Anti-fouling and anti-protein adhesion ureteral stent and method of making same

Abstract

The application discloses an anti-fouling and anti-protein adhesion ureteral stent and a preparation method thereof, and relates to the technical field of medical devices.The application comprises a braided layer used as a support framework; a bionic structure layer connected to the inner layer of the braided tube for preventing protein adhesion and biofilm formation; and a silk fibroin microneedle layer connected to the outer layer of the braided tube for carrying anti-stenosis drugs.The rough texture formed by the dermal denticles on the surface of the bionic anti-fouling and anti-protein adhesion silk fibroin film on the inner surface of the ureteral stent can reduce the adhesion area of organisms inside the ureteral stent and keep the surface clean; the lotus leaf surface is covered with randomly distributed protrusions with a size of about 10 microns, and has super-hydrophobic and self-cleaning functions; and the bionic surfaces all have the function of effectively preventing protein adhesion and biofilm formation.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, specifically to a ureteral stent that is resistant to contamination and protein adhesion, and its preparation method. Background Technology

[0002] Ureteral stricture refers to partial or complete obstruction of the ureter caused by various etiologies, resulting in varying degrees of upper urinary tract obstruction and hydronephrosis, which in turn damages kidney function or leads to kidney failure. Ureteral stent placement is an effective, safe, and simple method for treating ureteral stricture, which can quickly relieve symptoms and restore the patient's quality of life.

[0003] Currently, common ureteral stents include silicone stents, polyurethane ureteral stents, metal ureteral stents, polylactic acid or polyglycolic acid ureteral stents, and tissue-engineered ureteral stents, among others. The most widely used polyurethane and related material stents are prone to bacterial adhesion and biofilm formation on their surface, leading to urinary tract infections and crusting. Therefore, we propose a ureteral stent that is resistant to fouling and protein adhesion and its preparation method. Summary of the Invention

[0004] The purpose of this invention is to provide a ureteral stent that is resistant to fouling and protein adhesion, and a method for preparing the stent thereon, which can prevent the adhesion of carbonates, bacteria and proteins to the inner surface.

[0005] To achieve the above objectives, the present invention provides the following technical solution: a ureteral stent resistant to fouling and protein adhesion, and a method for preparing the same, comprising:

[0006] The woven layer serves as a supporting framework.

[0007] A biomimetic structural layer, which is connected to the inner layer of the braided tube, is used to prevent protein adhesion and biofilm formation.

[0008] A silk fibroin microneedle layer, wherein the silk fibroin microneedles are attached to the outer layer of the braided tube for carrying anti-stenosis drugs.

[0009] Furthermore, the braided layer is tubular.

[0010] Furthermore, the material of the braided layer is a biodegradable polymer monofilament, including yarns of one or more of polylactic acid (PLA), polydioxanone (PDO), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer (PLGA), and developing yarn.

[0011] Furthermore, the biomimetic structural layer is a shark skin-like structure, a lotus leaf-like structure, or a rose petal-like structure.

[0012] Furthermore, the biomimetic structural layer is a biomimetic silk fibroin membrane.

[0013] According to one aspect of the present invention, the present invention provides a method for preparing a ureteral stent that is resistant to fouling and protein adhesion, the specific method being as follows:

[0014] The braided layer is prepared using a vertical spindle braiding machine;

[0015] The biomimetic silk fibroin membrane was cut into strips 2mm wide and wrapped around a 2mm thick steel tube. A certain concentration of silk fibroin solution was coated on the outer layer of the biomimetic silk fibroin membrane. The steel tube wrapped with the biomimetic silk fibroin membrane was then placed inside the braided layer and placed in a 60℃ oven for heat setting for 30 minutes. After that, the steel tube was removed. Because the silk fibroin solution has a certain viscosity, the biomimetic silk fibroin membrane can successfully adhere to the inner surface of the bare ureteral stent.

