Coaxial calcium-silicon-based bioactive wire and preparation method and application thereof

Abstract

The application belongs to the technical field of biomedical materials and the technical field of regenerative medicine, and particularly relates to a coaxial calcium-silicon-based bioactive wire and a preparation method and application thereof. The coaxial calcium-silicon-based bioactive wire comprises a degradable polymer core layer and a calcium-silicon-based bioactive material shell layer, the calcium-silicon-based bioactive material shell layer comprises a natural biomaterial matrix and calcium-silicon-based bioactive material particles, and the natural biomaterial matrix is composed of one or more of natural polysaccharides and dopamine. A layer of calcium-silicon-based bioactive material is coated outside the degradable polymer core material, and the calcium-silicon-based bioactive material adheres to the surface of the degradable polymer core material by means of the natural biomaterial, which not only endows the degradable polymer with good bioactivity and biocompatibility, but also solves the problem of poor mechanical properties of calcium-silicon-based bioactive material fiber wire.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of biomedical materials and the technical field of regenerative medicine, and particularly relates to a coaxial calcium-silicon-based bioactive wire, a preparation method and application thereof. BACKGROUND

[0002] Medical wires have a wide range of applications in the medical field. Medical wire materials include common metal materials such as nickel-titanium, cobalt-chromium, stainless steel, and molybdenum wire, which are commonly used in instrument parts. In addition, medical wire materials also include polymer wires, especially biodegradable polymer wires, which can be used in absorbable surgical sutures and bone filling materials. After being prepared into films, they can be used as wound dressings and anti-adhesion films. However, polymer wires lack bioactivity and cannot promote tissue regeneration and repair. Moreover, they have poor cell adhesion and poor biocompatibility.

[0003] Calcium-silicon-based bioactive materials, including bioactive ceramics and bioactive glasses, are the only known bioactive materials that can chemically bond with bone tissue and also bond with soft tissue, and have good biocompatibility. Bioactive glass contains essential elements such as calcium, phosphorus, silicon, and oxygen. When in contact with body fluids, it releases a large amount of active ions, which mineralize to form a three-dimensional network of hydroxyapatite scaffolds on its surface and at the site of tissue damage, facilitating the orderly climbing and growth of cells. The release of active ions can induce cell differentiation, proliferation, and gene expression, promoting tissue regeneration.

[0004] Existing technologies use the good adhesion and biocompatibility of polydopamine to composite biodegradable polymers with bioactive glass, improving the bioactivity of biodegradable polymers and other issues. For example, one technology uses an electrospinning process to prepare polymer fibers, then immerses the polymer fibers in a dopamine solution, and the dopamine self-polymerizes into polydopamine on the surface of the fibers. The polymer fibers with polydopamine on their surface are immersed again in a bioactive glass solution, and the adhesion of polydopamine is used to adhere bioactive glass to the surface of the fibers. Another technology modifies polydopamine on the surface of bioactive glass and directly adds it to a polylactic acid electrospinning solution to obtain a mixed spinning solution, which is then prepared into a composite fiber through electrospinning technology.

[0005] However, in the process of implementing the above existing technologies, the inventors have found at least the following problems:

[0006] The method of immersing polymer fibers multiple times is complex and has a long production cycle, and it is difficult to ensure the loading amount of bioactive glass. Mixing the bioactive glass modified with polydopamine directly with the polylactic acid spinning solution can cause the mechanical properties of the polylactic acid fibers to decrease.

[0007] Therefore, the present application is proposed. SUMMARY

[0008] In view of the deficiencies of the prior art, one object of the present application is to provide a coaxial calcium-silicon-based bioactive wire, which is coated with a layer of calcium-silicon-based bioactive material outside a degradable polymer core material, and the calcium-silicon-based bioactive material adheres to the surface of the degradable polymer core material by means of natural biological material, thereby imparting good bioactivity and biocompatibility to the degradable polymer and solving the problem of poor mechanical properties of calcium-silicon-based bioactive material fiber wire.

[0009] Another object of the present application is to provide a preparation method and application of the coaxial calcium-silicon-based bioactive wire, which is integrally formed by coaxial spinning, thereby simplifying the production process and saving production costs.

[0010] The technical scheme of the present application is as follows:

[0011] In a first aspect, a coaxial calcium-silicon-based bioactive wire comprises a degradable polymer core layer and a calcium-silicon-based bioactive material shell layer, the calcium-silicon-based bioactive material shell layer contains a natural biological material matrix and calcium-silicon-based bioactive material particles, and the natural biological material matrix is composed of one or more of natural polysaccharides and dopamine.

[0012] Further, the degradable polymer core layer is composed of one or more of polylactide, polyglycolide-lactide copolymer, polycaprolactone, polyglycolic acid, polyvinyl alcohol, and polyhydroxyalkanoate;

[0013] And / or, the molecular weight of the degradable polymer used in the degradable polymer core layer is 100,000 to 1,500,000;

[0014] And / or, the natural polysaccharides include cellulose, chitin, chitosan, chondroitin sulfate, and algal polysaccharide;

[0015] And / or, the calcium-silicon-based bioactive material particles are composed of one or more of bioactive ceramics, bioactive glass, regenerated silicon, calcium phosphate silicate, and derivatives thereof.

[0016] Further, the diameter of the degradable polymer core layer is 1 μm to 1 mm;

[0017] And / or, the thickness of the calcium-silicon-based bioactive material shell layer is 500 nm to 500 μm;

[0018] And / or, in the calcium-silicon-based bioactive material shell layer, the mass percentage of calcium-silicon-based bioactive material particles is 0.1% to 60%.

[0019] Further, the diameter of the degradable polymer core layer is 5 μm to 760 μm;

[0020] And / or, the thickness of the calcium-silicon-based bioactive material shell layer is 800 nm to 250 μm.

[0021] And / or, the mass percentage of the calcium-silicon-based bioactive material particles in the calcium-silicon-based bioactive material shell layer is 1% to 35%.

[0022] In a second aspect, a preparation method of the coaxial calcium-silicon-based bioactive wire according to the first aspect comprises the following steps:

[0023] (1) Preparing a degradable polymer core layer solution: dissolving a degradable polymer in an organic solvent and mixing uniformly to obtain the degradable polymer core layer solution;

[0024] (2) Preparing a shell layer solution containing calcium-silicon-based bioactive material particles: first dissolving a natural biological material matrix in a suitable solvent and mixing uniformly to obtain a natural biological material matrix solution, then adding calcium-silicon-based bioactive material particles to the natural biological material matrix solution and mixing uniformly to obtain the shell layer solution containing calcium-silicon-based bioactive material particles;

[0025] (3) Injecting the degradable polymer core layer solution obtained in step (1) and the shell layer solution containing calcium-silicon-based bioactive material particles obtained in step (2) into a core layer solution syringe and a shell layer solution syringe respectively, using a coaxial needle to perform coaxial wet spinning, and then selecting anhydrous ethanol as a coagulation bath and / or an oven drying method to perform solidification, to obtain the calcium-silicon-based bioactive wire.

[0026] Further, the concentration of the degradable polymer core layer solution in step (1) is 0.05 g / mL to 0.50 g / mL;

[0027] And / or, the concentration of the natural biological material matrix solution in step (2) is 0.025 g / mL to 1.50 g / mL;

[0028] And / or, the particle size of the calcium-silicon-based bioactive material particles in step (2) is 20 nm to 80 μm.

[0029] Further, the concentration of the degradable polymer core layer solution in step (1) is 0.05 g / mL to 0.40 g / mL;

[0030] And / or, the concentration of the natural biological material matrix solution in step (2) is 0.025 g / mL to 1.20 g / mL;

[0031] And / or, the particle size of the calcium-silicon-based bioactive material particles in step (2) is 20 nm to 50 μm.

