CN115252906B - Sandwich structure bracket and preparation method and application thereof - Google Patents

Sandwich structure bracket and preparation method and application thereof Download PDF

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Publication number
CN115252906B
CN115252906B CN202210914517.6A CN202210914517A CN115252906B CN 115252906 B CN115252906 B CN 115252906B CN 202210914517 A CN202210914517 A CN 202210914517A CN 115252906 B CN115252906 B CN 115252906B
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layer
polylactic acid
sandwich structure
composite
polyvinyl alcohol
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CN115252906A (en
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韩颖超
赵康
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Foshan Xianhu Laboratory
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Foshan Xianhu Laboratory
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02W—CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO WASTEWATER TREATMENT OR WASTE MANAGEMENT
    • Y02W90/00—Enabling technologies or technologies with a potential or indirect contribution to greenhouse gas [GHG] emissions mitigation
    • Y02W90/10—Bio-packaging, e.g. packing containers made from renewable resources or bio-plastics

Abstract

The invention belongs to the technical field of medical supplies, and discloses a sandwich structure bracket and a preparation method and application thereof. The sandwich structure support comprises a layer A, a layer B and a layer A from bottom to top in sequence, wherein the layer A comprises a composite fiber film, the composite fiber film comprises polylactic acid and nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, and the composite microspheres comprise polylactic acid and nano hydroxyapatite. The composite fiber membrane plays a role in transverse mechanical support and provides a guiding function for tissue growth; the layer B plays a role in longitudinal mechanical support between fiber membrane layers, so that the compression resistance of the sandwich structure support is remarkably improved, the gap collapse between the layers A is further prevented, and a three-dimensional space structure is constructed for tissue growth between composite fiber membranes. The requirement of serving as a cell growth carrier material can be met in the field of tissue engineering by controlling the molecular weight of polylactic acid.

Description

Sandwich structure bracket and preparation method and application thereof
Technical Field
The invention belongs to the technical field of medical supplies, and particularly relates to a sandwich structure bracket and a preparation method and application thereof.
Background
At present, a large number of bone defect patients need to perform bone repair or bone grafting operations due to traffic accidents, natural disasters, orthopedic diseases and the like. Bone tissue repair has been a major hot spot and difficult problem in the field of tissue engineering. For a large-section bone defect, the bone cannot heal only by virtue of the repair capability of bone tissue, and a bone grafting operation is necessary, otherwise, the fibrous tissue fills the defect position to prevent new bone from forming, and the bone nonunion problem is caused. The functional artificial material is adopted for repairing, so that the problems of 'injury cure by injury' and limited sources of autologous bone grafting can be solved, and a plurality of problems of allogeneic bone grafting can be effectively avoided. The adoption of functional artificial materials for repairing becomes a main means for treating bone defect diseases besides the existing clinical autogenous/allogenic bone transplantation. With the rapid development of tissue engineering technology, higher and more new requirements are necessarily put forward on stent materials. Therefore, research and development of artificial bone tissue scaffolds satisfying clinical demands have become an important topic in the field of bone regeneration.
Hydroxyapatite is the main inorganic component of human bones, has good biocompatibility and bioactivity and good cell affinity, and can form firm osseous combination with bone tissues. The nano hydroxyapatite is compounded in the polylactic acid, so that the material can be endowed with osteogenic activity, the cell affinity is improved, and meanwhile, the alkaline nano hydroxyapatite can neutralize acidic products produced by degradation of the polylactic acid, and the aseptic inflammation is reduced. The combination of the two can provide better environment for the growth of cells and tissues. Polyvinyl alcohol is a high molecular polymer having water solubility. The polyvinyl alcohol contains a large amount of hydrophilic groups, so that the polyvinyl alcohol has good water absorbability, can be biodegraded, has excellent biocompatibility, dissolution resistance and the like, and the degradation products are water and carbon dioxide. Polylactic acid is a polymer material with good biocompatibility and biodegradability, has the characteristics of no toxicity, good thermoforming property and the like, and degradation products can participate in metabolism of human bodies.
With the development of biomedical engineering science, a material for promoting bone repair is put on a higher demand. The ideal cranio-prosthetic material should possess excellent biocompatibility, a suitable degradation rate and the ability to guide or induce bone regeneration.
The fiber membrane prepared by electrostatic spinning has a fibrous structure similar to an extracellular matrix, pores are mutually communicated, and the fiber membrane has extremely high specific surface area, and has wide application prospect in repairing various tissue injuries as a novel functional fiber membrane material. However, most fiber membranes shrink after contacting water, resulting in rapid structural damage, loss of gaps between layers, loss of mechanical support, loss of growth and proliferation space of cells, two-dimensional space of the fiber membranes, and no three-dimensional space, and no good mechanical support.
Accordingly, there is a need to provide a new scaffold material with good mechanical support, which is advantageous for the application of the scaffold material in the field of bone repair or bone regeneration.
Disclosure of Invention
The present invention aims to solve at least one of the technical problems in the prior art described above. Therefore, the invention provides the sandwich structure bracket, the preparation method and the application thereof, and the sandwich structure bracket has good mechanical supporting effect, which is beneficial to the application of the sandwich structure bracket in the field of bone repair.
The invention is characterized in that: the sandwich structure bracket sequentially comprises a layer A, a layer B and a layer A (namely the sandwich bracket with an ABA layered structure is formed, and a ABABA, ABABABA layered structure can be formed, namely a plurality of ABA repeating units are contained), wherein the layer A comprises a composite fiber membrane, the composite fiber membrane comprises polylactic acid/nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, the composite microspheres comprise polylactic acid and nano hydroxyapatite, the composite fiber membrane plays a role in transverse mechanical support, and a guiding function is provided for tissue growth; the B layer formed by the polyvinyl alcohol and the composite microspheres plays a role in longitudinal mechanical support between fiber film layers, so that the compression resistance of the sandwich structure support is remarkably improved, the gap collapse between the composite fiber film layers (namely the A layer) is further prevented, and a three-dimensional space structure is constructed between the composite fiber films for tissue growth.
Furthermore, in the sandwich structure bracket, the requirement of serving as a cell growth carrier material in the field of tissue engineering can be met by controlling the molecular weight of polylactic acid. Specifically, the composite fiber membrane adopts polylactic acid (80-150 ten thousand) with higher molecular weight, the composite microsphere adopts polylactic acid (2-30 ten thousand) with lower molecular weight, the composite microsphere is degraded before the composite fiber membrane, and the B layer can be prepared by mixing microspheres with different diameters (10-120 mu m) and composite microspheres with polylactic acid (2-30 ten thousand) with different molecular weights, so that the degradation performance of the B layer is further regulated and controlled. The application of the sandwich structure support in the biomedical field is facilitated.
The first aspect of the invention provides a sandwich structure support.
Specifically, a sandwich structure support comprises a layer A, a layer B and a layer A from bottom to top in sequence, wherein the layer A comprises a composite fiber membrane, the composite fiber membrane comprises polylactic acid and nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, and the composite microspheres comprise polylactic acid and nano hydroxyapatite.
Preferably, in the composite fiber membrane, the mass ratio of the nano hydroxyapatite is 6-20%; it is further preferable that the mass ratio of the nano hydroxyapatite is 8-15%.
Preferably, in the layer A, the weight average molecular weight of the polylactic acid is 80-150 ten thousand; further preferably, the polylactic acid has a weight average molecular weight of 80 to 100 ten thousand.
Preferably, the diameter of the fibers in the composite fiber film is 400-650nm; further preferably, the diameter of the fibers in the composite fiber film is 450-600nm.