[0016] The microneedle membrane is cut into strips 2 mm wide. A certain concentration of silk fibroin solution is applied to the back of the microneedle membrane. Then, the microneedles are wound onto the outer surface of the braided layer and placed in a 60°C oven for heat setting for 30 minutes to obtain a ureteral stent that is resistant to fouling and protein adhesion.

[0017] Furthermore, the method for preparing the braided layer is as follows:

[0018] The yarn is prepared using a vertical spindle braiding machine with a core function, the yarn thickness is 12 tex, the braiding structure is selected as regular braiding (2 / 2 interlacing), the braiding speed is set to 60 rpm, the inner diameter of the braided layer is designed to be 2 mm, and the gear ratio is selected as 82 / 30.

[0019] After weaving, place the woven layer in an 85℃ oven for heat setting for 15 minutes, then wash it several times in deionized water, and finally dry it.

[0020] Furthermore, the method for preparing the biomimetic structural layer is as follows:

[0021] Degummed silk is dissolved in a 9.3 mol / L lithium bromide solution and placed in a 60℃ oven for 4 hours to ensure complete dissolution. After that, it is dialyzed in pure water for 24-48 hours. Then, the concentration of silk fibroin is diluted or concentrated to obtain a silk fibroin solution with a mass fraction of 3-20%.

[0022] Polyethylene glycol with a mass fraction of 10-90% is added to a silk fibroin solution. First, polydimethylsiloxane and a crosslinking agent are mixed at a ratio of 10:1 (w / w) to obtain a polydimethylsiloxane (PDMS) solution. Then, shark skin, lotus leaves, or rose petals are obtained and their surfaces are cleaned and dehydrated. After complete dehydration, the above PDMS solution is poured into a dry biological structure mold for casting. It is cured in a vacuum oven at 60°C for 3 hours. The biological structure is removed to obtain a negative mold with a biomimetic structure (the mold cavity is concave). Then, the prepared silk fibroin solution is poured into the negative mold and cured in a vacuum oven at 60°C for 3 hours to obtain a biomimetic silk fibroin film.

[0023] Furthermore, the method for preparing the silk fibroin microneedle layer is as follows:

[0024] The microneedle array was prepared using a polydimethylsiloxane (PDMS) mold. The mold consisted of an 84×84 conical microneedle array, with each conical microneedle having a height of 700 μm, a tip diameter of 15 μm, a base diameter of 360 μm, and a final microneedle array area of ​​10 cm × 10 cm.

[0025] Then, a certain amount of SF, chitosan and sodium hyaluronate mixed solution was prepared. Rapamycin solution with a concentration of 0.5-2 mg / mL and paclitaxel solution with a concentration of 1-3 mg / mL were added to the mixed solution and mixed evenly to obtain microneedle solution.

[0026] Take 5-15 mL of the prepared microneedle solution and pipette it into the PDMS mold. Perform 6-10 vacuum treatments in a vacuum drying oven to allow the solution to enter the needle cavity and remove any trapped air. Then use a pipette to remove any remaining air bubbles so that the grooves of the PDMS mold are completely filled with the solution.

[0027] After filling, the mold should be left to dry completely for 18 hours under ambient temperature and humidity conditions.

[0028] This invention has at least the following beneficial effects:

[0029] (1) The middle fabric layer serves as the skeleton of the entire urethral stent and has good mechanical properties such as compressive strength, elasticity and bending resistance, which ensures mechanical support and drainage.

[0030] (2) Current ureteral stents have problems such as carbonate deposition, calcification, and adhesion of bacteria and specific proteins on the inner surface. The biomimetic antifouling and antiprotein adhesion silk fibroin membrane on the inner surface of the ureteral stent of this invention can effectively avoid such problems. For example, the rough texture formed by the dermal teeth on the surface of the shark skin silk fibroin membrane can reduce the adhesion area of ​​organisms on the inner side of the ureteral stent and keep the surface clean. The lotus leaf-like surface is covered with randomly distributed protrusions of about 10 μm in size, which have superhydrophobic and self-cleaning functions. These biomimetic surfaces all have the function of effectively preventing protein adhesion and biofilm formation.

