CN114668899A

CN114668899A - Ureteral stent based on bacterial cellulose composite coating and preparation method thereof

Info

Publication number: CN114668899A
Application number: CN202210144587.8A
Authority: CN
Inventors: 杜柘彬; 陈奇; 吕向国
Original assignee: Renji Hospital Shanghai Jiaotong University School of Medicine
Current assignee: Renji Hospital Shanghai Jiaotong University School of Medicine
Priority date: 2022-02-17
Filing date: 2022-02-17
Publication date: 2022-06-28

Abstract

The invention relates to a ureteral stent based on bacterial cellulose composite coating and a preparation method thereof, which comprises the steps of firstly preparing a hollow tubular bacterial cellulose membrane III, then weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III to form a degradable fiber woven tube, finally turning over the hollow tubular bacterial cellulose membrane III from one end to the other end along the length direction to form a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II, and enabling the degradable fiber woven tube to be positioned between two layers of tubular bacterial cellulose membranes, namely preparing the ureteral stent based on bacterial cellulose composite coating; the prepared ureteral stent tube is of a three-layer hollow tubular structure, the middle layer is a degradable fiber braided tube, and the outer layer and the inner layer are respectively a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II. The invention structurally avoids the safety problem caused by falling of degradation fragments, and the prepared ureteral stent has better comprehensive performance.

Description

Ureteral stent based on bacterial cellulose composite coating and preparation method thereof

Technical Field

The invention belongs to the technical field of medical instruments, and relates to a ureteral stent based on bacterial cellulose composite coating and a preparation method thereof.

Background

The ureteral stent is widely applied in urinary surgery, is mainly used for operations such as renal ureteral calculus, hydronephrosis, ureteral tumor, kidney transplantation and the like and expansion treatment of ureteral stenosis, and plays an important role in draining urine, preventing ureteral stenosis and adhesion blockage after being implanted into a ureter. At present, ureteral stent tubes for clinical application are mostly made of silicon rubber or polyurethane polymer composite materials which can not be degraded in human bodies, and have some insurmountable defects in clinical application, such as: the operation of the cystoscope requires no major operation, but the patient suffers pain, and more seriously, the urinary tract tissue is damaged to different degrees during the tube drawing, so that the urinary tract tissue is infected and edematous, and the emergency treatment is often needed.

The retention time of the ureteral stent tube is generally 4 weeks, but the clinically existing ureteral stent tubes are all non-degradable polyurethane stent tubes, and after 4 weeks, a secondary operation is required to take out the stent, so that the urinary tract system of a patient is damaged. For example, long term placement of stent tubes can lead to more serious consequences such as loss of kidney function and even the need to resect the kidney. Brings great physical, mental and economic damage to patients. Non-degradable ureteral stent tubes also often cause complications, and as the indwelling time of the ureteral stent tube is prolonged, these composite materials begin to affect the urothelium and urine components, leading to the formation of coatings, bacterial biofilms around the ureteral stent tube, and infection, all due to foreign body reactions caused by the long-term in vivo use of the non-degradable catheters. In addition, the surface friction coefficient of the silicone rubber ureteral stent is high, the intubation is difficult during the operation, and the silicone rubber ureteral stent is easy to slide after being placed in the body, so that the silicone rubber ureteral stent cannot well meet the requirements of practical application.

Over the past decades, research and clinical applications of degradable urethral and ureteral stents have been developed and are in wider use. The main materials are PLA, PGA and PLLA or PLGA. The degradation time is 2 to 12 months, depending on the material and process. In the earlier research, a single material is adopted, and the obtained stent tube is often difficult to control in degradation time, poor in mechanical property and poor in elasticity. The situation is improved after the composite material is adopted. For example, Chinese patent CN103041454B, a degradable ureteral stent is obtained by using L-lactide/epsilon-caprolactone copolymer and cross-linked polyvinylpyrrolidone as raw materials through blending and extrusion. The wet friction of the surface of the stent tube added with the polyvinylpyrrolidone is greatly reduced, the degradation rate is improved, the degradable components are promoted to be disintegrated into small fragments, and the ureter is prevented from being blocked by the degradable fragments to a certain extent. Chinese patent CN102266594B, two PGA and PGLA fibers with different degradation rates are adopted as raw materials to weave a tube, and chitosan is coated in the tube to obtain a gradually degradable woven ureteral stent. The Chinese patent CN103211671B adds a heat treatment process on the basis of weaving the tube, so that the low-melting-point component in the fiber material of the tube wall is melted into a film, and the film is tightly and uniformly combined with other fiber components in the tube wall to reinforce the tube wall of the weaving tube. The prepared ureteral stent has excellent axial tension and flexibility of a fiber stent and good mechanical support performance of a membrane material stent. In conclusion, these methods solve the problems of gradual degradation and mechanical strength to some extent, but from the structural point of view, the problem of fragment safety with respect to the degradation of the material of the pipe wall still exists. As reported by Boston Scientific, a degradable ureteral drainage system based on bioabsorbable sodium alginate, which will remain for 48 hours before degradation, but faces serious problems in clinical trials of the remaining debris, which have led to the discontinuation of the project. Therefore, in ureteral stent design, it is necessary to avoid this problem fundamentally.

Disclosure of Invention

The invention aims to solve the problems in the prior art and provides a ureteral stent based on bacterial cellulose composite coating and a preparation method thereof.

In order to achieve the purpose, the technical scheme adopted by the invention is as follows:

a ureteral stent based on bacterial cellulose composite coating is of a three-layer hollow tubular structure, wherein a degradable fiber braided tube is arranged in the middle layer, a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II are respectively arranged in the outer layer and the inner layer, and the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II are respectively attached to the inner wall and the outer wall of the degradable fiber braided tube;

the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II are formed by folding a hollow tubular bacterial cellulose membrane III from one end to the other end along the length direction, and the length of the tubular bacterial cellulose membrane I is half of that of the hollow tubular bacterial cellulose membrane III.

The material for coating the degradable fiber braided tube is Bacterial Cellulose (BC), is a natural nanofiber material obtained by Bacterial fermentation, and has great application potential in the field of biomedicine. BC is very similar to natural plant cellulose in chemical composition and fiber structure, and is connected by glucose group in beta-1, 4-glycosidic bond to form main chain and polymerized to form polymer. However, the BC is highly pure and free of lignin, pectin, hemicellulose and other associated products. During static culture, the BC forms a three-dimensional hydrogel film with a nanofiber bundle with random coils, and the water content can reach more than 99%. The strength and the tear resistance of the BC are extremely strong, and the elastic modulus can reach dozens of times of that of common plant fibers; the BC has higher mechanical strength, high tensile strength and elastic modulus; the large amount of hydroxyl groups on the surface of the nano-fiber enables the bacterial cellulose to have high water-holding capacity and high wet strength. The BC has good biocompatibility and biodegradability, has good cell compatibility to various cells, and can promote the proliferation and growth of the cells.

As a preferable technical scheme:

according to the ureteral stent based on bacterial cellulose composite coating, the outward surface of the tubular bacterial cellulose membrane I is provided with a plurality of rectangular grooves (the shape of the grooves includes but is not limited to a rectangle, and can also be a semicircle, a cone and the like) which are uniformly arranged in parallel, the length direction of the rectangular grooves is parallel to the axial direction of the tubular bacterial cellulose membrane I, so that the surface friction when the tubular bacterial cellulose membrane I is inserted into and pulled out of a urethra can be reduced, and the surface of the tubular bacterial cellulose membrane II is smooth.