[0032] Further, the organic solvent in step (1) is one or a mixture of several of ethyl acetate, dichloromethane, acetone, 1,4-dioxane, N-methyl pyrrolidone, chloroform, tetrahydrofuran, hexafluoroisopropanol, acetonitrile, dichloroacetic acid;

[0033] Further, the coaxial wet spinning spinning technique in step (3) is that the degradable polymer core layer solution and the shell layer solution containing calcium-silicon-based bioactive material particles are injected through an injection head to obtain the coaxial calcium-silicon-based bioactive filament structure, and the injection head is a coaxial needle head with coaxially arranged inner and outer channels.

[0034] Further, the degradable polymer core layer solution is injected at an injection speed of 40 μL / min to 10 mL / min; further, the injection speed of the degradable polymer core layer solution is 100 μL / min to 6 mL / min.

[0035] Further, the shell layer solution containing calcium-silicon-based bioactive material particles is injected at an injection speed of 10 μL / min to 5 mL / min; further, the injection speed of the shell layer solution containing calcium-silicon-based bioactive material particles is 40 μL / min to 2 mL / min.

[0036] Further, the drying temperature in step (3) is 35℃ to 45℃; further, the drying temperature is 35℃ to 40℃.

[0037] Further, the drying in step (3) is vacuum drying, and the vacuum drying time is 8h to 72h, and the vacuum degree is -0.1MPa to 0.1MPa; further, the vacuum drying time is 12h to 48h, and the vacuum degree is -0.08MPa to 0.06MPa.

[0038] In a third aspect, the application provides the use of the coaxial calcium-silicon-based bioactive filament prepared by the preparation method of the coaxial calcium-silicon-based bioactive filament according to the first aspect or the second aspect in the field of absorbable surgical sutures, bone filling, wound dressings, and anti-adhesion membranes.

[0039] Compared with the prior art, the application has the following advantages:

[0040] (1) The coaxial calcium-silicon-based bioactive filament provided by the application combines the core layer degradable polymer with the shell layer calcium-silicon-based bioactive material, and adds natural polysaccharides and other natural biological materials to enhance the adhesion between the two, which improves the shortcomings of the degradable polymer lacking bioactivity and poor biocompatibility, and at the same time solves the problem of poor mechanical properties of calcium-silicon-based bioactive material fiber filament;

[0041] (2) The calcium-silicon-based bioactive wire provided by the application is a coaxial wire structure with a shell layer covering a core layer, and the calcium-silicon-based bioactive material is quantitatively distributed on the surface of the degradable polymer, without damaging the mechanical properties of the polymer wire, and has excellent tensile strength and flexibility;

[0042] (3) The coaxial injection head and wet spinning technology provided by the application can accurately control the diameter and thickness of the core layer and the shell layer, and the amount of calcium-silicon-based bioactive material, and has the advantages of simple production process, mild conditions, easy operation, low energy consumption, low cost, and realization of large-scale continuous production.

[0043] (4) The coaxial calcium-silicon-based bioactive wire provided by the application has important application advantages in absorbable surgical sutures, bone filling, wound dressings, anti-adhesion membranes and other fields. BRIEF DESCRIPTION OF DRAWINGS

[0044] In order to more clearly illustrate the specific embodiments of the present application or the technical solutions in the prior art, the drawings needed in the specific embodiments or the prior art description will be briefly introduced below. Obviously, the drawings in the following description are some embodiments of the present application, and those skilled in the art can also obtain other drawings according to these drawings without creative labor.

[0045] Figure 1 Schematic diagram of coaxial needle head spinning. DETAILED DESCRIPTION

[0046] In order to make the purpose, technical scheme and advantages of the present application more clear, the following will further illustrate the present application by combining with the embodiments. The embodiments of the present application are implemented on the premise of the technical scheme of the present application, and detailed implementation manner and process are given. Those skilled in the art should understand that the embodiments are only to help understanding the present application, and should not be regarded as specific limitation to the present application, and the protection scope of the present application is not limited to the following embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor are within the protection scope of the present application.

[0047] In the present application, the endpoints and any values of the disclosed ranges are not limited to the precise range or value, and these ranges or values should be understood to include values approximately around these ranges or values. For numerical ranges, the endpoints between each range, the endpoints between each range and individual point values, and the individual point values can be combined with each other to obtain one or more new numerical ranges, which should be regarded as specifically disclosed in the present application.

[0048] The embodiment of the present application provides a coaxial calcium-silicon-based bioactive wire, which comprises a degradable polymer core layer and a calcium-silicon-based bioactive material shell layer; the calcium-silicon-based bioactive material shell layer comprises a natural biological material matrix and calcium-silicon-based bioactive material particles; and the natural biological material matrix is composed of one or more of natural polysaccharides and dopamine.

[0049] In the above technical solution, the coaxial calcium-silicon-based bioactive wire combines the degradable polymer as the core layer with the calcium-silicon-based bioactive material as the shell layer and forms a core-shell structure, improves the biocompatibility of the core layer degradable polymer, and endows it with cell activity; at the same time, the core layer provides mechanical support for the shell layer and plays a bioactivity. The natural polysaccharide and other natural biological materials in the shell layer are added to enhance the adhesion between the degradable polymer and the calcium-silicon-based bioactive material, further improving the shortcomings of the degradable polymer lacking bioactivity and poor biocompatibility, and the calcium-silicon-based bioactive material is quantitatively distributed on the surface of the degradable polymer, without damaging the mechanical properties of the polymer wire, and the coaxial calcium-silicon-based bioactive wire has excellent tensile strength and flexibility. The coaxial calcium-silicon-based bioactive wire can be applied in many scenes, can be used as an absorbable surgical suture, can be applied to bone filling, and can be woven into a wound dressing and an anti-adhesion membrane.

[0050] In the above coaxial calcium-silicon-based bioactive wire, as an optional implementation manner, the degradable polymer core layer is composed of one or more of polylactide, polyglycolide-co-lactide, polycaprolactone, polyglycolic acid, polyvinyl alcohol and polyhydroxyalkanoate;

[0051] And / or, the molecular weight of the degradable polymer used in the degradable polymer core layer is 100,000-1,500,000 (such as 100,000, 200,000, 300,000, 400,000, 500,000, 600,000, 700,000, 800,000, 900,000, 1,000,000, 1,100,000, 1,200,000, 1,300,000, 1,400,000 and any numerical interval range).

[0052] And / or, the natural polysaccharide comprises cellulose, chitin, chitosan, chondroitin sulfate, algal polysaccharide and the like.

[0053] And / or, the calcium-silicon-based bioactive material particles are composed of one or more of bioactive ceramics, bioactive glass, regenerated silicon, calcium-phosphorus silicate and derivatives thereof.

[0054] In the above technical solution, although the calcium-silicon-based bioactive material particles have the self-hardening property, the self-hardening needs a long reaction time, and the activity of the bioactive material is lost in the process because the self-hardening is caused by the mineralization process of the calcium-silicon-based bioactive material, the mineralization process releases calcium and phosphorus active ions, and the original activity is greatly lost after the formation of hydroxyapatite. Therefore, the natural biomaterial matrix is added to the shell of the calcium-silicon-based bioactive material, and the calcium-silicon-based bioactive material particles are adhered to the degradable polymer core layer by using the adhesion of the natural biomaterial matrix such as natural polysaccharide.

