Antibacterial and anti-inflammatory bile duct stent

Abstract

The invention provides an antibacterial and anti-inflammatory bile duct stent, and belongs to the technical field of biological materials, the antibacterial and anti-inflammatory bile duct stent comprises a stent body, the stent body comprises a plurality of wave-shaped rings arranged in a first direction and a connecting piece connected with a supporting piece, and the plurality of wave-shaped rings form a drainage channel; a functional coating is arranged on the stent body, and the functional coating comprises a ternary complex formed by self-assembly of metal ions, polyphenol compounds and quaternary ammonium salt compounds. According to the bile duct stent, the narrow biliary tract can be effectively expanded, normal flow of bile is recovered, smoothness of the biliary duct is kept, and the multiple synergistic effects of resisting tumor development, resisting bacterial infection and resisting inflammation can be achieved.

Description

Technical Field

[0001] This invention relates to the field of biomaterials technology, and in particular to an antibacterial and anti-inflammatory bile duct stent. Background Technology

[0002] Malignant biliary obstruction is a common and critical clinical condition, often caused by compression or infiltration of malignant tumors such as cholangiocarcinoma and pancreatic cancer. One of its most serious complications is acute obstructive cholangitis (AOSC), whose pathological process includes biliary obstruction, cholestasis, bacterial infection, and severe inflammatory response. Currently, endoscopic retrograde cholangiopancreatography (ERCP) with stent placement is the preferred treatment for relieving obstruction and draining bile; however, there is no effective treatment that simultaneously addresses tumor progression, bacterial infection, and inflammation. Summary of the Invention

[0003] To address the aforementioned problems in the prior art, this invention provides an antibacterial and anti-inflammatory bile duct stent that can effectively treat malignant biliary obstruction caused by bile duct cancer, liver cancer, or other metastatic cancers, and can synergistically exert anti-tumor, antibacterial, and anti-inflammatory effects, thereby enhancing the efficacy of tumor treatment.

[0004] To address the above problems, the present invention provides an antibacterial and anti-inflammatory bile duct stent, comprising:

[0005] The support body includes a plurality of wave-shaped rings arranged along a first direction, and a connector connecting the wave-shaped rings, wherein the plurality of wave-shaped rings form a drainage channel;

[0006] The scaffold body is provided with a functional coating, which includes a ternary complex formed by the self-assembly of metal ions, polyphenolic compounds and quaternary ammonium salt compounds.

[0007] As an embodiment of the present invention, the support body is provided with an anti-displacement structure, and the anti-displacement structure is provided with the functional coating.

[0008] As an embodiment of the present invention, the anti-displacement structure is a plurality of barbs disposed on the outer surface of the support body, and the barb structure is a biodegradable magnesium alloy biomaterial component.

[0009] As an embodiment of the present invention, the functional coating further includes a polydopamine coating, and the ternary composite is loaded onto the scaffold body through the polydopamine coating.

[0010] In one embodiment of the present invention, the waveform ring is a hollow tube, the hollow tube is filled with antibacterial and anti-inflammatory drugs, and the tube wall of the hollow tube is provided with drug release micropores.

[0011] As an embodiment of the present invention, the waveform ring includes multiple peak segments and multiple trough segments, with the peak segments of every two waveform rings arranged adjacent to each other, and the connector is connected to at least one peak segment of the two waveform rings.

[0012] As an embodiment of the present invention, the support body is a magnesium alloy elastic component.

[0013] As an embodiment of the present invention, the support body is a straight cylinder, or one or both ends are funnel-shaped.

[0014] As an embodiment of the present invention, the metal ion is selected from Cu. 2+ Fe 2+ Fe 3+ Mn 2+ Zn 2+ Mg 2+ At least one of them; and / or,

[0015] The polyphenolic compound is selected from at least one of gallic acid, epicatechin gallate, quercetin, curcumin, and tannic acid; and / or,

[0016] The quaternary ammonium salt compound is selected from at least one of dodecyltrimethylammonium bromide, hexadecyltrimethylammonium bromide, and benzalkonium chloride.

[0017] As an embodiment of the present invention, based on the total mass of the raw materials of the ternary composite, the mass percentage of the metal ions is 5% to 50%, the mass percentage of the polyphenolic compounds is 5% to 60%, and the mass percentage of the quaternary ammonium salt compounds is 5% to 60%.