According to the ureteral stent based on bacterial cellulose composite coating, the degradable fiber braided tube is obtained by adopting a diamond braiding or regular braiding method for degradable fibers capable of slowly releasing functional substances, and the wall thickness of the tube wall can be properly reduced by adopting the diamond braiding or regular braiding method;

the degradable fiber capable of slowly releasing the functional substances is a blended fiber of a synthetic fiber and a chitosan fiber, the synthetic fiber is a PLA fiber, a PLGA fiber, a PGA fiber, a PCL fiber or a polydioxanone fiber, the synthetic fiber contains silver ions or nano silver particles, and the chitosan fiber contains copper ions and zinc ions.

According to the ureteral stent compositely coated with the bacterial cellulose, the content of chitosan fibers in the degradable fibers capable of slowly releasing functional substances is 3-15 wt%;

The content of zinc ions is 0.1-5 wt% of the chitosan fiber, and the molar ratio of the zinc ions to the copper ions is 2: 1-1.4; the content of silver ions or nano silver particles is 0.1-2 wt% of the chitosan fiber.

Zinc ion (Zn)²⁺) As an essential component of enzymes that maintain structural integrity of proteins and regulate gene expression, participate in the regulation of immunity, cell growth and migration, and play a key role in tissue healing, it is required that zinc ions be able to penetrate the entire tissue healing process and meet the requirement of a greater amount of release at the early stage and also have a better sustained release capacity at the middle and later stages. Copper ion (Cu) in the anaphase of proliferation and remodeling in tissue healing²⁺) Can induce the expression of vascular endothelial growth factor, promote angiogenesis and maintain the stability of collagen. The silver ions or the nano silver particles have good antibacterial effect.

According to the ureteral stent based on bacterial cellulose composite coating, the length of each rectangular groove is equal to that of the tubular bacterial cellulose membrane I, the width of each rectangular groove is 50-200 nm, the height of each rectangular groove is 50-100 nm, and the distance between every two adjacent rectangular grooves is 50-200 nm. The size of the rectangular groove is set according to the experience of the existing research, the micro-nano scale can be identified by endothelial cells, and the endothelial cells can grow and rapidly proliferate along the groove, so that the rapid endothelialization is achieved, and the generation of scar tissues is reduced.

The ureteral stent based on bacterial cellulose composite coating has the advantages that the length of the ureteral stent is 15-40 cm, and the diameter of the ureteral stent is 1.5-3.5 mm; the wall thickness of the ureteral stent tube is 0.1-0.5 mm, the wall thickness of the degradable fiber woven tube in the middle layer is 0.08-0.45 mm, the wall thickness of the tubular bacterial cellulose membrane I is the same as that of the tubular bacterial cellulose membrane II, and the thickness of the tubular bacterial cellulose membrane I is 0.02-0.2 mm generally.

The invention also provides a preparation method of the ureteral stent based on the bacterial cellulose composite coating, which comprises the steps of firstly preparing a hollow tubular bacterial cellulose membrane III, then weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III to form a degradable fiber woven tube, finally turning over the hollow tubular bacterial cellulose membrane III from one end to the other end along the length direction to form a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II, and enabling the degradable fiber woven tube to be positioned between the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II, thus obtaining the ureteral stent based on the bacterial cellulose composite coating;

the weaving area of the degradable fiber is the outer wall of the tubular bacterial cellulose membrane II.

As a preferable technical scheme:

According to the method, the specific preparation steps of the ureteral stent based on the bacterial cellulose composite coating are as follows:

(1) uniformly mixing the fermentation strain with a fermentation culture solution, putting the mixture into a hollow tubular fermentation device, fermenting for 5-9 days, and purifying to obtain a hollow tubular bacterial cellulose membrane III; the hollow tubular fermentation device is a double-layer jacketed pipe, the inner layer is oxygen permeability (the test standard of the oxygen permeability is GB/T1038-⁵cm³A silica gel film of 24 h.0.1 MPa, wherein the fermentation strain and the fermentation culture solution are arranged between two layers of a hollow tubular fermentation device, the inner layer of the hollow tubular fermentation device is filled with mixed gas, and the pressure of the mixed gasThe force is 1.1 to 1.5 x 10⁵Pa, the volume ratio of oxygen in the mixed gas is 25-40% (the set purpose is that 1, the fermentation strain is oxygen consuming bacteria and can improve the fermentation speed under the condition of sufficient oxygen, 2, the mixed gas is adopted mainly because other gases in the mixed gas are inert gases and the like in consideration of cost and benefit, 3, the oxygen can better pass through the silica gel film by keeping a certain pressure, and simultaneously, the bacterial cellulose nano-fiber obtained by fermentation is more compact and has a smooth surface at the part contacted with the silica gel film); dividing the hollow tubular fermentation device into A, B hollow tubular objects, wherein the silica gel film on the inner layer of the hollow tubular object A has a smooth surface, and the outward surface of the silica gel film on the inner layer of the hollow tubular object B has a patterned structure; the patterning structure is formed by adopting a micro/nano forming patterning technology, a plurality of rectangular bulges are formed on the surface of the silica gel film and are uniformly arranged in parallel along the axial direction of the hollow tubular object B, the length of each rectangular bulge is equal to the length of the hollow tubular object B, the width of each rectangular bulge is 50-200 nm, the height of each rectangular bulge is 50-100 nm, and the distance between every two adjacent rectangular bulges is 50-200 nm;

(2) Placing a polytetrafluoroethylene rod in the purified hollow tubular bacterial cellulose membrane III (because pure bacterial cellulose is similar to hydrogel-shaped material, the polytetrafluoroethylene rod is used for supporting), weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III under the support of the polytetrafluoroethylene rod, and forming a degradable fiber woven tube on the hollow tubular bacterial cellulose membrane III;

(3) folding the hollow tubular bacterial cellulose membrane III from one end to the other end along the length direction, so that the degradable fiber woven tube is coated in the middle to form a three-layer composite tubular object, wherein the outer layer of the three-layer composite tubular object is a tubular bacterial cellulose membrane I, the inner layer of the three-layer composite tubular object is a tubular bacterial cellulose membrane II, and the outer wall of the tubular bacterial cellulose membrane I is provided with the rectangular groove;

(4) and sterilizing the obtained three-layer composite tubular object to obtain the bacterial cellulose composite coated ureteral stent.

The fermentation strain is Acetobacter xylinum, Rhizobium, Sarcina, Pseudomonas, Achromobacter, or the likeMore than one of bacillus, alcaligenes, aerobacter and azotobacter; the density of the fermentation strain added into the fermentation culture solution is 10 ¹⁰～10¹³The density is too low or too high, which affects the production efficiency;

the formula of the fermentation culture solution is as follows: every 100ml of the yeast extract contains 5-30 g of glucose, 1-5 g of peptone, 1-5 g of yeast extract, 0.5-2 g of citric acid, 0.2-5 g of sodium dihydrogen phosphate, 3-5 g of magnesium sulfate, 3-5 g of sodium alginate and the balance of water; the pH value of the fermentation culture solution is 4.0-6.0.

As mentioned above, the purification treatment is to soak the fermentation product in 3-10 wt% sodium hydroxide solution, keep the fermentation product at 30-100 ℃ for 3-24 hours, and then wash the fermentation product with water until the pH value is 7.0. A large number of researches prove that the purity of the bacterial cellulose membrane subjected to sodium hydroxide purification treatment can reach more than 99 percent, and the bacterial cellulose membrane has good biological safety and can be applied to the field of biomedicine.

