An antibacterial and anti-adhesion catheter based on smart responsive nanofiber membranes and a preparation method thereof

Abstract

The present application relates to a kind of antibacterial and anti-adhesion catheter based on intelligent response nanofiber membrane, which is composed of medical polymer catheter substrate, silane coupling agent transition layer grafted on the outer surface of the substrate and nanofunctional fiber membrane layer formed on the outer surface of the transition layer by electrospinning process, the nanofunctional fiber membrane layer is composed of polyvinyl alcohol loaded hyaluronic acid grafted copper-doped carbon dots (CCDH), CCDH takes copper-doped carbon dots as core, and forms core-shell structure by grafting hyaluronic acid on the surface. The present application solves the problem of easy peeling of catheter coating by chemical bonding, and the formed antibacterial and anti-adhesion catheter has very low water contact angle and friction coefficient, not only effectively blocks the initial adhesion of bacteria at the physical level by constructing hydration layer, but also releases copper ions and carbon dots by enzymatic hydrolysis of hyaluronic acid under bacterial infection microenvironment, induces the production of reactive oxygen species to kill bacteria efficiently, and has broad application prospect in reducing the risk of catheter-related urinary tract infection.

Description

Technical Field

[0001] This invention belongs to the field of medical material surface modification technology, specifically relating to an antibacterial and anti-adhesion catheter for preventing catheter-related urinary tract infections based on the surface modification of functional nanomaterials, and its preparation method. Background Technology

[0002] Catheter-associated urinary tract infections (CAUTIs) are among the most common hospital-acquired infections in healthcare settings worldwide.

[0003] The occurrence of CAUTIs is closely related to the prolonged indwelling of urinary catheters. When a medical catheter is inserted into the urethra and bladder, pathogenic microorganisms in the urine (such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) rapidly adhere to the catheter surface and multiply quickly. As bacteria accumulate in large numbers, their secreted extracellular polymers form a structurally stable bacterial biofilm on the catheter surface. Once the biofilm forms, it acts as a physical and chemical barrier, effectively resisting attacks from the host's immune system and greatly increasing bacterial resistance to conventional antibiotics. This leads to persistent and recurrent infections, prolonging hospital stays, increasing medical costs, and in severe cases, even causing sepsis and endangering life.

[0004] In recent years, with the continuous increase in the detection rate of multidrug-resistant bacteria, the effectiveness of traditional antimicrobial strategies has been limited, and biofilm clearance technology has become a key challenge in the prevention and control of catheter-associated urinary tract infections (CAUTIs). The 2025 edition of the "Guidelines for the Prevention of Catheter-Associated Urinary Tract Infections (CAUTI)" emphasizes that strengthening biofilm clearance technology and multidrug-resistant bacteria intervention programs has become a key focus of current prevention and control efforts.

[0005] To reduce the risk of CAUTIs, various catheter surface modification strategies have been explored in the clinical and research fields. These strategies can be mainly categorized into two types, but all have significant technical limitations.

[0006] 1. Physical Barrier Strategy (Hydrophilic / Anti-Adhesion Coating): This strategy involves coating the catheter surface with hydrophilic polymers such as polyvinyl alcohol (PVA) or polyethylene glycol (PEG). The coating forms a water film through hydration, physically hindering initial bacterial adhesion and improving the catheter's anti-infection performance. The core drawback of this modification is that the coating and catheter are only bonded by weak van der Waals forces or hydrogen bonds, lacking a strong chemical bond. This makes it prone to detachment and failure with long-term use, resulting in severely insufficient durability during actual clinical placement.

[0007] Currently, polydimethylsiloxane (PDMS) is the commonly used substrate for urinary catheters in clinical practice. While this material possesses excellent bioinertness and flexibility, its surface is chemically inert and highly hydrophobic (water contact angle > 100°), containing almost no active functional groups capable of participating in chemical reactions. This not only facilitates initial bacterial adhesion but also poses a fundamental challenge to the robust construction of its surface functional coating. Without deep chemical modification, the hydrophilic physical coating is only bonded to the substrate by weak van der Waals forces. Under prolonged urine flushing, catheter bending, and mechanical friction from urethral insertion and removal, the catheter coating is highly susceptible to cracking, peeling, and detachment. Once the coating detaches, the catheter loses its anti-infection function. Pollard D, et al. (Evaluation of an integrated amphiphilic surfactant as an alternative to traditional PVP coatings). Biotribology (2022, 32: 100218.) Using an in vitro agar model, it was observed that the hydrophilic coating of the polyvinylpyrrolidone-coated catheter detached when it was pulled out.

[0008] 2. Bactericide Loading Strategy (Active Bactericidal Coating): This strategy involves directly doping the catheter coating with antibiotics such as gentamicin and ciprofloxacin, or with metal ions such as silver and copper nanoparticles as antibacterial mediators. The release of the bactericide directly kills pathogenic microorganisms, achieving the goal of preventing infection. (Yang H, et al. (Synergistic antibacterial, anti-adhesion, and lubricating hydrogel coating with carbon quantum dots forurinary catheters)). Int J Biol Macromol (2025, 322: 146961.) Introducing carbon quantum dots into the hydrogel coating of urinary catheters achieves multifunctional integration of antibacterial, anti-adhesion and lubrication; Lin, Z., et al. (Mussel-inspired surface modification of urinary catheters with both zwitterionic and bactericidal properties for effectively preventing catheter-associated infection.) Chemical Engineering Journal(2023, 467: 143491.) Some studies have also constructed zwitterionic / quaternary ammonium salt bifunctional coatings based on mussel biomimicry principles, attempting to integrate anti-adhesion and bactericidal functions. However, the core defect of this type of modification is that the coating lacks intelligent response capability to the infection microenvironment. The bactericide is simply physically embedded in the coating, and it dissolves rapidly after contact with urine, exhibiting an uncontrollable "burst release" phenomenon in the early stages of sterility or low bacterial load.

[0009] This uncontrollable release pattern has multiple consequences: First, the initial blind release, regardless of whether there is a bacterial infection, leads to excessively high local bactericidal concentrations, which produce cytotoxic and irritating effects on normal cells such as the urethral mucosa and bladder wall, causing urethral irritation, cystitis, and other tissue inflammatory reactions, seriously affecting patients' clinical tolerance; Second, the bactericidal agent in the coating is rapidly depleted after the burst release, and the effective antibacterial time is drastically shortened, failing to meet the infection prevention needs of long-term indwelling urinary catheters; Third, blind release without intelligent response capabilities may also induce bacterial resistance or produce the toxicity of metal ions accumulated in the body.

[0010] Therefore, there is an urgent need to develop a new type of catheter surface modification technology that can not only achieve a strong covalent bond between the coating and the substrate to withstand long-term mechanical friction, but also has the dual functions of "early superhydrophilic anti-adhesion" and "intelligent microenvironment response sterilization during infection", while also having excellent biocompatibility, so as to safely and effectively reduce the risk of CAUTIs. Summary of the Invention

[0011] The purpose of this invention is to provide an antibacterial and anti-adhesion catheter based on a smart responsive nanofiber membrane. By solving the problem of interface bonding stability of modified catheters, a biosafety catheter with dual functions of "physical anti-adhesion barrier" and "intelligent response sterilization in infection microenvironment" is constructed.

