Bioactive multiphase textile scaffold, preparation method and application

Abstract

The invention discloses a bioactive multiphase textile scaffold as well as a preparation method and application thereof. The bioactive multiphase textile scaffold is formed by interweaving warp yarns and weft yarns, each of the warp yarns and the weft yarns comprises a core layer structure and a nanofiber yarn layer located on the outer layer of the core layer structure, and each warp yarn comprises a first core layer polymer yarn and a first nanofiber layer located on the outer layer of the first core layer polymer yarn; the weft comprises a second core layer polymer wire, and the weft comprises bone scaffold sections located at the two ends and a ligament scaffold section located in the middle. The bioactive multiphase textile scaffold is composed of two parts, namely bone scaffold sections at two ends and a ligament scaffold section in the middle, the bone scaffold section has osteoconductivity, promotes bone tunnel healing and guides osteogenesis; the middle ligament stent section has long-acting anti-inflammatory activity, and can regulate the postoperative immune microenvironment and guide and promote endogenous repair of tendons.

Description

Technical Field

[0001] The present application belongs to the field of medical antibacterial materials, and in particular relates to a bioactive multiphase textile scaffold, a preparation method and an application thereof. Background Art

[0002] Natural ligament tissue, composed of collagen molecules, collagen fibers, fiber bundles, and tendon units, is crucial to the musculoskeletal system, joint movement, and stability. The anterior cruciate ligament (ACL) of the knee is one of the most common sites of injury. Current tendon / ligament repair treatments are still subject to complications, such as tissue immune rejection and infectious diseases. Furthermore, long-term immune inflammatory responses after surgery often lead to the formation of scar tissue. This defective tissue is unable to withstand the same loads as natural tissue and cannot restore the function, structure, and biomechanical properties of healthy tendons. Therefore, finding new methods to promote tendon-bone regeneration and repair is of extremely important clinical significance. Summary of the Invention

[0003] Purpose of the Invention: This application provides a bioactive multiphase textile scaffold, preparation method, and application. The bioactive multiphase textile scaffold comprises two components: a bone scaffold segment at each end and a ligament scaffold segment in the middle. The bone scaffold segment exhibits osteoconductivity, promoting bone tunnel healing and guiding osteogenesis. The ligament scaffold segment exhibits long-lasting anti-inflammatory activity, modulating the postoperative immune microenvironment and guiding and promoting endogenous tendon repair.

[0004] Technical solution: An embodiment of the present application provides a bioactive multiphase textile scaffold, which is woven from warp and weft threads, and the warp and weft threads both include a core layer structure and a nanofiber thread layer located on the outer layer of the core layer structure, and the warp threads include a first core layer polymer thread and a first nanofiber layer located on the outer layer of the first core layer polymer thread; the core layer structure of the weft threads is a second core layer polymer thread; the weft threads include bone scaffold segments located at both ends and a ligament scaffold segment located in the middle of the bone scaffold segment, and the bone scaffold segment includes a second core layer polymer thread and a second nanofiber layer located on the outer layer of the second core layer polymer thread, and the second nanofiber layer is loaded with active particles having bioactive ions; the ligament scaffold segment includes a second core layer polymer thread and a third nanofiber layer located on the outer layer of the second core layer polymer thread, and the third nanofiber layer includes a PLA-small molecule natural drug graft.

[0005] In some embodiments, the core layer structure is a single wire with a diameter of 0.03 mm to 0.1 mm formed by combining and drawing polymer single fibers with a diameter of 20 μm to 50 μm.

[0006] In some embodiments, the first core layer polymer wire and the second core layer polymer wire may be the same or different; the first core layer polymer wire or the second core layer polymer wire is selected from one or more of polyethylene terephthalate (PET), polylactic acid (PLA), polycaprolactone (PCL), lactic acid-glycolic acid copolymer (PLGA), and silk fibroin (SF) wire.

[0007] In some embodiments, the first nanofiber layer includes a first polymer and a first natural polymer in a mass ratio of (10 to 90): (10 to 90); the first polymer includes one or more of lactic acid-caprolactone copolymer (PLCL), polycaprolactone (PCL) and lactic acid-glycolic acid copolymer (PLGA); the first natural polymer includes one or more of gelatin, collagen (COL) and silk fibroin.

[0008] In some embodiments, the second nanofiber layer includes a second polymer and a second natural polymer in a mass ratio of (10 to 90): (10 to 90), the second polymer includes one or more of lactic acid-caprolactone copolymer (PLCL), polycaprolactone (PCL) and lactic acid-glycolic acid copolymer (PLGA); the second natural polymer includes one or more of gelatin, collagen (COL) and silk fibroin.

[0009] In some embodiments, based on the total mass of the second nanofiber layer, the mass percentage of the active particles loaded in the second nanofiber layer is 0% to 1.5%; the bioactive ions include one or more of calcium, iron, zinc, magnesium, strontium and manganese ions.

[0010] In some embodiments, the small molecule natural drug in the PLA-small molecule natural drug graft is selected from one of curcumin, resveratrol, quercetin and magnolol.

[0011] In some embodiments, the PLA-small molecule natural drug graft is prepared by the following method: PLA is dissolved in an organic solvent, a condensing agent and a catalyst are added, a small molecule drug is added, the reaction is carried out at room temperature in a nitrogen atmosphere, and the product is separated to obtain the PLA-small molecule natural drug graft.

[0012] The present invention also provides a method for preparing a bioactive multiphase textile scaffold, comprising the following steps:

[0013] providing a first core polymer wire and a second core polymer wire as the core structure;

[0014] A first nanofiber layer is prepared on the outer layer of the first core layer polymer line to form a warp, a second nanofiber layer is prepared on the outer layer of the second core layer polymer line to form a bone scaffold segment, and a third nanofiber layer is prepared on the outer layer of the second core layer polymer line to form a ligament scaffold segment, with the bone scaffold segment and the ligament scaffold segment serving as wefts;

[0015] The warp and weft are woven by a weaving method to obtain a bioactive multiphase textile scaffold.

[0016] The embodiments of the present application also provide the use of the above-mentioned bioactive multiphase textile scaffold or the bioactive multiphase textile scaffold prepared by the above-mentioned method for preparing the bioactive multiphase textile scaffold as a tendon or ligament scaffold.

