Coating material with hemostasis, self-healing capacity and antibacterial activity, scalpel and preparation method and application of coating material

Abstract

The invention discloses a coating material with hemostasis and self-healing capabilities and antibacterial activity, a scalpel with hemostasis and self-healing capabilities and antibacterial activity, and a preparation method and application of the coating material and the scalpel with hemostasis and self-healing capabilities and the scalpel with hemostasis and self-healing capabilities and the scalpel with hemostasis and self-healing capabilities and antibacterial activity. And epsilon-polylysine carbon quantum dots are used as multifunctional nanoparticles with hemostatic and antibacterial properties, so that the antibacterial self-sealing hemostatic scalpel is invented. The hemostatic material not only can be used for invasive operation or the surface of a scalpel to play a hemostatic role, but also has good antibacterial activity and self-healing capacity, has great potential and can be used as a promising tool for preventing bleeding-related complications in clinical diagnosis and treatment, and complications in the operation process are further reduced.

Description

Technical Field

[0001] The present invention relates to the technical field of surgical instruments, and in particular to a scalpel coating with good hemostasis, self-healing ability and significant antibacterial activity and a preparation method thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance some understanding of the overall background of the invention and should not be necessarily regarded as an admission or any form of suggestion that the information constitutes the prior art already known to those skilled in the art.

[0003] Invasive procedures, including infusions, blood sampling, and biopsies, are integral to clinical diagnosis and treatment. However, in specific settings, such as patients with hemophilia or coagulation disorders, these invasive procedures often carry the risk of complications due to uncontrolled bleeding and infectious diseases transmitted through contaminated blood. For example, elderly individuals may experience severe bleeding after ultrasound-guided percutaneous liver puncture, which carries a higher risk of mortality. Scalpels are widely used for invasive procedures in clinical diagnosis and treatment, including pathological sampling for melanoma and surgical treatment of lumbar spinal stenosis. However, surgical procedures for lumbar spinal stenosis are prone to bleeding and spinal cord compression. Furthermore, even small incisions or minimally invasive cosmetic procedures carry the potential risk of nontuberculous mycobacterial infection, making the use of conventional scalpels challenging during diagnosis and treatment. In recent years, electrosurgical scalpels have gained widespread use as medical devices for bleeding control and have demonstrated excellent hemostatic efficacy. However, the electrical and thermal damage they inflict on surrounding tissues often results in poor self-healing capacity, and to date, reports of effective self-sealing hemostatic scalpels for invasive procedures remain limited. Summary of the Invention

[0004] In response to the shortcomings of the existing technology, the present invention develops a self-sealing hemostatic strategy for aseptically preventing bleeding, which is of great significance for invasive procedures involving surgical blades. Based on N-coordinated boroxane polydimethylsiloxane as an adhesive and ε-polylysine carbon quantum dots as multifunctional nanoparticles with hemostatic and antibacterial properties, the present invention invents an antibacterial self-sealing hemostatic scalpel. The scalpel has good self-healing ability and significant antibacterial activity, and can effectively prevent blood loss caused by tail vein puncture and liver bleeding in mouse models, thanks to promoting the conversion of fibrinogen to fibrin and accelerating the activation of coagulation. This material has great potential to become a promising tool for preventing bleeding-related complications in clinical diagnosis and treatment, further reducing complications during surgery.

[0005] The technical solution adopted in the present invention is as follows: In a first aspect of the present invention, a method for preparing a coating material is provided, the method comprising the following steps: (1) Preparation of N-coordinated boroxy polydimethylsiloxane (NBP): Aminopropyl-terminated polydimethylsiloxane (NH2-PDMS-NH2) and 2-formylphenylboronic acid (PBA) were dissolved in ethanol, mixed, and stirred for 2-4 days to form a bright yellow solution. The solution was then cooled to 0 °C and NaBH4 was added, causing the solution to turn white. After stirring for 8-16 hours, the reaction mixture was concentrated under vacuum and then dissolved in dichloromethane. The resulting solution was extracted with saturated NaHCO3 solution, water, and saturated NaCl solution. Finally, the solution was dried over MgSO4 and concentrated under vacuum to obtain a colorless solid, namely, N-coordinated boroxy-polydimethylsiloxane. (2) Preparation of nano-coating (NC): A solution is prepared by dissolving N-coordinated boroxy-polydimethylsiloxane and carbon quantum dots (PLCQDs) modified with amino groups in an ethanol solution, and then subjected to ultrasonic treatment to obtain a nanocoating, namely a scalpel coating material.