The principle of the invention is as follows:

in combination with current research and demand, we believe that an ideal ureteral stent should have the following properties: 1. the urine drainage has certain mechanical support to prevent the ureter from being narrow and blocked due to adhesion; 2. the controllable degradation performance can avoid the safety problem caused by degradation fragments from the structural design angle; 3. the surface wet friction coefficient is low, so that the ureteral stent is easy to implant and take out, and the discomfort of a patient is reduced; 4. in one month after the ureteral stent is placed, about 1/3 patients can suffer from urinary tract infection, so that the ideal ureteral stent has long-acting antibacterial property, broad-spectrum antibacterial property and low drug resistance; 5. the ureteral stent is used for replacing the function of a ureter to temporarily drain and support, and has great practical significance if the ureter can be promoted to heal through a ureteral stent tube.

According to the invention, the bacterial cellulose and the degradable fiber braided tube capable of slowly releasing the functional substances are compounded to obtain the ureteral stent based on the bacterial cellulose composite coating. Compared with the traditional stent tube, the stent tube obtained by adopting the fiber weaving method has better mechanical property, and can reduce the usage amount of materials and the wall thickness of the tube wall. The biggest problem restricting the use of the degradable ureteral stent at present is uncontrollable risk caused by material degradation and falling off when the stent is used in vivo, but the invention uses bacterial cellulose with good biocompatibility in vivo to carry out surface compounding on the degradable braided tube, and one end of the hollow tubular bacterial cellulose membrane along the length direction is folded towards the other end, thereby forming inner and outer coatings on the degradable fiber braided tube. After the degradable braided tube is implanted into a body, when the degradable braided tube in the middle layer is degraded in the body, the degradable fragments can be prevented from falling off and directly entering the body due to the compact structure formed by the bacterial cellulose three-dimensional nano-fiber, and the requirement on safety is met. The surface patterning design of the outer-layer tubular bacterial cellulose reduces the surface friction (on one hand, the surface pattern is along the axial direction, and is more beneficial to the entering of a ureteral stent tube when being inserted into a urethra, and on the other hand, the surface patterning structure after being implanted is more beneficial to the growth of surface cells, so that the formation of scar tissues by fibroblasts is inhibited, and the surface friction is reduced when being pulled out more easily), and the ureteral healing can be promoted. In addition, the functional ions slowly released by the degradable fibers have the functions of antibiosis, immunoregulation and the like.

Has the advantages that:

(1) according to the ureteral stent based on bacterial cellulose composite coating, the bacterial cellulose is used for coating the braided tube, so that the safety problem caused by falling of degradation fragments is structurally avoided, and the ureteral stent has good practical significance;

(2) the preparation method of the ureteral stent based on bacterial cellulose composite coating is simple and feasible, and can be used for industrial production, and the prepared ureteral stent has better comprehensive performance and can meet various requirements.

Drawings

FIG. 1 is a structural schematic diagram of a bacterial cellulose composite coating-based ureteral stent pipe of the invention;

FIG. 2 is a schematic view of a hollow tubular bacterial cellulose membrane III folded and coated with a degradable fiber braided tube;

FIG. 3 is a schematic drawing of the surface patterning of a tubular bacterial cellulose membrane I (with a plurality of parallel uniformly arranged rectangular grooves);

fig. 4 is a result of an ion release performance test of a ureteral stent based on a bacterial cellulose composite coating prepared in example 1;

wherein, 1-outer layer, 2-middle layer, 3-inner layer, and 4-hollow tubular bacterial cellulose membrane III.

Detailed Description

The invention will be further illustrated with reference to specific embodiments. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.

Example 1

A preparation method of a ureteral stent based on bacterial cellulose composite coating comprises the following specific steps:

(1) uniformly mixing a fermentation strain (acetobacter xylinum) with a fermentation culture solution (every 100ml of the fermentation culture solution contains 5g of glucose, 1g of peptone, 1g of yeast extract, 0.5g of citric acid, 0.2g of sodium dihydrogen phosphate, 3g of magnesium sulfate, 3g of sodium alginate and the balance of water), putting the mixture into a hollow tubular fermentation device, fermenting for 5 days, and then performing purification treatment (namely soaking a fermentation product into a sodium hydroxide solution with the mass concentration of 3 wt%, keeping the fermentation product at the temperature of 100 ℃ for 3 hours, and then washing the fermentation product with water until the pH value is 7.0) to obtain a hollow tubular bacterial cellulose membrane III; wherein the density of fermentation strain added into the fermentation culture solution is 10¹⁰Per ml; the hollow tubular fermentation device is a double-layer jacketed pipe, and the inner layer has oxygen permeability of 1 multiplied by 10⁵cm³A silica gel film of 24 h.0.1 MPa, the fermentation strain and the fermentation culture solution are placed between two layers of a hollow tubular fermentation device, and the hollow tubular fermentation device is used for hollow tubular fermentationThe inner layer of the device is filled with mixed gas with pressure of 1.1 × 10⁵Pa, the volume ratio of oxygen in the mixed gas is 25%, and the balance is argon; dividing the hollow tubular fermentation device into A, B hollow tubular objects, wherein the silica gel film on the inner layer of the hollow tubular object A has a smooth surface, and the outward surface of the silica gel film on the inner layer of the hollow tubular object B has a patterned structure; the patterning structure is formed by adopting a micro/nano forming patterning technology, a plurality of rectangular bulges which are uniformly arranged in parallel along the axial direction of the hollow tubular object B are formed on the surface of the silica gel film, the distance between every two adjacent rectangular bulges is 50nm, the length of each rectangular bulge is equal to the length of the hollow tubular object B, the width of each rectangular bulge is 50nm, and the height of each rectangular bulge is 50 nm;

(2) Placing a polytetrafluoroethylene rod in a purified hollow tubular bacterial cellulose membrane III, weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III by adopting a rhombic weaving method under the support of the polytetrafluoroethylene rod, wherein the weaving area is all areas between one end and half length of the hollow tubular bacterial cellulose membrane III along the length direction, and thus a degradable fiber weaving pipe is formed on the hollow tubular bacterial cellulose membrane III; the degradable fibers are blended fibers of PLA fibers containing silver ions and chitosan fibers containing copper ions and zinc ions, the content of the chitosan fibers in the blended fibers is 3 wt%, the content of the zinc ions is 0.1 wt% of the chitosan fibers, and the molar ratio of the zinc ions to the copper ions is 2: 1; the content of silver ions is 0.8 wt% of the chitosan fiber;

(3) as shown in fig. 2, a hollow tubular bacterial cellulose membrane iii 4 is folded from one end to the other end along the length direction, so that the degradable fiber woven tube is coated in the middle to form a three-layer composite tubular object;

(4) and (4) sterilizing the three-layer composite tubular object obtained in the step (3) to obtain the bacterial cellulose composite coating-based ureteral stent.