[0017] Beneficial effects: The present application provides a bioactive multiphase textile scaffold, preparation method and application. The bioactive multiphase textile scaffold of the present application is interwoven with warp and weft, and both the warp and weft include a core layer structure and a nanofiber layer located on the outer layer of the core layer structure, wherein the warp includes a first core layer polymer wire and a first nanofiber layer located on the outer layer of the first core layer polymer wire; the weft includes a second core layer polymer wire, wherein the weft includes bone scaffold segments located at both ends and a ligament scaffold segment located in the middle. The bioactive multiphase textile scaffold of the present application consists of two parts: bone scaffold segments at both ends and a middle ligament scaffold segment; the bone scaffold segment has osteoconductivity, promotes bone tunnel healing, and guides bone formation; the middle ligament scaffold segment has long-lasting anti-inflammatory activity, can regulate the postoperative immune microenvironment, and guide and promote endogenous repair of tendons. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present application. For those skilled in the art, other drawings can be obtained based on these drawings without creative work.

[0019] Figure 1 This is a schematic diagram of the preparation process of electrospinning nanofiber yarn in an embodiment of the present application;

[0020] Figure 2 This is a schematic diagram of the weaving preparation process of the bioactive multiphase textile scaffold in the embodiment of the present application;

[0021] Figure 3 This is a photo of the bioactive multiphase textile scaffold prepared in Example 1 of the present application;

[0022] Figure 4 This is the NMR spectrum of the PLA-resveratrol graft prepared in Example 1 of the present application;

[0023] Figure 5 This is the infrared spectrum of the PLA-resveratrol graft prepared in Example 1 of the present application;

[0024] Figure 6 The test results of nanofibers loaded with different contents of nano-magnesium oxide prepared in Example 1 of the present application, wherein Figure a is a transmission electron microscope, Figure b is a cross-sectional scanning electron microscope, Figure c is a surface scanning electron microscope, and Figure d is a scanning electron microscope of scaffolds with different concentrations of nano-magnesium oxide;

[0025] Figure 7 These are the test results of the PLA-resveratrol graft nanofibers prepared in Example 1 of the present application, wherein Figure a is a transmission electron microscopy, Figure b is a surface scanning electron microscopy, and Figure c is a surface scanning electron microscopy of the braided scaffold;

[0026] Figure 8 The mechanical properties of single yarns with different nano-magnesium oxide contents in Example 1 of the present application; Figure A shows the tensile strength at break (UTS) of the yarn, Figure B shows the Young's modulus of the yarn, and Figure C shows the elongation at break of the yarn;

[0027] Figure 9 The results of the antibacterial rate of nano-magnesium oxide scaffolds of different concentrations in Example 1 of the present application; wherein, Figure A is a colony photograph on an agar plate after the nano-magnesium oxide scaffolds of different concentrations in Example 1 of the present application acted on Staphylococcus aureus and Escherichia coli, Figure B is the antibacterial rate of nano-magnesium oxide scaffolds of different concentrations in Example 1 of the present application on Staphylococcus aureus, and Figure C is the antibacterial rate of nano-magnesium oxide scaffolds of different concentrations in Example 1 of the present application on Escherichia coli;

[0028] Figure 10 The results of the CCK-8 assay for the proliferation activity of BMSC cells using nano-magnesium oxide scaffolds at different concentrations were obtained in this application.

[0029] Figure 11 The results of the CCK-8 method test on the proliferation activity of BMSC cells in the scaffolds before and after grafting of PLA and resveratrol in this application are as follows;

[0030] Figure 12 The results of the test using the Alizarin Red quantitative detection kit in this application were used to detect the bone differentiation ability of BMSC cells induced by nano-magnesium oxide scaffolds with different concentrations;

[0031] Figure 13 For this application, an ELISA kit was used to detect the effects of the scaffolds before and after grafting of PLA and resveratrol on the expression of the inflammatory factor TNF-α. DETAILED DESCRIPTION

[0032] The following, in conjunction with the accompanying drawings, provides a clear and complete description of the technical solutions in the embodiments of the present application. It should be noted that the described embodiments are only a portion of the embodiments of the present application, and not all of the embodiments. All other embodiments derived by persons skilled in the art based on the embodiments of the present application without inventive effort are within the scope of protection of the present application. Furthermore, in the description of the present application, the term "including" means "including but not limited to." The terms "first," "second," and "third," etc., are used merely as designations and do not impose numerical requirements or establish a sequence. Various embodiments of the present application may be presented in the form of a range. It should be understood that describing in a range format is merely for convenience and brevity and should not be construed as a rigid limitation on the scope of the present application. Therefore, the range description should be considered to specifically disclose all possible subranges and individual numerical values ​​within the range. For example, a range description of 1 to 6 should be considered to specifically disclose subranges, such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, etc., as well as individual numerical values ​​within the range, such as 1, 2, 3, 4, 5, and 6, regardless of the range. Additionally, whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range.

[0033] Electrospun nanofibers can be similar to the structure of the extracellular matrix, with high porosity and high surface-to-volume ratio, which provides favorable conditions for cell adhesion, proliferation and differentiation, and can increase tendon / ligament-specific gene expression by controlling the orientation of the fibers, thereby improving the physiological function of the regenerated tissue. In order to solve the problems existing in the artificial ligaments of the prior art, a bioactive multiphase textile scaffold is provided in the embodiments of the present application. The bioactive multiphase textile scaffold in the embodiments of the present application combines electrospinning technology with traditional textile technology, designs the scaffold structure as a whole, conducts a holistic study on the bone tunnel segment and the joint cavity segment, constructs a new type of bioactive multiphase textile scaffold, realizes the integration of the ligament segment and the bone segment scaffold, reduces the regulation of immune inflammatory response and realizes tendon-bone fusion after anterior cruciate ligament reconstruction of the knee joint, realizes the simultaneous repair of the ligament part and the bone, and improves the normal recovery of the ligament function.

