents a representative image of TNF-α immunofluorescence staining. Figure 17 B in the image represents a typical image of IL-6 immunofluorescence staining.

[0043] Figure 18 The results of the mechanical property experiments on skin tissues in each group on day 14 are shown. Among them, Figure 18 A in the diagram represents a stretching of skin tissue; Figure 18 B in the figure represents the stress-strain statistics of the skin tissue tensile test. Figure 18 C in the figure represents the statistical result of the maximum tensile stress in the skin tissue.

[0044] P<0.05, ** P<0.01, *** P<0.001 indicate that the difference is statistically significant. Detailed Implementation

[0045] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0046] All raw materials used in the embodiments of this invention were commercially available. Halloysite (HNT) was purchased from Guangzhou Runwo Materials Technology Co., Ltd., lithium soapstone (Lap) from Beijing Yiwei Special Chemical Technology Development Co., Ltd., montmorillonite (MMT) from Shandong Yihe Pharmaceutical Co., Ltd., and attapulgite (PGS) from Xuyi County Junda Attapulgite Materials Co., Ltd. The commercially available PVDF sutures were non-absorbable surgical monofilament sutures (PVDF) purchased from Weigao Group Co., Ltd.

[0047] The mice used in this invention were SPF-grade male SD rats provided by the Beijing Vital River Laboratory Animal Center. The experimental animals were 6-8 weeks old and housed in a cage system at a room temperature of 24 ℃ and humidity of approximately 35-60%. They were fed regularly, provided with natural light, and their condition was observed until they had adapted for two weeks, reaching approximately 8-10 weeks of age or a weight of 250±10 g, at which point they were ready for experiments. All animal procedures were performed in accordance with the Wenzhou Medical University Laboratory Animal Care and Usage Guidelines and were approved by the Wenzhou Medical University Animal Ethics Committee.

[0048] Example 1: Preparation of Experimental Materials Acidification of natural silicate nanomaterials (clay): Weigh 5.0 g of each of the four types of clay, add 100 mL of hydrochloric acid solution (1 mol / L) to each, stir at 500 rpm for 4 h, then wash with distilled water until the pH of the supernatant is 6-7, discard the supernatant, dry the precipitate at 65 ℃, grind it, and store it at room temperature.

[0049] Preparation of CuS nanoparticles: 256.5 mg of CuCl2·2H2O was weighed and added to 180 mL of ultrapure water. The mixture was magnetically stirred at room temperature for 20 min at 500 rpm. Then, 300 mg of sodium citrate was added, and the mixture was magnetically stirred for 20 min at 500 rpm. Afterward, 30 mL of Na2S·9H2O (50 mmol / L) was added using a microfluidic pump. After the mixture turned black, it was stirred for 5 min and then transferred to a 90 ℃ oil bath. The mixture was magnetically stirred for 17 min at 500 rpm, followed by cooling in an ice bath. The particles were centrifuged with an appropriate amount of ethanol, washed three times with ethanol, and the supernatant was discarded. The precipitate was dried at 65 ℃, ground, and stored at room temperature.

[0050] Step (1) Preparation of photothermal nanocomposite particles (CuS-clay particles): Weigh 288.0 mg of each of the four types of clay after acidification, add 100 mL of ultrapure water, and break them in a cell disruptor for 20 min (power 200 W). Then add 282.5 mg of CuCl2·2H2O and 80 mL of ultrapure water, and stir magnetically at room temperature for 4 h at 500 rpm. Add 300.0 mg of sodium citrate, and stir magnetically for 4 h at 500 rpm. Then add 30 mL of Na2S·9H2O (50 mmol / L) using a microfluidic pump. After turning black, stir for 5 min, transfer to an oil bath at 90 ℃, and stir magnetically for 17 min at 500 rpm. Then cool in an ice bath, add an appropriate amount of ethanol to centrifuge all the particles, wash with ethanol three times, discard the supernatant, dry the precipitate at 65 ℃, grind it, and store it at room temperature. The four types of particles are designated as CuS-HNT, CuS-Lap, CuS-MMT, and CuS-PGS, respectively.