Preferably, in the layer B, the mass ratio of the polyvinyl alcohol to the composite microspheres is 1 (0.5-6); it is further preferable that the mass ratio of the polyvinyl alcohol to the composite microsphere is 1 (1-4).
Preferably, in the composite microsphere, the mass ratio of the nano hydroxyapatite is 5-20%; it is further preferable that the mass ratio of the nano hydroxyapatite is 8-15%.
Preferably, in the layer B, the molecular weight of the polylactic acid is 2-30 ten thousand; further preferably, the polylactic acid has a molecular weight of 5 to 30 ten thousand.
Preferably, the diameter of the composite microsphere is 10-120 μm; further preferably, the diameter of the composite microsphere is 10-100 μm.
Preferably, the thickness of the layer A is 5-60 mu m; further preferably, the thickness of the A layer is 5-50 μm.
Preferably, the thickness of the layer B is 30-300 mu m; further preferably, the thickness of the B layer is 50-200 μm.
Preferably, in the sandwich structure bracket, the polylactic acid accounts for 40-85% of the total mass of the sandwich structure bracket, the polyvinyl alcohol accounts for 5-52% of the total mass of the sandwich structure bracket, and the nano hydroxyapatite accounts for 3.5-15% of the total mass of the sandwich structure bracket; further preferably, in the sandwich structure bracket, the polylactic acid accounts for 45-80% of the total mass of the sandwich structure bracket, the polyvinyl alcohol accounts for 10-48% of the total mass of the sandwich structure bracket, and the nano hydroxyapatite accounts for 4.5-12% of the total mass of the sandwich structure bracket.
Preferably, the sandwich structure scaffold contains a plurality of ABA repeating units, for example, the number of ABA repeating units is 2-10.
The second aspect of the invention provides a preparation method of a sandwich structure bracket.
Specifically, the preparation method of the sandwich structure bracket comprises the following steps:
(1) Preparing polylactic acid, nano hydroxyapatite and a solvent into a polylactic acid/nano hydroxyapatite composite spinning solution, and then preparing a composite fiber membrane by using a spinning technology;
(2) Mixing polylactic acid, nano hydroxyapatite, polyvinyl alcohol and a solvent, stirring, centrifuging, and freeze-drying to obtain composite microspheres;
(3) Dissolving polyvinyl alcohol and water to obtain a polyvinyl alcohol solution, adding the composite microspheres prepared in the step (2), and stirring to obtain mixed slurry;
(4) And (3) taking the composite fiber membrane prepared in the step (1) as an A layer, placing a die on the surface of the A layer, adding the mixed slurry prepared in the step (3) into the die to form a B layer, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as the A layer, and drying to prepare the sandwich structure bracket.
Preferably, in step (1), the solvent comprises dichloromethane and N, N-dimethylformamide.
Preferably, in step (1), the spinning technology is an electrostatic spinning technology, which is a conventional technology.
Preferably, in the step (1), polylactic acid is firstly dissolved in methylene dichloride to obtain a polylactic acid solution, then nano hydroxyapatite is dispersed in N, N-dimethylformamide to obtain a nano hydroxyapatite mixture, and then the nano hydroxyapatite mixture is added into the polylactic acid solution and stirred to obtain the polylactic acid/nano hydroxyapatite composite spinning solution.
Preferably, in the step (1), 0.1 to 0.5g of polylactic acid is dissolved in 3 to 5mL of methylene chloride to obtain a polylactic acid solution.
Preferably, in step (1), 0.1 to 0.5g of nano-hydroxyapatite is dispersed in 1 to 5mLN, N-dimethylformamide to obtain a nano-hydroxyapatite mixture.
Preferably, in the step (2), polylactic acid is firstly dissolved in dichloromethane to obtain a polylactic acid solution, then polyvinyl alcohol is dissolved in water to obtain a polyvinyl alcohol solution, then nano hydroxyapatite is dispersed in the polylactic acid solution, the polyvinyl alcohol solution is added, and the composite microsphere is prepared by mixing, stirring, centrifuging and freeze-drying.
Preferably, in the step (2), 0.3-1g of polylactic acid is dissolved in 80-120mL of methylene chloride to obtain a polylactic acid solution.
Preferably, in the step (2), 4-10g of polyvinyl alcohol is dissolved in 800-1200mL of water to obtain a polyvinyl alcohol solution.
The polyvinyl alcohol is used as an emulsifier, the viscosity of the polyvinyl alcohol is obviously increased along with the increase of the concentration of the emulsifier, the mutual collision resistance among microspheres is increased, the microspheres are uniformly dispersed, and the coagulation phenomenon is reduced.
Preferably, in the step (2), the mass ratio of the addition amount of the nano hydroxyapatite to the polylactic acid is 0.01-0.5g (0.2-1.2 g); further preferably, the mass ratio of the nano-hydroxyapatite to the polylactic acid is 0.01-0.1g (0.3-1 g).
Preferably, in step (2), the freeze-drying temperature is from-40 ℃ to-10 ℃.
Preferably, in the step (3), the mass concentration of the polyvinyl alcohol solution is 4-20%; further preferably, the polyvinyl alcohol solution has a mass concentration of 5 to 15%.
Preferably, in the step (3), the mass ratio of the polyvinyl alcohol to the composite microspheres in the mixed slurry is 1 (0.5-6); it is further preferable that the mass ratio of the polyvinyl alcohol to the composite microsphere is 1 (1-4).
Preferably, in the step (4), the inner diameter of the die is 1-5cm, the outer diameter is 2-8cm, and the thickness is 100-350 μm respectively; further preferably, the size of the mold is 1-3cm in inner diameter, 2-5cm in outer diameter and 150-300 μm in thickness, respectively. The size of the die can be adjusted according to the requirement.
Preferably, in the step (4), the drying temperature is 30-90 ℃, and the drying process has the effect of drying and removing the solvent and also has the effect of curing.
The third aspect of the invention provides an application of the sandwich structure support.
The invention relates to application of a sandwich structure bracket in preparation of medical supplies.
Preferably, the medical article comprises a medical device.
Compared with the prior art, the invention has the following beneficial effects:
(1) The sandwich structure bracket sequentially comprises a layer A, a layer B and a layer A (namely the sandwich bracket with an ABA layered structure is formed, and a ABABA, ABABABA layered structure can be formed, namely a plurality of ABA repeating units are contained), wherein the layer A comprises a composite fiber membrane, the composite fiber membrane comprises polylactic acid/nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, the composite microspheres comprise polylactic acid and nano hydroxyapatite, the composite fiber membrane plays a role in transverse mechanical support, and a guiding function is provided for tissue growth; the B layer formed by the polyvinyl alcohol and the composite microspheres plays a role in longitudinal mechanical support between fiber film layers, so that the compression resistance of the sandwich structure support is remarkably improved, the gap collapse between the composite fiber film layers (namely the A layer) is further prevented, and a three-dimensional space structure is constructed between the composite fiber films for tissue growth.
(2) In the sandwich structure bracket, the requirements of serving as a cell growth carrier material in the field of tissue engineering can be met by controlling the molecular weight of polylactic acid. Specifically, the composite fiber membrane adopts polylactic acid (80-150 ten thousand) with higher molecular weight, the composite microsphere adopts polylactic acid (2-30 ten thousand) with lower molecular weight, the composite microsphere is degraded before the composite fiber membrane, and the B layer can be prepared by mixing microspheres with different diameters (10-120 mu m) and composite microspheres with polylactic acid (2-30 ten thousand) with different molecular weights, so that the degradation performance of the B layer is further regulated and controlled. The application of the sandwich structure support in the biomedical field is facilitated.