[0034] In some embodiments, the bioactive multiphase textile scaffold implemented in the present application is interwoven with warp and weft, each of which includes a core structure and a nanofiber layer located on the outer layer of the core structure. The warp includes a first core layer polymer thread and a first nanofiber layer located on the outer layer of the first core layer polymer thread; the core structure of the weft is a second core layer polymer thread; the weft includes a bone scaffold segment located at both ends and a ligament scaffold segment located in the middle of the bone scaffold segment, the bone scaffold segment includes a second core layer polymer thread and a second nanofiber layer located on the outer layer of the second core layer polymer thread, the second nanofiber layer is loaded with active particles having bioactive ions; the ligament scaffold segment includes a second core layer polymer thread and a third nanofiber layer located on the outer layer of the second core layer polymer thread, the third nanofiber layer includes a PLA-small molecule natural drug graft. The bioactive multiphase textile scaffold of the present application has a layered structure that better simulates natural tissue, has a stable structure, sufficient mechanical strength, good elasticity and flexibility, and can retain the characteristics of the constituent units. In addition, the bioactive multiphase textile scaffold of the present application can improve the immune microenvironment after tendon and ligament reconstruction surgery while promoting bone marrow tract repair through improvements in structural components. Specifically, the bioactive multiphase textile scaffold of the present application consists of two parts: the bone segment scaffold at both ends and the middle tendon end scaffold; the osteogenic segment has osteoconductivity, promotes bone tunnel healing, guides bone formation, and solves the graft-bone healing barrier during ACL reconstruction; the middle ligament scaffold segment of the present application includes PLA-small molecule natural drug grafts, which have long-lasting anti-inflammatory activity, can regulate the postoperative immune microenvironment, guide and promote endogenous tendon repair, reduce the inflammatory response during ligament healing, and promote the recovery of normal ligament function. The polymers and natural polymers used in the bioactive multiphase textile scaffold of the present application are all biodegradable materials, which can be gradually degraded within a certain period of time, which is conducive to the formation of regenerated tendon / ligament tissue. The degradation products can be discharged with the normal metabolism of the human body, without any side effects on the human body, and achieve a more ideal tendon / ligament reconstruction and repair.

[0035] In some embodiments, the bioactive multiphase textile scaffold is formed by weaving nanofiber yarns in both warp and weft directions using a weaving technique. The appearance of the bioactive multiphase textile scaffold includes but is not limited to a long strip, a flat shape, or a cylinder.

[0036] In some embodiments, the bioactive multiphase textile scaffold has a length of 25 mm to 50 mm and a width of 5 mm to 20 mm. The length of the middle ligament scaffold segment is 5 mm to 30 mm; and the length of the bone scaffold segments at both ends is 10 mm to 20 mm.

[0037] In some embodiments, the core layer structure of the bioactive multiphase textile scaffold is a single wire with a diameter of 0.03mm to 0.1mm formed by merging and stretching polymer single fibers with a diameter of 20μm to 50μm. In some embodiments, the thickness of the nanofiber layer in the outer layer of the core layer structure of the present application is 10μm to 15μm. The present application uses nanofiber yarns of composite materials as the smallest textile unit, and screens the materials and sizes of the multilayer structure. Compared with the use of yarns of a single material, the scaffold of the present application uses nanofibers of composite materials, which can give full play to the advantages of various repair materials. At the same time, the textile structure is finer and stronger, and can provide higher mechanical strength.

[0038] In some embodiments, the first core layer polymer wire and the second core layer polymer wire may be the same or different; the first core layer polymer wire or the second core layer polymer wire is selected from one or more of polyethylene terephthalate (PET), polylactic acid (PLA), polycaprolactone (PCL), lactic acid-glycolic acid copolymer (PLGA), and silk fibroin (SF) wire.

[0039] In some embodiments, the first nanofiber layer includes a first polymer and a first natural polymer in a mass ratio of (10-90):(10-90); the first polymer includes one or more of lactic acid-caprolactone copolymer (PLCL), polycaprolactone (PCL), and lactic acid-glycolic acid copolymer (PLGA); and the first natural polymer includes one or more of gelatin, collagen (COL), and silk fibroin. For example, the mass ratio of the first polymer to the first natural polymer is any value of 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80:20, 90:10, or a range consisting of any two values.

[0040] In some embodiments, the first polymer is a lactic acid-caprolactone copolymer (PLCL) and the first natural polymer is gelatin. In some embodiments, the mass ratio of the lactic acid-caprolactone copolymer (PLCL) in the first polymer to the first natural polymer gelatin is 70:30. In some embodiments, the mass ratio of the lactic acid to caprolactone copolymer in the PLCL is 75:25.

[0041] In some embodiments, the core layer structure of the warp is a PLA micron fiber line, and the first nanofiber layer adopts a composition of lactic acid-caprolactone copolymer (PLCL) and gelatin, and the mass ratio between lactic acid-caprolactone copolymer (PLCL) and gelatin is adjusted to improve the mechanical strength of the electrospun fiber structure and make it degradable, thereby solving the defect in the existing technology that electrospun nanomaterials are difficult to meet the size requirements and mechanical properties in tissue repair.

[0042] In some embodiments, the second core layer polymer yarn is a PLA micron fiber yarn, and the second nanofiber layer comprises a second polymer and a second natural polymer in a mass ratio of (10-90):(10-90), wherein the second polymer comprises one or more of lactic acid-caprolactone copolymer, polycaprolactone, and lactic acid-glycolic acid copolymer; and the second natural polymer comprises one or more of gelatin, collagen, and silk fibroin. For example, the mass ratio of the second polymer to the second natural polymer is any value selected from 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80:20, and 90:10, or a range consisting of any two of these values.

[0043] In some embodiments, the second polymer is a lactic acid-caprolactone copolymer (PLCL) and the second natural polymer is gelatin. In some embodiments, the mass ratio of the lactic acid-caprolactone copolymer (PLCL) in the second polymer to the second natural polymer gelatin is 70:30.

[0044] In some embodiments, the mass percentage of active particles loaded on the second nanofiber layer is 0% to 1.5% based on the total mass of the second nanofiber layer; the bioactive ions include one or more of calcium, iron, zinc, magnesium, strontium, and manganese ions. For example, the mass percentage of active particles is any value among 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, or a range consisting of any two values. In some embodiments, the active particles are nMgO. The active particles of the present application are added in the form of nMgO, which can not only increase the mechanical properties of the material, but also enhance the antibacterial properties of the material and promote bone cell proliferation.

[0045] In some embodiments, the third nanofiber layer comprises a PLA-small molecule natural drug graft, and in some specific embodiments, the third nanofiber layer comprises a PLA-resveratrol graft. The PLA-resveratrol graft provided herein can provide the stent with a long-lasting bactericidal effect while maintaining the strength of the fiber material.

[0046] In some embodiments, the core layer structure of the weft thread of the present application adopts PLA micron fiber thread, and the outer layer of the bone scaffold segment adopts a composition of lactic acid-caprolactone copolymer (PLCL) and gelatin. In addition, by adding nMgO to the composition of lactic acid-caprolactone copolymer (PLCL) and gelatin, the mechanical properties of the fiber material are increased while the bone cell proliferation function and antibacterial properties of the fiber material are increased. The ligament scaffold segment improves the long-term anti-inflammatory effect of the scaffold while ensuring the strength of the scaffold through modified grafting of PLA.