[0018] Due to the above technical solution, the present invention has at least the following beneficial effects:

[0019] The antibacterial and anti-inflammatory bile duct stent according to an embodiment of the present invention is composed of corrugated rings. This structure provides excellent flexibility and elasticity, allowing it to conform to the bends and changes of the bile duct during placement while providing sufficient support. It can effectively dilate narrowed bile ducts, restore normal bile flow, and maintain bile duct patency, thereby alleviating patient symptoms and improving quality of life. Furthermore, the surface of the stent body is coated with a functional coating comprising a ternary complex formed by the self-assembly of metal ions, polyphenolic compounds, and quaternary ammonium salts. This coating, through the self-assembly of metal ions, polyphenols, and quaternary ammonium salts, produces multiple synergistic effects of anti-tumor progression, anti-bacterial infection, and anti-inflammation, specifically addressing the core problems of infection and inflammation in AOSC (autoimmune cholangiocarcinoma syndrome). Attached Figure Description

[0020] Figure 1 This is a schematic diagram of the structure of the antibacterial and anti-inflammatory bile duct stent according to an embodiment of the present invention. Figure 1 ;

[0021] Figure 2 This is a schematic diagram of the structure of the antibacterial and anti-inflammatory bile duct stent according to an embodiment of the present invention. Figure 2 ;

[0022] Figure 3 This is a schematic diagram of the structure of the antibacterial and anti-inflammatory bile duct stent according to an embodiment of the present invention. Figure 3 ;

[0023] Figure 4 This is a schematic diagram of the structure of the antibacterial and anti-inflammatory bile duct stent according to an embodiment of the present invention. Figure 4 ;

[0024] Figure 5 This is a clone formation experiment of the scaffold and control in an embodiment of the present invention;

[0025] Figure 6 This is a Transwell migration experiment comparing the stent in this embodiment of the invention with a control.

[0026] Figure 7 This is a cell survival / death staining assay of the scaffold and control in an embodiment of the present invention;

[0027] Figure 8 These are stained microscope images of the support and control in an embodiment of the present invention;

[0028] Figure 9 This is a plate diagram of the antibacterial plate experiment of the scaffold and the control in an embodiment of the present invention;

[0029] Figure 10 These are scanning electron microscope (SEM) images of bacteria after an antibacterial experiment, comparing the scaffold and the control group in this embodiment of the invention.

[0030] Figure 11The TNF-α and IL-6 immunofluorescence staining of the scaffold and control in this embodiment of the invention;

[0031] Figure 12 This is a graph showing the bacterial quantification and cytokine analysis of the scaffold and control in an embodiment of the present invention.

[0032] Figure label:

[0033] Bracket 100;

[0034] 10. Support body; 11. Waveform ring; 12. Connector; 13. Barb; 14. Micropore; 15. Drainage channel. Detailed Implementation

[0035] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0036] To facilitate understanding of the technical solution of the present invention, the technical problem of the present invention will be explained first.

[0037] As described in the background above, acute suppurative obstructive cholangitis is a serious clinical disease caused by biliary obstruction, often resulting from tumors. Its pathological process includes biliary obstruction, cholestasis, bacterial infection, and a severe inflammatory response. Currently, endoscopic retrograde cholangiopancreatography (ERCP) with biliary stent placement is the mainstream treatment; however, existing stents have limited functionality and lack an effective treatment method that simultaneously addresses tumor progression, bacterial infection, and inflammation.

[0038] To address the aforementioned technical problems, this invention provides an antibacterial and anti-inflammatory bile duct stent, comprising a stent body and a functional coating. The stent body can effectively dilate narrowed bile ducts, restore normal bile flow, and maintain bile duct patency, thereby alleviating patient symptoms. The ternary complex (or composite material) provides broad-spectrum, long-lasting antibacterial and anti-inflammatory effects through synergistic action, effectively treating complex biliary tract diseases such as acute suppurative obstructive cholangitis, achieving the simultaneous treatment of tumor progression, bacterial infection, and inflammation.

[0039] The antibacterial and anti-inflammatory bile duct stent of the present invention will be described below with reference to specific embodiments.