[0031] (3) The microneedle drug-carrying structure on the outer surface of the stent can carry anti-stenosis drugs. Microneedle drug-carrying has the advantages of high drug loading capacity and high drug release rate. After placement, the drug can be slowly released into the ureter. The microneedle structure can carry the drug and directly penetrate the stenosis site, thereby achieving the effect of treating inflammatory and traumatic urethral stricture.

[0032] Of course, any product implementing this invention does not necessarily need to achieve all of the advantages described above at the same time. Attached Figure Description

[0033] Figure 1 This is a schematic diagram of the overall structure of the present invention;

[0034] Figure 2 This is a SEM image of the shark skin-like silk fibroin membrane structure of Embodiment 1 of the present invention;

[0035] Figure 3 This is a SEM image of the lotus leaf silk fibroin membrane structure from Embodiment 2 of the present invention.

[0036] Figure 4 This is a SEM image of the imitation rose petal silk fibroin membrane structure of Embodiment 3 of the present invention;

[0037] Figure 5 This is a SEM image of the outer silk fibroin microneedle structure of the present invention;

[0038] Figure 6 This is a schematic diagram of the water contact angle of the sharkskin-like silk fibroin membrane in Embodiment 1 of the present invention;

[0039] Figure 7 This is a schematic diagram of the water contact angle of the lotus leaf silk fibroin membrane in Embodiment 2 of the present invention;

[0040] Figure 8 This is a schematic diagram of the water contact angle of the imitation rose petal silk fibroin membrane in Embodiment 3 of the present invention;

[0041] Figure 9 This is a compression test diagram of the 5×5 silk fibroin microneedles of the present invention.

[0042] Figure label:

[0043] 1. Bionic structural layer; 2. Braided layer; 3. Silk fibroin microneedle layer. Detailed Implementation

[0044] The technical solutions of the embodiments of this disclosure will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this disclosure, and not all embodiments. Based on the embodiments of this disclosure, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this disclosure.

[0045] Example 1:

[0046] Please see Figure 1-5 This invention provides a technical solution: a ureteral stent resistant to fouling and protein adhesion, comprising:

[0047] The braided layer, which has a tubular structure, is mainly used as a supporting skeleton, playing a major role in mechanical support and drainage.

[0048] The biomimetic structural layer is connected to the inner layer of the braided tube to prevent protein adhesion and biofilm formation. The inner surface is functionalized with antifouling agents to prevent fouling and protein adhesion, thus keeping the ureter unobstructed.

[0049] The silk fibroin microneedle layer, which is attached to the outer layer of the braided tube, is used to carry anti-stenosis drugs. The drug is delivered in a controlled and long-lasting manner through the microneedles to achieve the effect of treating ureteral stricture.

[0050] The biomimetic structural layer is a biomimetic silk fibroin membrane, and the biomimetic structural layer is a shark skin-like structure.

[0051] It should be noted that the sharkskin-like structure mainly refers to the design that mimics the microscopic structure of the sharkskin surface. The rough texture formed by the small teeth on the surface can reduce the adhesion area of ​​organisms inside the ureteral stent and keep the surface clean.

[0052] A method for preparing a ureteral stent resistant to fouling and protein adhesion is described below:

[0053] (1) Preparation of the braided layer:

[0054] The yarn material is polydiaxone (PDO), with a yarn thickness of 12 tex. The weaving structure is regular weaving (2 / 2 interlacing). The weaving speed is set to 60 rpm. The inner diameter of the weaving layer is designed to be 2 mm. The gear ratio is selected as 82 / 30. The weaving process can then be carried out.

[0055] After weaving, place the woven layer in an 85℃ oven for heat setting for 15 minutes, then wash it several times in deionized water, and finally dry it.

[0056] (2) Preparation of biomimetic silk fibroin membrane:

[0057] Degummed silk was dissolved in a 9.3 mol / L lithium bromide solution and placed in a 60°C oven for 4 hours to ensure complete dissolution. After that, it was dialyzed in pure water for 36 hours. Then, it was diluted or concentrated according to the required silk fibroin concentration to obtain a silk fibroin solution with a mass fraction of 3-20%.