[0047] In some embodiments, PLA-small molecule natural drug grafts are prepared by the following method: PLA is dissolved in an organic solvent, a condensing agent and a catalyst are added, a small molecule drug is added, the reaction is carried out at room temperature under a nitrogen atmosphere, and the product is separated to obtain a PLA-small molecule natural drug graft.

[0048] In some embodiments, the organic solvent includes dichloromethane, the condensing agent includes 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), and the catalyst includes 4-dimethylaminopyridine (DMAP).

[0049] The room temperature mentioned in this application refers to a temperature range of 20°C to 30°C.

[0050] In some specific embodiments, the PLA-small molecule natural drug graft is PLA-resveratrol (PGR), which has the following structural formula:

[0051]

[0052] In some specific embodiments, PLA-resveratrol is prepared by the following method: under nitrogen protection, PLA is dissolved in dichloromethane, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) and 4-dimethylaminopyridine are added, and the mixture is stirred at room temperature. Subsequently, resveratrol is dissolved in anhydrous ethanol and slowly added to the dichloromethane system containing PLA, and stirred at room temperature for 3 to 12 hours. After the reaction is completed, the mixture is precipitated in deionized water overnight, extracted with dichloromethane, and the lower layer of solution is removed by removing dichloromethane and anhydrous ethanol on a rotary evaporator to obtain a PLA-resveratrol graft.

[0053] In some embodiments, the bioactive heterogeneous textile scaffold is prepared by the following method:

[0054] providing a first core polymer wire and a second core polymer wire as the core structure;

[0055] A first nanofiber layer is prepared on the outer layer of the first core layer polymer line to form a warp, a second nanofiber layer is prepared on the outer layer of the second core layer polymer line to form a bone scaffold segment, and a third nanofiber layer is prepared on the outer layer of the second core layer polymer line to form a ligament scaffold segment, with the bone scaffold segment and the ligament scaffold segment serving as wefts;

[0056] The warp and weft are woven by a weaving method to obtain a bioactive multiphase textile scaffold.

[0057] In some embodiments, the bioactive multiphase textile scaffold is prepared by the following method:

[0058] To prepare core-spun nanofiber yarn, two jet-spinning nozzles are used, each applying a positive and negative electric field. The core structure passes through a hollow rotating funnel, which serves as a receiving device. After the two nozzles spray nanofibers onto the rotating funnel and the core structure, the rotating funnel twists the nanofibers into the core structure, where they are received by a receiving roller, resulting in a continuous nanofiber yarn. The nanofiber yarns are then braided in both the warp and weft directions to create an integrated scaffold.

[0059] In this application, the warp of the bioactive multiphase textile scaffold is a nanofiber yarn with zero bioactive ion content, and the weft of the bioactive multiphase textile scaffold is a nanofiber yarn loaded with bioactive ions at the two end bone scaffold segments, and the weft of the middle ligament scaffold segment is a nanofiber yarn loaded with PLA-small molecule natural drug grafts.

[0060] In some specific embodiments, the bioactive multiphase textile scaffold of the present application is prepared by the following method:

[0061] Step (1): preparing spinning solutions respectively: a first polymer and a first natural polymer blend spinning solution; a second polymer, a second natural polymer and a blend spinning solution of different contents of active particles; and a spinning solution loaded with PLA-small molecule natural drug grafts;

[0062] Step (2): preparing nanofiber yarn: passing the core layer line through a hollow rotating funnel, connecting the spinning solution prepared in step (1) to two opposing jet spinning heads, applying positive and negative electric fields to the opposing jet spinning heads respectively, spraying nanofibers onto the middle rotating funnel and the core layer line, the rotating funnel twisting the nanofibers onto the core layer line, and receiving rollers receiving the nanofibers to obtain continuous nanofiber yarn;

[0063] Step (3): Preparation of bioactive multiphase textile scaffold: nanofiber yarn with zero bioactive ion content is used as the warp, the weft of the bone scaffold part at both ends is nanofiber yarn loaded with bioactive ions, and the middle section ligament scaffold part is nanofiber yarn loaded with PLA-small molecule natural drug grafts, and the nanofiber yarns in the warp and weft directions are interwoven by weaving method.

[0064] In some embodiments, in step (1), the mass percentage concentration of the blended spinning solution is 5% to 20%, such as the mass percentage concentration of the blended spinning solution is any value of 5%, 6%, 8%, 9%, 10.5%, 15%, 20% or a range consisting of any two values. More preferably, the mass percentage concentration of the blended spinning solution is 10%.

[0065] In some embodiments, in step (1), the mass ratio of the first polymer to the first natural polymer is 90:10 to 10:90; for example, the mass ratio of the first polymer to the first natural polymer is any one of 90:10, 80:20, 70:30, 75:25, 60:40, 50:50, 40:60, 25:75, 30:70, 20:80 or 10:90; the mass ratio of the second polymer to the second natural polymer is 90:10 to 10:90; for example, the mass ratio of the second polymer to the second natural polymer is any one of 90:10, 80:20, 70:30, 75:25, 60:40, 50:50, 40:60, 25:75, 30:70, 20:80 or 10:90.

[0066] In some embodiments, in step (1), the mass percentage concentration of active particles added to the spinning solution is 0-2%, such as the mass percentage concentration of bioactive ions is any value among 0.1%, 0.5%, 1%, 1.5%, or a range consisting of any two values.

[0067] In some embodiments, in step (1), the mass percentage concentration of the spinning solution loaded with PLA-small molecule natural drug grafts is 5% to 20%, such as the mass percentage concentration of the spinning solution loaded with PLA-small molecule natural drug grafts is any value of 5%, 6%, 8%, 9%, 10.5%, 15%, 20%, or a range consisting of any two values. More preferably, the mass percentage concentration of the spinning solution loaded with PLA-small molecule natural drug grafts is 15%.

[0068] In some embodiments, in step (1), the solvent for preparing the spinning solution is one or more of hexafluoroisopropanol, trifluoroethanol, dichloromethane and trifluoroacetic acid.

[0069] In some embodiments, in step (2), the nanofiber yarn includes a core polymer wire and electrospun nanofibers located on the outer layer of the core polymer wire, wherein the nanofibers wrap the polymer wire.

[0070] In some embodiments, in step (2), the specific process of electrospinning is: adding the spinning solution into the syringe, and then connecting the spinning nozzles at the left and right ends of the rotating funnel respectively, applying positive and negative high voltages of 10 kV respectively, pushing the pump speed at 1.5 mL / h, the receiving distance at 12 cm, the rotating funnel speed at 400 rpm, and the receiving roller at 8 rpm.