[0040] refer to Figure 1 , Figure 1 A schematic diagram of the structure of the antibacterial and anti-inflammatory bile duct stent according to an embodiment of the present invention is shown. Figure 1Among them, antibacterial and anti-inflammatory bile duct stents are hereinafter referred to as stents.

[0041] like Figure 1 As shown, the stent 100 includes a stent body 10 and a functional coating (not shown). The stent body 10 includes a plurality of wave-shaped rings 11 arranged along a first direction and a connector 12 connecting the wave-shaped rings 11. The plurality of wave-shaped rings 11 form a drainage channel 15. The functional coating is disposed on the stent body 10. The functional coating includes a ternary composite formed by the self-assembly of metal ions, polyphenolic compounds, and quaternary ammonium salt compounds.

[0042] In other words, the stent body 10 is composed of multiple wave-shaped rings 11 connected together to form a woven mesh-like structure. This structure provides good flexibility and elasticity, allowing it to conform to the bends and changes of the bile duct during the placement of the stent 100 within the bile duct, while providing sufficient support to ensure smooth drainage through the drainage channel 15 and maintain the patency of the bile duct. This design ensures both therapeutic efficacy and minimizes irritation and damage to surrounding tissues.

[0043] Furthermore, the metal ions in the ternary composite of the present invention, such as Cu... 2+ It can provide multiple functions, serving as a structural center for coordination with polyphenols, inducing cell death to inhibit tumors, and possessing antibacterial activity itself.

[0044] Polyphenolic compounds, such as gallic acid (GA), can act as ligands to form coordination networks with metal ions, specifically metal-phenolic networks. They can also inhibit HIF-1α, reverse tumor glycolysis, thereby enhancing copper death and the efficacy of intracellular protein glycolysis (ICB). Furthermore, polyphenolic compounds can provide anti-inflammatory and antioxidant effects.

[0045] Quaternary ammonium compounds, as cationic surfactants, adsorb and disrupt negatively charged bacterial cell membranes through electrostatic interactions, achieving rapid and broad-spectrum antibacterial activity. Furthermore, the long alkyl chains of quaternary ammonium compounds can be inserted into the complex to adjust the hydrophilicity or hydrophobicity of the material.

[0046] Therefore, the bile duct stent 100 of the present invention, due to its functional coating, can enhance the therapeutic effect of copper death by inhibiting HIF-1α and reducing glycolysis, a process that normally hinders copper-induced apoptosis, through polyphenols. Furthermore, the combination of CGQ with PD-L1 immune checkpoint inhibition therapy enhances the immune response by inhibiting HIF-1α and overcoming its inhibitory effect on PD-L1, thereby making the anti-tumor immune response more effective.

[0047] In some embodiments, the stent body 10 is provided with an anti-displacement structure, which has a multifunctional coating. The anti-displacement structure can anchor the stent to the bile duct wall tissue where close contact is required, or allow for slight embedding, preventing stent dislodgement or movement. However, this contact area is prone to mechanical irritation and inflammatory responses, and is also a site where bacteria easily adhere. Therefore, the functional coating allows for the direct release of antibacterial and anti-inflammatory components at the lesion site, effectively inhibiting local infection and proliferation, thereby achieving mechanical anchoring while preventing complications caused by the anchoring structure.

[0048] refer to Figure 2 , Figure 2 A schematic diagram of the structure of the antibacterial and anti-inflammatory bile duct stent according to an embodiment of the present invention is shown. Figure 2 .

[0049] like Figure 2 As shown, the anti-displacement structure consists of multiple barbs 13 on the outer surface of the stent body 10, which are made of biodegradable magnesium alloy biomaterial. This structure anchors the stent 100 in position, and the magnesium alloy gradually degrades in bodily fluids. In the initial implantation stage, the barbs 13 provide sufficient anchoring force to prevent stent displacement. Once the stent 100 is stable and bile duct obstruction is relieved, the barbs 13 gradually degrade and disappear, avoiding the long-term chronic irritation to the bile duct wall and the difficulty of removal caused by traditional permanent barbs. Simultaneously, the release of magnesium ions has anti-inflammatory and tissue-repair-promoting effects, further enhancing the antibacterial and anti-inflammatory effects.