[0012] Providing a method for preparing the antibacterial and anti-adhesion catheter and its application in preventing catheter-related urinary tract infections is another objective of this invention.

[0013] To achieve the above-mentioned objectives, this invention first provides an antibacterial and anti-adhesion catheter based on a smart responsive nanofiber membrane. By firmly anchoring a layer of superhydrophilic polyvinyl alcohol-loaded hyaluronic acid-grafted copper-doped carbon dot composite nanofiber membrane on the surface of an inert catheter substrate, a dual defense of physical anti-adhesion and smart on-demand sterilization is achieved, and it also has excellent in vivo tissue protection and anti-inflammatory functions.

[0014] Specifically, the catheter consists of the following three layers from the inside out: Medical polymer catheter substrate; The transition layer is a monomolecular grafted layer of silane coupling agent covalently grafted onto the outer surface of the substrate; and The nanofiber membrane is formed on the outer surface of the transition layer by electrospinning. The three-layer structure is connected layer by layer by covalent bonds, resulting in a stable overall structure without interface layering.

[0015] The nanofiber membrane is a composite nanofiber membrane formed by loading antibacterial carbon nanodots with polyvinyl alcohol. It has a hydrophilic and anti-adhesion surface and can respond to hyaluronidase secreted by bacteria.

[0016] Furthermore, the antibacterial carbon nanodots are hyaluronic acid-grafted copper-doped carbon dots, abbreviated as CCDH. It should be noted that the specific structure, preparation method, and properties of CCDH have been disclosed in Chinese Patent Application CN 121370947A, filed by the applicant on December 4, 2025, the entire contents of which are incorporated herein by reference.

[0017] Specifically, the CCDH is a core-shell structure formed by grafting hyaluronic acid molecules onto the surface of copper-doped carbon dots as the core and amide bonds. The copper element in the copper-doped carbon dot core exists in the form of Cu(II) and Cu(I), serving as an antibacterial active ingredient, and also possessing peroxidase-like activity and free radical scavenging ability.

[0018] More specifically, the CCDH is prepared by hydrothermal reaction of folic acid and soluble copper salt at 180-220°C to obtain copper-doped carbon dots, followed by carboxyl activation of the copper-doped carbon dots using EDC·HCl and NHS, and then amidation reaction with hyaluronic acid solution.

[0019] Preferably, the medical polymer catheter substrate of the present invention is a polydimethylsiloxane (PDMS) catheter, which, as a general medical implant-grade elastic substrate, has good flexibility, tissue compatibility and bioinertness.

[0020] However, the medical polymer catheter substrate of the present invention is not limited thereto. Any medical polymer material suitable for implantation in the body, including but not limited to polyurethane (PU), polyvinyl chloride (PVC) or silicone rubber catheters, can be used as the medical polymer catheter substrate of the present invention.

[0021] As another preferred embodiment, the silane coupling agent in the transition layer is an organosilicon compound capable of forming covalent bonds with the substrate surface and introducing active functional groups, including but not limited to γ-methacryloyloxypropyltrimethoxysilane (KH-570), γ-aminopropyltriethoxysilane (KH-550), γ-glycidoxypropyltrimethoxysilane (KH-560), or vinyltriethoxysilane (A-151), etc.

[0022] Furthermore, in the antibacterial and anti-adhesion conduit of the present invention, the loading amount of hyaluronic acid-grafted copper-doped carbon dots in the nanofiber membrane layer is preferably 1-5% of the mass of polyvinyl alcohol. More preferably, it is 3%.

[0023] The antibacterial and anti-adhesion catheter of this invention firstly overcomes the chemical inertness of the substrate surface by covalently grafting a silane coupling agent transition layer onto the substrate surface, introducing active functional groups such as carbon-carbon double bonds and hydroxyl groups, providing covalent bonding sites for the upper nanofiber membrane layer, thus fundamentally solving the problem of easy coating peeling. Furthermore, the nanofiber membrane layer is formed in situ using an electrospinning process, and the continuous porous nanofiber network structure maximizes the hydrophilic specific surface area, constructing a stable hydration anti-adhesion layer, thereby endowing the catheter surface with excellent antibacterial adhesion properties. Simultaneously, the CCDH antibacterial material uniformly loaded in the nanofiber membrane layer can respond to the hyaluronidase secreted by bacteria in the infection microenvironment, triggering the controlled release of antibacterial active ingredients, achieving intelligent responsive sterilization.

[0024] In particular, the hyaluronic acid in CCDH can specifically recognize hyaluronidase, which is highly expressed by pathogenic bacteria in the bacterial infection microenvironment. When there is no bacterial infection on the catheter surface, the hyaluronic acid structure is stable, and copper ions and carbon dots are encapsulated and fixed inside the fibrous membrane, preventing ineffective release and ensuring biosafety. When bacterial infection occurs and hyaluronidase overexpression occurs, hyaluronic acid specifically degrades, triggering the controlled release of active antibacterial components. By inducing bacteria to produce a large amount of reactive oxygen species, it destroys the bacterial cell membrane, DNA, and protein structure, achieving highly efficient sterilization and biofilm disintegration. By constructing a dual protection system of "physical anti-adhesion barrier + intelligent chemical sterilization," the problems of short antibacterial time, lack of targeted response, inability to remove biofilm, and poor biosafety are solved, significantly improving the indwelling safety and long-term stability of the catheter.

[0025] Secondly, the present invention also provides a specific method for preparing the antibacterial and anti-adhesion catheter, including: 1) The medical polymer catheter substrate is surface activated by ultraviolet irradiation in a photoinitiator solution to generate active free radicals on the substrate surface; 2) Chemical grafting of surface-activated substrate with silane coupling agent solution to form a transition layer on the substrate surface; 3) Dissolve polyvinyl alcohol in its good solvent, add antibacterial nano carbon dots and disperse evenly to obtain a composite spinning solution; 4) Using a substrate with a transition layer as a rotation receiver, the composite spinning solution is uniformly spun onto the surface of the transition layer of the substrate using an electrospinning process to form a nanofunctional fiber membrane in situ, thus preparing an antibacterial and anti-adhesion conduit based on a smart responsive nanofiber membrane.

[0026] As a specific implementation, the photoinitiator solution used for surface activation of medical polymer catheter substrates in this invention is preferably a 5-15 wt% benzophenone ethanol solution, more preferably a 10 wt% benzophenone ethanol solution.

[0027] More specifically, the present invention involves immersing the medical polymer catheter substrate in the photoinitiator solution for no less than 30 minutes, and then irradiating it with 365nm ultraviolet light at a power of 100W for no less than 10 minutes to activate its surface.