[0071] The embodiments of the present application also provide the application of the above-mentioned bioactive multiphase textile scaffold or the bioactive multiphase textile scaffold prepared by the preparation method of the above-mentioned bioactive multiphase textile scaffold as a tendon or ligament scaffold. The bioactive multiphase textile scaffold of the present application has an appropriate pore size, which solves the problem that the nanofiber scaffold has a small pore size and cells are difficult to grow into, and improves the three-dimensional cell growth ability. As the tendon / ligament tissue proliferates and grows into itself, the scaffold is reorganized into fibrosis and forms a community with the body's own tissue, providing patients with better motor function and movement experience.

[0072] Example 1: Preparation of bioactive multiphase textile scaffolds

[0073] In this example, a PLA micron fiber yarn was used as the core. The warp was a nanofiber yarn made of PLCL (75:25, Jinan Daigang Biotechnology Co., Ltd.) and gelatin. The weft of the bone scaffold at both ends was a nanofiber yarn made of PLCL (75:25, Jinan Daigang Biotechnology Co., Ltd.), gelatin, and nMgO. The weft of the ligament scaffold in the middle was a nanofiber yarn loaded with a PLA-resveratrol graft. The specific preparation process is as follows:

[0074] (1) Preparation of PLA-resveratrol (PGR) grafted product: Under nitrogen protection, 3 g of PLA was dissolved in 40 mL of dichloromethane. Subsequently, 0.204 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) and 0.086 g of 4-dimethylaminopyridine (DMAP) were added to the flask and stirred at room temperature for 30 min. 0.3 g of resveratrol was dissolved in 10 mL of anhydrous ethanol and slowly added to the dissolved PLA. The mixture was stirred at room temperature for 6 h. After the reaction, the mixture was precipitated in deionized water overnight and extracted with dichloromethane. The lower layer solution was removed and the dichloromethane and anhydrous ethanol were removed on a rotary evaporator to obtain the PLA-resveratrol grafted product. The mixture was then dissolved in dichloromethane three times and stored in a vacuum desiccator for later use.

[0075] (2) Preparation of spinning solution: 0.7 g of PLCL with a molecular weight of about 200,000 and 0.3 g of gelatin were weighed and dissolved in hexafluoroisopropanol (purchased from Shanghai Darui Fine Chemicals Co., Ltd.) to prepare a PLCL / gelatin spinning solution with a mass percentage concentration of 10%.

[0076] (3) Preparation of bioactive ion-loaded spinning solution: First, prepare a PLCL / gelatin spinning solution with a mass concentration of 10% according to step (2), then add nano-magnesium oxide (nMgO) with a mass percentage of 0%, 0.1%, 0.5%, 1%, and 1.5%, and disperse it evenly by ultrasonication and stirring.

[0077] (4) Preparation of spinning solution loaded with PLA-resveratrol graft: 1.5 g of PLA-resveratrol graft was weighed and dissolved in hexafluoroisopropanol to prepare a spinning solution of PLA-resveratrol graft with a mass concentration of 15%.

[0078] (5) Preparation of PLA-PLCL / gelatin nanofiber yarn: The PLA line is passed through the rotating funnel of the electrospinning nanofiber yarn preparation equipment as the core layer, the PLCL / gelatin spinning solution in step (2) is sprayed together, and the PLCL / gelatin nanofibers are twisted onto the core layer PLA line using the rotating funnel, and the receiving roller collects the continuous nMgO-0 nanofiber yarn.

[0079] (6) Preparation of PLA-PLCL / gelatin / nMgO nanofiber yarn: The PLA line was passed through the rotating funnel of the electrospinning nanofiber yarn preparation equipment as the core layer, the PLCL / gelatin / nMgO spinning solution in step (3) was sprayed, and the PLCL / gelatin / nMgO nanofibers were twisted onto the core layer PLA line using a rotating funnel. The continuous PLA-PLCL / gelatin / nMgO nanofiber yarn was collected by a receiving roller. The yarns with nMgO loading contents of 0.1%, 0.5%, 1%, and 1.5% were recorded as nMgO-0.1, nMgO-0.5, nMgO-1, and nMgO-1.5, respectively.

[0080] (7) Preparation of PLA-resveratrol graft nanofiber yarn: The PLA line is passed through the rotating funnel of the electrospinning nanofiber yarn preparation equipment as the core layer, the PLA-resveratrol graft spinning solution in step (4) is sprayed, and the PLA-resveratrol graft nanofiber is twisted onto the core layer PLA line using the rotating funnel, and the continuous PLA-resveratrol graft nanofiber yarn is collected by the receiving roller.

[0081] (8) The electrospinning process of nano yarn in steps (5) to (7) above is as follows: the spinning solution is added to the syringe, and then the spinning nozzles at the left and right ends of the yarn are connected respectively, and a positive and negative high voltage of 10 kV is applied respectively, the propulsion pump speed is 1.5 mL / h, the receiving distance is 12 cm, the rotating funnel speed is 400 rpm, and the receiving roller speed is 8 rpm.

[0082] (9) Preparation of bioactive multiphase textile scaffolds: nMgO-0 nanofiber yarns were used as warp threads, PLA-PLCL / gelatin / nMgO nanofiber yarns loaded with different contents of bioactive ions were used as weft threads for the bone scaffold parts at both ends, and nanofiber yarns loaded with PLA-resveratrol grafts were used as weft threads for the middle ligament scaffold part. The nanofiber yarns in the warp and weft directions were interwoven by hand weaving to prepare bioactive multiphase textile scaffolds.

[0083] (10) The weaving process of the above step (9) is as follows: nMgO-0 nanofiber yarn is used as the warp, the distance between the two warps is 0.5 to 2 mm, and each scaffold uses a total of 10 warps; the bone scaffold parts at both ends are PLA-PLCL / gelatin / nMgO nanofiber yarns loaded with different contents of bioactive ions as the weft, and the weft of the middle section ligament scaffold part is nanofiber yarn loaded with PLA-resveratrol grafts. The weft length of each weft is 2 to 10 mm, and the nanofiber yarns in the warp and weft directions are interwoven.

[0084] (11) After weaving, the prepared sheet scaffold was ultrasonically cleaned and freeze-dried, and then sterilized with ethylene oxide for 24 h, ultimately obtaining a bioactive multiphase textile scaffold that can be used for artificial tendons / ligaments.

[0085] In the above-mentioned embodiment 1, the bracket is made of nanofiber yarns woven in both the warp and weft directions, and the processing is relatively simple. The length and width of the bracket can be adjusted according to actual needs.