Drawings
FIG. 1 is a schematic structural diagram of a sandwich-structured stent according to embodiment 1 of the present invention;
FIG. 2 is a scanning electron microscope image of the composite fiber film produced in example 1 of the present invention;
FIG. 3 is a scanning electron microscope image of the composite microsphere prepared in example 1 of the present invention;
FIG. 4 is a cross-sectional scanning electron microscope view of a sandwich structure bracket prepared in embodiment 1 of the invention;
FIG. 5 is a cross-sectional scanning electron microscope view of a sandwich structure bracket made in embodiment 2 of the present invention;
FIG. 6 is a cross-sectional scanning electron microscope of a sandwich structure bracket according to embodiment 3 of the present invention;
FIG. 7 is a cross-sectional scanning electron microscope of a sandwich structure bracket according to embodiment 4 of the present invention;
FIG. 8 is a cross-sectional scanning electron microscope of a sandwich structure bracket according to example 5 of the present invention;
FIG. 9 is a cross-sectional scanning electron microscope of a sandwich structure bracket according to example 6 of the present invention;
FIG. 10 is a graph showing the load-displacement curve of the sandwich structure stent made in example 5 of the present invention;
FIG. 11 is a graph showing the load-displacement curve of the structural brace made in comparative example 1 of the present invention;
FIG. 12 is a graph showing load-displacement curves of the structural brace made in comparative example 2 of the present invention;
FIG. 13 is a graph showing Young's modulus of the structural scaffolds prepared in example 5, comparative example 1 and comparative example 2;
FIG. 14 is a graph showing degradation rates of the structural scaffolds prepared in example 5, comparative example 1 and comparative example 2;
FIG. 15 shows the pH change during degradation of the scaffolds prepared in example 5, comparative example 1 and comparative example 2;
FIG. 16 is a scanning electron microscope image of the composite microsphere after degradation of the structural scaffold 14d prepared in example 5;
FIG. 17 is a scanning electron microscope image of the composite microsphere after degradation of the structural scaffold 14d prepared in comparative example 2.
Detailed Description
In order to make the technical solutions of the present invention more apparent to those skilled in the art, the following examples will be presented. It should be noted that the following examples do not limit the scope of the invention.
The starting materials, reagents or apparatus used in the following examples are all available from conventional commercial sources or may be obtained by methods known in the art unless otherwise specified.
Example 1: preparation of sandwich structure bracket
The sandwich structure support comprises a layer A, a layer B, a layer A, a layer B and a layer A in sequence from bottom to top, wherein the layer A comprises a composite fiber membrane, the composite fiber membrane comprises polylactic acid and nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, and the composite microspheres comprise polylactic acid and nano hydroxyapatite.
In the sandwich structure bracket, polylactic acid accounts for 76.15 percent of the total mass of the sandwich structure bracket, polyvinyl alcohol accounts for 15.39 percent of the total mass of the sandwich structure bracket, and nano hydroxyapatite accounts for 8.46 percent of the total mass of the sandwich structure bracket.
The thickness of the layer A is 30 mu m; the thickness of layer B was 100. Mu.m.
In the layer A, the weight average molecular weight of the polylactic acid is 90 ten thousand; in the layer B, the weight average molecular weight of polylactic acid was 10 ten thousand.
The diameter of the fibers in the composite fiber film was 500nm.
The preparation method of the sandwich structure bracket comprises the following steps:
(1) Dissolving 0.3g of polylactic acid in 4mL of dichloromethane to obtain a polylactic acid solution, then ultrasonically dispersing 0.033g of nano-hydroxyapatite in 2mL of N, N-dimethylformamide for half an hour to obtain a nano-hydroxyapatite mixture, then adding the nano-hydroxyapatite mixture into the polylactic acid solution, stirring for 12 hours to obtain a polylactic acid/nano-hydroxyapatite composite spinning solution, and then utilizing an electrostatic spinning technology (the electrostatic spinning technology is carried out in an electrostatic spinning machine, during the spinning process, a 21-gauge needle is used, the positive voltage of the electrostatic spinning machine is 8.8KV, the negative voltage is 2.5KV, the receiving distance is 20cm, the indoor temperature is controlled at 25 ℃ by using an air conditioner, and the indoor relative humidity is controlled at 40% by using a dehumidifier to prepare a composite fiber membrane;
(2) Dissolving 0.5g of polylactic acid in 100mL of dichloromethane to obtain a polylactic acid solution, dissolving 5g of polyvinyl alcohol in 1000mL of ultrapure water to obtain a polyvinyl alcohol solution, ultrasonically dispersing 0.05g of nano hydroxyapatite in the polylactic acid solution, adding the polyvinyl alcohol solution, mixing and stirring (the stirring speed is 100 rpm), standing, centrifugally washing for 4 times by using ultrapure water, and freeze-drying at-20 ℃, thereby obtaining composite microspheres, wherein the diameter average value of the composite microspheres is 20 mu m;
(3) Adding 0.25g of polyvinyl alcohol into 3mL of ultrapure water, heating to 80 ℃ and stirring for dissolution for 1 hour, cooling to room temperature of 25 ℃ and continuing stirring to obtain a polyvinyl alcohol solution; adding 1g of the composite microsphere prepared in the step (2) into 2mL of ultrapure water, performing ultrasonic dispersion for 0.5 hour, then adding into a polyvinyl alcohol solution, and stirring for 2 hours to obtain mixed slurry;
(4) Paving the composite fiber membrane prepared in the step (1) on a workbench as an A layer, placing a die (the inner diameter of the die is 2cm, the outer diameter of the die is 2.5cm, the thickness of the die is 200 mu m respectively) on the surface of the A layer, adding the mixed slurry prepared in the step (3) into the die, horizontally spreading the mixed slurry in the die to form B layers, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as an A layer, then placing the die on the surface of the A layer, adding the mixed slurry into the die, horizontally spreading the mixed slurry in the die to form B layers, then placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as an A layer (namely, forming an ABABBA structure), firstly drying at 30 ℃ for 15 minutes, and then heating and curing at 90 ℃ for 1 hour to prepare the sandwich structure bracket, wherein the thickness of each A layer is 30 mu m, and the thickness of each B layer is 100 mu m.
FIG. 1 is a schematic structural diagram of a sandwich-structured stent according to embodiment 1 of the present invention; 100 in fig. 1 represents a layer a, and 200 represents a layer B.
FIG. 2 is a scanning electron microscope image of the composite fiber film produced in example 1 of the present invention; FIG. 3 is a scanning electron microscope image of the composite microsphere prepared in example 1 of the present invention; FIG. 4 is a cross-sectional scanning electron microscope image of a sandwich structure bracket made in example 1 of the present invention.
Example 2: preparation of sandwich structure bracket
The sandwich structure support comprises a layer A, a layer B, a layer A, a layer B and a layer A in sequence from bottom to top, wherein the layer A comprises a composite fiber membrane, the composite fiber membrane comprises polylactic acid and nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, and the composite microspheres comprise polylactic acid and nano hydroxyapatite.
In the sandwich structure bracket, polylactic acid accounts for 64.94 percent of the total mass of the sandwich structure bracket, polyvinyl alcohol accounts for 29.41 percent of the total mass of the sandwich structure bracket, and nano hydroxyapatite accounts for 5.65 percent of the total mass of the sandwich structure bracket.
The thickness of the layer A is 20 mu m; the thickness of layer B was 150. Mu.m.