[0058] Polyethylene glycol with a mass fraction of 80% was added to a silk fibroin solution. First, polydimethylsiloxane and a crosslinking agent were mixed at a ratio of 10:1 (w / w) to obtain a polydimethylsiloxane (PDMS) solution. Then, the obtained shark skin was washed with PBS and pure water, and then dehydrated sequentially with 50%, 60%, 70%, 80%, 90%, 95%, and 100% alcohol, respectively. After complete dehydration, the above polydimethylsiloxane (PDMS) solution was poured into a dry shark skin mold for casting. It was cured in a vacuum oven at 65°C for 3 hours. The real shark skin was removed to obtain a negative mold with a shark skin structure (the mold cavity is concave). Then, the prepared silk fibroin solution was poured into the negative mold and cured in a vacuum oven at 65°C for 3 hours to obtain a biomimetic silk fibroin film.

[0059] (3) Preparation of silk fibroin microneedle membrane:

[0060] The final polydimethylsiloxane (PDMS) mold uses an 84×84 conical microneedle array, with each conical microneedle having a height of 500μm, a tip diameter of 15μm, a base diameter of 380μm, and a final microneedle array area of ​​10×10cm.

[0061] Degummed silk was dissolved in a 9.3 mol / L lithium bromide solution and placed in a 60°C oven for 4 hours to ensure complete dissolution. After dissolution, the solution was dialyzed in pure water for 36 hours. Then, the solution was diluted or concentrated according to the required silk fibroin concentration to obtain a 5% (w / w) silk fibroin solution. 80% (w / w) polyethylene glycol was added to the silk fibroin solution and mixed thoroughly. Rapamycin solution with a concentration of 1.2 mg / mL was added to the mixed solution to obtain a microneedle solution, i.e., a silk fibroin drug-loaded mixed solution.

[0062] Take 5-15 mL of the prepared solution and transfer it into the PDMS mold. Perform 8 vacuum treatments in a vacuum drying oven to allow the solution to enter the needle cavity and remove all trapped air. Then remove the remaining air bubbles with a pipette to ensure that the mold grooves are completely filled with the silk solution. Then place the filled mold under ambient temperature and humidity conditions for 18 hours to dry completely.

[0063] (4) Fabrication of composite ureteral stent:

[0064] The biomimetic silk fibroin membrane was cut into strips 2mm wide and wrapped around a 2mm thick steel tube. A certain concentration of silk fibroin solution was coated on the outer layer of the biomimetic silk fibroin membrane. The steel tube wrapped with the biomimetic silk fibroin membrane was then placed inside the braided layer and placed in a 60℃ oven for heat setting for 30 minutes. After that, the steel tube was removed. Because the silk fibroin solution has a certain viscosity, the biomimetic silk fibroin membrane can successfully adhere to the inner surface of the bare ureteral stent.

[0065] The silk fibroin microneedle membrane is cut into strips 2 mm wide. A certain concentration of silk fibroin solution is applied to the back of the silk fibroin microneedle membrane. Then, it is wound onto the outer surface of the braided layer and placed in a 60°C oven for heat setting for 30 minutes to obtain a ureteral stent that is resistant to fouling and protein adhesion.

[0066] Example 2:

[0067] Please see Figure 1-5 This invention provides a technical solution: a ureteral stent resistant to fouling and protein adhesion, comprising:

[0068] The braided layer, which has a tubular structure, is mainly used as a supporting skeleton, playing a major role in mechanical support and drainage.

[0069] The biomimetic structural layer is connected to the inner layer of the braided tube to prevent protein adhesion and biofilm formation. The inner surface is functionalized with antifouling agents to prevent fouling and protein adhesion, thus keeping the ureter unobstructed.

[0070] The silk fibroin microneedle layer, which is attached to the outer layer of the braided tube, is used to carry anti-stenosis drugs. The drug is delivered in a controlled and long-lasting manner through the microneedles to achieve the effect of treating ureteral stricture.