[0050] In some embodiments, the functional coating further includes a polydopamine coating, through which the ternary composite is loaded onto the scaffold body 10. The polydopamine coating has extremely strong adhesion and can form a firm film on the material surface. The catechol groups on its surface can not only form strong coordination bonds with the surface of the scaffold body 10, but also form secondary coordination or hydrogen bonding with polyphenols and metal ions in the ternary composite, thereby firmly fixing the functional coating to the surface of the scaffold body 10 and improving the stability and service life of the functional coating.

[0051] refer to Figure 3 , Figure 3 A schematic diagram of the structure of the antibacterial and anti-inflammatory bile duct stent according to an embodiment of the present invention is shown. Figure 3 .

[0052] like Figure 3As shown, the waveform ring 11 is a hollow tube filled with antibacterial and anti-inflammatory drugs, and the tube wall has drug release micropores 14. In other words, by making the waveform ring 11 a hollow structure, it can be filled with drugs, such as the antibiotic levofloxacin, the potent anti-inflammatory drug dexamethasone, or the ternary complex of this invention, etc., and the drugs are slowly diffused and released through the micropores 14 on the tube wall. This provides a large-capacity backup drug reserve for the stent 100, maintaining a long-term effective local drug concentration even after the surface coating function weakens, greatly extending the effective treatment course of the stent.

[0053] In some embodiments, the waveform ring 11 includes multiple crest segments and multiple trough segments, with the crest segments of every two waveform rings 11 arranged adjacent to each other, and the connector 12 connected to at least one crest segment of the two waveform rings. This reduces the material of the connector 12, thereby reducing material costs. In some embodiments, the connector 12 may not be required, and the peaks may be directly connected; this invention is not limited to this.

[0054] Preferably, the stent body 10 is made of magnesium alloy elastic material. This biodegradable, fully functional stent avoids the need for a second removal surgery, and its degradation products are beneficial.

[0055] refer to Figure 4 , Figure 4 A schematic diagram of the structure of the antibacterial and anti-inflammatory bile duct stent according to an embodiment of the present invention is shown. Figure 4 .

[0056] like Figure 4 As shown, one end of the support body 10 can be flared. In some embodiments, the support body 10 can also be flared at both ends, or as shown in the figure. Figure 1 The straight cylindrical shape is better suited to the physiological structure of the bile duct.

[0057] In one embodiment of the present invention, the metal ion may be, but is not limited to, selected from Cu. 2+ Fe 2+ Fe 3+ Mn 2+ Zn 2+ Mg 2+ At least one of these metal ions. These metal ions are key to inducing copper death.

[0058] Polyphenolic compounds may be selected from, but are not limited to, at least one of gallic acid, epicatechin gallate, quercetin, curcumin, and tannic acid. These components can better inhibit HIF-1α.

[0059] Quaternary ammonium compounds may be, but are not limited to, selected from at least one of dodecyltrimethylammonium bromide, hexadecyltrimethylammonium bromide, and benzalkonium chloride. These substances ensure highly effective antibacterial activity.

[0060] In the embodiments of the present invention, based on the total mass of the raw materials of the ternary complex, the mass percentage of metal ions is 5% to 50%, the mass percentage of polyphenolic compounds is 5% to 60%, and the mass percentage of quaternary ammonium salt compounds is 5% to 60%.

[0061] The metal content is relatively low. For example, at 5%, it can also produce antibacterial effects when combined with polyphenols and quaternary ammonium salts. For instance, the tannic acid-copper metal-organic network (Cu-TA MOF) containing only a small amount of copper ions can significantly reduce the number of surviving colonies in E. coli and S. aureus, indicating that even if the metal proportion in the complex is very small, it still has strong bactericidal power as long as it forms a complex with phenols.

[0062] Furthermore, metal-phenolic complexes exhibit excellent antibacterial properties when the metal content is in the range of 15%–30%. For example, copper-quercetin nanocomposites, with a copper content of approximately 20%, such as quercetin and Cu... 2+ At a molar ratio of 1:1, the material achieved 100% sterilization at a concentration of 0.05 mg / mL against both *E. coli* and *S. aureus*. These data demonstrate that the material can achieve efficient sterilization even at moderate metal content.