[0006] In one or some embodiments of the present invention, in step (1), the molecular weight of the aminopropyl-terminated polydimethylsiloxane is 4000-6000 Daltons, preferably 5000 Daltons.

[0007] In one or some embodiments of the present invention, in step (1), the concentration ratio of the aminopropyl-terminated polydimethylsiloxane, 2-formylphenylboronic acid and NaBH4 in ethanol is (0.4-0.6): (2-3): (3-4), preferably 0.5:2.5:3.3.

[0008] In one or some embodiments of the present invention, in step (1), aminopropyl-terminated polydimethylsiloxane 2-formylphenylboronic acid is dissolved in ethanol, mixed, and stirred at room temperature for 3 days.

[0009] In one or some embodiments of the present invention, in step (2), the preparation of carbon quantum dots with amino groups on the surface is a prior art. Herein, a method for preparing carbon quantum dots with amino groups on the surface is provided, the method comprising the following steps: placing ε-polylysine powder in a corundum crucible and heating it in a box-type muffle furnace at 230-250°C for 2-4 hours; after cooling to room temperature, dissolving the powder in 20 mL of ultrapure water; sonicating the mixed solution and then centrifuging it, followed by dialysis of the supernatant with deionized water and freeze-drying to obtain carbon quantum dot powder with amino groups on the surface.

[0010] In one or some embodiments of the present invention, in step (2), the concentration ratio of the N-coordinated boroxy polydimethylsiloxane to the carbon quantum dots modified with amino groups is (1-2): (1-2), preferably 1:1.

[0011] In one or some embodiments of the present invention, in step (2), the ultrasonication time is 6 to 8 hours.

[0012] In a second aspect of the present invention, a coating material prepared by the method is provided.

[0013] In a third aspect of the present invention, there is provided use of the coating material in preparing a scalpel coating or other surgical instrument coating.

[0014] In a fourth aspect of the present invention, a hemostatic, self-healing and antibacterial scalpel is provided, comprising a scalpel base and a coating covering the scalpel base, wherein the coating is made of the above-mentioned coating material.

[0015] The preparation method of the scalpel comprises: sterilizing a scalpel base and then drying it with nitrogen (N2); then spraying the scalpel base with a coating material to obtain a scalpel with a nano-coating.

[0016] In one or some embodiments of the present invention, the fixed distance between the nozzle and the scalpel is 10 to 15 cm; and the number of spraying times of the spraying material is set to 15 to 45 times.

[0017] The hemostatic, self-healing and antibacterial scalpel of the present invention has the following functions: 1) ε-polylysine carbon quantum dots create a unique hydrophobic coating on the surface of the scalpel, minimizing bacterial adhesion and colonization, and can adhere to and destroy bacterial cell walls through electrostatic interactions, exerting an antibacterial effect, which is crucial for immunocompromised patients, preventing persistent wound closure from causing infection and scar formation, and promoting wound tissue repair; 2) ε-polylysine carbon quantum dots can accelerate the conversion of fibrinogen to fibrin, enhance blood coagulation ability, reduce bleeding events, and reduce the potential for secondary trauma to surrounding tissues.