[0086] The nuclear magnetic resonance spectrum of the PLA-resveratrol conjugate obtained in Example 1 is as follows: Figure 4 As shown in Figure 2, the structure of polylactic acid (PLA) shows two significant characteristic peaks labeled 1 (5.1 ppm) and 2 (1.5 ppm). Similarly, the structure of resveratrol shows that in addition to hydrogen, there are two phenolic hydroxyl peaks labeled 3 (9.54 ppm) and 4 (9.18 ppm), as well as two characteristic peaks labeled 5 (6.91 ppm) and 6 (6.83 ppm) in the aromatic ring structure.

[0087] The infrared spectrum of the PLA-resveratrol conjugate obtained in Example 1 is as follows: Figure 5 As shown in Figure 2, in the PLA-resveratrol graft, the characteristic peaks of the aromatic ring structure of PLA and resveratrol can be observed, but the phenolic hydroxyl groups (3 and 4) disappear, indicating that the esterification reaction is successful. The spectrum of polylactic acid is at 1747 cm -1 There is a strong C=O stretching vibration peak at 3166cm -1 、1509cm -1 , corresponding to the phenolic hydroxyl group and the aromatic ring, respectively. In the PLA-resveratrol grafted product, characteristic peaks of the aromatic ring structure of PLA and resveratrol can be observed, but the phenolic hydroxyl group peak disappears, indicating that the esterification reaction of the compound of the present application is successful.

[0088] The results of the nanofibers loaded with different contents of nMgO obtained in step (6) of Example 1 are as follows: Figure 6 As shown, Figure 6 Figure (a) shows a transmission electron micrograph, Figure (b) a cross-sectional scanning electron micrograph, Figure (c) a surface scanning electron micrograph, and Figure (d) a surface scanning electron micrograph of braided scaffolds with varying nMgO contents. The yarn without nMgO exhibits no nMgO deposition, and TEM results reveal no nMgO within individual nanofibers. With increasing nMgO content in the spinning solution, nMgO deposition increases on the yarn surface and within the nanofibers, demonstrating that nMgO is not only deposited on the fiber surface but also successfully electrospun into the nanofibers. The three-dimensional structure of the braided scaffold facilitates cell adhesion and proliferation and mimics the fibrous structure of the extracellular matrix of tendon tissue.

[0089] The test results of the PLA-resveratrol grafted nanofibers obtained in step (7) of Example 1 are as follows: Figure 7 As shown, Figure 7 Figure a is a cross-sectional scanning electron microscope, Figure b is a surface scanning electron microscope, and Figure c is a surface scanning electron microscope of the woven scaffold. It can be seen that after PLA is grafted with the small molecule natural drug resveratrol, the overall appearance of the nanofiber yarn and the scaffold is not affected.

[0090] The uniaxial tensile test results of the yarns with different nMgO contents obtained in step (6) of Example 1 are as follows: Figure 8 As shown. Figure 8 As shown in Figure A, compared with the PLA fiber line, the ultimate strength of the nMgO bonded yarn is significantly improved, and the ultimate tensile strength (UTS) of the nMgO bonded yarn (95.29±9.62~106.24±5.55MPa) is significantly higher than that of the PLA fiber bundle (33.43±0.96MPa) (p<0.05), indicating that the wrapping of electrospun nanofibers further improves the mechanical strength of the yarn. Figure 8 As shown in Figure B, the Young's modulus of nMgO-bonded yarn (0.85±0.07~1.14±0.10GPa) is significantly enhanced compared with that of polylactic acid fiber bundle (0.25±0.01GPa). Figure 8 As shown in Figure C, there is no significant difference in the failure strain between the PLA fiber bundle and yarns with different nMgO contents (25.87±1.62% to 30.62±1.91%). The results show that the mechanical properties of the nMgO-bonded yarns are superior to those of the PLA fiber bundle.

[0091] The plate coating method was used to test the in vitro antibacterial effect of nano-MgO scaffolds with different concentrations. The scaffolds with different nMgO contents were placed in a 24-well plate and sterilized by alcohol fumigation and UV irradiation for 30 minutes. 1 mL of 1×10 6 CFU / mL of bacterial suspension was added to a 24-well plate and cultured at 37°C, 1000 rpm for 24 hours. After the culture was completed, the bacterial suspension was diluted to 1×103 CFU / mL, take 100μL of the diluted bacterial solution and evenly spread it on the LB culture plate, place it in a 37℃ biochemical incubator and culture it overnight. After each group grows a single colony of appropriate size, place it under a bacterial counter to count the number of bacteria. The results are as follows Figure 9 As shown in Figure A, the nMgO braided stents with different contents prepared in step (6) of Example 1 of this application have good antibacterial effects on Escherichia coli and Staphylococcus aureus. Figure 9 It can be seen from the results of Figures B and C in the figure that the antibacterial effect of the braided stent of the present application is positively correlated with the content of nMgO. The more nMgO is added, the better the antibacterial effect.

[0092] The proliferation activity of BMSC cells in the magnesium oxide scaffolds of different concentrations prepared in step (6) of Example 1 was tested using the CCK-8 method. The scaffolds with different nMgO contents were placed in a 24-well plate and sterilized by alcohol fumigation and UV irradiation for 30 minutes. 15,000 BMSC cells were planted in each well and cultured in a carbon dioxide incubator. The absorbance of each well was measured at 450nm using CCK-8 reagent on the 1st, 3rd, and 5th day. The results are shown in Figure 2. Figure 10 As shown, the OD values ​​of each group increased significantly from day 1 to day 5, and the OD value of the nMgO-0.5 group on day 5 was significantly higher than that of the other groups. This indicates that the scaffold has no obvious cytotoxicity, good cell proliferation, and good cell compatibility. The best cell-promoting effect is achieved when the nMgO content is 0.5%.

[0093] The CCK-8 method was used to test the proliferation activity of the scaffolds prepared in step (7) before and after grafting with resveratrol on BMSC cells. Each part of the scaffold was placed in a 24-well plate, and sterilized by alcohol fumigation and ultraviolet irradiation for 30 minutes. 15,000 BMSC cells were planted in each well and cultured in a carbon dioxide incubator. The absorbance of each well was measured at 450nm using CCK-8 reagent on the 1st, 3rd, and 5th day. The results are as follows: Figure 11 As shown in the figure, PMR is the PLA blended with resveratrol experimental group, and PGR is the PLA grafted with resveratrol experimental group. Compared with the control group, except for the PLA blended with resveratrol (PMR) group, the OD values ​​of the other groups increased significantly, indicating that the scaffold had no obvious cytotoxicity.