[0055] The regenerated silicon mentioned in the present application can be prepared according to the method described in the patent application with publication number CN111017934A, or can use the regenerated silicon produced by Beijing Happiness Life Technology Co., Ltd. Any model of the regenerated silicon can be used in the present application. The material has a porous scaffold structure accumulated by nano-sized silicon dioxide particles, and calcium and phosphorus elements uniformly distributed in the scaffold, which is a biologically active calcium phosphate compound; the specific surface area of the regenerated silicon is 200-350 m2 / g. The regenerated silicon of the present application can also be a POSS-based regenerated medical material prepared according to the method described in the patent application with publication number CN109771692A, which is a polyhedral cage structure composed of Si-O-Si bonds in silicon oxide, and calcium and phosphorus elements embedded therein. The regenerated silicon of the present application can also be prepared according to the method described in the patent application with patent number CN110101904B.

[0056] In the above coaxial calcium-silicon-based bioactive wire, as an optional embodiment, the diameter of the degradable polymer core layer is 1 μm-1 mm (for example, 3 μm, 8 μm, 15 μm, 50 μm, 100 μm, 250 μm, 500 μm, 750 μm, 900 μm); further optionally, the diameter of the degradable polymer core layer is 5 μm-760 μm (for example, 10 μm, 25 μm, 50 μm, 80 μm, 120 μm, 250 μm, 400 μm, 600 μm, 750 μm);

[0057] In the above coaxial calcium-silicon-based bioactive wire, as an optional embodiment, the thickness of the calcium-silicon-based bioactive material shell is 500 nm-500 μm (for example, 550 nm, 750 nm, 1 μm, 5 μm, 10 μm, 50 μm, 100 μm, 200 μm, 400 μm); further optionally, the thickness of the calcium-silicon-based bioactive material shell is 800 nm-250 μm (for example, 950 nm, 1.5 μm, 4 μm, 12 μm, 35 μm, 60 μm, 100 μm, 200 μm);

[0058] In the coaxial calcium-silicon-based bioactive wire described above, as an optional embodiment, the mass percentage of calcium-silicon-based bioactive material particles in the calcium-silicon-based bioactive material shell layer is 0.1% to 60% (for example, 1%, 1.5%, 3%, 5%, 10%, 15%, 20%, 25%, 35%, 40%, 60%); further optionally, the mass percentage of calcium-silicon-based bioactive material particles is 1% to 35% (for example, 2%, 4%, 12%, 18%, 24%, 30%), and the mass percentage of calcium-silicon-based bioactive material particles has a greater impact on mechanical properties. Within this range, calcium-silicon-based bioactive material particles can be uniformly distributed in the shell layer, and the shell layer has better mechanical strength.

[0059] The preparation method of the coaxial calcium-silicon-based bioactive wire described above comprises the following steps:

[0060] (1) Prepare a degradable polymer core layer solution: dissolve the degradable polymer in an organic solvent, mix uniformly, such as continuous stirring until completely dissolved, to obtain the degradable polymer core layer solution;

[0061] (2) Prepare a shell layer solution containing calcium-silicon-based bioactive material particles: first, dissolve one or more of natural polysaccharides (including cellulose, chitin, chitosan, chondroitin sulfate, and algal polysaccharide) and dopamine in a suitable solvent, for example, cellulose, chitin, and chitosan are dissolved in a mixed aqueous solution of NaOH / urea (or carboxymethyl cellulose, carboxymethyl chitosan, etc. which can be directly dissolved in water), chondroitin sulfate and algal polysaccharide are dissolved in water, and dopamine is also dissolved in a Tris-HCl buffer solution, mix uniformly, such as continuous stirring until completely dissolved, to obtain a natural biomaterial matrix solution, then add calcium-silicon-based bioactive material particles to the natural biomaterial matrix solution, mix uniformly by stirring, to obtain the shell layer solution containing calcium-silicon-based bioactive material particles;

[0062] (3) Inject the degradable polymer core layer solution obtained in step (1) and the shell layer solution containing calcium-silicon-based bioactive material particles obtained in step (2) into a core layer solution syringe and a shell layer solution syringe, respectively, use a coaxial needle, perform coaxial wet spinning, then select anhydrous ethanol as a coagulation bath and / or an oven drying method for solidification, to obtain the calcium-silicon-based bioactive wire.

[0063] In the above technical solution, anhydrous ethanol can be selected as the coagulation bath for shaping. Some gaps will be generated between the materials during the process of coagulation of the shaped material in the coagulation bath, which will cause some pore structures of the calcium-silicon-based bioactive wire, and the pore structures will be retained after drying. The wire diameter will be small if the shaped material is directly dried without being immersed in the coagulation bath. In the present application, the coagulation mode can be selected according to the specific conditions of the wire, such as the required diameter and the required good shape of the fiber. If the required wire diameter is large, the wire can be shaped by using anhydrous ethanol coagulation bath + drying, which is helpful to maintain the shape of the coaxial fiber. If there is no coagulation bath, the shape of the coaxial fiber can be difficult to maintain. If the required wire diameter is small, the wire can be directly shaped by drying, so that the solvent volatilizes quickly and the wire will shrink seriously, thus becoming very small. In addition, in the case of using a coagulant, in order to maintain the shape of the coaxial fiber, the coagulant cannot dissolve the shell layer, and anhydrous ethanol is the most suitable coagulant. In the present application, when anhydrous ethanol is used as a coagulant for shaping, the wire needs to be placed in anhydrous ethanol for a certain period of time, generally 2-8 hours, which can completely shape the wire. In general, the wire can be basically shaped in 2 hours, and the static time of 2-8 hours has little effect on the mechanical properties of the wire.

[0064] As an optional embodiment, the concentration of the degradable polymer core layer solution in step (1) is 0.05 g / mL-0.50 g / mL (for example, 0.08 g / mL, 0.10 g / mL, 0.12 g / mL, 0.15 g / mL, 0.20 g / mL, 0.25 g / mL, 0.30 g / mL, 0.35 g / mL, 0.40 g / mL, 0.45 g / mL). The core layer in this range can provide sufficient mechanical support for the shell layer. If the concentration is too low, the shell layer cannot be provided with mechanical support, and the fiber extrusion difficulty increases beyond this concentration.

[0065] As an optional embodiment, the organic solvent in step (1) is one or a mixture of several of ethyl acetate, dichloromethane, acetone, 1,4-dioxane, N-methyl pyrrolidone, chloroform, tetrahydrofuran, hexafluoroisopropanol, acetonitrile, dichloroacetic acid. The core layer solvent can only dissolve the degradable polymer, which will be completely volatilized during the drying process and will not affect the mechanical properties.

[0066] As an optional embodiment, the concentration of the natural biomaterial matrix solution in step (2) is 0.025 g / mL to 1.50 g / mL (e.g., 0.05 g / mL, 0.08 g / mL, 0.12 g / mL, 0.20 g / mL, 0.35 g / mL, 0.50 g / mL, 0.80 g / mL, 1.0 g / mL, 1.20 g / mL, 1.40 g / mL); further optionally, the concentration of the natural biomaterial matrix solution is 0.025 g / mL to 1.20 g / mL (e.g., 0.05 g / mL, 0.08 g / mL, 0.11 g / mL, 0.15 g / mL, 0.18 g / mL, 0.25 g / mL, 0.30 g / mL, 0.40 g / mL, 0.60 g / mL, 1.10 g / mL).

[0067] As an optional embodiment, the particle size of the calcium-silicon-based bioactive material particles in step (2) is 20 nm to 80 μm (e.g., 30 nm, 80 nm, 150 nm, 350 nm, 500 nm, 800 nm, 1 μm, 5 μm, 10 μm, 30 μm, 50 μm, 75 μm); further optionally, the particle size of the calcium-silicon-based bioactive material particles is 20 nm to 50 μm (e.g., 30 nm, 80 nm, 150 nm, 350 nm, 600 nm, 750 nm, 1.2 μm, 3 μm, 8 μm, 12 μm, 20 μm, 35 μm, 45 μm).