[0018] Compared with the related art known to the inventors, one of the technical solutions of the present invention has the following beneficial effects: 1. This invention develops an antibacterial, self-sealing, hemostatic scalpel coating by comprehensively utilizing N-coordinated boroxane polydimethylsiloxane as an adhesive and ε-polylysine carbon quantum dots as multifunctional nanoparticles with hemostatic and antibacterial properties. 2. This study developed an antimicrobial, self-sealing, hemostatic scalpel coating by leveraging the anti-inflammatory, hydrophobic, and hemostatic properties of NBP binders and PLCQDs. This coating demonstrates the potential to alleviate pain and reduce secondary trauma to surrounding tissues by reducing surface roughness and achieving high friction resistance. The self-healing NC coating exhibits antimicrobial properties and accelerates blood coagulation by promoting the conversion of fibrinogen to fibrin. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The accompanying drawings, which constitute a part of the specification of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0020] Figure 1 This is the technical roadmap of the present invention.

[0021] Figure 2 (A) Schematic diagram of NBP synthesis; (B) ¹H NMR spectrum of NBP; (C) Transmission electron microscopy (TEM) image and size distribution of PLCQDs; (D) Fourier transform infrared (FTIR) spectrum of PLCQDs; (E) Zeta potential of PLCQDs.

[0022] Figure 3 (A) Photograph of NC-coated glass; (B) Scanning electron microscopy (SEM) images of a plain scalpel (blank) and a scalpel coated with NC, as well as energy dispersive spectroscopy (EDS) analysis of an NC3-coated scalpel; (C) UV image of an NC-coated scalpel and an SEM image of the scalpel after cutting porcine skin. The yellow dashed line marks the fat area of ​​the porcine skin, and the red dashed line marks the area where the NC coating has peeled off, exposing the scalpel blade; (D) Phase contrast microscopy and UV images of an NC3-coated needle.

[0023] Figure 4 (A) Atomic force microscopy (AFM) image and surface roughness of a surgical knife coated with NC3 coating; (BC) Water contact angle (WCA) image and quantitative analysis of a surgical knife coated with NC coating; (DE) Self-healing mechanism of the NC coating and its damage after oxidation in H2O2 for 1 minute and WCA changes after self-healing in H2O for 6 hours.

[0024] Figure 5 (AB) Antibacterial properties and quantitative effects of NC coatings against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus); (C) Potential antibacterial mechanism of NC coatings.

[0025] Figure 6 (A) APTT, TT, and FIB characteristic analysis of NBP and PLCQD samples; (B) Macroscopic observation and blood coagulation index (BCI) analysis of NC coating; (C) Side view morphology of NC3-coated scalpel after blood coagulation; (D) Morphological analysis of NC-coated scalpel after blood coagulation.

[0026] Figure 7(A) Hemostatic effect of NC3-coated scalpel on mouse liver and the associated blood loss and hemostasis time; (B) Hemostatic effect of NC3-coated needle on mouse tail; (C) Hemostatic mechanism of NC coating (intravascular view). DETAILED DESCRIPTION

[0027] It should be noted that the following detailed descriptions are exemplary and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs.

[0028] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations and / or combinations thereof.

[0029] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments. Example

[0030] The technical roadmap of the present invention is as follows: Figure 1 .

[0031] ① Preparation and characterization of PLCQDs PLCQDs were synthesized by a thermal decomposition method, as previously reported. Briefly, 1 g of ε-polylysine powder (molecular weight approximately 4000, provided by Dipu Chemical Technology Co., Ltd., China) was placed in a corundum crucible and heated at 240 °C for 3 hours in a box muffle furnace. After cooling to room temperature, the powder was dissolved in 20 mL of ultrapure water. The mixture was sonicated for 60 minutes and then centrifuged at 11,000 rpm for 30 minutes. The supernatant was then dialyzed against deionized water for 24 hours and freeze-dried using an Alpha1-2LD plus freeze dryer (CHRIST®, Germany). The resulting PLCQD powder was stored refrigerated at 4 °C.

