CN113633432A

CN113633432A - Biological functional antibacterial tracheal stent

Info

Publication number: CN113633432A
Application number: CN202110858173.7A
Authority: CN
Inventors: 叶健; 金华良; 邱晨辉; 刘加朋; 姚鑫骅; 傅建中
Original assignee: Hangzhou First Peoples Hospital
Current assignee: Hangzhou First Peoples Hospital
Priority date: 2021-07-28
Filing date: 2021-07-28
Publication date: 2021-11-12

Abstract

The invention discloses a biological functional antibacterial tracheal stent, which comprises a three-layer structure from inside to outside, wherein the inner layer is a porous polymer fiber cell-carrying layer, the middle layer is a support frame with a hollow structure and a flexible micropore filler filled in the hollow structure, and the outer surface is an antibacterial coating; the preparation method comprises the following steps: (1) preparing a porous polymer fiber cell-carrying layer by adopting a melting near electric field direct writing printing mode; (2) printing a support frame with a hollow structure on the porous polymer fiber cell-loaded layer by adopting an instant blending 4-axis printing mode; (3) printing flexible micropore fillers at the hollow-out structure by adopting an instant blending 4-axis printing mode; (4) soaking to remove the pore-foaming agent in the flexible micropore filler and then drying; (5) and (4) activating the outer surface, and spraying an antibacterial coating. The invention can provide enough radial support and avoid the complications of mucus retention, infection and the like which often occur after the existing stent is implanted.

Description

Biological functional antibacterial tracheal stent

Technical Field

The invention belongs to the technical field of tracheal stents, and particularly relates to a biological functional antibacterial tracheal stent.

Background

Tracheal and bronchial stenosis can be caused by a variety of etiologies, including: inflammatory granuloma, trauma, tracheomalacia. Tumors, and the like. Tracheal stenosis can cause obstructive pulmonary inflammation, atelectasis, and dyspnea, and can severely cause respiratory failure in patients and be life threatening.

The tracheal stent implantation is one of important means for treating tracheal stenosis, and can quickly relieve dyspnea and improve clinical symptoms.

For example, chinese patent publication No. CN112757660A discloses a carbon fiber C-ring tracheal stent and a method for preparing the same, which comprises weaving carbon fiber bundles into carbon fiber woven strips, and then sequentially performing mold-assisted baking and shaping, medium ultrasonic treatment, and deposition of DLC or F-DLC coating to obtain the carbon fiber C-ring tracheal stent;

chinese patent publication No. CN208756264U discloses a displacement-preventing tracheal stent, which comprises a tracheal stent body, wherein the tracheal stent body comprises an inner membrane and an outer membrane which are fixed to each other, a plurality of annular frameworks are sequentially arranged between the inner membrane and the outer membrane along the length direction of the tracheal stent body, and two ends of the tracheal stent body are respectively provided with a bell mouth.

However, the outer wall of the tracheal stent is attached to the inner wall of the airway, so that cilia cells of the airway epithelium are inevitably pressed, and the cilia cells can freely swing to play a role of a mucus escalator, so that the tracheal stent is a main means for clearing secretions and foreign matters on the inner wall of the trachea and the bronchus by a human body. Therefore, the pressure of the tracheal stent on the airway epithelium necessarily destroys the mucus clearing function, thereby causing mucus retention, causing secondary stenosis, and seriously even leading to suffocation of patients.

In addition, the trachea is directly communicated with the outside atmosphere, so that microorganisms such as outside bacteria and the like easily enter the trachea, and the surface of the implanted tracheal stent can become an ideal footdrop for the outside microorganisms, thereby easily causing infection. In fact, implant infection is one of the major complications throughout the interventional medical field, placing a significant burden on the patient as well as on the entire medical system.

Therefore, it is an ideal solution to the above problems to design a biofunctional antibacterial tracheal stent that can reproduce the ciliated epithelial mucus-clearing function on the inner wall of the stent while having an antibacterial function on the outer surface.