[0094] The ability of the nano-MgO scaffolds with different concentrations prepared in step (6) of Example 1 to induce bone differentiation of BMSC cells was detected using an Alizarin Red quantitative detection kit. The scaffolds with different nMgO contents were placed in a 24-well plate and sterilized by alcohol fumigation and UV irradiation for 30 minutes. 25,000 BMSC cells were planted in each well and cultured in a carbon dioxide incubator. On the 14th day, the absorbance of each well was measured at 562 nm using an Alizarin Red quantitative detection kit. The results are shown in Figure 2. Figure 12As shown, the OD value of the nMgO-0.5 group was significantly higher than that of the other groups on day 14, indicating that an appropriate concentration of nMgO can promote the bone differentiation of stem cells, and the best promoting effect on cells is achieved when the nMgO addition content is 0.5%.

[0095] The expression of inflammatory factor TNF-α was detected using ELISA kit. Each part of the scaffold was placed in a 24-well plate, sterilized by alcohol fumigation and UV irradiation for 30 minutes. Macrophages (RAW264.7) were cultured at 5×10 4 After the cells were completely attached to the wall, 10 μL LPS (1 μg / mL) was added to induce differentiation. After 24 hours, the cell supernatant was obtained by centrifugation and the content of inflammatory factor TNF-α was detected by ELISA kit. Figure 13 As shown, Figure 13 In the experiment, NC is the negative control group, LPS is the positive control group, PLA is the PLA experimental group, PMR is the PLA blended with resveratrol experimental group, and PGR is the PLA grafted with resveratrol experimental group. From the results, it can be seen that the inflammatory factors produced by the scaffold loaded with resveratrol are significantly reduced, so it can be concluded that the material prepared in this application has a certain effect of inhibiting the production of inflammatory factors.

[0096] The bioactive multiphase textile scaffold prepared in the examples of the present application is prepared by rationally designing the scaffold structure and screening the components of the scaffold. The obtained scaffold not only has osteoconductivity, can promote bone tunnel healing and guide osteogenesis, but also has long-lasting anti-inflammatory activity, can regulate the postoperative immune microenvironment, and guide and promote endogenous tendon repair.

[0097] Example 2: This example uses PLGA as the core, with the warp made of PCL (75:25, Jinan Daigang Biotechnology Co., Ltd.) and silk fibroin. The weft of the bone scaffold at both ends is made of PCL (75:25, Jinan Daigang Biotechnology Co., Ltd.), silk fibroin, and ZnO. The weft of the ligament scaffold in the middle section is a nanofiber yarn loaded with PLA-magnolia nobile grafts. The specific preparation process is as follows:

[0098] (1) Extraction of silk fibroin: Weigh 120 g of raw silk and chop it thoroughly. Add it to 3 L of 0.5% sodium bicarbonate aqueous solution and boil for 30 minutes. Repeat the above steps three times to remove the surface sericin. Rinse thoroughly with deionized water and air-dry to obtain pure silk fibroin fibers. Add the silk fibroin fibers to a 9.8 mol / L lithium bromide solution, heat to 60°C until completely dissolved, filter to remove impurities, and then place in a dialysis bag with a molecular cutoff of 14,000 Da and dialyze at room temperature for 7 days. Filter the solution to obtain a pure silk fibroin aqueous solution, which is freeze-dried to obtain a sponge-like silk fibroin.

[0099] (2) Preparation of PLA-Magnolol Graft: Under nitrogen protection, 3 g of PLA was dissolved in 40 mL of dichloromethane. Subsequently, 0.204 g of EDCI and 0.086 g of DMAP were added to the flask and stirred at room temperature for 30 min. 0.3 g of magnolol was dissolved in 10 mL of anhydrous ethanol and slowly added to the dissolved PLA. The mixture was stirred at room temperature for 6 h. After the reaction, the mixture was precipitated in deionized water overnight and extracted with dichloromethane. The lower layer was removed and the dichloromethane and anhydrous ethanol were removed on a rotary evaporator to obtain the PLA-Magnolol Graft. The mixture was then dissolved in dichloromethane three times and stored in a vacuum desiccator for later use.

[0100] (3) Preparation of spinning solution: 0.7 g of PCL with a molecular weight of about 200,000 and 0.3 g of silk fibroin were weighed and dissolved in hexafluoroisopropanol (purchased from Shanghai Darui Fine Chemicals Co., Ltd.) to prepare a PCL / silk fibroin spinning solution with a mass concentration of 10%.

[0101] (4) Preparation of bioactive ion-loaded spinning solution: First, prepare a PCL / silk fibroin spinning solution with a mass concentration of 10% according to step (3), then add nano-magnesium oxide with mass fractions of 0%, 0.1%, 0.5%, 1%, and 1.5%, and disperse evenly by ultrasonication and stirring.

[0102] (5) Preparation of spinning solution loaded with PLA-magnolia nobile graft: 1.5 g of PLA-magnolia nobile graft was weighed and dissolved in hexafluoroisopropanol to prepare a spinning solution with a mass concentration of 15% of PLA-magnolia nobile graft.

[0103] (6) Preparation of PLGA-PCL / silk fibroin nanofiber yarn: The PLGA thread was passed through the rotating funnel of the electrospinning nanofiber yarn preparation equipment as the core layer, the PCL / silk fibroin spinning solution in step (3) was sprayed, and the PCL / silk fibroin nanofibers were twisted onto the core layer PLGA thread using the rotating funnel, and the continuous ZnO-0 nanofiber yarn was collected by the receiving roller.

[0104] (7) Preparation of PLGA-PCL / silk fibroin / ZnO nanofiber yarn: The PLGA thread was passed through the rotating funnel of the electrospinning nanofiber yarn preparation equipment as the core layer, the PCL / silk fibroin / ZnO spinning solution in step (4) was sprayed, and the PCL / silk fibroin / ZnO nanofibers were twisted onto the core layer PLGA thread using a rotating funnel. The continuous PLGA-PCL / silk fibroin / ZnO nanofiber yarn was collected by a receiving roller. The yarns with ZnO loading contents of 0.1%, 0.5%, 1%, and 1.5% were recorded as ZnO-0.1, ZnO-0.5, ZnO-1, and ZnO-1.5, respectively.

[0105] (8) Preparation of PLA-magnolia officinalis graft nanofiber yarn: PLGA thread is passed through the rotating funnel of the electrospinning nanofiber yarn preparation equipment as the core layer, the PLA-magnolia officinalis graft spinning solution in step (5) is sprayed, and the PLA-magnolia officinalis graft nanofiber is twisted onto the core layer PLGA thread using the rotating funnel, and the continuous PLA-magnolia officinalis graft nanofiber yarn is collected by the receiving roller.

