CN113350571B - Composite artificial fiber element with supporting layer and artificial ligament - Google Patents

Abstract

The present disclosure provides a composite artificial fiber element with a support layer, comprising: the method comprises the following steps: a core wire made of degradable polymer fibers; and a support layer covering the core wire, wherein the support layer comprises a grid formed by weaving fibers obtained by electrostatic spinning and growth factors added into gaps formed among the fibers, the core wire is used as a collecting device in the electrostatic spinning process, and the fibers are made of degradable high polymer materials. According to the present disclosure, the hydrophilicity of a material can be improved while the biodegradable properties thereof are retained, and thus the creeping growth of cells can be facilitated.

Description

Composite artificial fiber element with supporting layer and artificial ligament

The application is filed as21/10/2019Application No. is2019110021346The invention is named asComposite person Artificial fiber element and artificial ligamentDivisional application of the patent application.

Technical Field

The disclosure belongs to the field of biomedical composite materials, and particularly relates to a composite artificial fiber element with a supporting layer and an artificial ligament.

Background

Among orthopedic injuries, injury and tear of the cruciate ligament of the knee joint is a common sports injury, and the incidence rate of the injury is high. Due to the special biological structure and activity of the cruciate ligament, once the cruciate ligament is damaged or torn, the cruciate ligament cannot heal naturally normally, and only the treatment effect can be achieved through a transplantation operation. There are three main types of currently used grafts: autologous, allogenic and artificial grafts. Wherein, autograft has the problems of large surgical trauma, more complications, slow recovery and the like; allografts have problems with source scarcity, risk of infection, immune rejection, etc. Therefore, in view of the above-mentioned problems with autografts and allografts, most surgical options use artificial grafts, i.e., artificial ligaments.

The existing artificial ligament mainly adopts a textile product of a high molecular polymer as a ligament substitute, for example, LARS and Neo-ligands artificial ligaments which are composed of a PET (polyethylene terephthalate) material as a main component have relatively stable mechanical properties, and thus are widely used in an operation. However, such artificial ligaments have been prohibited from being used clinically in most countries such as the united states and european countries because of their properties of being non-degradable in living bodies, hydrophobic, and the like, which are bio-inert against cell regeneration.

With the development of regenerative medicine, molecular modification on degradable materials to induce the interaction of cytointegrins and induce the proliferation and differentiation of cells and the synthesis and assembly of extracellular matrix to start the regeneration system of the body is gradually becoming the development trend of implantable medical devices. The subject of tissue engineering and the like is mainly dedicated to the formation and regeneration of tissues and organs, and the core of the subject is to establish a three-dimensional space complex of cells and biological materials, namely, living tissues with vitality, so as to reconstruct the morphological structure and function of damaged tissues and achieve permanent replacement. In patent document 1 (CN 105828846 a), an artificial ligament prosthesis composed entirely or partially of PCL (polycaprolactone) fibers is proposed, belonging to a biodegradable and biofusion artificial ligament which eliminates the concerns and uncertainties of non-degradable synthetic scaffolds. Such artificial ligaments are not only biodegradable, but can also be planted at will to promote the formation of functional tissues with controlled cellular and tissue activity, and maintain good mechanical properties. Such artificial ligaments can be slowly absorbed by the organism in which they are implanted, to be gradually replaced by functional tissues equivalent to natural ligaments.

However, tissue engineering is still in the early stage for the research of regeneration and repair of ligaments of human body, and there are many key technical problems to be solved, such as poor hydrophilic property of the material, inability to realize effective adsorption of cells, how to realize organic combination of growth factors and polymer materials, and the like.

Disclosure of Invention

The present disclosure has been made in view of the above-mentioned state of the art, and an object of the present disclosure is to provide a composite artificial fiber element and an artificial ligament which have excellent hydrophilic properties and can achieve organic fusion of a growth factor and a polymer material.

To this end, the present disclosure provides, in one aspect, a composite artificial fiber element, comprising: a core wire; and a support layer covering the outside of the core wire, the support layer having a mesh woven from fibers and a growth factor, wherein the fibers comprise a degradable hydrophobic polymer material and a hydrophilic polymer material.

In one aspect of the disclosure, the fiber containing degradable hydrophobic polymer material and hydrophilic polymer material is used as the support layer of the composite artificial fiber element, so that the composite artificial fiber element can improve hydrophilicity while maintaining the biodegradable characteristic of the material, and thus can contribute to the covering growth of cells. In addition, the growth factor is organically fused with the high molecular material, so that the problems of shrinkage, imperfect biological activity of only the surface and the like generated when the material is soaked in a biological reagent can be reduced, the biological activity of the composite artificial fiber element can be improved, and the regeneration of the ligament can be better promoted when the composite artificial fiber element is applied to the artificial ligament.