Disclosure of Invention

In order to solve the problems in the prior art, the invention provides a biological functional antibacterial tracheal stent which can provide enough radial support and simultaneously avoid complications such as mucus retention and infection which often occur after the existing stent is implanted.

A biological functional antibacterial tracheal stent comprises a three-layer structure from inside to outside, wherein the inner layer is a porous polymer fiber cell-carrying layer, the middle layer is a support frame with a hollow structure and a flexible micropore filler filled in the hollow structure, and the outer surface is an antibacterial coating;

the biological functional antibacterial tracheal stent is prepared by the following preparation method:

(1) preparing a porous polymer fiber cell-carrying layer of an inner layer by adopting a melting near electric field direct writing printing mode;

(2) printing a support frame with a hollow structure outside the porous polymer fiber cell-loaded layer by adopting an instant blending 4-axis printing mode;

(3) printing flexible micropore fillers at the hollow-out structure by adopting an instant blending 4-axis printing mode;

(4) soaking the product obtained in the step (3) to remove the pore-foaming agent in the flexible micropore filler, and drying;

(5) and (4) activating the outer surface of the product obtained in the step (4), and spraying an antibacterial coating to obtain the final biological functional antibacterial tracheal stent.

Preferably, the porous polymer fiber cell-carrying layer is made of degradable polymer materials, including but not limited to polylactic acid, polycaprolactone and polydioxanone; the layer thickness of the porous polymer fiber cell-carrying layer is less than 0.5mm, so as to avoid the too thick wall of the stent tube.

Preferably, the supporting frame and the flexible filler are both made of biocompatible medical silicone rubber materials, wherein the supporting frame is made of high-hardness silicone rubber, the Shore A hardness of the supporting frame is greater than or equal to 50 degrees, and the flexible microporous filler is made of low-hardness silicone rubber, the Shore A hardness of the flexible microporous filler is less than or equal to 10 degrees.

The supporting frame and the flexible microporous filler are made of silica gel materials, and the main purpose is to ensure the bonding strength between the supporting frame and the flexible microporous filler. In addition, the effect that flexible micropore filler here played is mainly two aspects, and the granulation tissue ingrowth is avoided the back at first to the support is put into, plays the function similar to the tectorial membrane on the metal tectorial membrane support, and the micropore support is still nutrient substance transmission window secondly, allows nutrient substance to pass through the support wall to guarantee the normal physiological activity of inner wall cell.

In the step (1), the melting near electric field direct writing printing is different from the traditional electrostatic spinning mode, and the distance between the spinning needle head and the fiber collector is short, so that the whip instability stage existing in the traditional electrostatic spinning is avoided, and the prepared micro-nano fiber is accurate and controllable. By utilizing the principle, the porosity and the size and the shape of the pores of the porous polymer fiber cell-carrying layer can be designed according to the characteristics of the airway epithelial cells, so that the adhesion, proliferation and functional differentiation of the epithelial cells on the surface of the porous polymer fiber cell-carrying layer are promoted.

In the step (2), the instant blending 4-axis printing mode is that a linked rotating shaft is additionally arranged on a traditional 3-axis printing platform to serve as a supporting platform of a supporting frame, an instant blending printing head is adopted, medical liquid silica gel materials of two components are respectively additionally arranged in two material troughs, silica gel is extruded in a mode of extruding through air pressure or a pressing rod, the silica gel is printed on the linked rotating shaft after being fully mixed through a static mixing pipe, and external heating is simultaneously given to improve the curing speed of the silica gel.

In the step (3), when the flexible micropore filler is printed, the low-hardness silica gel of the component A and the low-hardness silica gel of the component B are respectively mixed with the pore-foaming agent in proportion, then the mixture is filled in the hollow holes of the support frame in an instant blending 4-axis printing mode, and the mixture is cured at high temperature.

Further, the pore-foaming agent adopts sodium chloride particles, sodium bicarbonate particles or sugar particles.