The finally prepared ureteral stent based on the bacterial cellulose composite coating is of a three-layer hollow tubular structure as shown in figure 1, the length of the ureteral stent is 15cm, the diameter of the ureteral stent is 1.5mm, the thickness of the tube wall is 0.1mm, the middle layer 2 is a degradable fiber braided tube with the wall thickness of 0.08mm, the outer layer 1 and the inner layer 3 are respectively a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II with the same wall thickness, and the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II are respectively attached to the inner wall and the outer wall of the degradable fiber braided tube; the length of the tubular bacterial cellulose membrane I is half of that of the hollow tubular bacterial cellulose membrane III; as shown in FIG. 3, the outward surface of the tubular bacterial cellulose membrane I is provided with a plurality of rectangular grooves which are uniformly arranged in parallel, the length direction of each rectangular groove is parallel to the axial direction of the tubular bacterial cellulose membrane I, the distance between every two adjacent rectangular grooves is 50nm, the length of each rectangular groove is 7.5cm, the width of each rectangular groove is 50nm, and the height of each rectangular groove is 50 nm.

And (3) related performance detection:

and (3) detecting biocompatibility: referring to the biological evaluation of GB/T16886 medical instruments, the bacterial cellulose composite-coated ureteral stent tube of the final product is evaluated for cytotoxicity, delayed contact sensitization of guinea pigs, skin irritation and the like. The evaluation method is as follows: intracellular toxicity test according to GB/T16886-5, part 5 of the biological evaluation of medical devices: in vitro cytotoxicity test "; guinea pig delayed contact sensitization test according to GB/T16886-10, part 10 of the biological evaluation of medical devices: stimulation and delayed type hypersensitivity tests were performed using the Magnus method and the Kligman method for the maximum tests. Skin irritation test according to GB/T16886-10, part 10 of the biological evaluation of medical devices: stimulation and delayed type hypersensitivity tests. Evaluation results were as follows: the ureteral stent based on the bacterial cellulose composite coating prepared in the embodiment 1 has cytotoxicity lower than 1 level, no skin sensitization reaction and no skin irritation reaction, and has good biological safety.

In vitro degradation experiments: the artificial urine formula is prepared according to YY/T0872-2013 ureteral stent experimental method, appendix A and formula 1. The ureteral stent tube based on bacterial cellulose composite coating prepared in the embodiment 1 is sterilized and then placed into simulated urine, an in-vitro simulated degradation test is carried out in a constant-temperature constant-speed shaking table at 37 ℃ and 60r/min, and the degradation condition of the ureteral stent tube within 5 weeks is observed. The results show that the tubular structure of the test sample is completely degraded in 4 weeks, wherein the loosening and breaking of the fiber woven structure begin to occur in the middle layer 2 at 3 weeks, and further the condition that the degraded fibrous material is wrapped between the outer layer 1 and the inner layer 3 and no degradation fragments are released is observed, which indicates that the safety problem caused by the falling of the degradation fragments is structurally avoided by the invention.

Ion release performance test: the content of silver ions, zinc ions and copper ions released by the sample in the simulated urine is tested by an atomic absorption spectrometer, and the test lasts for 12 days. The test time points are 6h, 12h, 18h, 24h, 48h, 96h, 144h, 192h, 240h and 288h respectively. The ion release rate is the ion content in the simulated urine/the total ion content in the sample at different time points, and the test result is shown in fig. 4, which shows that the ureteral stent tube of the invention can continuously and effectively release a plurality of ions. Wherein the silver ions can provide lasting effective antibacterial performance; the zinc ions can penetrate through the whole tissue healing process, and meet the requirement of releasing a large amount in the early stage and have better sustained release capability in the middle and later stages; copper ion (Cu) in the anaphase of proliferation and remodeling in tissue healing ²⁺) Can induce the expression of vascular endothelial growth factor, promote angiogenesis and maintain the stability of collagen.

And (3) detecting the antibacterial performance: the ureteral stent based on bacterial cellulose composite coating prepared in the embodiment 1 is tested by adopting AATCC-100 for antibacterial performance, and the antibacterial rate is 99%; after 21 days of continuous use, the antibacterial performance of the product is tested by adopting AATCC-100, and the antibacterial rate is 99%. The test strains are escherichia coli and staphylococcus aureus.

Example 2

(1) uniformly mixing a fermentation strain (rhizobium) and a fermentation culture solution (each 100ml of the fermentation culture solution contains 5g of glucose, 1g of peptone, 1g of yeast extract, 0.5g of citric acid, 0.2g of sodium dihydrogen phosphate, 3g of magnesium sulfate, 3g of sodium alginate and the balance of water), putting the mixture into a hollow tubular fermentation device, and performing purification treatment (namely fermentation) after fermenting for 5 daysSoaking the product into a sodium hydroxide solution with the mass concentration of 4 wt%, keeping the solution at the temperature of 80 ℃ for 3 hours, and then washing the solution with water until the pH value is 7.0) to obtain a hollow tubular bacterial cellulose membrane III; wherein the density of fermentation strain added into the fermentation culture solution is 5 × 10 ¹⁰Per ml; the hollow tubular fermentation device is a double-layer jacketed pipe, and the inner layer has oxygen permeability of 1.2 multiplied by 10⁵cm³A silica gel film with 24 h.0.1 MPa, wherein the fermentation strain and the fermentation culture solution are arranged between two layers of a hollow tubular fermentation device, the inner layer of the hollow tubular fermentation device is filled with mixed gas, and the pressure of the mixed gas is 1.1 × 10⁵Pa, the volume ratio of oxygen in the mixed gas is 25%, and the balance is argon; dividing the hollow tubular fermentation device into A, B hollow tubular objects, wherein the silica gel film on the inner layer of the hollow tubular object A has a smooth surface, and the outward surface of the silica gel film on the inner layer of the hollow tubular object B has a patterned structure; the patterning structure is formed by adopting a micro/nano forming patterning technology, a plurality of rectangular bulges which are uniformly arranged in parallel along the axial direction of the hollow tubular object B are formed on the surface of the silica gel film, the distance between every two adjacent rectangular bulges is 50nm, the length of each rectangular bulge is equal to the length of the hollow tubular object B, the width of each rectangular bulge is 50nm, and the height of each rectangular bulge is 60 nm;

(2) placing a polytetrafluoroethylene rod in a purified hollow tubular bacterial cellulose membrane III, weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III by adopting a rhombus weaving method under the support of the polytetrafluoroethylene rod, wherein the weaving area is all areas between one end of the hollow tubular bacterial cellulose membrane III along the length direction and half of the length, and thus forming a degradable fiber weaving pipe on the hollow tubular bacterial cellulose membrane III; the degradable fiber is a blended fiber of PLGA fiber containing silver ions and chitosan fiber containing copper ions and zinc ions, the content of the chitosan fiber in the blended fiber is 4 wt%, the content of the zinc ions is 0.3 wt% of the chitosan fiber, and the molar ratio of the zinc ions to the copper ions is 2: 1; the content of silver ions is 1.1 wt% of the chitosan fiber;

(3) Folding the hollow tubular bacterial cellulose membrane III from one end to the other end along the length direction to ensure that the degradable fiber woven tube is coated in the middle to form a three-layer composite tubular object;

The finally prepared ureteral stent based on the bacterial cellulose composite coating is of a three-layer hollow tubular structure, the length of the ureteral stent is 20cm, the diameter of the ureteral stent is 1.5mm, the thickness of the wall of the tube is 0.1mm, the middle layer of the ureteral stent is a degradable fiber braided tube with the wall thickness of 0.10mm, the outer layer and the inner layer are respectively a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II with the same wall thickness, and the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II are respectively attached to the inner wall and the outer wall of the degradable fiber braided tube; the length of the tubular bacterial cellulose membrane I is half of that of the hollow tubular bacterial cellulose membrane III; the outward surface of the tubular bacterial cellulose membrane I is provided with a plurality of rectangular grooves which are uniformly arranged in parallel, the length direction of each rectangular groove is parallel to the axial direction of the tubular bacterial cellulose membrane I, the distance between every two adjacent rectangular grooves is 50nm, the length of each rectangular groove is 10cm, the width of each rectangular groove is 50nm, and the height of each rectangular groove is 60 nm.