[0068] As an optional embodiment, the coaxial wet spinning technique in step (3) is to inject the degradable polymer core layer solution and the shell layer solution containing calcium-silicon-based bioactive material particles through an injection head to obtain the coaxial calcium-silicon-based bioactive filament structure, and the injection head is a coaxial needle head with coaxially arranged inner and outer channels (as shown in FIG. 1). Figure 1 The filament diameter is determined by the core layer diameter and the shell layer thickness. The core layer diameter and the shell layer thickness are affected by the size of the injection head pipe diameter and the axial separation of the inner and outer channels, and also by the injection speed. Finally, the final filament diameter and the core layer diameter and the shell layer thickness are obtained after solidification and / or drying in the coagulation bath. Generally, in terms of the structure size of the injection head, the larger the diameter of the inner channel, the larger the core layer diameter. The closer the outer channel to the inner channel at the tip of the injection head, i.e., the smaller the shell layer exit spacing, the smaller the shell layer thickness. In terms of the injection speed, under the condition that the core layer injection speed is the same, the slower the shell layer speed, the greater the shell layer thickness. Under the condition that the shell layer injection speed is the same, the greater the core layer speed, the smaller the shell layer thickness, because the core layer speed is greater than the shell layer, which has a stretching effect on the shell layer. The greater the core layer speed, the more obvious the stretching effect, and the thinner the shell layer is stretched. In terms of the drying of the solvent, the greater the concentration of the solution of the shell layer and / or the core layer, the smaller the shrinkage degree, and the thicker the filament diameter.

[0069] As an optional embodiment, the degradable polymer core layer solution is injected at an injection rate of 40 μL / min to 10 mL / min (e.g., 60 μL / min, 80 μL / min, 100 μL / min, 250 μL / min, 500 μL / min, 800 μL / min, 1 mL / min, 2.5 mL / min, 5 mL / min, 8 mL / min); further optionally, the injection rate of the degradable polymer core layer solution is 100 μL / min to 6 mL / min (e.g., 150 μL / min, 250 μL / min, 350 μL / min, 450 μL / min, 550 μL / min, 750 μL / min, 1.2 mL / min, 2 mL / min, 2.5 mL / min, 3 mL / min, 4 mL / min, 5.5 mL / min);

[0070] As an optional embodiment, the shell layer solution containing calcium-silicon-based bioactive material particles is injected at an injection rate of 10 μL / min to 5 mL / min (e.g., 20 μL / min, 40 μL / min, 50 μL / min, 100 μL / min, 400 μL / min, 600 μL / min, 1 mL / min, 2 mL / min, 3 mL / min, 4 mL / min); further optionally, the injection rate of the shell layer solution containing calcium-silicon-based bioactive material particles is 40 μL / min to 2 mL / min (e.g., 50 μL / min, 60 μL / min, 75 μL / min, 1.2 mL / min, 2 mL / min, 2.5 mL / min, 3 mL / min, 4 mL / min, 5.5 mL / min);

[0071] As an optional embodiment, the temperature of the oven drying is 35°C to 45°C (e.g., 36°C, 38°C, 40°C, 42°C, 44°C); further optionally, the temperature of the oven drying is 35°C to 40°C (e.g., 36°C, 37°C, 38°C, 39°C); the upper limit of the temperature during drying should not exceed the tolerance temperature of the degradable polymer, such as the glass transition temperature of polylactic acid is about 55°C, so the maximum temperature for drying should not exceed 45°C.

[0072] As an optional embodiment, the drying in step (3) is vacuum drying, the vacuum drying time is 8h-72h (for example, 12h, 18h, 24h, 30h, 48h, 54h, 60h, 70h), and the vacuum degree of the vacuum drying is-0.1MPa-0.1MPa (for example, -0.08MPa, -0.05MPa, -0.03MPa, -0.01MPa, 0.01MPa, 0.03MPa, 0.05MPa, 0.08MPa); further optionally, the vacuum drying time is 12h-48h (for example, 16h, 20h, 24h, 32h, 36h, 45h), and the vacuum degree of the vacuum drying is-0.08MPa-0.06MPa (for example, -0.06MPa, -0.04MPa, -0.02MPa, -0.015MPa, 0MPa, 0.015MPa, 0.02MPa, 0.04MPa, 0.05MPa).

[0073] The application also provides application of the coaxial calcium-silicon-based bioactive wire in the fields of absorbable surgical sutures, bone filling, wound dressing, and anti-adhesion membranes.

[0074] The application will be further described below by examples, but the application is not limited to these examples.

[0075] The regenerated silicon used in the following examples or comparative examples is a product commercially available from Beijing Happiness Life Technology Co., Ltd.

[0076] Example 1

[0077] A coaxial calcium-silicon-based bioactive wire comprises a coaxial degradable polymer core layer and a calcium-silicon-based bioactive material shell layer, the degradable polymer core layer is composed of polylactide with a molecular weight of 30-50 thousand, the calcium-silicon-based bioactive material shell layer comprises a natural biological material matrix and calcium-silicon-based bioactive material particles, the natural biological material matrix is composed of carboxymethyl chitosan, and the calcium-silicon-based bioactive material particles are composed of regenerated silicon and account for 1.0% in the calcium-silicon-based bioactive material shell layer in terms of mass percentage, and other parameters can be seen from Table 1.

[0078] The preparation method comprises the following steps:

[0079] (1) preparing a polylactide core layer solution: 2g of polylactide is added into 20mL of 1,4-dioxane, and stirring is continuously performed at 40℃ until the polylactide is dissolved;

[0080] (2) preparing a shell layer solution containing regenerated silicon particles: 5g of carboxymethyl chitosan is added into 20mL of water, and stirring is performed at room temperature until the carboxymethyl chitosan is completely dissolved, then 0.05g of regenerated silicon particles with a particle size of 20-500nm is added, and stirring is performed until the regenerated silicon particles are uniformly mixed;

[0081] (3) The polylactide core layer solution and the shell solution containing regenerated silicon particles are injected into syringes respectively, and by means of coaxial needles, the polylactide core layer solution is injected into an anhydrous ethanol coagulation bath at a speed of 100 μL / min, and the shell solution containing regenerated silicon particles is injected into the anhydrous ethanol coagulation bath at a speed of 80 μL / min. The two solutions meet at the tip of the coaxial needle, and the shell solution containing regenerated silicon particles is wrapped outside the polylactide core layer solution, gradually solidified and shaped after entering the anhydrous ethanol, and placed in a vacuum drying oven at 37°C for drying for 48 h after standing in the anhydrous ethanol for 2 h. The vacuum degree of the vacuum drying oven is 0.01 MPa, and a coaxial regenerated silicon bioactive wire is obtained.

[0082] Example 2

[0083] A coaxial calcium-silicon-based bioactive wire, the main difference from Example 1 is that the degradable polymer core layer is composed of polylactide with a molecular weight of 100-150 thousand.