[0032] ② Preparation and characterization of NBP 0.5 mM aminopropyl-terminated polydimethylsiloxane (NH2-PDMS-NH2, molecular weight approximately 5000, Gelest) and 2.5 mM 2-formylphenylboronic acid (PBA, Ark Pharm) were dissolved in ethanol, mixed, and stirred at room temperature for 3 days to form a bright yellow solution. The solution was then cooled to 0°C in an ice-water container, and 3.3 mM NaBH4 (Sinopharm Chemical Reagent Co., Ltd., China) was slowly added, causing the solution to turn white. After stirring overnight, the reaction mixture was concentrated under vacuum and then dissolved in dichloromethane. The resulting solution was extracted sequentially with saturated NaHCO3 solution, deionized water, and saturated NaCl solution. Finally, the solution was dried over MgSO4 and concentrated under vacuum to obtain a colorless solid.

[0033] ③ Preparation and characterization of NC coating A solution was prepared by dissolving NBP (10 mg / mL) and PLCQDs (10 mg / mL) in an ethanol solution and sonicating for 7 hours. A substrate (e.g., a scalpel) was cleaned with water and ethanol and then dried with nitrogen (N2). Subsequently, a transparent substrate was sprayed with the NBP / PLCQD solution at a fixed distance of 15 cm between the nozzle and the substrate. The number of sprays was set to 15, 30, and 45, respectively, and these groups were designated as NC1, NC2, and NC3, respectively.

[0034] like Figure 2 As shown in A, NBP monomer was synthesized by the Schiff base reaction of NH2-PDMS-NH2 and PBA. The successful synthesis of NBP was confirmed by the appearance of characteristic peaks in the ¹H NMR spectrum (e.g. Figure 2 As shown in Figure B), this characteristic peak is attributed to the N donor at the ortho position of phenylboronic acid, which helps to form a coordinated NB bond at room temperature and then generate boroxane without the use of a Lewis base. PLCQDs are synthesized in a one-pot method using PL hydrochloride precursors. Figure 2 As shown in C, PLCQDs exhibit a spherical morphology with an average diameter of 2.31 ± 0.70 nm, uniform distribution and no obvious aggregation. FTIR spectrum of PL ( Figure 2 D) shows that the peak at 2932 cm⁻¹ corresponds to the stretching vibration of the amino group, while the two shoulders near 1600 cm⁻¹ correspond to the absorption bands of strong amide I (about 1654 cm⁻¹) and amide II (about 1454 cm⁻¹), respectively. After pyrolysis, the obtained PLCQDs retain the characteristic peaks of the PL precursor (such as 2932 cm⁻¹, 1654 cm⁻¹ and 1454 cm⁻¹). In addition, there is no significant difference in the zeta potential values ​​in water and ethanol (EA) (such as Figure 2 E), indicating that it maintains the positive charge characteristic of the PL precursor. This positive potential has been shown to have good antibacterial properties.

[0035] like Figure 3 As shown in Figure A, PLCQDs were attached to the surface of a scalpel via an adhesive NBP coating. The NBP group showed similar light transmittance to the blank group, indicating that NBP has high transparency. However, with the introduction of PLCQDs, the light transmittance decreased, and the coating surface exhibited a visible "golden" color that gradually darkened with the increase in the number of coating layers. In addition, the scalpel surface was evenly covered with an increase in the number of coating layers, and complete coverage was observed in the NC3 group ( Figure 3 B). EDS analysis of iron (scalpel element), silicon (NBP element), carbon (NBP and PLCQD element), and oxygen (NBP and PLCQD element) confirmed the uniform coating of NC3 on the scalpel surface. Due to the fluorescent properties of CQDs, a significant UV fluorescence response was observed after NC coating on the scalpel surface, and the fluorescence coverage area increased with the number of coating layers ( Figure 3 C). However, when the scalpel was used to cut pig skin, the surface coating wore and peeled. Wear tests on pig skin evaluated the structural stability of the NC coating. As expected, the degree of peeling decreased with increasing coating layer number, indicating improved adhesion to the scalpel surface. Furthermore, thicker coatings exhibited greater resistance to friction, so NC3 was selected for application on the needle surface to demonstrate the versatility of the NC coating approach ( Figure 3 D). Under fluorescence excitation, dense NC fluorescent particles are observed on the needle surface, which is attributed to the inherent aggregation tendency of the nanomaterial and the large curvature of the needle geometry.