Example 3

(1) uniformly mixing a fermentation strain (sarcina and acetobacter xylinum, the number ratio of the two strains is 1:1) and a fermentation culture solution (each 100ml of the fermentation culture solution contains 10g of glucose, 2g of peptone, 2g of yeast extract, 1g of citric acid, 0.8g of sodium dihydrogen phosphate, 3.4g of magnesium sulfate, 3g of sodium alginate and the balance of water), putting the mixture into a hollow tubular fermentation device, fermenting for 6 days, and then performing purification treatment (namely soaking a fermentation product into a sodium hydroxide solution with the mass concentration of 5 wt%, keeping the fermentation product at the temperature of 70 ℃ for 6 hours, and then washing the fermentation product with water until the pH value is 7.0) to obtain a hollow tubular bacterial cellulose membrane III; wherein the density of fermentation strain added into the fermentation culture solution is 8 × 10¹⁰Per ml; the hollow tubular fermentation device is a double-layer jacketed pipe, and the inner layer has oxygen permeability of 2.4 multiplied by 10⁵cm³A silica gel film of 24 h.0.1 MPa, a fermentation strain and a fermentation culture solution are placed in a hollow tubular shape for fermentationThe inner layer of the hollow tubular fermentation device is filled with mixed gas between the two layers of the device, and the pressure of the mixed gas is 1.2 multiplied by 10⁵Pa, the volume ratio of oxygen in the mixed gas is 28 percent, and the balance is argon; dividing the hollow tubular fermentation device into A, B hollow tubular objects, wherein the silica gel film on the inner layer of the hollow tubular object A has a smooth surface, and the outward surface of the silica gel film on the inner layer of the hollow tubular object B has a patterned structure; the patterning structure is formed by adopting a micro/nano forming patterning technology, a plurality of rectangular bulges which are uniformly arranged in parallel along the axial direction of the hollow tubular object B are formed on the surface of the silica gel film, the distance between every two adjacent rectangular bulges is 80nm, the length of each rectangular bulge is equal to the length of the hollow tubular object B, the width of each rectangular bulge is 60nm, and the height of each rectangular bulge is 60 nm;

(2) Placing a polytetrafluoroethylene rod in a purified hollow tubular bacterial cellulose membrane III, weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III by adopting a rhombus weaving method under the support of the polytetrafluoroethylene rod, wherein the weaving area is all areas between one end of the hollow tubular bacterial cellulose membrane III along the length direction and half of the length, and thus forming a degradable fiber weaving pipe on the hollow tubular bacterial cellulose membrane III; the degradable fibers are blended fibers of PGA fibers containing silver ions and chitosan fibers containing copper ions and zinc ions, the content of the chitosan fibers in the blended fibers is 6 wt%, the content of the zinc ions is 0.8 wt% of the chitosan fibers, and the molar ratio of the zinc ions to the copper ions is 2: 1.2; the content of silver ions is 1.4 wt% of the chitosan fiber;

(3) folding the hollow tubular bacterial cellulose membrane III from one end to the other end along the length direction to coat the degradable fiber woven tube in the middle to form a three-layer composite tubular object;

(4) and (4) sterilizing the three-layer composite tubular object obtained in the step (3) to obtain the ureteral stent based on bacterial cellulose composite coating.

The finally prepared ureteral stent based on the bacterial cellulose composite coating is of a three-layer hollow tubular structure, the length of the ureteral stent is 30cm, the diameter of the ureteral stent is 2.0mm, the thickness of the tube wall is 0.2mm, the middle layer of the ureteral stent is a degradable fiber braided tube with the wall thickness of 0.15mm, the outer layer and the inner layer are respectively a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II with the same wall thickness, and the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II are respectively attached to the inner wall and the outer wall of the degradable fiber braided tube; the length of the tubular bacterial cellulose membrane I is half of that of the hollow tubular bacterial cellulose membrane III; the outward surface of the tubular bacterial cellulose membrane I is provided with a plurality of rectangular grooves which are uniformly arranged in parallel, the length direction of each rectangular groove is parallel to the axial direction of the tubular bacterial cellulose membrane I, the distance between every two adjacent rectangular grooves is 80nm, the length of each rectangular groove is 15cm, the width of each rectangular groove is 60nm, and the height of each rectangular groove is 60 nm.

Example 4

(1) uniformly mixing a fermentation strain (pseudomonas) with a fermentation culture solution (each 100ml of the fermentation culture solution contains 10g of glucose, 2g of peptone, 2g of yeast extract, 1g of citric acid, 1.2g of sodium dihydrogen phosphate, 3.6g of magnesium sulfate, 4g of sodium alginate and the balance of water), putting the mixture into a hollow tubular fermentation device, fermenting for 8 days, and then performing purification treatment (namely soaking a fermentation product into a sodium hydroxide solution with the mass concentration of 6 wt%, keeping the fermentation product at the temperature of 60 ℃ for 6 hours, and then washing the fermentation product with water until the pH value is 7.0) to obtain a hollow tubular bacterial cellulose membrane III; wherein the density of fermentation strain added into the fermentation culture solution is 2 × 10¹¹Per ml; the hollow tubular fermentation device is a double-layer jacketed pipe, and the inner layer has oxygen permeability of 4 multiplied by 10⁵cm³A silica gel film of 24 h.0.1 MPa, wherein the fermentation strain and the fermentation culture solution are arranged between two layers of a hollow tubular fermentation device, the inner layer of the hollow tubular fermentation device is filled with mixed gas, and the pressure of the mixed gas is 1.2 multiplied by 10⁵Pa, the volume ratio of oxygen in the mixed gas is 30 percent, and the balance is argon; dividing the hollow tubular fermentation device into A, B hollow tubular objects, wherein the silica gel film on the inner layer of the hollow tubular object A has a smooth surface, and the outward surface of the silica gel film on the inner layer of the hollow tubular object B has a patterned structure; the patterned structure refers to a plurality of hollow tubular objects B formed on the surface of the silica gel film by adopting a micro/nano forming patterning technology Rectangular bulges are axially and uniformly arranged in parallel, the distance between every two adjacent rectangular bulges is 100nm, the length of each rectangular bulge is equal to the length of the hollow tubular object B, the width of each rectangular bulge is 80nm, and the height of each rectangular bulge is 80 nm;

(2) placing a polytetrafluoroethylene rod in a purified hollow tubular bacterial cellulose membrane III, weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III by adopting a rhombus weaving method under the support of the polytetrafluoroethylene rod, wherein the weaving area is all areas between one end of the hollow tubular bacterial cellulose membrane III along the length direction and half of the length, and thus forming a degradable fiber weaving pipe on the hollow tubular bacterial cellulose membrane III; the degradable fibers are blend fibers of PCL fibers containing silver ions and chitosan fibers containing copper ions and zinc ions, the content of the chitosan fibers in the blend fibers is 7.5 wt%, the content of the zinc ions is 1.2 wt% of the chitosan fibers, and the molar ratio of the zinc ions to the copper ions is 2: 1.2; the content of silver ions is 2 wt% of the chitosan fiber;

The finally prepared ureteral stent based on bacterial cellulose composite coating is of a three-layer hollow tubular structure, the length is 30cm, the diameter is 2.0mm, the thickness of the tube wall is 0.2mm, the middle layer is a degradable fiber braided tube with the wall thickness of 0.2mm, the outer layer and the inner layer are respectively a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II with the same wall thickness, and the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II are respectively attached to the inner wall and the outer wall of the degradable fiber braided tube; the length of the tubular bacterial cellulose membrane I is half of that of the hollow tubular bacterial cellulose membrane III; the outward surface of the tubular bacterial cellulose membrane I is provided with a plurality of rectangular grooves which are uniformly arranged in parallel, the length directions of the rectangular grooves are parallel to the axial direction of the tubular bacterial cellulose membrane I, the distance between every two adjacent rectangular grooves is 100nm, the length of each rectangular groove is 15cm, the width of each rectangular groove is 80nm, and the height of each rectangular groove is 80 nm.