[0084] The preparation method comprises the following steps:

[0085] (1) Prepare a polylactide core layer solution: take 2 g of polylactide and add it into 20 mL of dichloromethane, continuously stir at 40°C until dissolved;

[0086] (2) Prepare a shell solution containing regenerated silicon particles: take 5 g of carboxymethyl chitosan and add it into 20 mL of water, stir at room temperature until completely dissolved, then add 0.05 g of regenerated silicon particles with a particle size of 20-500 nm, and stir to mix uniformly;

[0087] (3) The polylactide core layer solution and the shell solution containing regenerated silicon particles are injected into syringes respectively, and by means of coaxial needles, the polylactide core layer solution is injected into an anhydrous ethanol coagulation bath at a speed of 100 μL / min, and the shell solution containing regenerated silicon particles is injected into the anhydrous ethanol coagulation bath at a speed of 80 μL / min. The two solutions meet at the tip of the coaxial needle, and the shell solution containing regenerated silicon particles is wrapped outside the polylactide core layer solution, gradually solidified and shaped after entering the anhydrous ethanol, and placed in a vacuum drying oven at 37°C for drying for 48 h after standing in the anhydrous ethanol for 2 h. The vacuum degree of the vacuum drying oven is 0.01 MPa, and a coaxial regenerated silicon bioactive wire is obtained.

[0088] Example 3

[0089] A coaxial calcium-silicon-based bioactive wire, the main difference from Example 1 is that the degradable polymer content is high.

[0090] The preparation method comprises the following steps:

[0091] (1) Preparation of the poly-L-lactide core solution: 4 g of poly-L-lactide was added to 20 mL of chloroform, and stirred continuously at 40°C until dissolved;

[0092] (2) Preparation of the shell solution containing regenerated silicon particles: 5 g of carboxymethyl chitosan was added to 20 mL of water, and stirred at room temperature until completely dissolved, then 0.05 g of regenerated silicon particles with a particle size of 20-500 nm was added, and stirred to mix uniformly;

[0093] (3) The poly-L-lactide core solution and the shell solution containing regenerated silicon particles were injected into syringes respectively, and with the aid of coaxial needles, the poly-L-lactide core solution was injected into an anhydrous ethanol coagulation bath at a speed of 100 μL / min, and the shell solution containing regenerated silicon particles was injected into the anhydrous ethanol coagulation bath at a speed of 80 μL / min. The two solutions met at the tip of the coaxial needle, and the shell solution containing regenerated silicon particles was wrapped outside the poly-L-lactide core solution, gradually solidified and shaped after entering the anhydrous ethanol, and placed in a vacuum drying oven at 37°C for drying for 48 h after standing in the anhydrous ethanol for 8 h. The vacuum degree of the vacuum drying oven was 0.01 MPa, and a coaxial regenerated silicon bioactive filament was obtained.

[0094] Example 4

[0095] A coaxial calcium-silicon-based bioactive filament, the main difference from Example 1 is that the mass percentage of calcium-silicon-based bioactive material particles in the calcium-silicon-based bioactive material shell is 4.8%.

[0096] The preparation method comprises the following steps:

[0097] (1) Preparation of the poly-L-lactide core solution: 4 g of poly-L-lactide was added to 20 mL of chloroform, and stirred continuously at 40°C until dissolved;

[0098] (2) Preparation of the shell solution containing regenerated silicon particles: 5 g of carboxymethyl chitosan was added to 20 mL of water, and stirred at room temperature until completely dissolved, then 0.05 g of regenerated silicon particles with a particle size of 20-500 nm was added, and stirred to mix uniformly;

[0099] (3) The poly-L-lactide core solution and the shell solution containing regenerated silicon particles were injected into syringes respectively, and with the aid of coaxial needles, the poly-L-lactide core solution was injected into an anhydrous ethanol coagulation bath at a speed of 100 μL / min, and the shell solution containing regenerated silicon particles was injected into the anhydrous ethanol coagulation bath at a speed of 80 μL / min. The two solutions met at the tip of the coaxial needle, and the shell solution containing regenerated silicon particles was wrapped outside the poly-L-lactide core solution, gradually solidified and shaped after entering the anhydrous ethanol, and placed in a vacuum drying oven at 37°C for drying for 48 h after standing in the anhydrous ethanol for 8 h. The vacuum degree of the vacuum drying oven was 0.01 MPa, and a coaxial regenerated silicon bioactive filament was obtained.

[0100] Example 5

[0101] A coaxial calcium-silicon-based bioactive filament, the main difference from Example 1 is that the degradable polymer core layer is composed of polylactide-glycolide with a molecular weight of 30-50 thousand, and the natural biomaterial matrix is composed of dopamine.

[0102] The preparation method comprises the following steps:

[0103] (1) Prepare a polylactide-glycolide core layer solution: take 2g of polylactide-glycolide and add it to 20mL of 1,4-dioxane, continuously stir at 50°C until dissolved;

[0104] (2) Prepare a shell solution containing regenerated silicon particles: take 5g of dopamine and add it to 20mL of water, stir at room temperature until completely dissolved, then add 0.05g of regenerated silicon particles with a particle size of 20-500nm, and stir to mix evenly;

[0105] (3) Inject the polylactide-glycolide core layer solution and the shell solution containing regenerated silicon particles into syringes respectively, use a coaxial needle, the polylactide-glycolide core layer solution is injected into an anhydrous ethanol coagulation bath at a speed of 100μL / min, and the shell solution containing regenerated silicon particles is injected into an anhydrous ethanol coagulation bath at a speed of 80μL / min. The two solutions meet at the tip of the coaxial needle, the shell solution containing regenerated silicon particles is wrapped outside the polylactide-glycolide core layer solution, and gradually solidifies into a shape after entering anhydrous ethanol. After standing in anhydrous ethanol for 8h, it is placed in a 37°C vacuum drying oven for drying for 48h, the vacuum degree of the vacuum drying oven is 0.01MPa, and a coaxial regenerated silicon bioactive filament is obtained.

[0106] Example 6

[0107] A coaxial calcium-silicon-based bioactive filament, the main difference from Example 1 is that the calcium-silicon-based bioactive material particles are composed of bioactive glass 45S5.

[0108] The preparation method comprises the following steps:

[0109] (1) Prepare a polylactide core layer solution: take 2g of polylactide and add it to 20mL of 1,4-dioxane, continuously stir at 50°C until dissolved;

[0110] (2) Prepare a shell solution containing 45S5 particles: take 5g of carboxymethyl chitosan and add it to 20mL of water, stir at room temperature until completely dissolved, then add 0.05g of bioactive glass 45S5 particles with a particle size of 20-500nm, and stir to mix evenly;

[0111] (3) The polylactide core layer solution and the shell layer solution containing bioactive glass 45S5 particles are injected into the syringes respectively, and by means of the coaxial needle, the polylactide core layer solution is injected into the anhydrous ethanol coagulation bath at a speed of 100 μL / min, and the shell layer solution containing bioactive glass 45S5 particles is injected into the anhydrous ethanol coagulation bath at a speed of 80 μL / min. The two solutions meet at the tip of the coaxial needle, the shell layer solution containing bioactive glass 45S5 particles is wrapped outside the polylactide core layer solution, and gradually solidifies into shape after entering the anhydrous ethanol. After being placed in the anhydrous ethanol for 8 h, it is placed in a vacuum drying oven at 37°C for drying for 48 h, the vacuum degree of the vacuum drying oven is 0.01 MPa, and a coaxial calcium-silicon-based bioactive wire is obtained.

[0112] Example 7

[0113] A coaxial calcium-silicon-based bioactive wire, the main difference from example 1 is that the injection speed of the core layer solution during preparation is different.