Preferably, the low-hardness silica gel of the component A and the low-hardness silica gel of the component B are respectively mixed with a pore-foaming agent according to the proportion of 1: 5-1: 2. It should be noted that the mass ratio of the pore-forming agent to the silica gel is greater than 2 here, so as to ensure that the pores in the prepared microporous filler have sufficient connectivity. In addition, since the fluidity of the mixture may be lowered by the porogen to make the extrusion printing impossible, a proper amount of silicone oil may be added to adjust the fluidity of the mixture.

Preferably, the thickness of the flexible microporous filler is smaller than that of the support frame, so that the friction force between the stent and the inner wall of the trachea can be improved, and the migration of the stent is reduced.

In the step (5), the external surface may be activated by plasma treatment, ultraviolet irradiation or silane coupling agent treatment. The antibacterial coating adopts a nano-silver antibacterial agent.

Compared with the prior art, the invention has the following beneficial effects:

according to the biological functional antibacterial tracheal stent, airway epithelial cells can be cultured and functional cilia cells can be induced and differentiated on the inner porous polymer fiber cell-carrying layer, so that the mucus removing function of the real tracheal inner wall is reproduced; the middle supporting frame and the micropore filling can provide enough radial supporting force, avoid secondary stenosis caused by the inward growth of granulation tissues and reserve a nutrition transmission channel for cells on the inner wall; the outer surface is sprayed with an antibacterial coating to avoid infection after implantation.

Drawings

FIG. 1 is a schematic structural view of a biofunctional antibacterial tracheal stent of the present invention;

FIG. 2 is a cross-sectional view of the wall of the multifunctional antibacterial tracheal stent of the present invention;

FIG. 3 is a schematic of the instant blend 4-axis printing platform of the present invention;

FIG. 4 is a flow chart of the preparation method of the present invention.

In the figure: 1. the device comprises a porous polymer fiber cell-carrying layer, 2, a supporting frame, 3, flexible micropore fillers, 3-1, a porous communication structure, 4, a fibrous porous structure, 5, an antibacterial coating, 6, a piston, 7, an AB storage pipe, 8, a static mixing pipe, 9, a static mixing blade, 10 and a rotating shaft.

Detailed Description

The invention will be described in further detail below with reference to the drawings and examples, which are intended to facilitate the understanding of the invention without limiting it in any way.

As shown in fig. 1 and 2, a biofunctional antibacterial tracheal stent comprises a three-layer structure from inside to outside, wherein the inner layer is a porous polymer fiber cell-carrying layer 1, the middle layer is a support frame 2 with a hollow structure and a flexible microporous filler 3 filled in the hollow structure, and the outer surface is an antibacterial coating 5.

Wherein, the fibrous porous structure 4 can be seen after the porous polymer fiber cell-carrying layer 1 is enlarged, and the porous communicating structure 3-1 can be seen after the flexible microporous filler 3 is enlarged.

As shown in fig. 2, the cross-sectional view of the wall of the biofunctional antibacterial tracheal stent, where the wall thickness of the porous polymer fiber cell-loaded layer 1 is 0.2 mm; the wall thickness of the intermediate support frame 2 is 1.5 mm; the wall thickness of the flexible microporous filler 3 is 1.0 mm; the antimicrobial coating 5 is relatively thin, typically below 100 μm.

The supporting frame 2 and the flexible microporous filler 3 are both made of biocompatible medical silicone rubber materials, wherein the supporting frame 2 uses high-hardness silicone (shore a hardness is greater than or equal to 50 °) to ensure sufficient axial support, and the flexible microporous filler 3 uses low-hardness silicone (shore a hardness is less than or equal to 10 °).

The main purpose of the supporting frame 2 and the flexible microporous filler 3 both being made of silica gel materials is to ensure the bonding strength between the two, and experimental results show that the two types of silica gel with different hardness can be fused with each other, and the interface bonding strength is even higher than that of the microporous silica gel sponge.