Further, in a composite artificial fiber unit according to an aspect of the present disclosure, optionally, the fiber includes a hydrophobic block composed of the hydrophobic polymer material and a hydrophilic block composed of the hydrophilic polymer material. In this case, the hydrophilic block can increase the hydrophilicity of the fiber, and thus can increase the hydrophilicity of the support layer, which can contribute to the creeping growth of cells.

In addition, in a composite artificial fiber unit according to an aspect of the present disclosure, the hydrophobic blocks and the hydrophilic blocks may be alternately arranged. Therefore, the support layer can have biodegradability and hydrophilicity, and can be beneficial to the creeping growth of cells.

Further, in a composite artificial fiber element according to an aspect of the present disclosure, optionally, the core wire is made of a polymer fiber having a young's modulus of 50GPa to 150GPa. Under the condition, the core wire has higher mechanical strength, and can provide effective strength support for the composite artificial fiber element, so that the composite artificial fiber element can have better mechanical supporting force in the pulling direction.

In addition, in the composite artificial fiber element according to an aspect of the present disclosure, the support layer is optionally prepared by electrospinning. In this case, the growth factor and the polymer material can be organically combined, and not only the fusion problem between the growth factor and the polymer material can be solved, but also problems such as shrinkage and incomplete bioactivity of the surface can be reduced when the material is impregnated with a biological agent. In addition, the support layer can reach a micro-nano superfine fiber porous structure through an electrostatic spinning process, the structure is very similar to a main component (collagen) of a natural extracellular matrix, and an in-vivo ECM (extracellular matrix) structure can be simulated to the maximum extent. In addition, the support layer prepared by electrostatic spinning has higher porosity and larger specific surface area, so that after the support layer is implanted into human tissues, the support layer can be more favorable for cell adhesion, differentiation, proliferation and ECM secretion.

Further, in the composite artificial fiber element according to an aspect of the present disclosure, optionally, the solvent for the growth factor is at least one selected from the group consisting of an aqueous solution, a salt solution, a buffer solution, and a cell culture medium. Therefore, different requirements on the structure, the performance and the like of the composite artificial fiber element material under different application environments can be met.

In addition, in the composite artificial fiber according to one aspect of the present disclosure, the growth factor may further include an antibacterial substance, and the antibacterial substance may include one or more selected from penicillins, cephalosporins, carbapenems, aminoglycosides, tetracyclines, macrolides, glycosides, sulfonamides, quinolones, nitroimidazoles, lincosamides, fosfomycin, chloramphenicol, colistin B, and bacitracin. Therefore, different requirements on the biological performance of the composite artificial fiber element material under different application environments can be met.

Additionally, in a composite artificial fiber element according to an aspect of the present disclosure, optionally, the glass transition temperature of the fiber is not higher than the normal body temperature of a human body. Therefore, when the composite artificial fiber element disclosed by the disclosure is applied to human tissue treatment, the fiber can be kept in a rubber state (high elastic state) in a human body, and the rubber fiber can release stress concentration caused by external force and the like, so that the toughness of the composite artificial fiber element is improved.

Further, in a composite artificial fiber element according to one aspect of the present disclosure, optionally, the hydrophobic polymer material is a polyester block, and the polyester block is a polymer of at least one monomer selected from lactide, caprolactone, p-dioxanone and glycolide, or a blend of polymers of at least one monomer selected from lactide, caprolactone, p-dioxanone and glycolide. Therefore, the composite artificial fiber element can be degraded while maintaining good biocompatibility, and is beneficial to application in implantable medical devices and the like.

In addition, in the composite artificial fiber according to an aspect of the present disclosure, optionally, the hydrophilic polymer material is one or more selected from starch, protein, cellulose-based natural polymer, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacrylamide, N- (2-hydroxypropyl) methacrylamide, divinyl ether maleic anhydride, poly (2-ethyl-2-oxazoline), polyphosphate, and polyphosphazene. Therefore, the composite artificial fiber element has good hydrophilicity, and can be helpful for the creeping growth of cells.

Another aspect of the present disclosure provides an artificial ligament comprising a plurality of the composite artificial fiber elements according to any one of the above aspects, and weaving the plurality of composite artificial fiber elements into a predetermined shape.

In addition, in the artificial ligament according to another aspect of the present disclosure, the fiber including the degradable hydrophobic polymer material and the hydrophilic polymer material is used as the support layer of the composite artificial fiber element, so that the composite artificial fiber element can improve hydrophilicity while maintaining the biodegradable property of the material, and the artificial ligament can have both degradability and hydrophilicity, thereby being advantageous for the creeping growth of cells. In addition, the growth factor is organically fused with the high polymer material, so that the problems of shrinkage, incomplete biological activity of the surface and the like generated when the material is soaked with a biological reagent can be reduced, the biological activity of the artificial ligament can be improved, and the regeneration of the ligament can be better promoted.