[0028] As a specific implementation, the concentration of the silane coupling agent solution of the present invention is preferably 3 to 8 wt%, more preferably 5 wt%.

[0029] More specifically, the chemical grafting reaction described in this invention is preferably carried out at 35–45°C for 2–5 hours.

[0030] As a specific implementation, the preferred solvent for polyvinyl alcohol in this invention is a 5-15 wt% aqueous solution of glacial acetic acid.

[0031] More specifically, the polyvinyl alcohol concentration in the composite spinning solution prepared by the present invention is preferably 6 to 10 wt%.

[0032] As a specific implementation scheme, the electrospinning process of the present invention adopts a dual-nozzle system, applying equal-amplitude and opposite-reverse positive and negative high voltages to two nozzles respectively, in order to enhance the orientation of the fiber and improve the adhesion and interfacial bonding strength between the fiber and the substrate.

[0033] More specifically, the parameters of the electrospinning process described in this invention are: positive voltage +12 to +16 kV, negative voltage -12 to -16 kV, composite spinning solution flow rate 1.0 to 2.0 mL / h, receiving distance 12 to 18 cm, and rotating receiver speed 250 to 350 rpm.

[0034] Furthermore, the specific preparation method of the antibacterial and anti-adhesion catheter of the present invention further includes drying the catheter with the in-situ formed nanofiber membrane layer in a vacuum oven at 40°C for no less than 24 hours to remove residual solvent, thereby preparing an antibacterial and anti-adhesion catheter based on a smart responsive nanofiber membrane.

[0035] Finally, the present invention also provides the use of the aforementioned antibacterial and anti-adhesion catheter in the preparation of medical devices for the prevention and / or relief of catheter-related urinary tract infections.

[0036] Specifically, CAUTIs are mainly caused by common pathogens such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, all of which exhibit high expression of hyaluronidase in the infection microenvironment. To address this characteristic, this invention introduces CCDH into a nanofiber membrane, utilizing hyaluronic acid as an enzyme-responsive switch. Upon infection with the aforementioned pathogens, the secreted hyaluronidase specifically degrades the hyaluronic acid shell in the nanofiber membrane, thereby triggering the controlled release of antibacterial active ingredients.

[0037] Based on the same enzyme-responsive antibacterial and anti-adhesion mechanism, the antibacterial and anti-adhesion catheter described in this invention is also applicable to other medical catheters that require long-term indwelling and are prone to hyaluronidase-related bacterial infections and biofilm formation. These medical catheters include, but are not limited to, central venous catheters, biliary drainage tubes, endotracheal tubes, peritoneal dialysis catheters, and other implantable or interventional medical catheters.

[0038] It should be noted that the above extended applications are based on the premise that the clinical complications of the medical catheter involve bacterial infections and biofilm formation related to hyaluronidase overexpression.

[0039] Compared with existing technologies, the antibacterial and anti-adhesion catheter based on the intelligent responsive nanofiber membrane of the present invention has the following beneficial effects:

[0040] 1. High interfacial bonding strength and excellent coating durability

[0041] This invention employs an interface strengthening strategy involving surface activation, silane coupling agent grafting, and in-situ electrospinning to construct a robust chemically bonded interface on the surface of an inert and highly hydrophobic medical polymer substrate. After simulating 50 rigorous continuous reciprocating friction cycles and 14 days of dynamic artificial urine flushing, the functional fiber membrane showed no cracking, delamination, or detachment, and the water contact angle and dynamic friction coefficient remained highly stable.

[0042] 2. Super-hydrophilic and lubricating surface with significant physical anti-adhesion effect.

[0043] The nanofiber membrane of this invention endows the catheter with excellent surface physicochemical properties. After modification, the water contact angle of the catheter drops sharply from 108° and stabilizes at around 28°, exhibiting superhydrophilic properties. The dynamic friction coefficient in the wetted state decreases significantly from 0.54 to about 0.20, forming a stable hydration lubricating layer on the superhydrophilic surface. On the one hand, it constructs a strong physical barrier, effectively blocking the initial colonization of hydrophobic bacteria, with an anti-adhesion rate of over 98% against Escherichia coli and Staphylococcus aureus. On the other hand, it significantly reduces the mechanical damage and irritation to the urethral mucosa caused by catheter insertion and removal.

[0044] 3. Intelligent response to the infection microenvironment, enabling precise sterilization on demand.

[0045] The hyaluronic acid in the CCDH of this invention can be specifically degraded by hyaluronidase overexpressed by bacteria at the site of infection, triggering the controlled release of copper ions and carbon dots at the site of infection. The released active ingredients induce a burst of reactive oxygen species within the bacteria, destroying the cell membrane, DNA, and protein structure. The bactericidal rate against Escherichia coli and Staphylococcus aureus is close to 100%, and it can effectively break down and remove the already formed dense mature biofilm. The antibacterial efficiency remains above 98% in a simulated urine environment for up to 14 days.

[0046] 4. It exhibits significant anti-infective and anti-inflammatory effects in vivo, and demonstrates excellent biosafety.

[0047] In vivo experiments using a 29-day rabbit CAUTIs model demonstrated that the antibacterial and anti-adhesion catheter of this invention effectively inhibited the occurrence of urinary tract infections in vivo, maintained the bacterial load in urine at an extremely low level, and suppressed the overexpression of pro-inflammatory factors in the bladder and urethra from the source; the bladder and urethral epithelial structures remained intact and undamaged, blocking the vicious cycle of "infection-inflammation-tissue damage"; no abnormalities were found in the pathological sections of major organs, and it will not cause systemic cumulative toxicity. Attached Figure Description

[0048] Figure 1 This is a schematic diagram of the preparation process of the modified catheter PDMS / PCDH of the present invention.

[0049] Figure 2 This is the FT-IR spectrum of PDMS substrate and pretreated catheter PDMS / KH-570.

[0050] Figure 3 These are actual photos of PDMS substrate, pretreated catheter PDMS / KH-570, and modified catheters PDMS / PVA and PDMS / PCDH.

[0051] Figure 4 These are scanning electron microscope (SEM) images of the surface and cross-section of the modified PDMS / PCDH catheter.

[0052] Figure 5 This is a comparison chart of the surface water contact angles of PDMS substrate, pretreated PDMS / KH-570 conduit, and modified PDMS / PVA and PDMS / PCDH conduits.

[0053] Figure 6 This is a comparison chart of the dynamic friction coefficients of PDMS substrate, pretreated catheter PDMS / KH-570, and modified catheters PDMS / PVA and PDMS / PCDH under dry and wet conditions.

[0054] Figure 7 This shows the variation trends of the friction coefficient and water contact angle of the modified PDMS / PCDH conduit during cyclic friction.

[0055] Figure 8 This is a plate antibacterial performance test chart of PDMS substrate and modified conduit PDMS / PVA and PDMS / PCDH against Escherichia coli and Staphylococcus aureus.

[0056] Figure 9 These are SEM images of ROS fluorescence in bacteria treated with PDMS / PCDH using the DCFH-DA probe, and images of the integrity of the bacterial cell membrane after treatment.