[0106] (9) The electrospinning process of nano yarn in the above steps (6)-(8) is as follows: the spinning solution is added to the syringe, and then the spinning nozzles at the left and right ends of the yarn are connected respectively, and a positive and negative high voltage of 10KV is applied respectively, the propulsion pump speed is 1.5mL / h, the receiving distance is 12cm, the rotating funnel speed is 400 rpm, and the receiving roller speed is 8 rpm.

[0107] (10) Preparation of bioactive multiphase textile scaffolds: ZnO-0 nanofiber yarns were used as warp threads, PLGA-PCL / silk fibroin / ZnO nanofiber yarns loaded with different contents of bioactive ions were used as weft threads for the bone scaffold parts at both ends, and nanofiber yarns loaded with PLA-magnolia bark phenol grafts were used as weft threads for the middle ligament scaffold part. The nanofiber yarns in the warp and weft directions were interwoven by hand weaving to prepare bioactive multiphase textile scaffolds.

[0108] (11) The weaving process of the above step (10) is as follows: ZnO-0 nanofiber yarn is used as the warp, the distance between the two warps is 0.5 to 2 mm, and each scaffold uses a total of 10 warps; the bone scaffold parts at both ends are loaded with PLGA-PCL / silk fibroin / ZnO nanofiber yarns with different contents of bioactive ions as the weft, and the weft of the middle section ligament scaffold part is loaded with PLA-magnolia bark phenol grafted nanofiber yarn, the weaving length of each weft is 2 to 10 mm, and the nanofiber yarns in the warp and weft directions are interwoven.

[0109] (12) After weaving, the prepared sheet scaffold was ultrasonically cleaned and freeze-dried, and then sterilized with ethylene oxide for 24 h, ultimately obtaining a bioactive multiphase textile scaffold that can be used for artificial tendons / ligaments.

[0110] In the above-mentioned embodiment 2, the bracket is made of nanofiber yarns woven in both the warp and weft directions, and the processing is relatively simple. The length and width of the bracket can be adjusted according to actual needs.

[0111] The above is a detailed introduction to a bioactive multiphase textile scaffold, preparation method and application provided in the examples of the present application. Specific examples are used in this article to illustrate the principles and implementation methods of the present application. The description of the above embodiments is only used to help understand the method of the present application and its core idea; at the same time, for technical personnel in this field, based on the ideas of the present application, there will be changes in the specific implementation methods and application scope. In summary, the content of this specification should not be understood as a limitation on the present application.

Claims

1. A bioactive multiphase textile scaffold, characterized in that: The bioactive multiphase textile scaffold is interwoven with warp and weft, wherein the warp and weft each include a core structure and a nanofiber layer located on the outer layer of the core structure, and the warp includes a first core polymer thread and a first nanofiber layer located on the outer layer of the first core polymer thread; The core layer structure of the weft thread is a second core layer polymer thread; the weft thread includes bone scaffold segments located at both ends and a ligament scaffold segment located in the middle of the bone scaffold segments, the bone scaffold segment includes a second core layer polymer thread and a second nanofiber layer located on the outer layer of the second core layer polymer thread, the second nanofiber layer is loaded with active particles having bioactive ions; the ligament scaffold segment includes a second core layer polymer thread and a third nanofiber layer located on the outer layer of the second core layer polymer thread, the third nanofiber layer includes a PLA-small molecule natural drug graft.

2. The bioactive multiphase textile scaffold according to claim 1, characterized in that: The first core layer polymer wire and the second core layer polymer wire may be the same or different; the material of the first core layer polymer wire or the second core layer polymer wire is selected from one or more of polyethylene terephthalate, polylactic acid, polycaprolactone, lactic acid-glycolic acid copolymer, and silk fibroin wire.

3. The bioactive multiphase textile scaffold according to claim 1, characterized in that: The first nanofiber layer includes a first polymer and a first natural polymer in a mass ratio of (10 to 90): (10 to 90); the first polymer includes one or more of lactic acid-caprolactone copolymer, polycaprolactone and lactic acid-glycolic acid copolymer; the first natural polymer includes one or more of gelatin, collagen (COL) and silk fibroin.

4. The bioactive multiphase textile scaffold according to claim 1, characterized in that: The second nanofiber layer includes a second polymer and a second natural polymer in a mass ratio of (10 to 90): (10 to 90), the second polymer includes one or more of lactic acid-caprolactone copolymer, polycaprolactone and lactic acid-glycolic acid copolymer; the second natural polymer includes one or more of gelatin, collagen and silk fibroin.

5. The bioactive multiphase textile scaffold according to claim 1, characterized in that: Based on the total mass of the second nanofiber layer, the mass percentage of the active particles loaded in the second nanofiber layer is 0% to 1.5%; the bioactive ions include one or more of calcium, iron, zinc, magnesium, strontium and manganese ions.

6. The bioactive multiphase textile scaffold according to claim 1, characterized in that: The small molecule natural drug in the PLA-small molecule natural drug graft is selected from one of curcumin, resveratrol, quercetin and magnolol.

7. The bioactive multiphase textile scaffold according to claim 1, characterized in that: The PLA-small molecule natural drug graft is prepared by the following method: PLA is dissolved in an organic solvent, a condensing agent and a catalyst are added, a small molecule drug is added, the reaction is carried out at room temperature in a nitrogen atmosphere, and the product is separated to obtain the PLA-small molecule natural drug graft.

8. A method for preparing the bioactive multiphase textile scaffold according to claim 1, characterized in that: The following steps are involved: providing a first core polymer wire and a second core polymer wire as the core structure; A first nanofiber layer is prepared on the outer layer of the first core layer polymer line to form a warp, a second nanofiber layer is prepared on the outer layer of the second core layer polymer line to form a bone scaffold segment, and a third nanofiber layer is prepared on the outer layer of the second core layer polymer line to form a ligament scaffold segment, with the bone scaffold segment and the ligament scaffold segment serving as wefts; The warp and weft are woven by a weaving method to obtain a bioactive multiphase textile scaffold.

9. The method for preparing a bioactive multiphase textile scaffold according to claim 8, characterized in that: The core layer structure is a single wire with a diameter of 0.03mm to 0.1mm formed by combining and stretching polymer single fibers with a diameter of 20μm to 50μm.

10. Use of the bioactive multiphase textile scaffold according to any one of claims 1 to 7 or the bioactive multiphase textile scaffold prepared by the preparation method of the bioactive multiphase textile scaffold according to any one of claims 8 to 9 as a tendon or ligament scaffold.

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