[0071] The biomimetic structural layer is a biomimetic silk fibroin membrane, and the biomimetic structural layer is a lotus leaf-like structure.

[0072] It should be noted that the lotus leaf-like structure mainly refers to the design that imitates the microstructure of the lotus leaf surface. The lotus leaf surface is covered with randomly distributed protrusions of about 10μm in size, which have superhydrophobic and self-cleaning functions. The biomimetic structure layer of the lotus leaf-like structure has the hydrophobic properties of the lotus leaf surface, thus effectively preventing protein adhesion and biofilm formation.

[0073] A method for preparing a ureteral stent resistant to fouling and protein adhesion is described below:

[0074] (1) Preparation of the braided layer:

[0075] The yarn is prepared using a vertical spindle braiding machine with a core function, the yarn material is polylactic acid (PLA), the yarn thickness is 12 tex, the braiding structure is selected as regular braiding (2 / 2 interlacing), the braiding speed is set to 60 rpm, the inner diameter of the braided layer is designed to be 2 mm, and the gear ratio is selected as 82 / 30.

[0076] After weaving, place the woven layer in an 85℃ oven for heat setting for 15 minutes, then wash it several times in deionized water, and finally dry it.

[0077] (2) Preparation of biomimetic silk fibroin membrane:

[0078] Degummed silk was dissolved in a 9.3 mol / L lithium bromide solution and placed in a 60°C oven for 4 hours to ensure complete dissolution. After that, it was dialyzed in pure water for 36 hours. Then, it was diluted or concentrated according to the required silk fibroin concentration to obtain a 5% silk fibroin solution.

[0079] Polyethylene glycol with a mass fraction of 80% was added to a silk fibroin solution. First, polydimethylsiloxane and a crosslinking agent were mixed at a ratio of 10:1 (w / w) to obtain a polydimethylsiloxane (PDMS) solution. Then, fresh lotus leaves were washed with PBS buffer and pure water. The above polydimethylsiloxane (PDMS) solution was poured into a dried lotus leaf mold for casting. After curing in a vacuum oven at 60°C for a certain time, the lotus leaves were removed to obtain a negative mold with a lotus leaf structure (the mold cavity is concave). Then, the prepared silk fibroin solution was poured into the negative mold and cured in a vacuum oven at 65°C for a certain time to obtain a biomimetic silk fibroin film.

[0080] (3) Preparation of silk fibroin microneedle membrane:

[0081] The final polydimethylsiloxane (PDMS) mold uses an 84×84 conical microneedle array, with each microneedle having a height of 700μm, a tip diameter of 15μm, a base diameter of 380μm, and a final microneedle array area of ​​10×10cm.

[0082] A certain amount of chitosan was dissolved in acetic acid solution to obtain a 4%-15% chitosan solution. Rapamycin solution with a concentration of 1.2 mg / mL was added to the chitosan solution to obtain a chitosan-drug-loaded mixture. The prepared chitosan-drug-loaded mixture was transferred into a PDMS mold and subjected to several vacuum treatments in a vacuum drying oven to allow the solution to enter the needle cavity and remove all trapped air. Afterwards, any remaining air bubbles were removed with a pipette, ensuring the mold grooves were completely filled with the silk solution. The filled mold was then left to dry completely under ambient temperature and humidity conditions for a certain period.

[0083] (4) Fabrication of composite ureteral stent:

[0084] The biomimetic silk fibroin membrane was cut into strips 2mm wide and wrapped around a 2mm thick steel tube. A certain concentration of silk fibroin solution was coated on the outer layer of the biomimetic silk fibroin membrane. The steel tube wrapped with the biomimetic silk fibroin membrane was then placed inside the braided layer and placed in a 60℃ oven for heat setting for 30 minutes. After that, the steel tube was removed. Because the silk fibroin solution has a certain viscosity, the biomimetic silk fibroin membrane can successfully adhere to the inner surface of the bare ureteral stent.