[0057] Figure 10 The crystal violet staining test assesses the ability of PDMS / PCDH to remove bacterial biofilms.

[0058] Figure 11 The antibacterial performance of the catheter was measured after immersion in a simulated artificial urine environment for different durations.

[0059] Figure 12 This is an HE staining image of the main visceral tissues of a rabbit model after catheter treatment.

[0060] Figure 13 Immunohistochemical staining (IL-1) of urethral and bladder tissues from a rabbit model treated with a catheter.

[0061] Figure 14 Immunohistochemical staining (TNF-α) of urethral and bladder tissues from a rabbit model treated with a catheter.

[0062] Figure 15 It is the cytotoxicity of CCK-8 cells treated with different catheters.

[0063] Figure 16 The curves show the slow-release curves of multivalent copper ions from PVA / CCDH before and after enzyme treatment. Implementation

[0064] The embodiments of the present invention will now be described in detail with reference to the accompanying drawings and specific examples. It should be noted that the embodiments are merely illustrative and are intended to provide a thorough understanding of the technical solutions of the present invention and to provide guidance for those skilled in the art to implement and apply the present invention. It should be understood that these descriptions do not constitute any limitation on the scope of protection of the present invention.

[0065] Unless otherwise expressly stated, the production processes, experiments, tests or analysis methods involved in the embodiments of the present invention are all considered to be conventional methods known to those skilled in the art, and only need to be implemented in accordance with conventional conditions or relevant product instructions. The steps and names involved are also generally clear and unambiguous in the art.

[0066] The instruments, equipment, raw materials, reagents, or samples used in the embodiments are not subject to any special restrictions on their source. They are all conventional products that can be purchased through regular commercial channels or prepared by known methods, and their source does not have a substantial impact on the implementation results of the present invention.

[0067] Unless otherwise expressly defined, the scientific and technical terms used in this invention have the meanings commonly understood by one of ordinary skill in the art. In case of any conflict, the definitions in this specification shall prevail.

[0068] The terms “comprising,” “including,” “having,” etc., used in this invention should be understood as open-ended, meaning “including but not limited to.” The term “and / or” includes any and all combinations of one or more of the associated listed items. Quantitative terms such as “a,” “one,” etc., do not exclude multiples; “multiple” or “a variety” refers to quantities greater than or equal to two.

[0069] The terms "preferred", "better", and "exemplary" used in this invention are only used to describe specific solutions or effects and are not intended to limit the necessary scope of the solution or the scope of protection.

[0070] This invention relates to the description of numerical parameters (such as quantity, concentration, temperature, time, etc.), and it should be understood that reasonable deviations naturally exist due to measuring instruments, operational errors, statistical fluctuations, etc. The range of such deviations should be within limits acceptable to those skilled in the art based on common sense.

[0071] As described in the background section, existing catheter surface modification technologies face two major bottlenecks: first, the coating lacks a strong chemical bond with the inert hydrophobic substrate, especially PDMS, leading to easy detachment and failure after long-term placement; second, the bactericide lacks responsiveness to the infection microenvironment, exhibiting uncontrollable burst release, resulting in short effective antibacterial time and high cytotoxicity risk. To address these issues, this invention provides an antibacterial and anti-adhesion catheter based on a smart responsive nanofiber membrane and its preparation method.

[0072] The core technology of this invention is to construct a smart responsive nanofiber membrane with both strong interfacial bonding and dual protective functions on the surface of an inert, hydrophobic medical polymer catheter substrate. To achieve this goal, the antibacterial and anti-adhesion catheter designed in this invention consists of three progressively layered structures from the inside out: a medical polymer catheter substrate (preferably PDMS), a silane coupling agent transition layer covalently grafted onto the outer surface of the substrate, and a nanofiber membrane layer formed in situ on the outer surface of the transition layer through an electrospinning process. The nanofiber membrane layer is composed of polyvinyl alcohol (PVA) loaded with hyaluronic acid and grafted with copper-doped carbon dots (CCDH). The CCDH is a core-shell structure formed with copper-doped carbon dots (Cu-CDs) as the core and hyaluronic acid (HA) as the outer shell.

[0073] To achieve the above structure and ensure its functional controllability, this invention designs... Figure 1 The preparation process shown is as follows:

[0074] 1) Substrate surface activation and transition layer construction

[0075] To address the issues of strong chemical inertness and lack of active functional groups on the surface of medical polymer substrates such as PDMS, this invention first employs ultraviolet irradiation treatment with a photoinitiator (benzophenone) to generate active free radicals on the substrate surface. Subsequently, a chemical grafting reaction is carried out with a silane coupling agent (such as KH-570) to form a covalently bonded monomolecular transition layer. This transition layer not only overcomes the surface inertness of the substrate but also provides stable anchoring points for the upper nanofiber membrane.

[0076] (ii) Preparation of antibacterial nanocarbon dots CCDH

[0077] The CCDH described in this invention is synthesized using folic acid and soluble copper salts as precursors via a hydrothermal reaction at 180–220°C to form copper-doped carbon dots (Cu-CDs). The carboxyl groups on the surface of the Cu-CDs are then activated using EDC·HCl / NHS, followed by an amidation reaction with hyaluronic acid solution. This allows hyaluronic acid to be grafted onto the Cu-CDs surface via amide bonds, forming a core-shell structure. Detailed preparation methods and structural characterization of this material (including XPS evidence of Cu(I) / Cu(II) coexistence, peroxidase-like activity, etc.) are fully disclosed in Chinese Patent Application CN 121370947A, filed by the applicant on December 4, 2025, the entire contents of which are incorporated herein by reference.

[0078] III) Electrospinning in-situ forming of nanofunctional fiber membranes

[0079] Polyvinyl alcohol (PVA) was dissolved in an aqueous solution of glacial acetic acid, and CCDH nanoparticles were added and ultrasonically dispersed to prepare a composite spinning solution. Using a conduit with a transition layer as a rotary receiver, conjugate electrospinning technology (a dual-nozzle system applying equal-amplitude, reverse positive and negative high voltages) was employed to deposit a continuous, porous nanofiber membrane in situ on the conduit surface. This process allows CCDH to be uniformly loaded onto the interior or surface of PVA fibers, and significantly enhances interfacial bonding strength through the mechanical interlocking of the fiber network with the transition layer and possible chemical interactions.

[0080] The unique features of the above-mentioned structural design of the present invention are as follows: on the one hand, the superhydrophilic polyvinyl alcohol fiber network can form a stable hydration lubrication layer on the surface of the catheter, which can effectively block the initial adhesion of bacteria from a physical level; on the other hand, the hyaluronic acid shell in CCDH can specifically recognize the overexpressed hyaluronidase in the bacterial infection microenvironment, trigger the controllable release of the copper-doped carbon dot core, and use its peroxidase-like activity to induce the generation of reactive oxygen species, thereby achieving on-demand and precise sterilization of the infection site.