[0114] The preparation method comprises the following steps:

[0115] (1) Preparation of polylactide core layer solution: 2 g of polylactide is taken into 20 mL of 1,4-dioxane, and continuously stirred at 50°C until dissolved;

[0116] (2) Preparation of shell layer solution containing regenerated silicon particles: 5 g of carboxymethyl chitosan is taken into 20 mL of water, stirred at room temperature until completely dissolved, and then 0.05 g of regenerated silicon particles with a particle size of 20-500 nm is added, and stirred and mixed uniformly;

[0117] (3) The polylactide core layer solution and the shell layer solution containing regenerated silicon particles are injected into the syringes respectively, and by means of the coaxial needle, the polylactide core layer solution is injected into the anhydrous ethanol coagulation bath at a speed of 500 μL / min, and the shell layer solution containing regenerated silicon particles is injected into the anhydrous ethanol coagulation bath at a speed of 80 μL / min. The two solutions meet at the tip of the coaxial needle, the shell layer solution containing regenerated silicon particles is wrapped outside the polylactide core layer solution, and gradually solidifies into shape after entering the anhydrous ethanol. After being placed in the anhydrous ethanol for 8 h, it is placed in a vacuum drying oven at 37°C for drying for 48 h, the vacuum degree of the vacuum drying oven is 0.01 MPa, and a coaxial regenerated silicon bioactive wire is obtained.

[0118] Example 8

[0119] A coaxial calcium-silicon-based bioactive wire, the main difference from example 1 is that the injection speed of the core layer solution during preparation is different.

[0120] The preparation method comprises the following steps:

[0121] (1) Preparation of the polylactide core solution: 2 g of polylactide was added to 20 mL of 1,4-dioxane, and stirred at 50°C until dissolved;

[0122] (2) Preparation of the shell solution containing regenerated silicon particles: 5 g of carboxymethyl chitosan was added to 20 mL of water, and stirred at room temperature until completely dissolved. Then, 0.05 g of regenerated silicon particles with a particle size of 20-500 nm was added, and stirred until mixed evenly;

[0123] (3) The polylactide core solution and the shell solution containing regenerated silicon particles were injected into syringes, respectively. With the aid of coaxial needles, the polylactide core solution was injected into an anhydrous ethanol coagulation bath at a speed of 100 μL / min, and the shell solution containing regenerated silicon particles was injected into the anhydrous ethanol coagulation bath at a speed of 40 μL / min. The two solutions met at the tip of the coaxial needle, and the shell solution containing regenerated silicon particles was wrapped outside the polylactide core solution. After entering the anhydrous ethanol, it gradually solidified and formed a shape. After being placed in the anhydrous ethanol for 8 h, it was placed in a vacuum drying oven at 37°C for drying for 48 h. The vacuum degree of the vacuum drying oven was 0.01 MPa, and a coaxial regenerated silicon bioactive wire was obtained.

[0124] Example 9

[0125] A coaxial calcium-silicon-based bioactive wire includes a coaxial degradable polymer core layer and a calcium-silicon-based bioactive material shell layer. The degradable polymer core layer is composed of polylactide with a molecular weight of 10-15 thousand. The calcium-silicon-based bioactive material shell layer contains a natural biological material matrix and calcium-silicon-based bioactive material particles. The natural biological material matrix is composed of carboxymethyl chitosan, and the calcium-silicon-based bioactive material particles are composed of regenerated silicon and have a mass percentage of 9.1% in the calcium-silicon-based bioactive material shell layer. Other parameters are shown in Table 1.

[0126] The preparation method includes the following steps:

[0127] (1) Preparation of the polylactide core solution: 1 g of polylactide was added to 20 mL of 1,4-dioxane, and stirred at 40°C until dissolved;

[0128] (2) Preparation of the shell solution containing regenerated silicon particles: 0.5 g of carboxymethyl chitosan was added to 20 mL of water, and stirred at room temperature until completely dissolved. Then, 0.05 g of regenerated silicon particles with a particle size of 20-500 nm was added, and stirred until mixed evenly;

[0129] (3) respectively into the syringe poly-lactide core layer solution and containing recycled silicon particles shell solution, with coaxial needle, poly-lactide core layer solution at a speed of 100 μL / min, containing recycled silicon particles shell solution at a speed of 80 μL / min directly extruded silk, dried into silk at 45℃. Because not extruded into the coagulation bath, using direct drying, solvent volatilization is very fast, silk will be severely shrinked, so directly obtain the diameter becomes very small silk.

[0130] Example 10

[0131] A coaxial calcium-silicon-based bioactive silk material, comprising a coaxial degradable polymer core layer and a calcium-silicon-based bioactive material shell layer, the degradable polymer core layer is composed of poly-lactide with a molecular weight of 30-50 thousand; the calcium-silicon-based bioactive material shell layer contains a natural biological material matrix and calcium-silicon-based bioactive material particles, the natural biological material matrix is composed of dopamine, and the calcium-silicon-based bioactive material particles are composed of recycled silicon and have a mass percentage of 33.3% in the calcium-silicon-based bioactive material shell layer. Other parameters are shown in Table 1.

[0132] The preparation method comprises the following steps:

[0133] (1) preparing a poly-lactide core layer solution: taking 4 g of poly-lactide and adding it into 10 mL of 1,4-dioxane, continuously stirring at 40℃ until dissolved;

[0134] (2) preparing a shell solution containing recycled silicon particles: taking 20 g of dopamine and adding it into 20 mL of water, stirring at room temperature until completely dissolved, then adding 10 g of recycled silicon particles with a particle size of 20-500 nm and stirring to mix uniformly;

[0135] (3) respectively into the syringe poly-lactide core layer solution and containing recycled silicon particles shell solution, with coaxial needle, poly-lactide core layer solution at a speed of 4 mL / min into anhydrous ethanol coagulation bath, containing recycled silicon particles shell solution at a speed of 2 mL / min into anhydrous ethanol coagulation bath. Two kinds of solutions meet at the tip of the coaxial needle, the shell solution containing recycled silicon particles is wrapped outside the poly-lactide core layer solution, gradually solidified into shape after entering anhydrous ethanol, placed in a vacuum drying oven at 39℃ for 12 h after standing for 8 h, the vacuum degree of the vacuum drying oven is 0.05 MPa, to obtain a coaxial recycled silicon bioactive silk material.

[0136] Comparative Example 1

[0137] A coaxial calcium-silicon-based bioactive filament, which is only different from the example 8 in that the water coagulation bath is used instead of the anhydrous ethanol coagulation bath in step (3) during preparation, and the rest of the settings are the same as those of the example 8. It is found during the preparation process that after the two solutions meet at the tip of the coaxial needle, the shell solution containing the regenerated silicon particles is wrapped outside the polylactide core layer solution, but gradually diffuses and partially dissolves in water after entering the coagulant water, and the shell is lost.

[0138] Comparative example 2

[0139] A calcium-silicon-based bioactive filament, which has only a shell without a core compared with the coaxial calcium-silicon-based bioactive filament of the example, and is specifically as follows: it is composed of a calcium-silicon-based bioactive material containing a natural biological material matrix and calcium-silicon-based bioactive material particles, the natural biological material matrix is composed of carboxymethyl chitosan, and the calcium-silicon-based bioactive material particles are composed of regenerated silicon and have a mass percentage of 1.0% in the calcium-silicon-based bioactive material, and other parameters are shown in Table 1.

[0140] The preparation method thereof includes the following steps:

[0141] (1) Preparation of a solution containing regenerated silicon particles: 5 g of carboxymethyl chitosan is added to 20 mL of water, stirred at room temperature until completely dissolved, and then 0.05 g of regenerated silicon particles with a particle size of 20-500 nm is added and stirred to mix uniformly;

[0142] (2) The solution containing regenerated silicon particles is injected into an anhydrous ethanol coagulation bath at a speed of 80 μL / min. After entering the anhydrous ethanol, it gradually solidifies and forms, and is placed in a 37℃ vacuum drying oven for 8 h after standing in the anhydrous ethanol for 8 h, and is dried for 48 h in the vacuum drying oven with a vacuum degree of 0.01 MPa to obtain a calcium-silicon-based bioactive filament.