[0085] The silk fibroin microneedle membrane is cut into strips 2 mm wide. A certain concentration of silk fibroin solution is applied to the back of the silk fibroin microneedle membrane. Then, it is wound onto the outer surface of the braided layer and placed in a 60°C oven for heat setting for 30 minutes to obtain a ureteral stent that is resistant to fouling and protein adhesion.

[0086] Example 3:

[0087] Please see Figure 1-5 This invention provides a technical solution: a ureteral stent resistant to fouling and protein adhesion, comprising:

[0088] The braided layer, which has a tubular structure, is mainly used as a supporting skeleton, playing a major role in mechanical support and drainage.

[0089] The biomimetic structural layer is connected to the inner layer of the braided tube to prevent protein adhesion and biofilm formation. The inner surface is functionalized with antifouling agents to prevent fouling and protein adhesion, thus keeping the ureter unobstructed.

[0090] The silk fibroin microneedle layer, which is attached to the outer layer of the braided tube, is used to carry anti-stenosis drugs. The drug is delivered in a controlled and long-lasting manner through the microneedles to achieve the effect of treating ureteral stricture.

[0091] The biomimetic structural layer is a biomimetic silk fibroin membrane, and the biomimetic structural layer is a structure that resembles rose petals.

[0092] It should be noted that the imitation rose petal structure mainly refers to the design that mimics the microstructure of the surface of a rose petal. The surface of a rose petal has an array of nanoscale papillae, and each papillae has a folded structure of about 400-500nm at its tip, which has good antibacterial properties, can prevent protein adhesion and biofilm formation, and keep the surface clean.

[0093] A method for preparing a ureteral stent resistant to fouling and protein adhesion is described below:

[0094] (1) Preparation of the braided layer:

[0095] The yarn is prepared using a vertical spindle braiding machine with a core function. The yarn material is polylactic acid-glycolic acid copolymer (PLGA), the yarn thickness is 12 tex, the braiding structure is selected as regular braiding (2 / 2 interlacing), the braiding speed is set to 60 rpm, the inner diameter of the braided layer is designed to be 2 mm, and the gear ratio is selected as 82 / 30.

[0096] After weaving, place the woven layer in an 85℃ oven for heat setting for 15 minutes, then wash it several times in deionized water, and finally dry it.

[0097] (2) Preparation of biomimetic silk fibroin membrane:

[0098] Degummed silk was dissolved in a 9.3 mol / L lithium bromide solution and placed in a 60°C oven for 4 hours to ensure complete dissolution. After that, it was dialyzed in pure water for 36 hours. Then, it was diluted or concentrated according to the required silk fibroin concentration to obtain a 5% silk fibroin solution.

[0099] Polyethylene glycol (80% by mass) was added to a silk fibroin solution. First, polydimethylsiloxane and a crosslinking agent were mixed at a ratio of 10:1 (w / w) to obtain a PDMS solution. Then, the obtained rose petals were washed with PBS and pure water to obtain a negative mold (a mold with a concave cavity) with a rose petal structure. After curing in a vacuum oven at 60°C for a certain time, the rose petals were removed, and the prepared silk fibroin solution was poured into the negative mold. The mold was then cured in a vacuum oven at 65°C for a certain time to obtain a biomimetic silk fibroin membrane.

[0100] (3) Preparation of silk fibroin microneedle membrane:

[0101] The final polydimethylsiloxane (PDMS) mold uses an 84×84 conical microneedle array, with each microneedle having a height of 700μm, a tip diameter of 15μm, a base diameter of 380μm, and a final microneedle array area of ​​10×10cm.

[0102] A certain amount of sodium hyaluronate (SH) is slowly added to a beaker and placed in a constant temperature shaker at 37°C until the sodium hyaluronate (SH) is completely dissolved to obtain an 8% solution. Rapamycin solution with a concentration of 0.5-2 mg / mL is added to the sodium hyaluronate (SH) solution to obtain a sodium hyaluronate (SH) drug-loaded mixed solution. The prepared sodium hyaluronate (SH) solution is transferred into a polydimethylsiloxane (PDMS) mold and subjected to several vacuum treatments in a vacuum drying oven to allow the solution to enter the needle cavity and expel trapped air. Then, the remaining air bubbles are removed with a pipette, ensuring the mold grooves are completely filled with the silk solution. The filled mold is then placed under ambient temperature and humidity conditions for a certain period of time to allow it to dry completely.