In the layer A, the weight average molecular weight of the polylactic acid is 100 ten thousand; in the layer B, the weight average molecular weight of polylactic acid was 10 ten thousand.
The diameter of the fibers in the composite fiber film was 450nm.
The preparation method of the sandwich structure bracket comprises the following steps:
(1) Dissolving 0.3g of polylactic acid in 4mL of dichloromethane to obtain a polylactic acid solution, then ultrasonically dispersing 0.026g of nano hydroxyapatite in 2mL of N, N-dimethylformamide for half an hour to obtain a nano hydroxyapatite mixture, then adding the nano hydroxyapatite mixture into the polylactic acid solution, stirring for 12 hours to obtain a polylactic acid/nano hydroxyapatite composite spinning solution, and then utilizing an electrostatic spinning technology (the electrostatic spinning technology is carried out in an electrostatic spinning machine, during the spinning process, a 21-gauge needle is used, the positive voltage of the electrostatic spinning machine is 8.8KV, the negative voltage is 2.5KV, the receiving distance is 20cm, the indoor temperature is controlled at 25 ℃ by using an air conditioner, and the indoor relative humidity is controlled at 40% by using a dehumidifier to prepare a composite fiber membrane;
(2) Dissolving 0.5g of polylactic acid in 100mL of dichloromethane to obtain a polylactic acid solution, then dissolving 5g of polyvinyl alcohol in 1000mL of ultrapure water to obtain a polyvinyl alcohol solution, then ultrasonically dispersing 0.04g of nano hydroxyapatite in the polylactic acid solution, adding the polyvinyl alcohol solution, mixing and stirring, standing, centrifugally washing for 4 times by using the ultrapure water, and freeze-drying at-20 ℃ to obtain composite microspheres, wherein the diameter average value of the composite microspheres is 20 mu m;
(3) Adding 0.4g of polyvinyl alcohol into 3mL of ultrapure water, heating to 80 ℃ and stirring for dissolution for 1 hour, cooling to room temperature of 25 ℃ and continuing stirring to obtain a polyvinyl alcohol solution; adding 1.2g of the composite microsphere prepared in the step (2) into 2mL of ultrapure water, ultrasonically dispersing for 0.5 hour, then adding into a polyvinyl alcohol solution, and stirring for 2 hours to obtain mixed slurry;
(4) Paving the composite fiber membrane prepared in the step (1) on a workbench as an A layer, placing a die (the inner diameter of the die is 2cm, the outer diameter of the die is 2.5cm, the thickness of the die is 250 mu m) on the surface of the A layer, adding the mixed slurry prepared in the step (3) into the die, horizontally spreading the mixed slurry in the die to form B layers, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as an A layer, then placing the die on the surface of the A layer, adding the mixed slurry into the die, horizontally spreading the mixed slurry in the die to form B layers, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as an A layer (namely, forming an ABABBA structure), firstly drying at 40 ℃ for 15 minutes, and then heating and curing at 80 ℃ for 1 hour to prepare the sandwich structure bracket, wherein the thickness of each A layer is 20 mu m, and the thickness of each B layer is 150 mu m.
FIG. 5 is a cross-sectional scanning electron microscope image of a sandwich structure bracket made in example 2 of the present invention.
Example 3: preparation of sandwich structure bracket
The sandwich structure support comprises a layer A, a layer B, a layer A, a layer B and a layer A in sequence from bottom to top, wherein the layer A comprises a composite fiber membrane, the composite fiber membrane comprises polylactic acid and nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, and the composite microspheres comprise polylactic acid and nano hydroxyapatite.
In the sandwich structure bracket, polylactic acid accounts for 46.36 percent of the total mass of the sandwich structure bracket, polyvinyl alcohol accounts for 45.46 percent of the total mass of the sandwich structure bracket, and nano hydroxyapatite accounts for 8.18 percent of the total mass of the sandwich structure bracket.
The thickness of the layer A is 5 mu m; the thickness of layer B was 50. Mu.m.
In the layer A, the weight average molecular weight of the polylactic acid is 80 ten thousand; in the layer B, the weight average molecular weight of polylactic acid was 15 ten thousand.
The diameter of the fibers in the composite fiber film was 600nm.
The preparation method of the sandwich structure bracket comprises the following steps:
(1) Dissolving 0.3g of polylactic acid in 4mL of dichloromethane to obtain a polylactic acid solution, then ultrasonically dispersing 0.053g of nano-hydroxyapatite in 2mL of N, N-dimethylformamide for half an hour to obtain a nano-hydroxyapatite mixture, then adding the nano-hydroxyapatite mixture into the polylactic acid solution, stirring for 12 hours to obtain a polylactic acid/nano-hydroxyapatite composite spinning solution, and then utilizing an electrostatic spinning technology (the electrostatic spinning technology is carried out in an electrostatic spinning machine, during the spinning process, a 21-gauge needle is used, the positive voltage of the electrostatic spinning machine is 8.8KV, the negative voltage is 2.5KV, the receiving distance is 20cm, the indoor temperature is controlled at 25 ℃ by using an air conditioner, and the indoor relative humidity is controlled at 40% by using a dehumidifier to prepare a composite fiber membrane;
(2) Dissolving 0.5g of polylactic acid in 100mL of dichloromethane to obtain a polylactic acid solution, then dissolving 5g of polyvinyl alcohol in 1000mL of ultrapure water to obtain a polyvinyl alcohol solution, then ultrasonically dispersing 0.075g of nano hydroxyapatite in the polylactic acid solution, adding the polyvinyl alcohol solution, mixing and stirring, standing, centrifugally washing for 4 times by using the ultrapure water, and freeze-drying at-30 ℃, thereby obtaining composite microspheres, wherein the diameter average value of the composite microspheres is 40 mu m;
(3) Adding 0.4g of polyvinyl alcohol into 3mL of ultrapure water, heating to 80 ℃ and stirring for dissolution for 1 hour, cooling to room temperature of 25 ℃ and continuing stirring to obtain a polyvinyl alcohol solution; adding 0.8g of the composite microsphere prepared in the step (2) into 2mL of ultrapure water, performing ultrasonic dispersion for 0.5 hour, adding the mixture into a polyvinyl alcohol solution, and stirring for 2 hours to obtain mixed slurry;
(4) Paving the composite fiber membrane prepared in the step (1) on a workbench as an A layer, placing a die (the inner diameter of the die is 2cm, the outer diameter of the die is 2.5cm, the thickness of the die is 250 mu m) on the surface of the A layer, adding the mixed slurry prepared in the step (3) into the die, horizontally spreading the mixed slurry in the die to form B layers, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as an A layer, then placing the die on the surface of the A layer, adding the mixed slurry into the die, horizontally spreading the mixed slurry in the die to form B layers, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as an A layer (namely, forming an ABBA structure), firstly drying at 45 ℃ for 15 minutes, and then heating and curing at 60 ℃ for 1 hour to obtain the sandwich structure bracket, wherein the thickness of each A layer is 5 mu m, and the thickness of each B layer is 50 mu m.
FIG. 6 is a cross-sectional scanning electron microscope image of a sandwich structure bracket made in example 3 of the present invention.
Example 4: preparation of sandwich structure bracket
The sandwich structure support comprises a layer A, a layer B, a layer A, a layer B and a layer A in sequence from bottom to top, wherein the layer A comprises a composite fiber membrane, the composite fiber membrane comprises polylactic acid and nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, and the composite microspheres comprise polylactic acid and nano hydroxyapatite.