[0051] Preparation of piezoelectric suture P: Weigh 1.2 g of PVDF powder, add 4 mL of acetone and 6 mL of DMF, place in a 60 ℃ water bath, and stir magnetically at 500 rpm. After the PVDF powder is completely dissolved, transfer to a room temperature magnetic stirrer and cool to room temperature at 500 rpm. Then, load into a 10 mL syringe with an 18 G needle and place in an electrospinning apparatus. Electrospin at 150 rpm with a voltage of 20 KV, a push speed of 0.0030 mm / s, a spinning time of 30 min, a receiver distance of 12 cm, and a dish receiver. After spinning, remove the sample from the tip of the dish receiver, gently rub it by hand, and hang it at room temperature for storage. This sample is designated as suture P.

[0052] Step (2) Preparation of inorganic-organic hybrid suture (CuS-clay suture): Weigh 120.0 mg of each of the four types of CuS-clay, add 4 mL of acetone and 6 mL of DMF respectively, sonicate for 30 min, add 1.2 g of PVDF powder, put into a 60℃ water bath, stir magnetically at 500 rpm, after the PVDF powder is completely dissolved, transfer to a room temperature magnetic stirrer, stir magnetically at 500 rpm for 12 h, then put into a 10 mL syringe, select 18 G needle, place in an electrospinning instrument, with a voltage of 20KV, a push speed of 0.0030 mm / s, a spinning time of 30 min, a receiving distance of 12 cm, and a dish receiver, electrospinning at 150 rpm. After spinning is completed, take off the sample at the tip of the dish receiver, rub it gently by hand, and hang it at room temperature for storage. These are respectively denoted as CuH@P suture, CuL@P suture, CuM@P suture, and CuP@P suture.

[0053] Example 2: Particle performance 2.1 Characterization of Particles The peak values ​​of the nine particles in Example 1 were analyzed using a wide-angle X-ray diffractometer (D8 ADVANCE, Bruker, USA) equipped with CuKα radiation (λ=1.5418 Å). The 2θ angle scan range was 5°–80° with a step size of 0.02°.

[0054] Figure 1 XRD patterns of CuS, four types of clay, and four types of CuS-clay particles are shown. The diffraction crystallography pattern is in good agreement with the standard CuS pattern (JCPDS 79-2321), indicating the successful preparation of CuS particles. Peaks of both CuS and clay can be observed simultaneously in the four types of CuS-clay particles, demonstrating the successful preparation of photothermal nanocomposite particles.

[0055] 2.2 Microscopic images of particles The microstructure of particles was observed using scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and transmission electron microscopy-energy dispersive spectroscopy (TEM-EDS).

[0056] Figure 2 Figure A shows a schematic diagram of five types of particles. CuS nanoparticles tend to aggregate easily when present alone. However, when CuS is modified onto the clay surface, uniform dispersion is achieved, reducing CuS aggregation. This was demonstrated by SEM-EDS (…). Figure 2 (B) and TEM-EDS ( Figure 2 In step C), observing the microstructure of the composite material reveals a uniform distribution of Cu and S elements, indicating that CuS particles are uniformly loaded onto the surface of several natural silicates. This avoids CuS particle agglomeration, achieves particle refinement, increases the specific surface area of ​​the system, lays the foundation for the efficient application of CuS, and proves the successful preparation of CuS-clay particles.

[0057] 2.3 Photothermal performance test of particles The photothermal properties of CuS-clay particles were investigated by measuring the temperature change of the particles under laser irradiation. Four types of CuS-clay particles were prepared into suspensions of 180 μg / mL using physiological saline. After mixing, 1 mL of each suspension was placed in a 1.5 mL EP tube and placed on a fixed rack. The irradiation was performed using an 808 nm wavelength laser at 1.5 W / cm². 2 The sample was irradiated for 10 minutes at a certain power, cooled to room temperature, and then irradiated for another 10 minutes, followed by cooling to room temperature. This cycle was repeated three times. The real-time temperature change was observed using a FLIR infrared imager, and thermal images were taken every 30 seconds.