[0036] like Figure 4 As shown in Figure A, modification of the NC coating significantly reduced surface roughness, a factor that helps to reduce pain intensity and alleviate secondary trauma caused by friction to surrounding tissues. Figure 4 B compares the surface hydrophilicity of untreated scalpels and scalpels coated with NC. The contact angle of the untreated scalpel was 82.93 ± 1.6° (less than 90°), indicating that it has inherent hydrophilicity. After modification with NC coating, the contact angle of the NC1 group increased to 98.49 ± 2.39°, the NC2 group was 111.24 ± 0.55°, and the NC3 group was 115.02 ± 1.92°, indicating that the NC coating imparted higher hydrophobicity. It is worth noting that NBP has the ability to restore its original surface energy through surface reorganization, which is attributed to the reversible breaking and reforming of N-coordinated boroxane with the addition and removal of water at ambient temperature. As Figure 4As shown in Figure D, after H2O2 oxidation, the contact angle of the scalpel surface decreased from 115.02 ± 1.92° to 86.34 ± 0.91°. After the coating self-repaired in water, the participation of H2O promoted the regeneration of boroxane and the recovery of NC3 coating, and finally the contact angle of the scalpel was restored to 110.21 ± 0.9° ( Figure 4 DE). This self-healing ability ensures the integrity of the NC coating under complex transportation and storage conditions.

[0037] like Figure 5 As shown in A, after co-culturing the scalpel with Escherichia coli (E. coli) or Staphylococcus aureus (S. aureus) suspension for 12 hours, the NC group showed significant antibacterial activity, which was significantly superior to the control group and NBP group. Specifically, the antibacterial rate of the NC sample against E. coli and S. aureus was close to 100% ( Figure 5 B). Given the limited antibacterial effects of the blank and NBP groups, the antibacterial properties of the NC coating are primarily attributed to PLCQDs. PLCQDs damage bacterial cell walls / membranes and DNA / RNA by triggering the production of reactive oxygen species (ROS) and oxidative stress, ultimately leading to mutations or overexpression of key genes ( Figure 5 C).

[0038] like Figure 6 As shown in Figure A, the PLCQD-treated group showed a shortened APTT, decreased TT, and increased FIB values ​​compared to NBP, indicating that PLCQDs can accelerate the conversion of fibrinogen to fibrin and enhance blood coagulation. To verify this, activated fresh blood was added to a blade coated with NC, followed by ultrapure water to lyse the uncoagulated portion. A decrease in red intensity was observed, indicating that PLCQD treatment increased BCI (blood coagulation index). Figure 6 As shown in B, although no significant changes were observed among the control group, blank group, and NBP group, the liquid in the EP tube became more transparent as the number of coating layers increased ( Figure 6 B). Notably, the BCI values ​​of the NC coating were significantly higher compared to the blank group, and further increased with the increase in the number of coating layers. The dense fibrin network observed in the NC3 group further supports the enhancement of blood coagulation ( Figure 6 Furthermore, an increase in the number of adsorbed erythrocytes was observed on the NC coating compared with the blank group, and the activation of this coagulation process was positively correlated with the number of NC coating layers.

[0039] like Figure 7Although the NC1-coated scalpel had a limited effect in preventing blood loss compared to the significant bleeding in the control group, the NC3-coated scalpel exhibited significant coagulation and hemostatic effects. Specifically, the untreated scalpel resulted in normal bleeding with a bleeding time of 190.33 ± 13.01 seconds and a blood loss of 216.67 ± 30.55 mg. In contrast, the bleeding time of mice treated with the NC3-coated scalpel was significantly reduced to 58.67 ± 8.62 seconds and the blood loss was reduced to 36.67 ± 15.28 mg. These results indicate that the NC3-coated scalpel has significant hemostatic potential in invasive surgery. Notably, the hemostatic effect of the NC-coated scalpel depends on the number of NC coating layers, and the hemostatic performance decreases significantly as the number of coating layers decreases. As Figure 7 As shown in Figure B, after a 5-second needle removal experiment in the mouse tail vein, clear blood droplets were observed at the tail vein puncture site in the control group. In contrast, as the number of needle coating layers increased, blood droplet exudation in the tail vein gradually decreased. In particular, in the NC3 group, no clear blood droplets were observed, leaving only a slight trace of blood. Subsequently, the adsorbed fibrinogen converted to fibrin, quickly forming a blood clot to seal the vascular incision after the scalpel was withdrawn, ultimately preventing blood loss in a sterile manner ( Figure 7 C).