In the sandwich structure bracket, polylactic acid accounts for 75.6 percent of the total mass of the sandwich structure bracket, polyvinyl alcohol accounts for 16 percent of the total mass of the sandwich structure bracket, and nano hydroxyapatite accounts for 8.4 percent of the total mass of the sandwich structure bracket.
The thickness of the layer A is 25 mu m; the thickness of layer B was 100. Mu.m.
In the layer A, the weight average molecular weight of the polylactic acid is 100 ten thousand; in the layer B, the weight average molecular weight of polylactic acid was 20 ten thousand.
The diameter of the fibers in the composite fiber film was 550nm.
The preparation method of the sandwich structure bracket comprises the following steps:
(1) Dissolving 0.3g of polylactic acid in 4mL of dichloromethane to obtain a polylactic acid solution, then ultrasonically dispersing 0.033g of nano-hydroxyapatite in 2mL of N, N-dimethylformamide for half an hour to obtain a nano-hydroxyapatite mixture, then adding the nano-hydroxyapatite mixture into the polylactic acid solution, stirring for 12 hours to obtain a polylactic acid/nano-hydroxyapatite composite spinning solution, and then utilizing an electrostatic spinning technology (the electrostatic spinning technology is carried out in an electrostatic spinning machine, during the spinning process, a 21-gauge needle is used, the positive voltage of the electrostatic spinning machine is 8.8KV, the negative voltage is 2.5KV, the receiving distance is 20cm, the indoor temperature is controlled at 20 ℃ by using an air conditioner, and the indoor relative humidity is controlled at 40% by using a dehumidifier to prepare a composite fiber membrane;
(2) Dissolving 0.5g of polylactic acid in 100mL of dichloromethane to obtain a polylactic acid solution, then dissolving 5g of polyvinyl alcohol in 1000mL of ultrapure water to obtain a polyvinyl alcohol solution, then ultrasonically dispersing 0.05g of nano hydroxyapatite in the polylactic acid solution, adding the polyvinyl alcohol solution, mixing and stirring, standing, centrifugally washing for 4 times by using the ultrapure water, and freeze-drying at-20 ℃ to obtain composite microspheres, wherein the diameter average value of the composite microspheres is 30 mu m;
(3) Adding 0.5g of polyvinyl alcohol into 3mL of ultrapure water, heating to 80 ℃ and stirring for dissolution for 1 hour, cooling to room temperature of 25 ℃ and continuing stirring to obtain a polyvinyl alcohol solution; adding 2g of the composite microsphere prepared in the step (2) into 2mL of ultrapure water, performing ultrasonic dispersion for 0.5 hour, then adding into a polyvinyl alcohol solution, and stirring for 2 hours to obtain mixed slurry;
(4) Paving the composite fiber membrane prepared in the step (1) on a workbench as an A layer, placing a die (the inner diameter of the die is 1cm, the outer diameter of the die is 2cm, the thickness of the die is 200 mu m respectively) on the surface of the A layer, adding the mixed slurry prepared in the step (3) into the die, horizontally spreading the mixed slurry in the die to form B layers, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as the A layer, then placing the die on the surface of the A layer, adding the mixed slurry prepared in the step (3) into the die, horizontally spreading the mixed slurry in the die to form B layers, then placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as the A layer (namely, forming an ABABBA structure), firstly drying at 40 ℃ for 15 minutes, and then heating and curing at 90 ℃ for 1 hour to prepare the sandwich structure bracket, wherein the thickness of each A layer is 25 mu m, and the thickness of each B layer is 100 mu m.
FIG. 7 is a cross-sectional scanning electron microscope image of a sandwich structure bracket made in example 4 of the present invention.
Example 5: preparation of sandwich structure bracket
The sandwich structure support comprises a layer A, a layer B, a layer A, a layer B and a layer A in sequence from bottom to top, wherein the layer A comprises a composite fiber membrane, the composite fiber membrane comprises polylactic acid and nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, and the composite microspheres comprise polylactic acid and nano hydroxyapatite.
In the sandwich structure bracket, polylactic acid accounts for 72 percent of the total mass of the sandwich structure bracket, polyvinyl alcohol accounts for 21.74 percent of the total mass of the sandwich structure bracket, and nano hydroxyapatite accounts for 6.26 percent of the total mass of the sandwich structure bracket.
The thickness of the layer A is 30 mu m; the thickness of layer B was 200. Mu.m.
In the layer A, the weight average molecular weight of the polylactic acid is 100 ten thousand; in the layer B, the weight average molecular weight of polylactic acid was 15 ten thousand.
The diameter of the fibers in the composite fiber film was 550nm.
The preparation method of the sandwich structure bracket comprises the following steps:
(1) Dissolving 0.3g of polylactic acid in 4mL of dichloromethane to obtain a polylactic acid solution, then ultrasonically dispersing 0.026g of nano hydroxyapatite in 2mL of N, N-dimethylformamide for half an hour to obtain a nano hydroxyapatite mixture, then adding the nano hydroxyapatite mixture into the polylactic acid solution, stirring for 12 hours to obtain a polylactic acid/nano hydroxyapatite composite spinning solution, and then utilizing an electrostatic spinning technology (the electrostatic spinning technology is carried out in an electrostatic spinning machine, during the spinning process, a 21-gauge needle is used, the positive voltage of the electrostatic spinning machine is 8.8KV, the negative voltage is 2.5KV, the receiving distance is 20cm, the indoor temperature is controlled at 20 ℃ by using an air conditioner, and the indoor relative humidity is controlled at 40% by using a dehumidifier to prepare a composite fiber membrane;
(2) Dissolving 0.5g of polylactic acid in 100mL of dichloromethane to obtain a polylactic acid solution, then dissolving 5g of polyvinyl alcohol in 1000mL of ultrapure water to obtain a polyvinyl alcohol solution, then ultrasonically dispersing 0.04g of nano hydroxyapatite in the polylactic acid solution, adding the polyvinyl alcohol solution, mixing and stirring, standing, centrifugally washing for 4 times by using the ultrapure water, and freeze-drying at-20 ℃ to obtain composite microspheres, wherein the mass content of the nano hydroxyapatite in the composite microspheres is 10%, and the diameter average value of the composite microspheres is 45 mu m;
(3) Adding 0.5g of polyvinyl alcohol into 3mL of ultrapure water, heating to 80 ℃ and stirring for dissolution for 1 hour, cooling to room temperature of 25 ℃ and continuing stirring to obtain a polyvinyl alcohol solution; adding 1.5g of the composite microsphere prepared in the step (2) into 2mL of ultrapure water, performing ultrasonic dispersion for 0.5 hour, adding into a polyvinyl alcohol solution, and stirring for 2 hours to obtain mixed slurry;
(4) Paving the composite fiber membrane prepared in the step (1) on a workbench as an A layer, placing a die (the inner diameter of the die is 3cm, the outer diameter of the die is 5cm, the thickness of the die is 300 mu m respectively) on the surface of the A layer, adding the mixed slurry prepared in the step (3) into the die, horizontally spreading the mixed slurry in the die to form B layers, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as the A layer, then placing the die on the surface of the A layer, adding the mixed slurry prepared in the step (3) into the die, horizontally spreading the mixed slurry in the die to form B layers, then placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as the A layer (namely, forming an ABABBA structure), firstly drying at 40 ℃ for 15 minutes, and then heating and curing at 90 ℃ for 1 hour to prepare the sandwich structure bracket, wherein the thickness of each A layer is 30 mu m, and the thickness of each B layer is 200 mu m.