[0081] The modified catheter of this invention not only achieves a strong covalent bond between the functional layer and the substrate (verified by 50 simulated reciprocating friction cycles and 14 days of dynamic artificial urine flushing), but also simultaneously acquires excellent physicochemical properties such as a superhydrophilic surface (water contact angle reduced from 108° to 28°) and a low coefficient of friction (wet dynamic friction coefficient reduced from 0.54 to 0.20). In vitro antibacterial experiments show that it has a near 100% bactericidal rate against Escherichia coli and Staphylococcus aureus, an antibacterial adhesion rate of over 98%, and can effectively disrupt established mature biofilms. In vivo experiments using a rabbit CAUTIs model further confirm that this catheter can suppress urinary bacterial load to extremely low levels during a 29-day indwelling period, significantly inhibit the overexpression of pro-inflammatory factors IL-1β and TNF-α in bladder and urethral tissues, and has no significant toxic effects on major organs such as the heart, liver, spleen, lungs, and kidneys.

[0082] The preparation process and performance verification of the present invention are described in detail below through specific embodiments. Example

[0083] Example 1

[0084] Commercial polydimethylsiloxane (PDMS) catheters were placed in anhydrous ethanol and ultrasonically cleaned for 15 minutes at a power of 200W and a frequency of 40kHz to remove surface contaminants. The catheters were then rinsed three times with deionized water and allowed to air dry at room temperature for 12 hours to ensure the catheter surface remained clean.

[0085] The dried conduit was immersed in a 10wt% benzophenone (BP) ethanol solution for 30 minutes in the dark to allow BP to be fully adsorbed onto the conduit surface. After removing the conduit and removing excess droplets from the surface, it was placed under a UVP B-100AP ultraviolet lamp with a wavelength of 365nm and a power of 100W at a distance of 5-10cm for 10 minutes to generate free radicals on the PDMS surface to activate the surface for subsequent grafting reactions.

[0086] The activated conduit was immersed in a 5 vol% KH-570 ethanol solution and reacted in a 40°C water bath for 2 h to introduce reactive functional groups via silane grafting. The conduit was then rinsed three times each with ethanol and deionized water and dried under vacuum at 60°C for 12 h to obtain a surface-pretreated conduit, denoted as PDMS / KH-570, which was then placed in a desiccator for later use.

[0087] Figure 2 The surface composition of PDMS and PDMS / KH-570 was tested using FTIR. Compared with PDMS, PDMS / KH-570 showed better surface composition at 1718 cm⁻¹. -1 A significant carbonyl (C=O) stretching vibration peak appeared nearby, and at 2900 cm⁻¹ -1 The CH peaks above are enhanced.

[0088] Furthermore, XPS analysis using PDMS / KH-570 confirmed the presence of the OC=O characteristic peak in the high-resolution C 1s and O 1s spectra.

[0089] Therefore, infrared and photoelectron spectroscopy characterization strongly confirmed that the KH-570 silane coupling agent was successfully and firmly grafted onto the surface of the PDMS substrate through covalent bonds. Through chemical activation and silane grafting strategies, the chemical inertness and hydrophobicity of the PDMS substrate were overcome, providing a stable interface anchoring point for the subsequent construction of composite nanofiber membranes.

[0090] Example 2

[0091] Antibacterial carbon nanodots (CCDH) were prepared according to the method in CN 121370947A.

[0092] Weigh 0.5g of copper sulfate pentahydrate (CuSO4·5H2O) and 1g of folic acid and add them to 100mL of deionized water. Stir at room temperature in the dark for 30min and then sonicate for 30min to obtain a uniformly dispersed precursor solution.

[0093] The precursor solution was transferred to a polytetrafluoroethylene-lined high-pressure reactor, sealed, and heated to 220°C for hydrothermal reaction for 8 hours. After the reaction was completed, it was allowed to cool naturally to room temperature to obtain a dark brown reaction solution.

[0094] The reaction solution was filtered using a 0.45 μm microporous membrane to remove any potentially large particles or carbonized impurities. The filtrate was collected and transferred to a high-speed centrifuge tube, centrifuged at 8500 rpm for 15 min, and the supernatant was collected and placed in a dialysis bag with a molecular weight cutoff of 1000 Da. Dialysis was performed continuously in ultrapure water for 7 days, with the ultrapure water being changed every 4 hours to thoroughly remove unreacted Cu. 2+ Ions, folic acid residues, and small molecule byproducts.

[0095] The dialysate was transferred to a clean freeze-drying bottle, pre-frozen in an ultra-low temperature freezer at -80℃ for 24 hours, and then transferred to a freeze dryer for vacuum freeze-drying for 48 hours to prepare a fluffy black-brown Cu-CDs solid powder, which was stored at 4℃ away from light.

[0096] Weigh 50.0 mg of the Cu-CDs powder prepared above, disperse it in 10 mL of 0.1 M MES (2-(N-morpholino)ethanesulfonic acid) buffer solution with pH 5.5, and sonicate for 30 min to form a uniform and stable black Cu-CDs dispersion.

[0097] 50.0 mg EDC·HCl (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) and 25.0 mg NHS (N-hydroxysuccinimide) were added sequentially to the above dispersion. The mixture was magnetically stirred at room temperature in the dark for 1 h to carry out the carboxyl activation reaction, thereby activating the carboxyl groups on the surface of Cu-CDs and forming an active ester intermediate, which facilitates subsequent grafting.

[0098] Weigh out 100.0 mg of a substance with a molecular weight of approximately 1×10⁻⁶. 6 Da's hyaluronic acid (HA) was dissolved in 10 mL of deionized water to obtain an HA solution.

[0099] The HA solution was slowly added dropwise to the activated Cu-CDs dispersion under stirring. After the addition was complete, the pH of the mixture was adjusted to 7.0 with 0.1M NaOH solution. The mixture was stirred for 12 hours at room temperature in the dark to allow the amidation grafting reaction to proceed fully and achieve the grafting and coating of Cu-CDs by HA.

[0100] After the reaction, the mixture was placed in a dialysis bag with a molecular weight cutoff of 10,000 Da and dialyzed in ultrapure water for 48 hours, with the water changed every 6 to 8 hours during the process, in order to completely remove unreacted EDC, NHS, byproducts (such as isourea) and ungrafted free hyaluronic acid.

[0101] The dialysate was collected into a clean freeze-drying bottle, pre-frozen in an ultra-low temperature freezer at -80℃ for 24 hours, and then transferred to a freeze dryer for vacuum freeze-drying for 48 hours to prepare enzyme-responsive antibacterial carbon dots Cu-CDs@HA brown solid. It was stored at 4℃ in the dark and denoted as CCDH.

[0102] Example 3

[0103] Using conjugate electrospinning technology, a PVA / CCDH composite nanofiber membrane was in situ constructed on the surface of a pretreated PDMS / KH-570 catheter, achieving integrated antibacterial and anti-adhesion functions. The preparation process is as follows: Figure 1 As shown.