[0058] Based on the photothermal conversion efficiency formulas (1)-(3), the photothermal conversion efficiency of CuS-clay is calculated as follows: Figure 3 As shown, the photothermal conversion efficiencies of the four types of particles are CuS-MMT (44.06%) > CuS-HNT (43.38%) > CuS-PGS (42.63%) > CuS-Lap (34.13%).

[0059] (1) (2) (3) Among them, T max,sam T represents the highest temperature induced by the sample. max,water Represents the highest temperature induced by water; I represents the laser power; A 808 This represents the absorbance of the sample at 808 nm; m i Represents the weight of water; C p,i represents the heat capacity of water; 𝜃 represents the system constant.

[0060] Example 3 Characterization of sutures Characterization experiments were conducted on the PVDF powder in Example 1 and five types of sutures prepared by electrospinning.

[0061] The structural morphology of P-sutures and CuS-clay sutures was observed using scanning electron microscopy (SEM). For example... Figure 4 As shown in Figure B, SEM observations reveal that all five suture types consist of multiple fibers arranged in approximately parallel lines. Among them, the fiber orientation of the CuH@P and CuM@P sutures is closer to that of the P suture.

[0062] Fourier transform infrared spectrometer (FTIR) 4000-400 cm⁻¹ -1 The infrared absorption spectrum below is as follows Figure 4 As shown in C, it can be observed that the sutures prepared by electrospinning, compared with PVDF powder, exhibit better performance in the α phase (975, 762, 614, 487 cm⁻¹). -1 The peak intensity of ) decreases in the β phase (840 cm⁻¹). -1 The peak intensity at point () increases.

[0063] The peak values ​​of the five sutures and PVDF powders in Example 1 were analyzed using a wide-angle X-ray diffractometer (D8 ADVANCE, Bruker, USA) equipped with CuKα radiation (λ=1.5418 Å). The scanning range was 5°–80° (2θ) with a step size of 0.02°. Figure 4In the D, the characteristic peaks of PVDF powder can be observed at approximately 18.5° (α phase), 20° (β phase), and 26.5° (α phase) at 2θ, while the five types of sutures prepared by electrospinning only show a peak at approximately 20.2° (β phase), with virtually no peak at the α phase position.

[0064] XRD and FTIR characterization showed that under the action of high-voltage polarization and stretching peaks in electrospinning, α-phase PVDF powder was successfully transformed into β-phase PVDF sutures with piezoelectric properties.

[0065] Example 4 Mechanical property testing of sutures The diameter, bending stiffness, and mechanical properties of the five types of sutures in Example 1 were tested.

[0066] Cut the sutures randomly into 5 cm segments, fix them naturally on the glass slide without stretching, secure both ends with tape, and photograph them under an upright microscope at 20X. Photograph each type of suture five times in parallel. Figure 4 As shown in A, the diameter of all five types of sutures is 0.35 ± 0.5 mm.

[0067] The bending stiffness of the suture was measured using the cantilever method. A 5 cm long suture was placed horizontally and connected to a force (F = 2.5 × 10⁻⁶). -3 One end (L) of the suture (N) was suspended in mid-air at 1 cm. After loading for 15 s, the vertical distance (X) between the horizontal plane and the loading end was measured. The bending stiffness of the five sutures was 2.9 ± 0.2 cN / cm. 2 .

[0068] The mechanical properties of five types of sutures were tested using a universal testing machine (Instron (Shanghai) Testing Equipment Trading Co., Ltd.). The sutures were randomly cut into 4 cm segments and placed between the clamps of the universal testing machine, with a 2 cm gap between the upper and lower clamps. The top clamp was moved upwards at a speed of 10 mm / min, and the changes in force were recorded during the process. Figure 5 As shown in A and B, the maximum tensile stress of the five types of sutures is approximately 20 MPa, which is sufficient to withstand the force required to penetrate the skin; the maximum strain of the five types of sutures can reach approximately 220%. Figure 5 As shown in C, the elastic modulus of the five types of sutures is approximately 0.35 MPa.