FIG. 8 is a cross-sectional scanning electron microscope image of a sandwich structure bracket made in example 5 of the present invention.
Example 6: preparation of sandwich structure bracket
The sandwich structure support comprises a layer A, a layer B, a layer A, a layer B and a layer A in sequence from bottom to top, wherein the layer A comprises a composite fiber membrane, the composite fiber membrane comprises polylactic acid and nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, and the composite microspheres comprise polylactic acid and nano hydroxyapatite.
In the sandwich structure bracket, polylactic acid accounts for 63.16 percent of the total mass of the sandwich structure bracket, polyvinyl alcohol accounts for 25.69 percent of the total mass of the sandwich structure bracket, and nano hydroxyapatite accounts for 11.15 percent of the total mass of the sandwich structure bracket.
The thickness of the layer A is 15 mu m; the thickness of layer B was 50. Mu.m.
In the layer A, the weight average molecular weight of the polylactic acid is 90 ten thousand; in the layer B, the weight average molecular weight of polylactic acid was 20 ten thousand.
The diameter of the fibers in the composite fiber film was 500nm.
The preparation method of the sandwich structure bracket comprises the following steps:
(1) Dissolving 0.3g of polylactic acid in 4mL of dichloromethane to obtain a polylactic acid solution, then ultrasonically dispersing 0.053g of nano-hydroxyapatite in 2mL of N, N-dimethylformamide for half an hour to obtain a nano-hydroxyapatite mixture, then adding the nano-hydroxyapatite mixture into the polylactic acid solution, stirring for 12 hours to obtain a polylactic acid/nano-hydroxyapatite composite spinning solution, and then utilizing an electrostatic spinning technology (the electrostatic spinning technology is carried out in an electrostatic spinning machine, during the spinning process, a 21-gauge needle is used, the positive voltage of the electrostatic spinning machine is 8.8KV, the negative voltage is 2.5KV, the receiving distance is 20cm, the indoor temperature is controlled at 20 ℃ by using an air conditioner, the indoor relative humidity is controlled at 40% by using a dehumidifier to obtain a composite fiber membrane, wherein the mass content of the nano-hydroxyapatite is 8%;
(2) Dissolving 0.5g of polylactic acid in 100mL of dichloromethane to obtain a polylactic acid solution, then dissolving 5g of polyvinyl alcohol in 1000mL of ultrapure water to obtain a polyvinyl alcohol solution, then ultrasonically dispersing 0.075g of nano hydroxyapatite in the polylactic acid solution, adding the polyvinyl alcohol solution, mixing and stirring, standing, centrifugally washing for 4 times by using the ultrapure water, and freeze-drying at-20 ℃ to obtain composite microspheres, wherein the mass content of the nano hydroxyapatite in the composite microspheres is 10%, and the diameter average value of the composite microspheres is 30 mu m;
(3) Adding 0.25g of polyvinyl alcohol into 3mL of ultrapure water, heating to 80 ℃ and stirring for dissolution for 1 hour, cooling to room temperature of 25 ℃ and continuing stirring to obtain a polyvinyl alcohol solution; adding 0.5g of the composite microsphere prepared in the step (2) into 2mL of ultrapure water, performing ultrasonic dispersion for 0.5 hour, adding the mixture into a polyvinyl alcohol solution, and stirring for 2 hours to obtain mixed slurry;
(4) Paving the composite fiber membrane prepared in the step (1) on a workbench as an A layer, placing a die (the inner diameter of the die is 2cm, the outer diameter of the die is 2.5cm, the thickness of the die is 150 mu m) on the surface of the A layer, adding the mixed slurry prepared in the step (3) into the die, horizontally spreading the mixed slurry in the die to form B layers, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as an A layer, then placing the die on the surface of the A layer, adding the mixed slurry into the die, horizontally spreading the mixed slurry in the die to form B layers, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as an A layer (namely, forming an ABABBA structure), firstly drying at 35 ℃ for 15 minutes, and then heating and curing at 90 ℃ for 1 hour to prepare the sandwich structure bracket, wherein the thickness of each A layer is 15 mu m, and the thickness of each B layer is 50 mu m.
FIG. 9 is a cross-sectional scanning electron microscope image of a sandwich structure bracket made in example 6 of the present invention.
Example 7: preparation of sandwich structure bracket
The sandwich structure support comprises a layer A, a layer B and a layer A from bottom to top in sequence, wherein the layer A comprises a composite fiber film, the composite fiber film comprises polylactic acid and nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, and the composite microspheres comprise polylactic acid and nano hydroxyapatite.
In the sandwich structure bracket, polylactic acid accounts for 72 percent of the total mass of the sandwich structure bracket, polyvinyl alcohol accounts for 20 percent of the total mass of the sandwich structure bracket, and nano hydroxyapatite accounts for 8 percent of the total mass of the sandwich structure bracket.
The thickness of the layer A is 50 mu m; the thickness of layer B was 200. Mu.m.
In the layer A, the weight average molecular weight of the polylactic acid is 100 ten thousand; in the layer B, the weight average molecular weight of polylactic acid was 10 ten thousand.
The diameter of the fibers in the composite fiber film was 450nm.
The preparation method of the sandwich structure bracket comprises the following steps:
(1) Dissolving 0.3g of polylactic acid in 4mL of dichloromethane to obtain a polylactic acid solution, then ultrasonically dispersing 0.033g of nano-hydroxyapatite in 2mL of N, N-dimethylformamide for half an hour to obtain a nano-hydroxyapatite mixture, then adding the nano-hydroxyapatite mixture into the polylactic acid solution, stirring for 12 hours to obtain a polylactic acid/nano-hydroxyapatite composite spinning solution, and then utilizing an electrostatic spinning technology (the electrostatic spinning technology is carried out in an electrostatic spinning machine, during the spinning process, a 21-gauge needle is used, the positive voltage of the electrostatic spinning machine is 8.8KV, the negative voltage is 2.5KV, the receiving distance is 20cm, the indoor temperature is controlled at 20 ℃ by using an air conditioner, the indoor relative humidity is controlled at 40% by using a dehumidifier to obtain a composite fiber membrane, wherein the mass content of the nano-hydroxyapatite is 8%;
(2) Dissolving 0.5g of polylactic acid in 100mL of dichloromethane to obtain a polylactic acid solution, then dissolving 5g of polyvinyl alcohol in 1000mL of ultrapure water to obtain a polyvinyl alcohol solution, then ultrasonically dispersing 0.05g of nano hydroxyapatite in the polylactic acid solution, adding the polyvinyl alcohol solution, mixing and stirring, standing, centrifugally washing for 4 times by using the ultrapure water, and freeze-drying at-20 ℃ to obtain composite microspheres, wherein the mass content of the nano hydroxyapatite in the composite microspheres is 10%, and the diameter average value of the composite microspheres is 40 mu m;
(3) Adding 0.25g of polyvinyl alcohol into 3mL of ultrapure water, heating to 80 ℃ and stirring for dissolution for 1 hour, cooling to room temperature of 25 ℃ and continuing stirring to obtain a polyvinyl alcohol solution; adding 0.75g of the composite microsphere prepared in the step (2) into 2mL of ultrapure water, performing ultrasonic dispersion for 0.5 hour, adding the mixture into a polyvinyl alcohol solution, and stirring for 2 hours to obtain mixed slurry;
(4) Paving the composite fiber membrane prepared in the step (1) on a workbench as an A layer, placing a die (the inner diameter of the die is 2cm, the outer diameter of the die is 2.5cm, the thickness of the die is 150 mu m respectively) on the surface of the A layer, then adding the mixed slurry prepared in the step (3) into the die, horizontally spreading the mixed slurry in the die to form a B layer, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as an A layer, freeze-drying at-40 ℃ for 15 minutes, and then heating and curing at 90 ℃ for 1 hour to prepare the sandwich structure bracket, wherein the thickness of each A layer is 50 mu m, and the thickness of each B layer is 200 mu m.