[0104] The electrospinning equipment is a multifunctional conjugate electrospinning system independently built in the laboratory. It mainly consists of a conjugate nozzle driven by a syringe pump, a high-voltage power supply, and a rotating receiver. The PVA / CCDH composite spinning solution is precisely propelled to both ends of the conjugate nozzle by the syringe pump with controlled propulsion rate. The high-voltage power supply applies positive and negative electric fields respectively, causing the spinning solution at the nozzle tip to stretch into a Taylor cone and eject nanofibers. Under the synergistic effect of the opposing stretching of the positive and negative electric fields and the rotating receiver, the fibers are deposited in situ on the rotating receiver, ultimately forming a PVA / CCDH composite nanofiber membrane.

[0105] Weigh 8g of polyvinyl alcohol (PVA) powder with a molecular weight of 100,000 to 200,000 Da, add it to 92mL of a pre-prepared 10vol% glacial acetic acid aqueous solution, and stir magnetically at 80℃ for 4h until completely dissolved to obtain an 8wt% PVA solution.

[0106] Weigh 240 mg of CCDH nanoparticles with a particle size of 5-10 nm and slowly add them to the cooled PVA solution. Then, use an ultrasonic dispersion device to ultrasonically disperse the CCDH particles at 300 W and 20 kHz for 30 min to obtain a uniform and stable PVA / CCDH composite spinning solution.

[0107] The PVA / CCDH composite spinning solution was loaded into a 20G syringe. The PDMS / KH-570 conduit prepared in Example 1 was fixed on a rotating receiver, and the receiver rotation speed was set to 300 rpm. The parameters of the conjugate electrospinning equipment were adjusted to: +14kV positive voltage, -14kV negative voltage, spinning solution propulsion flow rate of 1.5mL / h, spinning receiver distance of 15cm, constant ambient temperature of 25℃, and relative humidity controlled at 40-50% for continuous spinning. This allowed the composite spinning solution to be deposited and stretched in situ on the surface of the conduit, forming a continuous porous network composite nanofiber membrane with a thickness of 50-100μm.

[0108] After spinning, the conduit was removed and dried in a vacuum drying oven at 40℃ and -0.1MPa for 24 hours to completely remove residual solvent inside the fiber membrane and solidify it into a fiber network structure. A smart responsive antibacterial and anti-adhesion conduit with a CCDH loading of 3% was prepared, denoted as PDMS / PCDH.

[0109] Comparative Example 1

[0110] Except for the direct preparation of PVA spinning solution without adding CCDH, the other steps are the same as in Example 3. A PVA nanofiber film is formed on the surface of the PDMS / KH-570 catheter, and the resulting catheter is denoted as PDMS / PVA.

[0111] Example 4

[0112] Figure 3 The exhibition showcases photographs of catheters after different treatments. The original PDMS catheter has a smooth, transparent surface and excellent flexibility, allowing it to be bent freely. The surface-pretreated PDMS / KH-570 catheter maintains an appearance essentially identical to the original PDMS catheter, retaining its smoothness, transparency, and good flexibility. The electrospinning-treated PDMS / PVA and PDMS / PCDH modified catheters are uniformly covered with a white fiber membrane, changing their appearance from transparent to opaque. However, the catheters still maintain good flexibility, can withstand severe bending, and the membrane shows no peeling or cracking.

[0113] The microstructure of PDMS / PCDH was then observed using scanning electron microscopy. Figure 4 The surface SEM images in (a) show that the PVA / CCDH composite nanofiber membrane formed on the duct surface is a uniform, continuous, dense, and highly porous nonwoven network structure. CCDH nanoparticles are uniformly dispersed within the fibers without obvious aggregation. Cross-sectional SEM images (b-d) at different magnifications (scale bars of 1 cm, 100 μm, and 20 μm) collectively confirm that the PVA / CCDH composite nanofiber membrane is tightly bonded to the PDMS substrate, with no obvious gaps or delamination at the interface. Furthermore, as the magnification increases (…), the bonding between the PVA / CCDH composite nanofiber membrane and the PDMS substrate deepens. Figure 4 d) It can be seen that the fibers form a good mechanical interlock with the substrate surface, which provides a structural basis for the membrane layer to remain intact and adhered during the severe bending operation of the catheter.

[0114] Example 5

[0115] The surface properties of four groups of samples—original PDMS, PDMS / KH-570, PDMS / PVA (Comparative Example 1), and PDMS / PCDH (Example 3)—were compared.

[0116] The static water contact angle of each group of samples was measured at room temperature using a contact angle measuring instrument, such as... Figure 5 As shown, the original PDMS conduit exhibits extremely strong hydrophobicity, with a water contact angle of approximately 108°; the water contact angle of the PDMS / KH-570 conduit remains essentially unchanged, still exhibiting strong hydrophobicity; however, after electrospinning modification, the water contact angle of the PDMS / PVA and PDMS / PCDH conduits rapidly and significantly decreased to 28°, exhibiting superhydrophilic properties on the surface and readily forming a hydration layer.

[0117] The coefficient of friction of each group of catheters was tested under both dry and simulated urine-wet conditions, and the results are as follows: Figure 6 As shown, the dynamic friction coefficients of the four groups of ducts showed little difference under dry conditions, but significant differences under wet conditions. The original PDMS had a wet dynamic friction coefficient as high as 0.54, and PDMS / KH-570 also had a coefficient of 0.51. After electrospinning modification, the wet dynamic friction coefficients of PDMS / PVA and PDMS / PCDH were significantly reduced to approximately 0.20, a 63% reduction compared to the original PDMS, exhibiting superlubricating properties similar to cartilage surfaces. This indicates that the PVA nanofiber film forms a stable hydration lubricating layer through its superhydrophilic surface, which is the main source of improved lubrication performance. In contrast, the introduction of CCDH had no significant impact on lubrication performance.

[0118] Furthermore, under wet conditions, simulated artificial urine was used as the lubricating medium to conduct reciprocating mechanical friction cycle tests on the PDMS / PCDH modified catheter to verify the interfacial bonding strength between the nanofiber membrane and the substrate. The surface water contact angle and wet dynamic friction coefficient of the catheter were recorded after 0, 10, 20, 30, 40 and 50 friction cycles, respectively.

[0119] Figure 7 The test results showed that the water contact angle of PDMS / PCDH increased only slightly from 28° before friction and remained at around 30°, while the wet dynamic friction coefficient remained stable below 0.21, with no significant degradation in either. In contrast, the PVA fiber membrane coating constructed using the traditional physical adsorption method exhibited obvious peeling and detachment after 10-20 friction cycles under the same test conditions. This excellent durability proves that the BP / UV activation plus KH-570 chemical grafting process of this invention successfully constructed a stable covalent bond interface on the surface of the inert PDMS substrate, effectively solving the problem of easy friction detachment of traditional physical fiber membrane coatings.

[0120] Example 6

[0121] To evaluate the in vitro bactericidal performance of different modified catheters against common clinical pathogens, Escherichia coli (E. coli) was used as a control. E. coli Gram-negative) and Staphylococcus aureus ( S.aureus (Gram-positive) strains were used for antibacterial rate testing.