[0063] When the metal content accounts for nearly 30% or even higher by mass, ternary complexes can still maintain strong antibacterial activity and good stability. For example, Cu-TA nanosheets contain approximately 30.9 wt% copper, and at a concentration of 0.5 mg / mL, the powder exhibits a near 100% kill rate against *E. coli* and *B. subtilis*, corresponding to a MIC of approximately 0.25 mg / mL for *E. coli*. Even when this complex is added to the coating at a low loading of 5%, it still shows excellent inhibitory effects on bacteria. This indicates that even with a higher metal content, approaching the upper limit of 50%, and with sufficient phenolic stabilizers, ternary complexes can still self-assemble and provide sustained broad-spectrum antibacterial properties. The main reason for this is that metal ions endow ternary complexes with ion-release bactericidal and catalytic oxygen-generating capabilities. For example, Ag... + Cu 2 + These substances can damage cell membranes and generate reactive oxygen species through reactions such as Fenton's reaction, thereby killing bacteria.

[0064] Polyphenolic compounds, such as gallic acid (GA), epicatechin gallate (EGCG), quercetin, curcumin, and tannic acid (TA), can constitute approximately 5% to 60% of the composite material by mass. The polyphenol content needs to be sufficient to adequately complex the metal and provide auxiliary antibacterial and antioxidant effects. When the polyphenol content is low, its molar amount must be at least equal to that of the metal ions to form coordination bonds. For example, quercetin:Cu 2+At a 1:1 molar ratio, quercetin accounts for over 80% of the complex by mass. Even if the polyphenol content is only a few percent, it can still form a stable system and function effectively with the assistance of quaternary ammonium salts.

[0065] When phenols and metal ions are in near-stoichiometric ratios, they can form dense coordination polymers. This ratio is commonly used in tannic acid-metal coatings, enabling rapid deposition of thin films of approximately 10 nm on various material surfaces. (Cu) 2+ The addition of tannic acid to the tannic acid composite hydrogel significantly enhances its long-term antibacterial efficacy, indicating that phenols contribute to both the sustained release of metal ions and direct antibacterial action.

[0066] In some cases, polyphenols can be the main component. For example, coatings with high tannin (TA) content form a dense network through the multivalent bonding of polyphenols, exhibiting long-lasting antibacterial and anti-corrosion effects against bacteria. A high proportion of phenols provides abundant phenolic hydroxyl sites, which can form a cross-linked network structure with a small amount of metal. These coatings exhibit long-term antibacterial and anti-biofilm properties on the surface of medical devices. It should be noted that excessive amounts of phenols may have slight toxicity to cells in their free state, but studies have shown that adding metal ions to form complexes can eliminate the negative effects of tannins on cells. Therefore, in practical applications, the phenol content can be increased to 50% or even higher to enhance coating stability and biocompatibility, while ensuring that the composite material maintains good antibacterial effects throughout the entire range of 5%–60%.

[0067] The main function of polyphenolic components is to stabilize metal ions through complexation and provide intrinsic antibacterial activity. For example, tannic acid and gallic acid can chelate metals to form insoluble networks, controlling the release rate of metal ions and preventing their rapid inactivation.

[0068] Quaternary ammonium salts can be used as cationic surfactants, such as dodecyltrimethylammonium bromide (DTAB), cetyltrimethylammonium bromide (CTAB), and benzalkonium chloride (BAC). Their mass percentage in composite materials can range from approximately 5% to 60%, preferably around 20% to 50%. The quaternary ammonium salt content directly affects the rapid and broad-spectrum bactericidal ability of the composite material; even at an addition level of 5%–10%, quaternary ammonium salts exhibit potent bactericidal effects. In actual studies, quaternary ammonium salt-coated fabrics can reduce bacterial colony counts by 98%–100% within 4 hours of contact with bacteria. Although quaternary ammonium salts are highly effective bactericides, their low-dose release is relatively safe for human cells. For example, after immersion washing, quaternary ammonium salt coatings release approximately 24±5 µg / mL of active ingredient without showing acute cytotoxicity (in vitro IC50 approximately 95 µg / mL). Therefore, even with a quaternary ammonium salt content of only 5%, the composite material can rapidly kill Gram-positive and Gram-negative bacteria in antibacterial tests due to its strong cationic surface activity.

[0069] The preparation method of the multifunctional nanocomposite material according to the embodiments of the present invention will be described below.