Example 8: preparation of sandwich structure bracket
Compared with the embodiment 1, the sandwich structure bracket in the embodiment 8 sequentially comprises an A layer, a B layer, an A layer, a B layer and an A layer from bottom to top, namely the embodiment 8 is more than the embodiment 1 in the B layer and the A layer, and other structures and processes are the same as the embodiment 1.
Comparative example 1
The structural support comprises an A layer, a B layer, an A layer, a B layer and an A layer from bottom to top in sequence, wherein the A layer comprises a composite fiber membrane, the composite fiber membrane comprises polylactic acid and nano hydroxyapatite, and the B layer comprises polyvinyl alcohol.
In the structural scaffold, polylactic acid accounts for 12% of the total mass of the structural scaffold, polyvinyl alcohol accounts for 86.95% of the total mass of the structural scaffold, and nano hydroxyapatite accounts for 1.05% of the total mass of the structural scaffold.
The thickness of the layer A is 30 mu m; the thickness of layer B was 200. Mu.m.
In the layer A, the weight average molecular weight of polylactic acid is 100 ten thousand.
The diameter of the fibers in the composite fiber film was 550nm.
The preparation method of the structural support comprises the following steps:
(1) Dissolving 0.3g of polylactic acid in 4mL of dichloromethane to obtain a polylactic acid solution, then ultrasonically dispersing 0.026g of nano hydroxyapatite in 2mL of N, N-dimethylformamide for half an hour to obtain a nano hydroxyapatite mixture, then adding the nano hydroxyapatite mixture into the polylactic acid solution, stirring for 12 hours to obtain a polylactic acid/nano hydroxyapatite composite spinning solution, and then utilizing an electrostatic spinning technology (the electrostatic spinning technology is carried out in an electrostatic spinning machine, during the spinning process, a 21-gauge needle is used, the positive voltage of the electrostatic spinning machine is 8.8KV, the negative voltage is 2.5KV, the receiving distance is 20cm, the indoor temperature is controlled at 20 ℃ by using an air conditioner, and the indoor relative humidity is controlled at 40% by using a dehumidifier to prepare a composite fiber membrane;
(2) Adding 0.5g of polyvinyl alcohol into 5mL of ultrapure water, heating to 80 ℃ and stirring for dissolution for 1 hour, cooling to room temperature of 25 ℃ and continuing stirring to obtain a polyvinyl alcohol solution;
(3) Laying the composite fiber film prepared in the step (1) on a workbench to serve as an A layer, placing a die (the inner diameter of the die is 3cm, the outer diameter of the die is 5cm, the thickness of the die is 300 mu m respectively) on the surface of the A layer, adding the polyvinyl alcohol solution prepared in the step (2) into the die, horizontally spreading the polyvinyl alcohol solution in the die to form B layers, placing the composite fiber film prepared in the step (1) on the surface of the B layer to serve as the A layer, then placing the die on the surface of the A layer, adding the polyvinyl alcohol solution in the step (2) into the die, horizontally spreading the polyvinyl alcohol solution in the die to form B layers, then placing the composite fiber film prepared in the step (1) on the surface of the B layer to serve as the A layers (namely, forming an ABA structure), firstly drying at 40 ℃ for 15 minutes, and then heating and curing at 90 ℃ for 1 hour to obtain the structural support, wherein the thickness of each A layer is 30 mu m, and the thickness of each B layer is 200 mu m.
Comparative example 2
The structural support only comprises a composite fiber film, wherein the composite fiber film comprises polylactic acid and nano hydroxyapatite.
In the structural scaffold, polylactic acid accounts for 92% of the total mass of the structural scaffold, and nano hydroxyapatite accounts for 8% of the total mass of the structural scaffold.
The thickness of the composite fiber film was 30. Mu.m.
In the composite fiber membrane, the weight average molecular weight of polylactic acid is 100 ten thousand.
The diameter of the fibers in the composite fiber film was 550nm.
The preparation method of the structural support comprises the following steps:
(1) Dissolving 0.3g of polylactic acid in 4mL of dichloromethane to obtain a polylactic acid solution, then ultrasonically dispersing 0.026g of nano hydroxyapatite in 2mL of N, N-dimethylformamide for half an hour to obtain a nano hydroxyapatite mixture, then adding the nano hydroxyapatite mixture into the polylactic acid solution, stirring for 12 hours to obtain a polylactic acid/nano hydroxyapatite composite spinning solution, and then utilizing an electrostatic spinning technology (the electrostatic spinning technology is carried out in an electrostatic spinning machine, during the spinning process, a 21-gauge needle is used, the positive voltage of the electrostatic spinning machine is 8.8KV, the negative voltage is 2.5KV, the receiving distance is 20cm, the indoor temperature is controlled at 20 ℃ by using an air conditioner, and the indoor relative humidity is controlled at 40% by using a dehumidifier to prepare a composite fiber membrane;
(2) And (3) spreading one layer of composite fiber membrane prepared in the step (1) on a workbench, continuing spreading another layer of composite fiber membrane on the workbench, accumulating and spreading six layers of composite fiber membranes, clamping the six layers of composite fiber membranes by using two cover slips, and drying at 40 ℃ for 10 minutes to prepare the structural support, wherein the thickness of the composite fiber membrane is 30 mu m.
Product effect test
1. Mechanical property test
The structural brackets prepared in example 5, comparative example 1 and comparative example 2 were subjected to nanoindentation experiments to test compressive strength.
The experimental procedure was as follows:
1. fixing the sample: the bottom surface of the sample is fixed to the slide using an adhesive, and the sample is firmly fixed to the slide waiting for the adhesive to sufficiently dry.
2. Defining a test area: placing the fixed sample and the glass slide on an objective table, fixing the glass slide in a vacuum adsorption mode with the test surface facing upwards, observing the test surface of the sample by using a self-contained microscope of equipment, selecting a proper area, and defining the area to be tested of the sample into software.
3. Selecting a position to be tested (a cross cursor in the center of a visual field), selecting a standard berkovich pressure head test method, clicking to start the test, removing a light mirror after the test starts, moving a probe to a target position, touching the surface of a sample with a very small contact force, then staying on the surface of the sample for waiting, starting to test according to the set maximum load of 1000 mu N after the system is stable, and completing the test, and withdrawing the probe from the surface of the sample.
The test samples were divided into the structural supports prepared in example 5, comparative example 1 and comparative example 2, and each group was tested for 6 indentation points. The results are shown in FIGS. 10-12.
FIG. 10 is a graph showing the load-displacement curve of the sandwich structure stent made in example 5 of the present invention; FIG. 11 is a graph showing the load-displacement curve of the structural brace made in comparative example 1 of the present invention; FIG. 12 is a graph showing load-displacement curves of the structural brace made in comparative example 2 of the present invention; in fig. 10 to 12, the ordinate "Load" represents the Load, and the abscissa "Depth" represents the displacement.
FIG. 13 is a graph showing Young's modulus of the structural scaffolds prepared in example 5, comparative example 1 and comparative example 2 (Young's modulus is shown on the ordinate in FIG. 13).