[0122] Raw PDMS, PDMS / PVA, and PDMS / PCDH were co-cultured with either *Escherichia coli* or *Staphylococcus aureus* culture, with a blank control group included. After co-culture, the culture media from each group were plated on nutrient agar plates and incubated overnight at 37°C. Colony counts were then performed, and the sterilization rate of each catheter was calculated. The results are as follows: Figure 8 As shown.

[0123] Depend on Figure 8 As can be seen, the colonies grew normally on the blank control group plates; however, the surfaces of the original PDMS and PDMS / PVA catheters were covered with dense bacterial colonies, and their antibacterial rates were both at a low level. S.aureus Below 30%, E. coli The kill rate was approximately 45-60%. However, the PDMS / PCDH catheter achieved nearly 100% kill rate against both pathogens, with almost no colony growth on the corresponding plates. This result indicates that simple PDMS substrate and hydrophilic PVA modification alone cannot endow the catheter with effective antibacterial capabilities; only through PCDH functionalization modification can the catheter achieve broad-spectrum and highly efficient bactericidal activity against both Gram-negative and Gram-positive bacteria.

[0124] To further elucidate the bactericidal mechanism of PDMS / PCDH, multi-dimensional verification was conducted from biochemical and morphological perspectives, and the results are as follows: Figure 9 As shown, the DCFH-DA fluorescent probe experiment confirmed that the experimental group (PDMS / PCDH) exhibited extremely strong green fluorescence intracellularly after interaction with bacteria, with an intensity comparable to the positive control. This indicates that CCDH can induce bacteria to produce a large amount of ROS, triggering a strong oxidative stress response. Bacterial morphology SEM characterization results further reinforced this conclusion. E. coli It is a smooth, rod-shaped cluster. S.aureus It is a smooth sphere; while on PDMS / PCDH E. coli Wrinkled, sunken, and fragmented, S.aureus Deformation accompanied by leakage of endosomal contents. These changes indicate that ROS and copper binding to proteins / DNA leads to cell wall lysis.

[0125] Example 7

[0126] The amount of biofilm formed was further assessed using crystal violet staining, and the effect of PDMS / PCDH extract on biofilm was quantitatively studied.

[0127] like Figure 10 As shown, PDMS / PCDH extract also exhibits a strong destructive effect on already formed, mature biofilms. With increasing extract dosage, S.aureus and E. coli The biofilm biomass showed a significant dose-dependent decrease. When the dose reached 40 μL, the biofilm formation rate dropped to below 20%, indicating that the antibacterial components released by the PDMS / PCDH catheter effectively interfered with the bacterial community aggregation process. At a dose of 100 μL, the originally dense membrane structure was significantly disrupted. This is crucial for patients with long-term indwelling urinary catheters, effectively preventing luminal stenosis or complete blockage caused by biofilm accumulation.

[0128] Example 8

[0129] PDMS / PCDH was immersed in simulated urine to simulate the durability of the composite nanofiber membrane on the surface of the antibacterial and anti-adhesion catheter under complex urinary conditions. Samples were taken every 7 days, and the number of viable bacteria adhering to the catheter surface was determined using a plate count method. Results are as follows: Figure 11 As shown, after continuous soaking for 0, 7, and 14 days, the modified catheter showed [results in...]. E. coli and S.aureus The antibacterial rate remained above 98%, with no significant performance degradation.

[0130] This remarkable long-lasting effect is primarily due to the chemical grafting between KH-570 and the PDMS substrate, which ensures the stability of the fiber membrane and the controlled release mechanism of CCDH within the PVA fiber membrane. This result also indicates that the catheter is capable of meeting the needs of long-term clinical placement.

[0131] Example 9

[0132] A clinical CAUTIs infection model was constructed using healthy adult Japanese white rabbits to comprehensively evaluate the in vivo efficacy and safety of antibacterial and anti-adhesion catheters. The experimental period was 29 days.

[0133] A standard PDMS catheter and a PDMS / PCDH catheter were implanted into rabbits. Post-operatively, urine was collected for bacterial culture and counting, and the results were alarming. By day 29, the experimental endpoint, the control group (PDMS) showed an exponential bacterial outbreak in urine, with a concentration as high as (54.6 ± 2.37) × 10⁻⁶. 5 CFU / mL, while the PDMS / PCDH group maintained an extremely low bacterial load of only (6.38±0.25)×10⁻⁶ throughout the month-long period. 5 The CFU / mL indicates that the PDMS / PCDH catheter has extremely superior in vivo antibacterial and purifying effects.

[0134] Regarding the systemic biosafety of in vivo catheter application, at the end of the experiment, five major organs (heart, liver, spleen, lung, and kidney) of rabbits in the PDMS group and PDMS / PCDH group were collected for H&E staining. Figure 12 The results showed that all organ sections from both groups of animals exhibited normal histological morphology. Myocardial fibers were neatly arranged without breakage or degeneration; liver lobule structures were clear, hepatocyte cords were regularly arranged, and there was no necrosis or vacuolar degeneration; the red and white pulp boundaries of the spleen were clear, and the lymphoid follicle structure was normal; the alveolar structure was intact, and no thickening or inflammatory exudation was observed in the alveolar walls; the glomeruli and renal tubules had normal morphology and structure, without congestion or cast formation. No significant pathological differences were observed between the two groups, demonstrating that the in vivo use of the catheter did not cause cumulative toxicity to systemic organs.

[0135] Macroscopic improvements in histopathology often stem from effective regulation of inflammatory pathways at the microscopic molecular level. To quantify the local immune response induced by catheter implantation, immunohistochemical (IHC) analysis was performed on key pro-inflammatory factors interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α).

[0136] IL-1 is a core pro-inflammatory factor that initiates acute inflammatory responses. Figure 13IHC staining results revealed IL-1 expression. In the PDMS group, bladder and urethral tissues showed deep brown positive staining from weeks 1 to 4, with extensive staining. Statistical analysis showed that IL-1 expression levels in the PDMS group remained consistently high over time, indicating a persistent and strong acute inflammatory response. In contrast, tissue sections from the PDMS / PCDH group showed lighter staining. Statistical analysis indicated that IL-1 expression levels in both the bladder and urethra were significantly lower in the PDMS / PCDH group than in the control group at all time points, especially at week 4, where IL-1 levels in the PDMS / PCDH urethral tissue were extremely low, indicating that the inflammatory response had largely subsided.

[0137] TNF-α is an initiator of the inflammatory cascade. Figure 14 The TNF-α expression analysis results were highly consistent with the IL-1 trend. The PDMS group showed extremely high TNF-α positive expression, suggesting that bacterial infection and foreign body stimulation activated signaling pathways such as NF-κB, leading to the massive release of pro-inflammatory factors and forming a vicious cycle of infection-inflammation-tissue damage. In the PDMS / PCDH group, the expression levels of IL-1 and TNF-α, the main culprits leading to the cytokine storm, were significantly inhibited, effectively interrupting the pathway of histopathological evolution.