[0040] In summary, the present invention successfully prepared an antibacterial self-sealing hemostatic scalpel coating, and confirmed that it has good self-healing ability and significant antibacterial activity. It can also effectively prevent blood loss caused by tail vein puncture and liver bleeding in a mouse model by promoting the conversion of fibrinogen to fibrin and accelerating the activation of coagulation.

[0041] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be considered as equivalent replacement methods and are included in the scope of protection of the present invention.

Claims

1. A method for preparing a coating material, characterized in that: The method comprises the following steps: (1) Preparation of N-coordinated boroxy polydimethylsiloxane: Aminopropyl-terminated polydimethylsiloxane and 2-formylphenylboronic acid were dissolved in ethanol, mixed, and stirred for 2-4 days to form a bright yellow solution. The solution was then cooled to 0 °C and NaBH4 was added, causing the solution to turn white. After stirring for 8-16 hours, the reaction mixture was concentrated under vacuum and then dissolved in dichloromethane. The resulting solution was extracted with saturated NaHCO3 solution, water, and saturated NaCl solution. Finally, the solution was dried over MgSO4 and concentrated under vacuum to obtain a colorless solid, namely, N-coordinated boroxy-polydimethylsiloxane. (2) Preparation of nano coating: A solution is prepared by dissolving N-coordinated boroxy polydimethylsiloxane and carbon quantum dots with amino groups modified on the surface in an ethanol solution, and performing ultrasonic treatment to obtain a nano coating, which is a scalpel coating material.

2. The method for preparing a coating material according to claim 1, wherein: In step (1), the molecular weight of the aminopropyl-terminated polydimethylsiloxane is 4000-6000 Daltons.

3. The method for preparing a coating material according to claim 1, wherein: In step (1), the concentration ratio of the aminopropyl-terminated polydimethylsiloxane, 2-formylphenylboronic acid and NaBH4 in ethanol is (0.4-0.6): (2-3): (3-4).

4. The method for preparing a coating material according to claim 1, wherein: In step (1), aminopropyl-terminated polydimethylsiloxane 2-formylphenylboronic acid is dissolved in ethanol, mixed, and stirred at room temperature for 3 days.

5. The method for preparing a coating material according to claim 1, wherein: In step (2), the concentration ratio of the N-coordinated boroxy polydimethylsiloxane and the carbon quantum dots with surface modified amino groups is (1-2): (1-2).

6. The method for preparing a coating material according to claim 1, wherein: In step (2), the ultrasonication time is 6 to 8 hours.

7. A coating material prepared by the preparation method according to any one of claims 1 to 6.

8. Use of the coating material according to claim 7 in preparing scalpel coatings or other surgical instrument coatings.

9. A hemostatic, self-healing and antibacterial surgical knife, characterized by: The scalpel includes a scalpel base and a coating covering the scalpel base, wherein the coating is made of the coating material according to claim 7.

10. The hemostatic, self-healing and antibacterial surgical knife according to claim 9, characterized in that: The scalpel is prepared by the following method: sterilizing a scalpel base and then drying it with nitrogen; then spraying the scalpel base with a coating material to obtain a hemostatic, self-healing and antibacterial scalpel; The fixed distance between the nozzle and the scalpel base was 10-15 cm; the number of spraying times of the coating material was set to 15-45 times.

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