[0069] The above results indicate that the addition of CuS-clay particles did not change the diameter, bending stiffness, or mechanical properties of the P-suture.

[0070] Example 5: Photothermal properties of sutures The photothermal properties of five sutures were studied by measuring the temperature change of sutures irradiated with an 808 nm wavelength laser. The sutures were tightly coiled into a disc shape of approximately 1 cm and placed on white printing paper. First, an 808 nm wavelength laser was applied at a rate of 1.5 W / cm². 2 The white printing paper was irradiated with a power of 1.5 W / cm², and the distance was adjusted to ensure that the temperature of the white printing paper did not change significantly after irradiating it alone for 10 minutes. Then, an 808 nm wavelength laser was used at 1.5 W / cm². 2 The P, CuH@P, CuL@P, CuM@P and CuP@P sutures were irradiated with the same power at the same distance for 10 min each, and the temperature changes were recorded in real time and thermal images were taken using a FLIR infrared imager.

[0071] like Figure 6 As shown, the temperature of the P-suture remained essentially unchanged within 10 minutes under near-infrared light irradiation. The CuS-clay suture, however, experienced a rapid temperature increase after 1 minute of near-infrared light irradiation, followed by a slower but still increasing temperature after 2 minutes, until it stabilized at approximately 42±1 ℃ after 10 minutes. This indicates that the P-suture itself has no photothermal properties, but the suture prepared with the addition of photothermal nanocomposite particles exhibits a significant temperature change under near-infrared light irradiation, thus acquiring a photothermal effect that meets the temperature requirements for low-temperature photothermal effects.

[0072] Example 6: Antibacterial properties of CuS-clay sutures Gram-positive bacteria Staphylococcus aureus (Staphylococcus aureus) S. aureus ) and Gram-negative bacteria Escherichia coli ( E. coli The antibacterial properties of four types of CuS-clay sutures were tested. Among them, the near-infrared response group was irradiated with an 808 nm near-infrared laser for 10 min during the co-culture stage of sutures and bacterial suspension.

[0073] Add 3 mL of bacterial suspension (10) to a 5 mL EP tube. 6 CFU / mL), and 15 and 30 mg of the five sutures were added respectively to make their final concentrations 5 and 10 mg / mL; the control group was given only 3 mL of bacterial suspension (10 CFU / mL). 6 (CFU / mL). EP tubes were placed in a 37℃ shaking incubator for 4 h. 100 μL from each EP tube was then evenly spread onto a nutrient agar plate. The agar plate was then inverted and placed in a 37℃ incubator for 12 h. The plate was then photographed against a black background for observation.

[0074] like Figure 7As shown in A and C, the antibacterial effects of the four CuS-clay sutures against Staphylococcus aureus and Escherichia coli all increased with increasing concentration. Among them, the antibacterial effects of CuH@P and CuM@P sutures were stronger than those of CuL@P and CuP@P sutures.

[0075] Figure 7 Figures B and D indicate that the antibacterial effect of CuS-clay sutures against Staphylococcus aureus and Escherichia coli was significantly enhanced after treatment with 808 nm near-infrared laser. Specifically, at a concentration of 10 mg / mL, the antibacterial efficiency of CuS-clay sutures against both Staphylococcus aureus and Escherichia coli reached 100%.

[0076] Example 7: Piezoelectric properties of CuS-clay sutures The piezoelectric properties of the five sutures in Example 1 were measured using an oscilloscope (Keysight InfiniiVision 1000 X, Keysight Technologies, USA). Figure 8 In the diagram, A represents a piezoelectric performance test. The seam is pressed with a finger at the same frequency and force, and the voltage change displayed on the oscilloscope is observed. For example... Figure 8 As shown in the BF diagram, a good periodic alternation of positive and negative voltage peaks can be observed, indicating that the introduction of CuS-clay particles has no effect on the piezoelectric properties of PVDF, and all sutures can generate stable electrical signals.