[0138] like Figure 15 As shown, the PBS group served as a negative control, with cell viability defined as 100%. The results indicated that the cell viability of the original PDMS group remained at a high level, demonstrating the good safety of the substrate material itself. The surface-modified PDMS / PVA group and the PDMS / PCDH group, ultimately loaded with antibacterial agents, also exhibited excellent cell viability. Specifically, the cell viability of the PDMS / PCDH group remained stable above 90%, showing no significant decrease compared to the control group. This demonstrates that the PCDH composite nanofiber membrane constructed in this study, along with the CCDH it contains, effectively kills bacteria without producing significant toxicity to normal mammalian cells.

[0139] Example 10

[0140] Using L929 mouse fibroblasts as model cells, the cell compatibility of the materials was evaluated using the CCK-8 assay.

[0141] Figure 15 In the test results, the PBS group was used as a negative control and its cell viability was defined as 100%. The cell viability of the original PDMS group remained at a high level, but the cell viability of the PDMS / PVA group and the PDMS / PCDH group was also stable at over 90%, with no significant decrease compared with the control group. This indicates that the composite nanofiber membrane of the present invention has no obvious toxic effect on normal mammalian cells.

[0142] The intelligent response of the PDMS / PCDH catheter of this invention is mainly achieved by releasing antibacterial nano carbon dots CCDH prepared by adding CN 121370947A, which utilizes the hyaluronidase secreted by bacteria in the infection environment to accelerate the release of antibacterial agents.

[0143] Figure 16 A comparison of the sustained-release curves of copper ions in PVA / CCDH before and after hyaluronidase treatment is presented. It can be seen that under enzyme-free conditions, the release of copper ions exhibits a slow trend, with a release amount of approximately 10 μg / L at 1 h, increasing to approximately 20 μg / L at 3 h, approximately 30 μg / L at 8 h, and stabilizing at approximately 40 μg / L at 72 h. This sustained-release characteristic indicates diffusion-controlled release in neutral PBS, reducing unnecessary exposure. However, in the presence of HAase (simulated bacterial infection), the release behavior shows an accelerated trend, with a release amount of approximately 20 μg / L at 1 h, approximately 40 μg / L at 3 h, approximately 60 μg / L at 8 h, approximately 80 μg / L from 24 to 48 h, and approximately 90 μg / L at 72 h. This indicates that after hyaluronidase degradation of HA, the PVA / CCDH membrane triggers faster dissociation of internal CCDH and release of copper ions. This burst of enzyme response confirms the intelligent design that releases ions on demand at the site of infection, improving targeting efficacy while maintaining biocompatibility under normal conditions.

[0144] The above embodiments of the present invention do not describe all details exhaustively, nor do they limit the present invention to the embodiments described above. Various changes, modifications, substitutions, and variations made by those skilled in the art to these embodiments without departing from the principles and spirit of the present invention should be included within the scope of protection of the present invention.

Claims

1. An antibacterial and anti-adhesion conduit based on a smart responsive nanofiber membrane, comprising the following three layers from the inside out: Medical polymer catheter substrate; The transition layer is a monomolecular grafted layer of silane coupling agent covalently grafted onto the outer surface of the substrate; The nanofiber membrane is formed on the outer surface of the transition layer by electrospinning. The nanofiber membrane is a composite nanofiber membrane with polyvinyl alcohol loaded with antibacterial nanocarbon dots. It has a hydrophilic and anti-adhesion surface and can respond to hyaluronidase secreted by bacteria. The antibacterial nano carbon dots are hyaluronic acid-grafted copper-doped carbon dots. The copper-doped carbon dots are used as the core, and hyaluronic acid molecules are grafted onto the surface with amide bonds to form a core-shell structure. The copper element in the core of the copper-doped carbon dots exists in the form of Cu(II) and Cu(I). As an antibacterial active ingredient, it also has peroxidase-like activity and free radical scavenging ability. When the nanofiber membrane comes into contact with bacteria that secrete hyaluronidase, the hyaluronic acid is enzymatically hydrolyzed, releasing a copper-doped carbon dot core. This core then exerts peroxidase-like activity in the infection microenvironment, inducing the generation of reactive oxygen species to achieve sterilization.

2. The antibacterial, anti-adhesive catheter of claim 1, wherein The substrate is a PDMS catheter, which has medical implant-grade flexibility and bioinertness.

3. The antimicrobial, anti-adhesive catheter of claim 1, wherein The hyaluronic acid-grafted copper-doped carbon dots are prepared by hydrothermal reaction of folic acid and soluble copper salt at 180–220 °C to obtain copper-doped carbon dots in the form of Cu(II) and Cu(I), followed by carboxyl activation of the copper-doped carbon dots using EDC·HCl and NHS, and then amidation reaction with hyaluronic acid solution.

4. The antibacterial and anti-adhesion catheter according to claim 1, characterized in that: The loading amount of copper-doped carbon dots grafted with hyaluronic acid in the nanofiber membrane is 1 to 5% of the mass of polyvinyl alcohol.

5. The method for preparing the antibacterial and anti-adhesion catheter according to claim 1, comprising: 1) The medical polymer catheter substrate is surface activated by ultraviolet irradiation in a photoinitiator solution to generate active free radicals on the substrate surface; 2) Chemical grafting of surface-activated substrate with silane coupling agent solution to form a transition layer on the substrate surface; 3) Dissolve polyvinyl alcohol in its good solvent, add antibacterial nano carbon dots and disperse evenly to obtain a composite spinning solution; 4) Using a substrate with a transition layer as a rotation receiver, the composite spinning solution is uniformly spun onto the surface of the transition layer of the substrate using an electrospinning process to form a nanofunctional fiber membrane in situ, thus preparing an antibacterial and anti-adhesion conduit based on a smart responsive nanofiber membrane.

6. The preparation method according to claim 5, characterized in that: The photoinitiator solution is a 5-15 wt% benzophenone ethanol solution.

7. The preparation method according to claim 5, characterized in that chemical grafting is performed using a 3-8 wt% silane coupling agent alcohol solution.

8. The preparation method according to claim 5, characterized in that: The good solvent for the polyvinyl alcohol is a 5-15 wt% aqueous solution of glacial acetic acid, the concentration of polyvinyl alcohol in the composite spinning solution is 6-10 wt%, and the amount of antibacterial nano carbon dots added is 1-5% of the mass of polyvinyl alcohol.

9. The preparation method according to claim 5, characterized in that: In the electrospinning process, the positive voltage is set to +12 to +16 kV, the negative voltage is set to -12 to -16 kV, the flow rate of the composite spinning solution is 1.0 to 2.0 mL / h, the receiving distance of the rotating receiver is 12 to 18 cm, and the rotation speed is 250 to 350 rpm.

10. The use of the antibacterial and anti-adhesion catheter of claim 1 in the preparation of a medical device for the prevention and / or relief of catheter-related urinary tract infections.

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