Example 5

(1) uniformly mixing a fermentation strain (achromobacter) and a fermentation culture solution (each 100ml of the fermentation culture solution contains 16g of glucose, 3g of peptone, 3g of yeast extract, 1.2g of citric acid, 2.4g of sodium dihydrogen phosphate, 4.1g of magnesium sulfate, 4g of sodium alginate and the balance of water), putting the mixture into a hollow tubular fermentation device, and performing purification treatment after 9 days of fermentation (namely soaking a fermentation product into a sodium hydroxide solution with the mass concentration of 7 wt%, keeping the fermentation product at the temperature of 50 ℃ for 8 hours, and then washing the fermentation product with water until the pH value is 7.0) to obtain a hollow tubular bacterial cellulose membrane III; wherein the density of fermentation strain added into the fermentation culture solution is 6 × 10 ¹¹Per ml; the hollow tubular fermentation device is a double-layer jacketed pipe, and the inner layer has oxygen permeability of 6 multiplied by 10⁵cm³A silica gel film of 24 h.0.1 MPa, wherein the fermentation strain and the fermentation culture solution are arranged between two layers of a hollow tubular fermentation device, the inner layer of the hollow tubular fermentation device is filled with mixed gas, and the pressure of the mixed gas is 1.2 multiplied by 10⁵Pa, the volume ratio of oxygen in the mixed gas is 32 percent, and the balance is argon; dividing the hollow tubular fermentation device into A, B hollow tubular objects, wherein the silica gel film on the inner layer of the hollow tubular object A has a smooth surface, and the outward surface of the silica gel film on the inner layer of the hollow tubular object B has a patterned structure; the patterning structure is formed by adopting a micro/nano forming patterning technology, a plurality of rectangular bulges which are uniformly arranged in parallel along the axial direction of the hollow tubular object B are formed on the surface of the silica gel film, the distance between every two adjacent rectangular bulges is 120nm, the length of each rectangular bulge is equal to the length of the hollow tubular object B, the width of each rectangular bulge is 100nm, and the height of each rectangular bulge is 80 nm;

(2) placing a polytetrafluoroethylene rod in a purified hollow tubular bacterial cellulose membrane III, weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III by adopting a regular weaving method under the support of the polytetrafluoroethylene rod, wherein the weaving area is all areas between one end of the hollow tubular bacterial cellulose membrane III along the length direction and half of the length, and thus forming a degradable fiber weaving pipe on the hollow tubular bacterial cellulose membrane III; the degradable fiber is a blend fiber of PLA fiber containing nano silver particles and chitosan fiber containing copper ions and zinc ions, the content of the chitosan fiber in the blend fiber is 8 wt%, the content of the zinc ions is 1.5 wt% of the chitosan fiber, and the molar ratio of the zinc ions to the copper ions is 2: 1.2; the content of the nano silver particles is 0.1 wt% of the chitosan fiber;

The finally prepared ureteral stent based on the bacterial cellulose composite coating is of a three-layer hollow tubular structure, the length of the ureteral stent is 35cm, the diameter of the ureteral stent is 2.5mm, the thickness of the tube wall is 0.3mm, the middle layer of the ureteral stent is a degradable fiber braided tube with the wall thickness of 0.25mm, the outer layer and the inner layer are respectively a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II with the same wall thickness, and the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II are respectively attached to the inner wall and the outer wall of the degradable fiber braided tube; the length of the tubular bacterial cellulose membrane I is half of that of the hollow tubular bacterial cellulose membrane III; the outward surface of the tubular bacterial cellulose membrane I is provided with a plurality of rectangular grooves which are uniformly arranged in parallel, the length directions of the rectangular grooves are parallel to the axial direction of the tubular bacterial cellulose membrane I, the distance between every two adjacent rectangular grooves is 120nm, the length of each rectangular groove is 17.5cm, the width of each rectangular groove is 100nm, and the height of each rectangular groove is 80 nm.

Example 6

(1) mixing fermentation strains (alcaligenes, rhizobium and acetobacter xylinum, the number ratio of the three strains is 1:1:1) with fermentation culture solution (each 100ml of the fermentation culture solution contains 18g of glucose, 4g of peptone, 4g of yeast extract, 1.5g of citric acid and 4.2g of phosphorusSodium dihydrogen acid, 4.5g magnesium sulfate, 4g sodium alginate and the balance of water) are uniformly mixed, put into a hollow tubular fermentation device, and are fermented for 9 days, and then are purified (namely, a fermentation product is soaked into a sodium hydroxide solution with the mass concentration of 8 wt%, kept for 10 hours at the temperature of 40 ℃, and then washed by water until the pH value is 7.0) to obtain a hollow tubular bacterial cellulose membrane III; wherein the density of fermentation strain added into the fermentation culture solution is 10¹²Per ml; the hollow tubular fermentation device is a double-layer jacketed pipe, and the inner layer has oxygen permeability of 8 multiplied by 10⁵cm³A silica gel film of 24 h.0.1 MPa, wherein the fermentation strain and the fermentation culture solution are arranged between two layers of a hollow tubular fermentation device, the inner layer of the hollow tubular fermentation device is filled with mixed gas, and the pressure of the mixed gas is 1.3 multiplied by 10⁵Pa, the volume ratio of oxygen in the mixed gas is 36 percent, and the balance is argon; dividing the hollow tubular fermentation device into A, B hollow tubular objects, wherein the silica gel film on the inner layer of the hollow tubular object A has a smooth surface, and the outward surface of the silica gel film on the inner layer of the hollow tubular object B has a patterned structure; the patterning structure is formed by adopting a micro/nano forming patterning technology, a plurality of rectangular bulges which are uniformly arranged in parallel along the axial direction of the hollow tubular object B are formed on the surface of the silica gel film, the distance between every two adjacent rectangular bulges is 150nm, the length of each rectangular bulge is equal to the length of the hollow tubular object B, the width of each rectangular bulge is 100nm, and the height of each rectangular bulge is 90 nm;

(2) Placing a polytetrafluoroethylene rod in a purified hollow tubular bacterial cellulose membrane III, weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III by adopting a regular weaving method under the support of the polytetrafluoroethylene rod, wherein the weaving area is all areas between one end of the hollow tubular bacterial cellulose membrane III along the length direction and half of the length, and thus forming a degradable fiber weaving pipe on the hollow tubular bacterial cellulose membrane III; the degradable fiber is a blended fiber of polydioxanone fiber containing nano silver particles and chitosan fiber containing copper ions and zinc ions, the content of the chitosan fiber in the blended fiber is 10 wt%, the content of the zinc ions is 2.2 wt% of the chitosan fiber, and the molar ratio of the zinc ions to the copper ions is 2: 1.3; the content of the nano silver particles is 0.4 wt% of the chitosan fiber;

The finally prepared ureteral stent based on bacterial cellulose composite coating is of a three-layer hollow tubular structure, the length is 35cm, the diameter is 2.5mm, the thickness of the tube wall is 0.3mm, the middle layer is a degradable fiber braided tube with the wall thickness of 0.3mm, the outer layer and the inner layer are respectively a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II with the same wall thickness, and the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II are respectively attached to the inner wall and the outer wall of the degradable fiber braided tube; the length of the tubular bacterial cellulose membrane I is half of that of the hollow tubular bacterial cellulose membrane III; the outward surface of the tubular bacterial cellulose membrane I is provided with a plurality of rectangular grooves which are uniformly arranged in parallel, the length direction of each rectangular groove is parallel to the axial direction of the tubular bacterial cellulose membrane I, the distance between every two adjacent rectangular grooves is 150nm, the length of each rectangular groove is 17.5cm, the width of each rectangular groove is 100nm, and the height of each rectangular groove is 90 nm.