[0077] Example 8: Biocompatibility of Sutures 8.1 Hemolysis rate of sutures Hemolysis tests were conducted on P-sutures and CuS-clay sutures. The hemolysis rates of all five sutures were less than 5%, indicating that P-sutures and CuS-clay sutures meet the requirements for hemolysis tests of bioengineering materials and have good biocompatibility.

[0078] 8.2 Cytotoxicity test of sutures NIH-3T3 cells were selected as the in vitro research model, and the cytotoxicity of the sutures was detected by the MTT assay. Five types of sutures (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5 mg) were weighed and prepared into solutions of 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5 mg / mL using complete culture medium. Other steps were the same as in routine experiments. The results showed that P sutures exhibited good cell compatibility and did not produce cytotoxicity at all concentrations, with cell viability exceeding 90% at all concentrations. Four types of CuS-clay sutures also showed good cell compatibility and did not produce cytotoxicity at concentrations ranging from 0.5 to 3 mg / mL.

[0079] Example 9: Photothermal antibacterial surgical sutures reduce postoperative wound infection and scarring. 9.1 Establishment of a rat infected surgical wound model and acquisition of experimental materials Eighty-four male SD rats aged 8-10 weeks were used.

[0080] like Figure 9 As shown in Figure A, at day -2, rats (0.2 mL / 100 g rat) were anesthetized with 2% sodium pentobarbital solution. The hair on their backs was shaved, and after the hair removal cream was left to stand for 1 minute, the skin on their backs was cleaned and disinfected. A vertical line was drawn in the middle of the back skin. Approximately 1.5 cm to either side of this line, symmetrical 2 cm dotted lines were drawn. A 2 cm longitudinal full-thickness incision was made along the dotted lines, and the exudate at the incision site was cleaned with a cotton swab. 100 μL of Staphylococcus aureus (1×10⁻⁶) was dripped into the incision site. 8 After the bacterial culture was absorbed for 10 minutes, a 3M film was applied to the incision, and a bandage was applied. Seven sutures were then placed at the bandage fixation point using 4-0 sutures. On day 0, animals were randomly assigned to seven groups of 12 each: control group (no sutures), SP group (commercially available PVDF sutures), P group (P sutures), CuH@P group (CuH@P sutures), CuM@P group (CuM@P sutures), CuH@P+NIR group (CuH@P sutures + NIR treatment), and CuM@P+NIR group (CuM@P sutures + NIR treatment). Each wound was sutured with four interrupted sutures, inserted vertically. After suturing, a 3M film was applied to the incision, and a bandage was applied. Seven sutures were then placed at the bandage fixation point using 4-0 sutures. Animals continued to be raised for 14 days. Among them, the CuH@P+NIR group and the CuM@P+NIR group underwent NIR treatment (808 nm near-infrared laser at 1.5 W / cm²) after wound closure on day 0. 2 The wound was irradiated for 10 minutes, and the temperature changes of the wound were recorded and thermal distribution images were captured using a FLIR thermal imager.

[0081] Bacterial samples were collected from wounds using cotton swabs soaked in physiological saline on days 0, 3, 7, 10, and 14. After collection, the swabs were placed into centrifuge tubes containing 10 mL of physiological saline. 100 μL from each centrifuge tube was evenly spread onto nutrient agar plates. The agar plates were inverted and placed in a 37 ℃ incubator for 12 h. Afterward, photos were taken against a black background for observation.

[0082] In addition, skin samples were randomly collected from one-third of the rats on days 3, 7, and 14. Using sterilized scissors, a square approximately 2×2 cm was cut from the incision site. The collected skin was washed with physiological saline, and the surface moisture was absorbed with filter paper. The skin was then flattened on the filter paper and divided in half. One half was placed in an embedding cassette and fixed in pre-prepared 4% paraformaldehyde solution. Following dehydration, embedding, sectioning, and drying, the slides were prepared for subsequent histological evaluation. The other half was placed in centrifuge tubes and stored at -80 °C for later use.