[0143] Comparative example 3

[0144] A polylactic acid filament, which has only a core without a shell compared with the coaxial calcium-silicon-based bioactive filament of the example, and is specifically as follows: it is composed of a degradable polymer, and the degradable polymer is composed of polylactide with a molecular weight of 30-50 thousand.

[0145] The preparation method thereof includes the following steps:

[0146] (1) Preparation of a polylactide solution: 2 g of polylactide is added to 20 mL of 1,4-dioxane, and continuously stirred at 50℃ until dissolved;

[0147] (2) The polylactide solution was injected into the anhydrous ethanol coagulation bath at a speed of 100 μL / min. The polylactide solution gradually solidified into a shape after entering the anhydrous ethanol and was placed in a vacuum drying oven at 37°C for 48 h after being placed in the anhydrous ethanol for 8 h. The vacuum degree of the vacuum drying oven was 0.01 MPa. The polylactic acid filament was obtained.

[0148] Comparative Example 4

[0149] A calcium-silicon-based bioactive filament, which is coaxial with the calcium-silicon-based bioactive filament of Example 6, is only different from the calcium-silicon-based bioactive filament of Example 6 in structure and preparation method. The preparation method comprises the following steps:

[0150] (1) Preparation of a polylactide solution: 2 g of polylactide was added to 20 mL of 1,4-dioxane, and stirring was continued at 50°C until dissolution;

[0151] (2) Preparation of a carboxymethyl chitosan solution containing 45S5 particles: 5 g of carboxymethyl chitosan was added to 20 mL of water, and stirring was continued at room temperature until complete dissolution. Then, 0.05 g of bioactive glass 45S5 particles with a particle size of 20-500 nm was added, and stirring was continued until uniform mixing;

[0152] (3) Preparation of a mixed spinning solution: the solution in step (2) was poured into the solution in step (1), and stirring was continued until uniform mixing. The mixed solution was injected into an anhydrous ethanol coagulation bath at a speed of 90 μL / min to solidify into a shape. The calcium-silicon-based bioactive filament was obtained after being placed in a vacuum drying oven at 37°C for 48 h after being placed in anhydrous ethanol for 8 h. The vacuum degree of the vacuum drying oven was 0.01 MPa.

[0153] Table 1: Parameters of coaxial regenerated silicon bioactive filaments of various examples

[0154] Item Wire diameter (pm) Core layer diameter (pm) Shell layer thickness (pm) Tensile strength (MPa) Example 1 245±5 205±2 40±2 71 Example 2 243±5 198±2 45±2 180 Example 3 605±5 565±2 47±2 206 Example 4 295±5 215±2 80±2 63 Example 5 250±5 208±2 42±2 103 Example 6 233±5 194±2 39±2 69 Example 7 189±5 155±2 34±2 57 Example 8 226±5 201±2 25±2 67 Example 9 8.85±0.5 6±0.5 2.85±0.05 3 Example 10 985±5 750±0.5 235±0.5 325 Comparative Example 1 213±2 205±2 8±2 65 Comparative Example 2 42±2 - 42±2 25 Comparative Example 3 205±5 205±5 - 62 Comparative Example 4 233±5 - - 38

[0155] As can be seen from Table 1, the tensile strength of the filaments obtained in Examples 1-10 is between 3-325 MPa. The filaments can be used in the field of absorbable surgical sutures, bone filling, wound dressings or anti-adhesion membranes according to the needs of mechanical properties, etc. For example, filaments with a strength of 60 MPa or more can be used to make absorbable surgical sutures, filaments with a strength of 100 MPa or more can be used for fixation in bone filling applications, and filaments with a strength of more than 25 MPa can be used to make wound dressings and anti-adhesion membranes and applied to wound repair and postoperative anti-adhesion fields, respectively.

[0156] Further, it can be seen from the comparison of Examples 1 and 2 that the tensile strength of Example 2 is significantly higher than that of Example 1, when the polymer concentration, the concentration of natural biomaterial matrix, the content of calcium-silicon-based bioactive material, the solution flow rate of the core layer and the shell layer, and the filament diameter, the core layer diameter and the shell layer thickness are all equivalent, because the molecular weight of the polymer is the main factor affecting the mechanical properties, and when the polymer concentration, the shell layer composition and the core-shell size are all equivalent, the higher the molecular weight of the polymer, the higher the tensile strength of the filament.

[0157] It can be seen from the comparison of Examples 1 and 3 that the tensile strength of Example 3 is significantly higher than that of Example 1, when the polymer molecular weight, the concentration of natural biomaterial matrix, the content of calcium-silicon-based bioactive material, the solution flow rate of the core layer and the shell layer are all equivalent, because the polymer concentration of Example 3 is high, and the core layer diameter and the filament diameter are large, so it can be known that when the polymer molecular weight, the shell layer composition and the shell layer size are all equivalent, the higher the polymer concentration, the larger the core layer diameter and the filament diameter, the higher the tensile strength of the filament.

[0158] It can be seen from the comparison of Examples 1 and 4 that the tensile strength of Example 1 is higher than that of Example 4, when the composition of the core layer is the same and the diameter is equivalent, and the content of regenerated silicon is low and the shell layer is thin, because the content of active particles in the shell layer affects the mechanical properties of the shell layer, and the higher the content, the worse the mechanical properties, thus affecting the overall mechanical properties of the filament.

[0159] It can be seen from the comparison of Examples 1 and 5 that the tensile strength of Example 5 is higher than that of Example 1, when the polymer molecular weight and the core-shell material concentration are the same and the filament diameter, the core layer diameter and the shell layer thickness are all equivalent, because the bonding force between the shell layer and the core layer also affects the overall mechanical properties, and the adhesion of dopamine is stronger than that of carboxymethyl chitosan, so the bonding force between the shell layer containing dopamine and the core layer is strong, and the overall mechanical properties of the filament are strong.

[0160] It can be seen from the comparison of Examples 1 and 7 that the faster the injection speed of the core layer solution, the smaller the core layer diameter, and the smaller the tensile strength, and it has a certain influence on the shell layer thickness, which may be that the shell layer is thinned due to the stretching effect of the core layer solution under the condition of fast injection speed.

[0161] It can be seen from the comparison of Examples 1 and 8 that the injection speed of the shell layer solution has little effect on the core layer diameter and the tensile strength, but has a certain effect on the shell layer thickness, although the slow speed of the shell layer can better stop and diffuse in the solution, the slower the injection speed of the shell layer solution, the greater the speed difference with the core layer solution, and the tensile effect makes the shell layer thickness smaller.

[0162] It can be seen from the comparison of the shell thickness of Example 8 and Comparative Example 1 that the effect of using anhydrous ethanol as the coagulant is much better than that of using water as the coagulant, and the anhydrous ethanol coagulant can well maintain the shape of the coaxial fiber, so that the shell is well coagulated and adhered to the core layer.

[0163] It can be seen from the comparison of the tensile strength of Examples 1-3 and Comparative Example 2 that the degradable polymer core layer can provide mechanical support for the calcium-silicon-based bioactive material shell layer, solving the problem of poor mechanical properties of calcium-silicon-based bioactive material fiber.

[0164] It can be seen from the comparison of the tensile strength of Examples 1, 4, 6, 8 and Comparative Example 3 that distributing the calcium-silicon-based bioactive material quantitatively on the surface of the degradable polymer to form a coaxial fiber structure with a shell layer covering the core layer will not damage the mechanical properties of the polymer fiber, and the coaxial calcium-silicon-based bioactive fiber with a shell layer covering the core layer has excellent tensile strength and flexibility.