[0103] (4) Fabrication of composite ureteral stent:

[0104] The prepared biomimetic silk fibroin membrane was cut into strips 2 mm wide and wrapped around a 2 mm thick steel tube. A certain concentration of silk fibroin solution was coated on the outer layer of the biomimetic silk fibroin membrane. Then, the 2 mm steel tube wrapped with the biomimetic protein membrane was placed inside the ureteral stent and placed in a 60℃ oven for heat setting for 30 minutes before the steel tube was removed.

[0105] Because of the viscosity of the silk fibroin solution, the biomimetic silk fibroin membrane can successfully adhere to the inner surface of the bare ureteral stent. Similarly, by cutting the microneedle membrane into strips 2 mm wide, coating the back of the microneedle membrane with a certain concentration of silk fibroin solution, and then winding the microneedles onto the outer surface of the ureteral stent, and heat-setting it in a 60°C oven for 30 minutes, a composite ureteral stent resistant to protein adhesion can be obtained.

[0106] In summary, the biomimetic antifouling and antiadhesion silk fibroin membrane on the inner surface of this invention can effectively avoid problems such as carbonate deposition, calcification, and adhesion of bacteria and specific proteins on the inner surface. For example, the rough texture formed by the dermal denticles on the surface of the shark skin-inspired silk fibroin membrane can reduce the adhesion area of ​​organisms on the inner side of the ureteral stent, keeping the surface clean. The outer silk fibroin membrane microneedle layer carries anti-stenosis drugs, which can be slowly released into the ureter after implantation to achieve the effect of treating ureteral stenosis. The microneedle structure can carry more drugs and directly penetrate to the stenotic site to achieve the effect of local transdermal drug delivery, which can effectively treat ureteral stenosis. The middle braided layer, as the main part of the ureteral stent, mainly plays a role in mechanical support and drainage, and has excellent mechanical properties. Compared with existing clinical stents, the ureteral stent of this invention does not need to be removed twice after being placed in the body, greatly reducing the patient's pain.

[0107] It should be noted that, in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0108] For those skilled in the art, the specific meaning of the above terms in this invention can be understood according to the specific circumstances. When an element is referred to as being "assembled on," "mounted on," "fixed to," or "set on" another element, it may be directly on the other element or there may be an intermediate element present. When an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be an intermediate element present. The terms "vertical," "horizontal," "upper," "lower," "left," "right," and similar expressions used herein are for illustrative purposes only and do not represent the only possible embodiments.

[0109] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

[0110] In the description of this specification, references to terms such as "an embodiment," "example," "specific example," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this disclosure. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

Claims

1. A ureteral stent resistant to fouling and protein adhesion, comprising: The woven layer serves as a supporting framework. A biomimetic structural layer, which is connected to the inner layer of the braided tube, is used to prevent protein adhesion and biofilm formation. A silk fibroin microneedle layer, wherein the silk fibroin microneedles are connected to the outer layer of the braided tube for carrying anti-stenosis drugs; The biomimetic structural layer is a shark skin-like structure and a lotus leaf-like structure; The biomimetic structural layer is a biomimetic silk fibroin membrane.

2. The ureteral stent with anti-fouling and anti-protein adhesion properties according to claim 1, characterized in that, The braided layer is tubular.

3. The ureteral stent with antifouling and antiprotein adhesion according to claim 2, characterized in that: The braided layer is made of biodegradable polymer monofilaments, including yarns of one or more of polylactic acid (PLA), polydioxanone (PDO), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer (PLGA), and developing yarn.