[0083] 9.2 CuS-clay sutures reduce postoperative infection and wound scarring. Take and record photos of the wound on days -2, 0, 3, 7, 10, and 14.

[0084] Wound healing effect Figure 9 As shown in Figure B, compared with the control group, SP group, and P group, the CuH@P and CuM@P groups produced fewer visible scars. The CuH@P+NIR and CuM@P+NIR groups showed the best incision healing, with almost no visible scars. This indicates that the CuH@P+NIR and CuM@P+NIR groups have a promoting effect on the healing of infected incisions. Through the synergistic effect of electrical stimulation and photothermal therapy, they have a significant effect on incision healing and reduce scar formation.

[0085] 9.3 In vivo photothermal properties of CuS-clay sutures like Figure 10 As shown, under near-infrared laser irradiation on day 0, the wound temperatures of the CuH@P+NIR and CuM@P+NIR groups rapidly increased to 41.2 °C within 5 minutes, and slowly increased to 44 °C within 10 minutes before stabilizing. This verifies the photothermal capabilities of CuH@P and CuM@P sutures in vivo.

[0086] 9.4 In vivo antibacterial effect of CuS-clay sutures Figure 11 The figures show the in vivo antibacterial test results for each group of sutures. Compared with the control group, SP group, and P group, the CuH@P and CuM@P groups showed better antibacterial effects, while the CuH@P+NIR and CuM@P+NIR groups showed almost no bacterial colonies at the wound site on day 7. In conclusion, the CuH@P+NIR and CuM@P+NIR groups showed stronger antibacterial effects than the CuH@P and CuM@P groups, and were stronger than the P, SP, and control groups.

[0087] 9.5 CuS-clay sutures promote granulation tissue growth in wounds. Granulation tissue gradually forms and accumulates in the early stages of wound healing, playing a crucial role in the healing process. Generally, scar tissue does not contain hair follicles or sebaceous glands. For example... Figure 9 As shown in B, the superficial images of the wounds show vigorous hair growth at the wound sites in the CuH@P+NIR and CuM@P+NIR groups, indicating that the hair follicles at the wound sites have returned to normal.

[0088] Complete skin tissue sections were selected, and H&E staining was used to observe granulation tissue growth and the formation of some appendages (hair follicles, sebaceous glands). The average wound bed length for each group was also calculated. The H&E staining results are shown below. Figure 12 As shown, statistical analysis revealed that on day 7, the wound beds of the control group, SP group, and P group were significantly smaller, with the control group at 1.32 mm, the SP group at 0.79 mm, and the P group at 0.50 mm. The wound beds of the CuH@P and CuM@P groups were significantly reduced, with the CuH@P group at 0.20 mm and the CuM@P group at 0.17 mm. The wound beds of the CuH@P+NIR and CuM@P+NIR groups were the smallest, with the CuH@P+NIR group at 0.067 mm and the CuM@P+NIR group at 0.06 mm. By day 14, the wound beds of all groups had decreased, with the control group at 0.86 mm, the SP group at 0.28 mm, the P group at 0.20 mm, the CuH@P group at 0.083 mm, the CuM@P group at 0.08 mm, the CuH@P+NIR group at 0.033 mm, and the CuM@P+NIR group at 0.033 mm. mm; however, no skin appendages grew in the wounds treated in the control group and SP group, while skin appendages were visible in the incisions treated with CuH@P and CuM@P groups, and even more skin appendages were visible in the wounds treated with CuH@P+NIR and CuM@P+NIR groups. This indicates that treatment with CuH@P and CuM@P groups reduced the formation of incision scars, consistent with the appearance of the incision.