In addition, the micropore filling plays two main roles, firstly, granulation tissue ingrowth is avoided after the stent is placed in, the function similar to that of a film on a metal film-covered stent is played, and secondly, the micropore stent is also a nutrient substance transmission window, nutrient substances are allowed to pass through the stent wall, so that normal physiological activities of cells on the inner wall are guaranteed.

In the preparation process of the biofunctional antibacterial tracheal stent, an instant blending 4-axis printing platform is required, specifically, as shown in fig. 3, the instant blending 4-axis printing platform consists of an instant blending printing head moving along with a three-axis moving platform and a linkage rotating shaft 10, and the instant blending printing head mainly comprises the following components: piston 6, AB stock pipe 7, static mixing pipe 8 and static mixing blade 9.

As shown in fig. 4, the biofunctional antibacterial tracheal stent of the present invention was prepared by the following preparation method:

step 1, preparing a porous polymer fiber cell-carrying layer of an inner layer by adopting a melting near electric field direct writing printing mode.

The porous polymer fiber cell-carrying layer is prepared by a melting near electric field direct-writing printing mode, the polymer material is a biocompatible degradable polymer material such as polylactic acid, polycaprolactone, polydioxanone and the like, and the layer thickness is controlled within 0.5mm to avoid the too thick wall of the stent tube.

The melting near electric field direct writing printing is different from the traditional electrostatic spinning mode, and the distance between the spinning needle head and the fiber collector is short, so that the whip instability stage existing in the traditional electrostatic spinning is avoided, and the prepared micro-nano fiber is accurate and controllable. By utilizing the principle, the porosity and the size and the shape of the pores of the porous polymer fiber cell-carrying layer can be designed according to the characteristics of the airway epithelial cells, so that the adhesion, proliferation and functional differentiation of the epithelial cells on the surface of the porous polymer fiber cell-carrying layer are promoted.

And 2, printing a support frame with a hollow structure outside the porous polymer fiber cell-loaded layer by adopting an instant blending 4-axis printing mode.

The support frame is printed in an instant blending printing mode, because the two components of the medical liquid silica gel material of the AB storage pipe 7 are solidified after being mixed, the rheological property of the material begins to change, and if the material is blended and then extruded for printing, the uniformity of discharging is difficult to ensure due to the change of the rheological property.

The instant blending 4-axis printing adopted by the invention is characterized in that a linked rotating shaft is additionally arranged on a traditional 3-axis printing platform to serve as a support supporting platform, in addition, a printing head is changed into an instant blending printing head, silica gel of an AB component is respectively additionally arranged in two material tanks, the silica gel is extruded in an air pressure or pressure bar extruding mode, then the silica gel is fully mixed by a static mixing pipe and then printed on a supporting shaft, and meanwhile, external heating is required to be given so as to improve the curing speed of the silica gel.

And 3, printing the flexible micropore filler at the hollow structure by adopting an instant blending 4-axis printing mode.

The filling in the step is a blend, the low-hardness silica gel of the component A and the low-hardness silica gel of the component B are respectively mixed with the pore-forming agent according to a proportion (the mass ratio of the pore-forming agent to the silica gel is 2: 1-5: 1), and then the mixture is filled in the holes of the support frame in an instant blending printing mode and is cured at a high temperature. It should be noted that the mass ratio of the pore-forming agent to the silica gel is greater than 2 here, so as to ensure that the pores in the prepared microporous filler have sufficient connectivity. In addition, since the fluidity of the mixture may be lowered by the porogen to make the extrusion printing impossible, a proper amount of silicone oil may be added to adjust the fluidity of the mixture.

The thickness of the flexible micropore filler is smaller than that of the support frame, so that the friction force between the support and the inner wall of the trachea can be improved, and the migration of the support is reduced.

And 4, soaking the product obtained in the step 3 to remove the pore-foaming agent in the flexible micropore filler, and drying.

And (3) removing the pore-foaming agent in the step (3) by adopting a solvent soaking mode, wherein the pore-foaming agent adopts sodium chloride particles, sodium bicarbonate particles or sugar particles and the like which are easy to remove materials.