[0070] The preparation method of the ternary composite material in this invention may include mixing a metal salt solution, a polyphenol compound solution, and a quaternary ammonium salt compound solution through a self-assembly reaction, followed by separation and purification to obtain a multifunctional nanocomposite material. This method is simple and can directly synthesize multifunctional nanocomposite materials.

[0071] In some embodiments, the self-assembly reaction includes:

[0072] S10 involves first mixing a metal salt solution with a polyphenol compound solution to initiate a first self-assembly reaction, forming a metal-polyphenol complex.

[0073] For example, a metal salt solution and a stabilizer can be mixed under vigorous stirring and reacted for 0.5-2 hours to obtain a mixed solution;

[0074] A polyphenol compound solution was added to the mixture, and stirring was continued. The metal salt solution and the polyphenol compound solution underwent the first self-assembly reaction.

[0075] S20, then add a quaternary ammonium salt compound solution to the reaction system to carry out a second self-assembly reaction, and obtain a metal-polyphenol-quaternary ammonium salt ternary complex.

[0076] The composition and content of each substance, as well as the effects achieved, have been described in detail in the above embodiments and will not be repeated here.

[0077] The antitumor effect of the stent in this embodiment of the invention is described below based on experimental results. The sample in this embodiment is the stent containing composite materials described in the previous embodiments, and the stent preparation process is as follows:

[0078] 1) Prepare the solutions: copper chloride (CuCl2) solution (13.4 mg CuCl2 dissolved in 8 mL solvent), polyvinylpyrrolidone (PVP) solution (50 mg PVP dissolved in 1 mL solvent), gallic acid (GA) solution (10 mg GA dissolved in 1 mL solvent), and sodium hydroxide (NaOH) solution (8 mg / mL). 2) Mix the copper chloride solution and polyvinylpyrrolidone solution under vigorous stirring and react for 1 hour. Then, add the gallic acid solution and continue stirring to allow the GA to react with the CuCl2 solution. 2+ A self-assembly reaction occurs, generating a copper-gallic acid (Cu-GA) complex. The pH of the system is adjusted to 13 using sodium hydroxide solution, and stirring continues. 3) Dodecyltrimethylammonium bromide (DTAB) solution (30 mg DTAB dissolved in 3 mL solvent) is added, and stirring continues overnight to promote the self-assembly reaction between the Cu-GA complex and DTAB. 4) After the reaction is complete, the product is separated by centrifugation, washed several times with deionized water to remove unreacted substances and solvent, and then dried in a vacuum drying oven to obtain the final product—copper-gallic acid-dodecyltrimethylammonium bromide (Cu-GA-DTAB) multifunctional nanocomposite material. The multifunctional nanocomposite material is sprayed onto a magnesium alloy scaffold to obtain sample S1.

[0079] To demonstrate the performance of the composite material-containing stent in the embodiments of the present invention, a control group was provided, specifically divided into four groups of experiments: blank experiment (Control), stent without load (BXM, no composite material), stent loaded with Cu, stent loaded with Ga, and stent loaded with CuGaQ (S1 in the present invention) – five anti-tumor experiments.

[0080] refer to Figure 5 , Figure 5 The illustration shows a clone formation experiment of a composite material scaffold (hereinafter referred to as the scaffold) and a control, according to an embodiment of the present invention. This experiment was used to evaluate the effect of the composite material scaffold on the proliferative capacity of tumor cells.

[0081] like Figure 5 As shown, the Control and BXM groups had the highest number of cell clones, indicating that they were not significantly inhibited; the Cu and Ga groups showed a significant reduction in the number of clones, demonstrating a certain anti-tumor effect; the CuGaQ group had almost no clone formation, indicating that it could significantly inhibit cell proliferation and had the strongest anti-tumor activity.

[0082] refer to Figure 6 , Figure 6 The Transwell migration assay of the scaffold and control according to an embodiment of the present invention is shown. This assay reflects cell migration ability.

[0083] like Figure 6 As shown, the Control and BXM groups had the highest number of migrating cells; the Cu and Ga groups showed reduced migration, while the CuGaQ group had the lowest number of migrating cells, indicating that it can significantly inhibit the migration and invasion of tumor cells.

[0084] refer to Figure 7 , Figure 7 The cell survival / death staining assay of the scaffold and control according to an embodiment of the present invention is shown.