[0089] 9.6 Collagen Deposition and Remodeling in Wounds Complete skin tissue sections were selected, and Masson staining was used to examine collagen deposition during the healing process of infected incisions in rats. In the image, red represents muscle fibers, and blue represents collagen fibers. Figure 13 As shown in Figure A, in the tissues on day 7, the blue color at the wound sites in each group was relatively light, while the red color at the wound sites in the control group and SP group was more pronounced. The blue color at the wound sites treated with CuH@P and CuM@P groups was more pronounced than that in the control group and SP group. Figure 13As shown in Figure B, on day 14, magnified microscopic images of the wound areas in each group revealed that the control group's wounds still showed significant redness, indicating that the collagen was not fully mature and wound healing was incomplete. In the SP group, red was still visible within the blue collagen in the wounds, suggesting that collagen was still proliferating. In contrast, the CuH@P and CuM@P groups showed a uniform, almost colorless blue color in their wounds. The collagen deposition in the CuH@P+NIR and CuM@P+NIR groups was closer to that of normal skin tissue, and hair follicles were also observed in the center of the wounds, indicating that the CuH@P+NIR and CuM@P+NIR groups tended to heal through regeneration rather than scarring.

[0090] Complete skin tissue sections were selected, and Sirius red staining was used to analyze the composition and arrangement of collagen in the wound. Different collagen types showed different colors under a polarized light microscope; mature COL1 appeared orange-red, while early COL3 appeared yellow-green. The birefringence images are shown in Figure 14. It can be observed that on day 7 of wound treatment, immature green collagen accounted for a larger proportion. Wound tissues treated with CuH@P, CuM@P, CuH@P+NIR, and CuM@P+NIR showed collagen arrangement more similar to normal tissue. On day 14, the collagen distribution in wound tissues treated with CuH@P, CuM@P, CuH@P+NIR, and CuM@P+NIR was uniform and orderly, similar to the surrounding normal tissue; the control group and SP group showed more COL1 distribution with disordered arrangement. Although increased secretion of mature COL1 can improve the mechanical properties of the wound, excessive secretion can easily lead to scarring. When collagen fibers are arranged between -20° and 20°, it indicates a regular arrangement, closer to normal tissue. Collagen fibers located in the vertical direction at (±) 60° to 90° indicate mostly irregular fibrous tissue. Figure 15 Based on collagen orientation analysis, the CuH@P+NIR and CuM@P+NIR groups showed a higher concentration of collagen fibers arranged between -20° and 20°, followed by the CuH@P and CuM@P groups. The P group had fewer collagen fibers arranged between -20° and 20°, while the SP and control groups had the fewest. These collagen fiber orientation results also demonstrate that the collagen arrangement in the wound tissue treated with CuH@P+NIR and CuM@P+NIR groups is closer to that of normal tissue.

[0091] 9.7 CuS-clay sutures promote wound re-epithelialization. Complete skin tissue sections were selected for keratin immunohistochemical staining, and the results are as follows: Figure 16 As shown.

[0092] On day 7 of wound healing, epidermal re-epithelialization was slow and incomplete in the control and SP groups, and was disrupted in the center of the wound. In contrast, the CuH@P, CuM@P, CuH@P+NIR, and CuM@P+NIR groups showed high levels of re-epithelialization, with complete epidermal closure in the center of the wound. These results indicate that the CuH@P, CuM@P, CuH@P+NIR, and CuM@P+NIR groups were more effective than other groups in promoting re-epithelial formation.

[0093] Further evaluation of re-epithelialization on day 14 of wound healing was conducted. It was observed that complete epidermal re-epithelialization was achieved in all groups, but the thickness of the regenerated epidermis varied among groups. The epidermis in the CuH@P, CuM@P, CuH@P+NIR, and CuM@P+NIR groups was thin, approaching the thickness of normal marginal skin. In contrast, the control group and SP group had slightly thicker epidermis. As re-epithelialization progressed, the epithelial layer underwent a transformation from thick to thin. This result suggests that re-epithelialization was essentially complete in the CuH@P, CuM@P, CuH@P+NIR, and CuM@P+NIR groups, while the other groups were still in the final sprint towards completion.

[0094] In summary, the above results confirm that the CuH@P, CuM@P, CuH@P+NIR, and CuM@P+NIR groups can effectively promote epidermal re-epithelialization and ultimately promote wound healing.