As can be seen from fig. 13, the young's modulus of the sandwich stent prepared in example 5 is 49.56 ±5.81MPa, the young's modulus of the sandwich stent prepared in comparative example 1 is 27.04±0.84MPa, and the young's modulus of the sandwich stent prepared in comparative example 2 is 4.64±2.05MPa. Therefore, the structural layer formed by the polyvinyl alcohol and the composite microspheres plays a role in longitudinal mechanical support between the fiber film layers, so that the compression resistance of the sandwich structure support is remarkably improved, and the gap collapse between the composite fiber film layers is further prevented.
2. In vitro degradation experiments
The structural scaffolds prepared in example 5, comparative example 1 and comparative example 2 were subjected to in vitro accelerated degradation experiments.
In order to accelerate the experimental progress, the experimental degradation temperature was set at 50 ℃. The specific experimental operation is as follows: the structural supports prepared in example 5, comparative example 1 and comparative example 2 were prepared in several masses and were first dried to constant weight in a thermostatic oven. Record the mass M of each group of materials Y Put into a 50mL centrifuge tube, then 40mL PBS (phosphate buffered saline) was added to make a label. Three replicates were set per material set. 1d, 3d, 7d, 14d ("d" means day) and removing the corresponding material, soaking the PBS in deionized water, centrifuging with a low-speed centrifuge for three times, freeze-drying, and finally drying to constant weight, wherein the mass is M J . The quality residual rate is calculated by a formula, and the degradation degree is reflected (the higher the quality residual rate is, the lower the degradation degree is, and the higher the degradation degree is).
Mass residual rate=m J /M Y ×100％。
And (3) carrying out scanning electron microscope photographing on the material with the calculated mass residual rate, and observing the fiber morphology change after the degradation of the fiber membrane. In addition, pH testing was performed on the liquid (PBS) that soaked the structural scaffold to observe the liquid pH change. The results are shown in FIGS. 14-17.
FIG. 14 is a graph showing the mass residual rate of the structural scaffolds prepared in example 5, comparative example 1 and comparative example 2 (the ordinate Mass residual rate in FIG. 14 represents the mass residual rate, and the abscissa Degradation time represents the Degradation time); FIG. 15 is a graph showing the pH change during Degradation of the structural scaffolds prepared in example 5, comparative example 1 and comparative example 2 (the abscissa "Degradation time" in FIG. 15 represents Degradation time); FIG. 16 is a scanning electron microscope image of the composite microsphere after degradation of the structural scaffold 14d prepared in example 5; FIG. 17 is a scanning electron microscope image of the composite microsphere after degradation of the structural scaffold 14d prepared in comparative example 2.
As can be seen from fig. 14 to 15, the structural stent manufactured in comparative example 2 had no tendency to decrease in mass residual rate and no change in pH, so that it was considered that comparative example 2 had substantially no degradation phenomenon within 14 days. The mass residual rate of both example 5 and comparative example 1 was significantly reduced, most significantly 1 day because the polyvinyl alcohol was dissolved in the solution, but because comparative example 1 was spread with the polyvinyl alcohol solution without composite microspheres, comparative example 1 was degraded more; the mass residual ratio of comparative example 1 remained substantially unchanged from 3 days to 14 days because comparative example 1 remained only the composite fiber which was difficult to degrade at this time; the mass residual rate of example 5 was slowly decreased according to the old trend from 3 days to 14 days, indicating that the composite microsphere was degrading at this time. In terms of pH, both example 5 and comparative example 1 had a decrease in pH, indicating that the slightly acidic polyvinyl alcohol dissolved in the solution, example 5 decreased more in pH than comparative example 1 due to degradation of the composite microspheres.
From the sem images of fig. 16-17, it is evident that the spherical state of the composite microsphere is no longer complete, and there is a significant defect, which demonstrates that the composite microsphere is degraded within 14d, while the composite fiber membrane remains substantially the same, so that the degradation rate and pH decrease is due to degradation of the composite microsphere rather than degradation of the composite fiber membrane.

Claims (10)

1. The sandwich structure support is characterized by sequentially comprising a layer A, a layer B and a layer A from bottom to top, wherein the layer A comprises a composite fiber membrane, the composite fiber membrane comprises polylactic acid and nano hydroxyapatite, the layer B comprises polyvinyl alcohol and composite microspheres, and the composite microspheres comprise polylactic acid and nano hydroxyapatite;
the sandwich structure bracket is prepared by a preparation method comprising the following steps:
(1) Preparing polylactic acid, nano hydroxyapatite and a solvent into a polylactic acid/nano hydroxyapatite composite spinning solution, and then preparing a composite fiber membrane by using a spinning technology;
(2) Mixing polylactic acid, nano hydroxyapatite, polyvinyl alcohol and a solvent, stirring, centrifuging, and freeze-drying to obtain composite microspheres;
(3) Dissolving polyvinyl alcohol and water to obtain a polyvinyl alcohol solution, adding the composite microspheres prepared in the step (2), and stirring to obtain mixed slurry;
(4) And (3) taking the composite fiber membrane prepared in the step (1) as an A layer, placing a die on the surface of the A layer, adding the mixed slurry prepared in the step (3) into the die to form a B layer, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as the A layer, and drying to prepare the sandwich structure bracket.
2. The sandwich structure scaffold of claim 1, wherein the mass ratio of nano-hydroxyapatite in the composite fiber film is 6-20%.
3. The sandwich structure scaffold of claim 1, wherein the molecular weight of the polylactic acid in the a layer is 80-150 ten thousand; in the layer B, the molecular weight of the polylactic acid is 2-30 ten thousand.
4. The sandwich structure scaffold of claim 1, wherein the mass ratio of polyvinyl alcohol to composite microspheres in the layer B is 1 (0.5-6).
5. The sandwich scaffold of claim 1, wherein the mass ratio of nano-hydroxyapatite in the composite microsphere is 5-20%.
6. The sandwich structure scaffold of claim 1, wherein the a layer has a thickness of 5-60 μιη; the thickness of the layer B is 30-300 mu m.
7. The sandwich structure scaffold of claim 1, wherein in the sandwich structure scaffold, the polylactic acid accounts for 40-85% of the total mass of the sandwich structure scaffold, the polyvinyl alcohol accounts for 5-52% of the total mass of the sandwich structure scaffold, and the nano-hydroxyapatite accounts for 3.5-15% of the total mass of the sandwich structure scaffold.
8. The sandwich structure scaffold of claim 1, wherein the sandwich structure scaffold comprises a plurality of ABA repeat units.
9. The method for preparing the sandwich structure bracket as claimed in any one of claims 1 to 8, which is characterized by comprising the following steps:
(1) Preparing polylactic acid, nano hydroxyapatite and a solvent into a polylactic acid/nano hydroxyapatite composite spinning solution, and then preparing a composite fiber membrane by using a spinning technology;
(2) Mixing polylactic acid, nano hydroxyapatite, polyvinyl alcohol and a solvent, stirring, centrifuging, and freeze-drying to obtain composite microspheres;
(3) Dissolving polyvinyl alcohol and water to obtain a polyvinyl alcohol solution, adding the composite microspheres prepared in the step (2), and stirring to obtain mixed slurry;
(4) And (3) taking the composite fiber membrane prepared in the step (1) as an A layer, placing a die on the surface of the A layer, adding the mixed slurry prepared in the step (3) into the die to form a B layer, placing the composite fiber membrane prepared in the step (1) on the surface of the B layer as the A layer, and drying to prepare the sandwich structure bracket.
10. Use of a sandwich scaffold according to any one of claims 1 to 8 in the manufacture of a medical article.
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