Example 7

(1) uniformly mixing a fermentation strain (aerobacter) and a fermentation culture solution (every 100ml of the fermentation culture solution contains 25g of glucose, 4.5g of peptone, 4g of yeast extract, 1.8g of citric acid, 4.6g of sodium dihydrogen phosphate, 5g of magnesium sulfate, 5g of sodium alginate and the balance of water), putting the mixture into a hollow tubular fermentation device, fermenting for 9 days, and then performing purification treatment (namely soaking a fermentation product into a sodium hydroxide solution with the mass concentration of 9 wt%, keeping the fermentation product at the temperature of 35 ℃ for 12 hours, and then washing the fermentation product with water until the pH value is 7.0) to obtain a hollow tubular bacterial cellulose membrane III; wherein the density of fermentation strain added into the fermentation culture solution is 8 × 10 ¹²Per ml; the hollow tubular fermentation device is a double-layer jacketed pipe, the inner layer is a transparent pipeOxygen performance of 9.3X 10⁵cm³A silica gel film with 24 h.0.1 MPa, wherein the fermentation strain and the fermentation culture solution are arranged between two layers of a hollow tubular fermentation device, the inner layer of the hollow tubular fermentation device is filled with mixed gas, and the pressure of the mixed gas is 1.5 multiplied by 10⁵Pa, the volume ratio of oxygen in the mixed gas is 40 percent, and the balance is argon; dividing the hollow tubular fermentation device into A, B hollow tubular objects, wherein the silica gel film on the inner layer of the hollow tubular object A has a smooth surface, and the outward surface of the silica gel film on the inner layer of the hollow tubular object B has a patterned structure; the patterning structure is formed by adopting a micro/nano forming patterning technology, a plurality of rectangular bulges which are uniformly arranged in parallel along the axial direction of the hollow tubular object B are formed on the surface of the silica gel film, the distance between every two adjacent rectangular bulges is 150nm, the length of each rectangular bulge is equal to the length of the hollow tubular object B, the width of each rectangular bulge is 120nm, and the height of each rectangular bulge is 100 nm;

(2) placing a polytetrafluoroethylene rod in a purified hollow tubular bacterial cellulose membrane III, weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III by adopting a regular weaving method under the support of the polytetrafluoroethylene rod, wherein the weaving area is all areas between one end of the hollow tubular bacterial cellulose membrane III along the length direction and half of the length, and thus forming a degradable fiber weaving pipe on the hollow tubular bacterial cellulose membrane III; the degradable fiber is a blended fiber of PLGA fiber containing nano silver particles and chitosan fiber containing copper ions and zinc ions, the content of the chitosan fiber in the blended fiber is 12.3 wt%, the content of the zinc ions is 3.6 wt% of the chitosan fiber, and the molar ratio of the zinc ions to the copper ions is 2: 1.4; the content of the nano silver particles is 0.6 wt% of the chitosan fiber;

The finally prepared ureteral stent based on the bacterial cellulose composite coating is of a three-layer hollow tubular structure, the length of the ureteral stent is 40cm, the diameter of the ureteral stent is 3.0mm, the thickness of the tube wall is 0.4mm, the middle layer of the ureteral stent is a degradable fiber braided tube with the wall thickness of 0.4mm, the outer layer and the inner layer are respectively a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II with the same wall thickness, and the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II are respectively attached to the inner wall and the outer wall of the degradable fiber braided tube; the length of the tubular bacterial cellulose membrane I is half of that of the hollow tubular bacterial cellulose membrane III; the outward surface of the tubular bacterial cellulose membrane I is provided with a plurality of rectangular grooves which are uniformly arranged in parallel, the length direction of each rectangular groove is parallel to the axial direction of the tubular bacterial cellulose membrane I, the distance between every two adjacent rectangular grooves is 150nm, the length of each rectangular groove is 20cm, the width of each rectangular groove is 120nm, and the height of each rectangular groove is 100 nm.

Example 8

(1) uniformly mixing a fermentation strain (azotobacter) and a fermentation culture solution (each 100ml of the fermentation culture solution contains 30g of glucose, 5g of peptone, 5g of yeast extract, 2g of citric acid, 5g of sodium dihydrogen phosphate, 5g of magnesium sulfate, 5g of sodium alginate and the balance of water), putting the mixture into a hollow tubular fermentation device, fermenting for 9 days, and then performing purification treatment (namely soaking a fermentation product into a sodium hydroxide solution with the mass concentration of 10 wt%, keeping the fermentation product at the temperature of 30 ℃ for 24 hours, and then washing the fermentation product with water until the pH value is 7.0) to obtain a hollow tubular bacterial cellulose membrane III; wherein the density of fermentation strain added into the fermentation culture solution is 10¹³Per ml; the hollow tubular fermentation device is a double-layer jacketed pipe, and the inner layer has oxygen permeability of 10 multiplied by 10⁵cm³A silica gel film with 24 h.0.1 MPa, wherein the fermentation strain and the fermentation culture solution are arranged between two layers of a hollow tubular fermentation device, the inner layer of the hollow tubular fermentation device is filled with mixed gas, and the pressure of the mixed gas is 1.5 multiplied by 10⁵Pa, the volume ratio of oxygen in the mixed gas is 40 percent, and the balance is argon; dividing the hollow tubular fermentation device into A, B hollow tubular objects, wherein the silica gel film on the inner layer of the hollow tubular object A has a smooth surface, and the silica gel film on the inner layer of the hollow tubular object B faces outwards The surface is provided with a patterned structure; the patterning structure is formed by adopting a micro/nano forming patterning technology, a plurality of rectangular bulges which are uniformly arranged in parallel along the axial direction of the hollow tubular object B are formed on the surface of the silica gel film, the distance between every two adjacent rectangular bulges is 200nm, the length of each rectangular bulge is equal to the length of the hollow tubular object B, the width of each rectangular bulge is 200nm, and the height of each rectangular bulge is 100 nm;

(2) placing a polytetrafluoroethylene rod in a purified hollow tubular bacterial cellulose membrane III, weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III by a regular weaving method under the support of the polytetrafluoroethylene rod, wherein the weaving area is all areas between one end of the hollow tubular bacterial cellulose membrane III along the length direction and half of the length of the hollow tubular bacterial cellulose membrane III, and thus a degradable fiber weaving pipe is formed on the hollow tubular bacterial cellulose membrane III; the degradable fibers are blended fibers of PCL fibers containing nano silver particles and chitosan fibers containing copper ions and zinc ions, the content of the chitosan fibers in the blended fibers is 15 wt%, the content of the zinc ions is 5 wt% of the chitosan fibers, and the molar ratio of the zinc ions to the copper ions is 2: 1.4; the content of the nano silver particles is 0.1 wt% of the chitosan fiber;