[0085] like Figure 7 As shown, green represents live cells and red represents dead cells. The Control and BXM groups are almost entirely green; red areas appear in the Cu and Ga groups, indicating that the material causes some cell death; the CuGaQ group has the strongest red signal, indicating that the material has a significant killing effect on tumor cells.

[0086] refer to Figure 8 , Figure 8 The illustration shows stained microscopic images of the scaffold and control according to embodiments of the present invention. These include stained microscopic images of DLAT protein acetyltransferase in the scaffold and control; stained microscopic images of calreticulin in the scaffold and control; and stained microscopic images of JC-1 in the direct and control samples.

[0087] like Figure 8 As shown in the first row of images, DLAT (Dihydrolipoamide acetyltransferase) is involved in mitochondrial metabolism. Strong DLAT fluorescence signals in the Control and BXM groups indicate active metabolism; weakened signals in Cu and Ga groups; and the weakest fluorescence in the CuGaQ group, suggesting that it can significantly inhibit cellular metabolic processes and reduce energy production.

[0088] In the second row of images, calreticulin (CRT) is a marker of immunogenic cell death, and CRT exposure typically indicates immunogenic cell death (ICD). The Cu and Ga groups showed enhanced CRT signals; the CuGaQ group exhibited the strongest fluorescence, indicating that this material induces significant CRT eversion across the cell membrane, promoting the ICD process and supporting its potential immune activation.

[0089] The third row corresponds to the JC-1 staining assay for the scaffolds and controls. This experiment detected mitochondrial membrane potential; red fluorescence in JC-1 represents normal membrane potential, while green represents loss of membrane potential. In the Control and BXM groups, red predominated, indicating normal mitochondrial function; the Cu and Ga groups showed mixed red and green signals; the CuGaQ group showed predominantly green, indicating a significant decrease in mitochondrial membrane potential and enhanced apoptosis activity.

[0090] The above experimental results demonstrate that the Cu-GA-QAS (CuGaQ) scaffold exhibited the strongest antitumor effects in all in vitro experiments: significantly inhibiting cell proliferation and colony formation; effectively preventing cell migration and invasion; inducing tumor cell death and disrupting mitochondrial function; and promoting immunogenic cell death (increased CRT eversion). These results indicate that the CuGaQ composite material not only possesses direct cytotoxic effects but may also achieve a comprehensive antitumor effect by activating cell death signaling pathways and immune mechanisms.

[0091] The following compares the effects of several comparative examples with the CuGaQ composite material scaffold of the present invention in in vivo antitumor experiments. The control group includes a blank test, a scaffold without BXM loading (no composite material), a scaffold loaded with CuGa, and a scaffold loaded with CuGaQ.

[0092] refer to Figure 9 , Figure 9 The plate diagrams of the antibacterial plate experiments of the scaffold and the control according to an embodiment of the present invention are shown.

[0093] like Figure 9 As shown in (a), the Control group showed a large number of colonies, indicating no significant antibacterial effect; the BXM group had more colonies, showing a certain antibacterial effect; the CuGA group had a significantly reduced number of colonies, showing a significant antibacterial effect; and the CuGaQ group had almost no colonies, indicating that it had the strongest antibacterial activity.

[0094] like Figure 9 As shown in (b), statistical data indicate that the CuGaQ group had the highest antibacterial rate, which was much higher than that of the Control, BXM and CuGA groups (p < 0.0001).

[0095] refer to Figure 10 , Figure 10 The image shows scanning electron microscope (SEM) images of bacteria after an antibacterial experiment, comparing the scaffold of this invention with the control group.

[0096] like Figure 10 As shown, the Control group showed intact bacteria, indicating no inhibition; the BXM and CuGA groups showed less bacterial surface damage; the CuGaQ group showed obvious bacterial surface rupture and severe cell membrane damage, indicating that CuGaQ had the strongest antibacterial activity.

[0097] refer to Figure 11 , Figure 11 The TNF-α and IL-6 immunofluorescence staining of the scaffold and control of the present invention is shown.

[0098] like Figure 11 As shown, the expression of TNF-α and IL-6 was strong in the Control and BXM groups, indicating a significant inflammatory response. The expression of TNF-α and IL-6 was significantly weakened in the CuGA and CuGaQ groups, especially in the CuGaQ group, where the inflammatory response was significantly suppressed. These results indicate that CuGaQ not only has antibacterial effects but also effectively inhibits the release of inflammatory factors.