[0165] It can be seen from the comparison of the tensile strength of Example 6 and Comparative Example 4 that the present application distributes the calcium-silicon-based bioactive material quantitatively on the surface of the degradable polymer to form a coaxial fiber structure with a shell layer covering the core layer, and the strength thereof is much higher than that of the conventional electrospun fiber obtained by mixing the calcium-silicon-based bioactive material into the degradable polymer spinning solution.

[0166] Finally, it should be noted that: the above examples are only used to illustrate the technical solutions of the present application, and not to limit them; although the present application has been described in detail with reference to the foregoing examples, those skilled in the art should understand that: it can still modify the technical solutions recorded in the foregoing examples, or make equivalent replacement for part or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A coaxial calcium-silicon-based bioactive filament, characterized in that: The coaxial calcium-silicon-based bioactive filament is composed of a biodegradable polymer core and a calcium-silicon-based bioactive material shell. The calcium-silicon-based bioactive material shell is composed of a natural biomaterial matrix and calcium-silicon-based bioactive material particles. The natural biomaterial matrix is ​​composed of natural polysaccharides. The biodegradable polymer core layer is composed of one or more of polylactide, polyglycolic acid-lactide copolymer, polyglycolic acid, and polyhydroxyalkanoate. The biodegradable polymer used in the biodegradable polymer core layer has a molecular weight of 10,000 to 150,000. The natural polysaccharides include carboxymethyl cellulose, carboxymethyl chitosan, chondroitin sulfate, and seaweed polysaccharides; In the shell of the calcium-silicon-based bioactive material, the mass percentage of calcium-silicon-based bioactive material particles is 1% to 35%; the calcium-silicon-based bioactive material particles are composed of regenerated silicon, which has a porous scaffold structure formed by the accumulation of nano-sized silica particles, and calcium and phosphorus elements uniformly distributed in the scaffold, and is a bioactive calcium phosphosilicate compound; the specific surface area of ​​the regenerated silicon is 200-350 m² / g. 2 / g; The preparation method of the coaxial calcium-silicon-based bioactive filament includes the following steps: (1) Preparation of biodegradable polymer core layer solution: Dissolve the biodegradable polymer in an organic solvent and mix evenly to obtain the biodegradable polymer core layer solution; (2) Preparation of shell solution containing calcium-silicon-based bioactive material particles: First, dissolve the natural biomaterial matrix in water and mix evenly to obtain a natural biomaterial matrix solution. Then, add calcium-silicon-based bioactive material particles to the natural biomaterial matrix solution and mix evenly to obtain the shell solution containing calcium-silicon-based bioactive material particles. The particle size of the calcium-silicon-based bioactive material particles mentioned in step (2) is 20 nm to 80 µm; (3) The biodegradable polymer core solution obtained in step (1) and the shell solution containing calcium-silicon-based bioactive material particles obtained in step (2) are injected into the core solution syringe and the shell solution syringe respectively. Coaxial wet spinning is performed using a coaxial needle. Then, anhydrous ethanol is selected as the coagulation bath for curing or anhydrous ethanol is selected as the coagulation bath and dried for curing to obtain the calcium-silicon-based bioactive filament. Anhydrous ethanol is chosen as the coagulation bath for shaping. During the coagulation process, some gaps will be generated between the materials, which will result in some porous structure in the calcium-silicon-based bioactive filaments. After shaping and drying, the porous structure will be retained.

2. The coaxial calcium-silicon-based bioactive filament as described in claim 1, characterized in that: The diameter of the biodegradable polymer core layer is 1 µm to 1 mm; And / or, the thickness of the shell of the calcium-silicon-based bioactive material is 500 nm to 500 µm.

3. The coaxial calcium-silicon-based bioactive filament as described in claim 1, characterized in that: The diameter of the biodegradable polymer core layer is 5 µm to 760 µm; And / or, the thickness of the shell of the calcium-silicon-based bioactive material is 800 nm to 250 µm.

4. A method for preparing coaxial calcium-silicon-based bioactive filaments as described in any one of claims 1-3, characterized in that: Includes the following steps: (1) Preparation of biodegradable polymer core layer solution: Dissolve the biodegradable polymer in an organic solvent and mix evenly to obtain the biodegradable polymer core layer solution; (2) Preparation of shell solution containing calcium-silicon-based bioactive material particles: First, dissolve the natural biomaterial matrix in a suitable solvent and mix evenly to obtain a natural biomaterial matrix solution. Then, add calcium-silicon-based bioactive material particles to the natural biomaterial matrix solution and mix evenly to obtain the shell solution containing calcium-silicon-based bioactive material particles. (3) The biodegradable polymer core solution obtained in step (1) and the shell solution containing calcium-silicon-based bioactive material particles obtained in step (2) are injected into the core solution syringe and the shell solution syringe, respectively. Coaxial wet spinning is performed using a coaxial needle. Then, anhydrous ethanol is selected as the coagulation bath for curing or anhydrous ethanol is selected as the coagulation bath and dried for curing to obtain the calcium-silicon-based bioactive filament.

5. The preparation method according to claim 4, characterized in that: The concentration of the biodegradable polymer core solution in step (1) is 0.05 g / mL to 0.50 g / mL; And / or, the concentration of the natural biomaterial matrix solution in step (2) is 0.025 g / mL to 1.50 g / mL.

6. The preparation method according to claim 5, characterized in that: The concentration of the biodegradable polymer core solution in step (1) is 0.05 g / mL to 0.40 g / mL; And / or, the concentration of the natural biomaterial matrix solution in step (2) is 0.025 g / mL to 1.20 g / mL; And / or, the particle size of the calcium-silicon-based bioactive material particles in step (2) is 20 nm to 50 µm.

7. The preparation method according to claim 4, characterized in that: The organic solvent mentioned in step (1) is one or a mixture of several of the following: ethyl acetate, dichloromethane, acetone, 1,4-dioxane, N-methylpyrrolidone, chloroform, tetrahydrofuran, hexafluoroisopropanol, acetonitrile, and dichloroacetic acid; And / or, the coaxial wet spinning technology in step (3) is to inject the biodegradable polymer core solution and the shell solution containing calcium-silicon-based bioactive material particles through an injection head to obtain the coaxial calcium-silicon-based bioactive filament structure. The injection head is a coaxial needle with coaxial inner and outer channels.

8. The preparation method according to claim 7, characterized in that: The biodegradable polymer core solution is injected at an injection rate of 40 µL / min to 10 mL / min. And / or, the shell solution containing calcium-silicon-based bioactive material particles is injected at an injection rate of 10 µL / min to 5 mL / min; And / or, the drying temperature in step (3) is 35 ℃~45 ℃; And / or, the drying in step (3) is vacuum drying, the vacuum drying time is 8 h to 72 h, and the vacuum degree is -0.1 MPa to 0.1 MPa.

9. The preparation method according to claim 8, characterized in that: The injection rate of the biodegradable polymer core solution is 100 µL / min to 6 mL / min; And / or, the injection rate of the shell solution containing calcium-silicon-based bioactive material particles is 40 µL / min to 2 mL / min; And / or, the drying temperature is 35 ℃~40 ℃; And / or, the vacuum drying time is 12 h to 48 h, and the vacuum degree is -0.08 MPa to 0.06 MPa.

10. The coaxial calcium-silicon-based bioactive filament as described in any one of claims 1-3 or the coaxial calcium-silicon-based bioactive filament prepared by the preparation method of any one of claims 4-9, and its application in the preparation of absorbable surgical sutures, bone filling materials, wound dressings, and anti-adhesion membranes.

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