The finally prepared ureteral stent based on the bacterial cellulose composite coating is of a three-layer hollow tubular structure, the length of the ureteral stent is 40cm, the diameter of the ureteral stent is 3.5mm, the thickness of the tube wall is 0.5mm, the middle layer of the ureteral stent is a degradable fiber braided tube with the wall thickness of 0.45mm, the outer layer and the inner layer are respectively a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II with the same wall thickness, and the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II are respectively attached to the inner wall and the outer wall of the degradable fiber braided tube; the length of the tubular bacterial cellulose membrane I is half of that of the hollow tubular bacterial cellulose membrane III; the outward surface of the tubular bacterial cellulose membrane I is provided with a plurality of rectangular grooves which are uniformly arranged in parallel, the length direction of each rectangular groove is parallel to the axial direction of the tubular bacterial cellulose membrane I, the distance between every two adjacent rectangular grooves is 200nm, the length of each rectangular groove is 20cm, the width of each rectangular groove is 200nm, and the height of each rectangular groove is 100 nm.

Claims

1. A ureteral stent based on bacterial cellulose composite coating is characterized in that: the degradable fiber woven tube is of a three-layer hollow tubular structure, the middle layer is a degradable fiber woven tube, the outer layer and the inner layer are respectively a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II, and the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II are respectively attached to the inner wall and the outer wall of the degradable fiber woven tube;

2. The ureteral stent based on bacterial cellulose composite coating according to claim 1, wherein the outward surface of the tubular bacterial cellulose membrane I is provided with a plurality of parallel and uniformly arranged rectangular grooves, and the length direction of each rectangular groove is parallel to the axial direction of the tubular bacterial cellulose membrane I.

3. The bacterial cellulose composite coating-based ureteral stent tube according to claim 1 or 2, wherein the degradable fiber braided tube is obtained by diamond braiding or regular braiding of degradable fibers capable of slowly releasing functional substances;

4. The bacterial cellulose composite coating-based ureteral stent tube according to claim 3, wherein the content of chitosan fibers in the degradable fibers capable of slowly releasing the functional substances is 3-15 wt%;

the content of zinc ions is 0.1-5 wt% of the chitosan fiber, and the molar ratio of the zinc ions to the copper ions is 2: 1-1.4; the content of the silver ions or the nano silver particles is 0.1-2 wt% of the chitosan fiber.

5. The ureteral stent based on bacterial cellulose composite coating according to claim 2, wherein the length of the rectangular grooves is equal to the length of the tubular bacterial cellulose membrane I, the width is 50-200 nm, the height is 50-100 nm, and the distance between two adjacent rectangular grooves is 50-200 nm.

6. The bacterial cellulose composite coating-based ureteral stent tube according to claim 1, wherein the ureteral stent tube has a length of 15-40 cm and a diameter of 1.5-3.5 mm; the wall thickness of the ureteral stent tube is 0.1-0.5 mm, the wall thickness of the degradable fiber woven tube in the middle layer is 0.08-0.45 mm, and the wall thickness of the tubular bacterial cellulose membrane I is the same as that of the tubular bacterial cellulose membrane II.

7. The method for preparing the ureteral stent based on the bacterial cellulose composite coating of claim 1, wherein the method comprises the following steps: firstly, preparing a hollow tubular bacterial cellulose membrane III, weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III to form a degradable fiber woven tube, and finally turning over the hollow tubular bacterial cellulose membrane III from one end to the other end along the length direction to form a tubular bacterial cellulose membrane I and a tubular bacterial cellulose membrane II, so that the degradable fiber woven tube is positioned between the tubular bacterial cellulose membrane I and the tubular bacterial cellulose membrane II, and the ureteral stent tube based on the bacterial cellulose composite coating is prepared;

the weaving area of the degradable fibers is the outer wall of the tubular bacterial cellulose membrane II.

8. The method according to claim 7, wherein the bacterial cellulose composite coated ureteral stent-based tube is prepared by the following steps:

(1) uniformly mixing the fermentation strain with a fermentation culture solution, putting the mixture into a hollow tubular fermentation device, fermenting for 5-9 days, and purifying to obtain a hollow tubular bacterial cellulose membrane III; the hollow tubular fermentation device is a double-layer jacketed pipe, and the inner layer is oxygen permeable with the oxygen permeability of 1-10 multiplied by 10 ⁵cm³A silica gel film with 24 h.0.1 MPa, wherein a fermentation strain and a fermentation culture solution are arranged between two layers of a hollow tubular fermentation device, the inner layer of the hollow tubular fermentation device is filled with mixed gas, and the pressure of the mixed gas is 1.1-1.5 multiplied by 10⁵Pa, the volume ratio of oxygen in the mixed gas is 25-40%; dividing the hollow tubular fermentation device into A, B hollow tubular objects, wherein the silica gel film on the inner layer of the hollow tubular object A has a smooth surface, and the outward surface of the silica gel film on the inner layer of the hollow tubular object B has a patterned structure; the patterning structure is formed by adopting a micro/nano forming patterning technology, a plurality of rectangular bulges are formed on the surface of the silica gel film and are uniformly arranged in parallel along the axial direction of the hollow tubular object B, the length of each rectangular bulge is equal to the length of the hollow tubular object B, the width of each rectangular bulge is 50-200 nm, the height of each rectangular bulge is 50-100 nm, and the distance between every two adjacent rectangular bulges is 50-200 nm;

(2) placing a polytetrafluoroethylene rod in a purified hollow tubular bacterial cellulose membrane III, weaving degradable fibers on the outer wall of the hollow tubular bacterial cellulose membrane III under the support of the polytetrafluoroethylene rod, and forming a degradable fiber woven tube on the hollow tubular bacterial cellulose membrane III;

(3) Turning over the hollow tubular bacterial cellulose membrane III from one end to the other end along the length direction, so that the degradable fiber woven tube is coated in the middle to form a three-layer composite tubular object, wherein the outer layer of the three-layer composite tubular object is a tubular bacterial cellulose membrane I, the inner layer of the three-layer composite tubular object is a tubular bacterial cellulose membrane II, and the outer wall of the tubular bacterial cellulose membrane I is provided with a rectangular groove;

9. The method of claim 8, wherein the fermentation strain is one or more of acetobacter xylinum, rhizobium, sarcina, pseudomonas, achromobacter, alcaligenes, aerobacter, and azotobacter; the density of the fermentation strain added into the fermentation culture solution is 10¹⁰～10¹³Per ml;

the formula of the fermentation culture solution is as follows: every 100ml of the nutrient solution contains 5-30 g of glucose, 1-5 g of peptone, 1-5 g of yeast extract, 0.5-2 g of citric acid, 0.2-5 g of sodium dihydrogen phosphate, 3-5 g of magnesium sulfate, 3-5 g of sodium alginate and the balance of water; the pH value of the fermentation culture solution is 4.0-6.0.

10. The method according to claim 8, wherein the purification treatment is performed by soaking the fermentation product in a sodium hydroxide solution with a mass concentration of 3-10 wt%, maintaining the fermentation product at 30-100 ℃ for 3-24 hours, and washing the fermentation product with water to a pH of 7.0.