[0099] Combination Figure 11 And refer to Figure 12 , Figure 12 The diagram shows the bacterial quantification and cytokine analysis of the scaffold and control in an embodiment of the present invention.

[0100] like Figure 12 The statistical data shown indicates that the CuGaQ group significantly reduced the concentrations of IL-6 and TNF-α (p < 0.0001). This immunosuppressive effect suggests that CuGaQ has a strong anti-inflammatory effect and can alleviate the inflammatory response induced by bacterial infection.

[0101] As can be seen from the above figure, the scaffold containing CuGaQ composite material showed excellent effects in in vivo anti-infection experiments: the strongest antibacterial activity, effectively inhibiting bacterial growth and reproduction; significantly inhibiting the inflammatory response, and reducing the immune response induced by infection by lowering IL-6 and TNF-α levels;

[0102] Excellent tissue repair effects, reducing post-infection tissue damage. Scaffolds containing Cu-GA-QAS (CuGaQ) composite materials not only possess strong antibacterial effects but also reduce post-infection inflammatory responses and promote tissue repair by inhibiting the secretion of immune factors (such as IL-6 and TNF-α). This makes them highly promising for biomedical applications in anti-infection, immunomodulation, and wound healing, especially in the treatment of infectious diseases and immunomodulation, showing excellent potential.

[0103] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. An antibacterial and anti-inflammatory bile duct stent, characterized in that, include: The support body includes a plurality of wave-shaped rings arranged along a first direction, and a connector connecting the wave-shaped rings, wherein the plurality of wave-shaped rings form a drainage channel; The scaffold body is provided with a functional coating, which includes a ternary complex formed by the self-assembly of metal ions, polyphenolic compounds and quaternary ammonium salt compounds.

2. The antibacterial and anti-inflammatory bile duct stent according to claim 1, characterized in that, The support body is provided with an anti-displacement structure, and the anti-displacement structure is provided with the functional coating.

3. The antibacterial and anti-inflammatory bile duct stent according to claim 2, characterized in that, The anti-displacement structure consists of multiple barbs on the outer surface of the support body, and the barbs are made of biodegradable magnesium alloy biomaterial.

4. The antibacterial and anti-inflammatory bile duct stent according to claim 1, characterized in that, The functional coating also includes a polydopamine coating, and the ternary composite is loaded onto the scaffold body through the polydopamine coating.

5. The antibacterial and anti-inflammatory bile duct stent according to any one of claims 1-4, characterized in that, The waveform ring is a hollow tube, which is filled with antibacterial and anti-inflammatory drugs, and the tube wall is provided with drug release micropores.

6. The antibacterial and anti-inflammatory bile duct stent according to any one of claims 1-4, characterized in that, The waveform ring includes multiple peak segments and multiple trough segments, with the peak segments of every two waveform rings arranged adjacent to each other, and the connector is connected to at least one peak segment of two waveform rings.

7. The antibacterial and anti-inflammatory bile duct stent according to any one of claims 1-4, characterized in that, The support body is made of magnesium alloy elastic material.

8. The antibacterial and anti-inflammatory bile duct stent according to any one of claims 1-4, characterized in that, The support body is a straight cylinder, or one or both ends are funnel-shaped.

9. The antibacterial and anti-inflammatory bile duct stent according to claim 1, characterized in that, The metal ions are selected from Cu. 2+ Fe 2+ Fe 3+ Mn 2+ Zn 2+ Mg 2+ At least one of them; and / or, The polyphenolic compound is selected from at least one of gallic acid, epicatechin gallate, quercetin, curcumin, and tannic acid; and / or, The quaternary ammonium salt compound is selected from at least one of dodecyltrimethylammonium bromide, hexadecyltrimethylammonium bromide, and benzalkonium chloride.

10. The antibacterial and anti-inflammatory bile duct stent according to claim 1 or 9, characterized in that, Based on the total mass of the raw materials of the ternary composite, the mass percentage of the metal ions is 5% to 50%, the mass percentage of the polyphenolic compounds is 5% to 60%, and the mass percentage of the quaternary ammonium salt compounds is 5% to 60%.

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