[0095] 9.8 Anti-inflammatory effect of CuS-clay sutures Select intact skin tissue sections for immunofluorescence staining. For example... Figure 17 As shown, the control group and SP group had the highest inflammatory expression, indicating severe infection. The inflammatory expression in the P group was weakened, but the infection was still relatively severe. The CuH@P and CuM@P groups had a small inflammatory response, with only a weak inflammatory response. The CuH@P+NIR and CuM@P+NIR groups had almost no TNF-α and IL-6 expression, and their anti-inflammatory effects were significantly better than those of other groups.

[0096] 9.9 Mechanical properties of CuS-clay sutures in restoring damaged skin Mechanical repair of injured skin is crucial for maintaining normal skin function, and there are significant mechanical differences between healthy skin tissue and scar tissue. Scar tissue exhibits lower stress and strain than healthy skin. Skin tissue samples were collected from each group on day 14 for mechanical property testing. Figure 18 As shown in Figure A, the collected skin sample is fixed to the two holders of the universal testing machine and pulled at a speed of 10 mm / min. Figure 18As shown in B and C, the tensile stress and strain of the control group were significantly lower than those of the suture group. The tensile strain of the CuH@P+NIR and CuM@P+NIR groups was approximately 60%, that of the CuH@P and CuM@P groups was approximately 45%, and that of the SP group was approximately 20%. The results indicate that the mechanical repair effect on the skin, from strongest to weakest, is as follows: CuH@P+NIR and CuM@P+NIR groups, CuH@P and CuM@P groups, P group, SP group, and control group.

[0097] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A photothermal antibacterial surgical suture, characterized in that, The invention includes an inorganic-organic hybrid suture with piezoelectric and photothermal properties, wherein the inorganic-organic hybrid suture comprises an organic piezoelectric polymer loaded with photothermal nanocomposite particles, wherein the photothermal nanocomposite particles comprise silicate clay with CuS nanoparticles modified on its surface.

2. The photothermal antibacterial surgical suture according to claim 1, characterized in that, The photothermal conversion efficiency of the photothermal nanocomposite particles is not less than 30%.

3. The photothermal antibacterial surgical suture according to claim 1, characterized in that, The CuS nanoparticles have a particle size of less than 100 nm, and the silicate clay has a particle size of 200-3000 nm.

4. The photothermal antibacterial surgical suture according to claim 1, characterized in that, The feed ratio of photothermal nanocomposite particles to organic piezoelectric polymer in the inorganic-organic hybrid suture is 1:

10.

5. The photothermal antibacterial surgical suture according to claim 1, characterized in that, The silicate clay includes one or more of halloysite, lithium saponite, montmorillonite, and attapulgite.

6. The photothermal antibacterial surgical suture according to claim 1, characterized in that, The silicate clay is acidified silicate clay.

7. The photothermal antibacterial surgical suture according to claim 1, characterized in that, The inorganic-organic hybrid suture is a surgical suture that reduces skin fibrosis or scarring during wound healing, or the inorganic-organic hybrid suture is a surgical suture that promotes the healing of infected wounds.

8. The method for preparing the photothermal antibacterial surgical suture according to any one of claims 1-7, characterized in that, The preparation method includes the following steps: Step (1): CuS nanoparticles are modified onto the surface of silicate clay to obtain the photothermal nanocomposite particles; Step (2): The photothermal nanocomposite particles are uniformly dispersed in an electrospinning solution containing an organic piezoelectric polymer, and the inorganic-organic hybrid suture is obtained under high-voltage polarization of electrospinning.

9. The method for preparing photothermal antibacterial surgical sutures according to claim 8, characterized in that, The step (1) also includes acidification of silicate clay, and the acidified natural silicate clay and CuS nanoparticles are prepared by co-precipitation to obtain the photothermal nanocomposite particles.

10. The method for preparing photothermal antibacterial surgical sutures according to claim 8, characterized in that, The parameters for electrospinning in step (2) are: voltage 20 KV, pushing speed 0.0030 mm / s, receiving distance 12 cm, receiver rotation speed 150 rpm, and spinning time 20-40 min.

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