4. A method for preparing a ureteral stent with antifouling and antiprotein adhesion as described in any one of claims 1 to 3, characterized in that, The specific method is as follows: The braided layer is prepared using a vertical spindle braiding machine; The biomimetic silk fibroin membrane was cut into strips 2mm wide and wrapped around a 2mm thick steel tube. A certain concentration of silk fibroin solution was coated on the outer layer of the biomimetic silk fibroin membrane. The steel tube wrapped with the biomimetic silk fibroin membrane was then placed inside the braided layer and placed in a 60℃ oven for heat setting for 30 minutes. After that, the steel tube was removed. Because the silk fibroin solution has a certain viscosity, the biomimetic silk fibroin membrane can successfully adhere to the inner surface of the bare ureteral stent. The microneedle membrane is cut into strips 2 mm wide. A certain concentration of silk fibroin solution is applied to the back of the microneedle membrane. Then, the microneedles are wound onto the outer surface of the braided layer and placed in a 60°C oven for heat setting for 30 minutes to obtain a ureteral stent that is resistant to fouling and protein adhesion.

5. The method for preparing a ureteral stent with antifouling and antiprotein adhesion according to claim 4, characterized in that, The method for preparing the braided layer is as follows: The yarn is prepared using a vertical spindle braiding machine with a core function, the yarn thickness is 12 tex, the braiding structure is selected as regular 2 / 2 interlacing, the braiding speed is set to 60 rpm, the inner diameter of the braided layer is designed to be 2 mm, and the gear ratio is selected as 82 / 30. After weaving, place the woven layer in an 85℃ oven for heat setting for 15 minutes, then wash it several times in deionized water, and finally dry it.

6. The method for preparing a ureteral stent with antifouling and antiprotein adhesion according to claim 4, characterized in that, The preparation method of the biomimetic silk fibroin membrane is as follows: Degummed silk is dissolved in a 9.3 mol / L lithium bromide solution and placed in a 60℃ oven for 4 hours to ensure complete dissolution. After that, it is dialyzed in pure water for 24-48 hours. Then, the concentration of silk fibroin is diluted or concentrated to obtain a silk fibroin solution with a mass fraction of 3-20%. Polyethylene glycol (PEG) with a mass fraction of 10-90% is added to a silk fibroin solution. First, polydimethylsiloxane and a crosslinking agent are mixed at a ratio of 10:1 w / w to obtain a polydimethylsiloxane (PDMS) solution. Then, shark skin, lotus leaves, or rose petals are obtained and their surfaces are cleaned and dehydrated. After complete dehydration, the PDMS solution is poured into a dry biological structure mold for casting. The mold is then cured in a vacuum oven at 60°C for 3 hours. The biological structure is removed to obtain a negative mold with a biomimetic structure. The prepared silk fibroin solution is then poured into the negative mold and cured in a vacuum oven at 60°C for 3 hours to obtain a biomimetic silk fibroin film.

7. The method for preparing a ureteral stent with antifouling and antiprotein adhesion according to claim 4, characterized in that, The microneedle membrane is prepared as follows: The microneedle array was prepared using a polydimethylsiloxane (PDMS) mold. The mold consisted of an 84×84 conical microneedle array, with each conical microneedle having a height of 400-700µm, a tip diameter of 15µm, a base diameter of 360-380µm, and a final microneedle array area of ​​10cm×10cm. Then, a certain amount of silk fibroin SF, chitosan and sodium hyaluronate mixed solution was prepared. Rapamycin solution with a concentration of 0.5-2 mg / mL and paclitaxel solution with a concentration of 1-3 mg / mL were added to the mixed solution and mixed evenly to obtain microneedle solution. Take 5-15 mL of the prepared microneedle solution and pipette it into the PDMS mold. Perform 6-10 vacuum treatments in a vacuum drying oven to allow the solution to enter the needle cavity and remove any trapped air. Then use a pipette to remove any remaining air bubbles so that the grooves of the PDMS mold are completely filled with the solution. After filling, the mold should be left to dry completely for 18 hours under ambient temperature and humidity conditions.

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