And 5, activating the outer surface of the product obtained in the step 3, and spraying an antibacterial coating to obtain the final biological functional antibacterial tracheal stent.

The outer surface antibacterial coating is prepared by a spraying method, and before spraying, the surface of the outer surface antibacterial coating is activated by a physical method (such as plasma treatment and ultraviolet irradiation) or a chemical method (such as a silane coupling agent and other surfactants) to enhance the adhesive strength of the antibacterial coating. The activation treatment is adopted because the surface energy of the silica gel surface is low, the antibacterial coating is difficult to adhere, and the adhesion strength of the antibacterial coating can be obviously enhanced after the activation treatment.

Further, the antibacterial material sprayed here preferably adopts a nano silver antibacterial agent with broad-spectrum bactericidal effect, but other antibacterial materials may also be used, such as: nano copper particles, carbon nano tubes and other nano materials, antibiotics and the like.

The embodiments described above are intended to illustrate the technical solutions and advantages of the present invention, and it should be understood that the above-mentioned embodiments are only specific embodiments of the present invention, and are not intended to limit the present invention, and any modifications, additions and equivalents made within the scope of the principles of the present invention should be included in the scope of the present invention.

Claims

1. A biological functional antibacterial tracheal stent is characterized by comprising a three-layer structure from inside to outside, wherein the inner layer is a porous polymer fiber cell-carrying layer, the middle layer is a support frame with a hollow structure and a flexible micropore filler filled in the hollow structure, and the outer surface is an antibacterial coating;

2. The multifunctional antibacterial tracheal stent of claim 1, wherein the porous polymer fiber cell-carrying layer is made of degradable polymer materials, including but not limited to polylactic acid, polycaprolactone and polydioxanone; the layer thickness of the porous polymer fiber cell-carrying layer is less than 0.5 mm.

3. The multifunctional antibacterial tracheal stent of claim 1, wherein the supporting frame and the flexible filler are made of biocompatible medical silicone rubber material, wherein the supporting frame is made of high-hardness silicone rubber with Shore A hardness of 50 degrees or more, and the flexible microporous filler is made of low-hardness silicone rubber with Shore A hardness of 10 degrees or less.

4. The multifunctional antibacterial tracheal stent of claim 1, wherein in step (2), the instant blending 4-axis printing mode is that a linked rotating shaft is additionally installed on a traditional 3-axis printing platform, an instant blending printing head is adopted, two components of medical liquid silica gel materials are respectively and additionally installed in two material tanks of the printing head, silica gel is extruded in an air pressure or pressure rod extrusion mode, then the two components are fully mixed by a static mixing tube and then printed on the linked rotating shaft, and external heating is simultaneously applied, so that the curing speed of the silica gel is increased.

5. The multifunctional antibacterial tracheal stent of claim 4, wherein in the step (3), when the flexible microporous filler is printed, the low-hardness silica gel of the component A and the low-hardness silica gel of the component B are respectively mixed with the pore-forming agent in proportion, and then the mixture is filled in the hollow holes of the support frame in an instant blending 4-axis printing manner and is cured at high temperature.

6. The multifunctional antibacterial tracheal stent of claim 5, wherein the pore-forming agent is sodium chloride particles, sodium bicarbonate particles or sugar particles.

7. The biofunctional antibacterial tracheal stent of claim 5 wherein the low hardness silica gel of component A and component B are mixed with pore-forming agent at a ratio of 1:5 to 1:2, respectively.

8. The biofunctional antimicrobial tracheal stent of claim 1, wherein the flexible microporous filler has a thickness less than the thickness of the support frame.

9. The biofunctional antibacterial tracheal stent as claimed in claim 1, wherein in the step (5), the outer surface is activated by plasma treatment, ultraviolet irradiation or silane coupling agent treatment.

10. The biofunctional antibacterial tracheal stent according to claim 1 wherein in step (5), the antibacterial coating employs a nano-silver antibacterial agent.