In addition, in the artificial ligament according to another aspect of the present disclosure, the predetermined shape may be one or more selected from the group consisting of a membrane shape, a tubular shape, and a columnar shape. In some examples, artificial ligaments of different shapes can be prepared, so that special requirements on the shape of the artificial ligament in different application scenes can be met.

According to the present disclosure, it is possible to provide a composite artificial fiber element and an artificial ligament which have excellent hydrophilic properties and can achieve organic fusion of a growth factor and a polymer material.

Drawings

Fig. 1 is a schematic diagram showing an example of an application scenario of an artificial ligament to which an example of the present embodiment relates.

Fig. 2 is a schematic structural view showing a composite artificial fiber element according to an example of the present embodiment.

Fig. 3 is a schematic view showing the microstructure of the support layer of the composite artificial fiber element according to the example of the present embodiment.

Fig. 4 is a schematic structural view showing any one of fibers in the microstructure of the support layer of the composite artificial fiber element according to the example of the present embodiment.

Fig. 5 is a schematic structural view showing an artificial ligament according to an example of the present embodiment.

Fig. 6 is a partial schematic view showing an artificial ligament structure according to an example of the present embodiment.

Fig. 7 is a graph showing the results of HE staining involved in example 3 of the present disclosure.

Fig. 8 is a graph showing the results of Masson staining involved in example 3 of the present disclosure.

Description of the symbols:

1 … artificial ligament, 10 … composite artificial fiber element, 11 … core wire, 12 … support layer, 121 … fiber, 122 … growth factor, 1211 … hydrophobic block, 1212 … hydrophilic block, 20 … sheath, 30 … strapping.

Detailed Description

Hereinafter, preferred embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. In the following description, the same components are denoted by the same reference numerals, and redundant description thereof is omitted. The drawings are schematic and the ratio of the dimensions of the components and the shapes of the components may be different from the actual ones.

In the following description, the description is made in the manner of using subtitles for convenience of description, but these subtitles merely play a role of cue and are not intended to limit the contents described under the subtitles to the subject matter of the subtitles.

Fig. 1 is a schematic diagram showing an example of an application scenario of an artificial ligament 1 according to an example of the present embodiment. Fig. 2 is a schematic structural view showing a composite artificial fiber element 10 according to an example of the present embodiment. Fig. 3 is a schematic view showing the microstructure of the support layer 12 of the composite artificial fiber element 10 relating to the example of the present embodiment, and fig. 4 is a schematic view showing the structure of any one of the fibers in the microstructure of the support layer 12 of the composite artificial fiber element 10 relating to the example of the present embodiment.

In the present embodiment, as shown in fig. 2 to 4, the composite artificial fiber element 10 may include a core wire 11 and a support layer 12. Wherein the support layer 12 may cover the outside of the core wire 11, and the support layer 12 may have a mesh woven by the fibers 121 and the growth factors 122. In addition, the fibers 121 may include a degradable hydrophobic polymer material and a hydrophilic polymer material.

In the composite artificial fiber element 10 according to the present embodiment, the fiber 121 including the degradable hydrophobic polymer material and the hydrophilic polymer material is used as the support layer 12 of the composite artificial fiber element 10, and the composite artificial fiber element 10 can improve hydrophilicity while maintaining the biodegradable properties of the material, and thus can contribute to the creeping growth of cells. In addition, the growth factor 122 is organically fused with the polymer material, which can reduce the occurrence of problems such as shrinkage, imperfect biological activity of only the surface, and the like, which are generated when the material is impregnated with a biological agent, so that the biological activity of the composite artificial fiber element 10 can be improved, and when the composite artificial fiber element is applied to the artificial ligament 1, the regeneration of the ligament can be better promoted.

In clinical applications, the composite artificial fiber element 10 can be fabricated into the artificial ligament 1 (see fig. 5 and 6), and the artificial ligament 1 is implanted into the body (e.g., a bone joint cavity). In some examples, as shown in fig. 1, the artificial ligament 1 may be implanted into a bone joint cavity by fixing the artificial ligament 1 to a bone by compression of a bone nail or the like. In this case, since the composite artificial fiber element 10 in the artificial ligament 1 is formed by covering the core wire 11 with the support layer 12, wherein the support layer 12 is composed of the fiber 121 including the degradable hydrophobic polymer material and the hydrophilic polymer material, and the growth factor 122, the artificial ligament 1 can have both biodegradable property and hydrophilic property, thereby being capable of facilitating the creeping growth of cells (e.g., fiber cells), and the growth factor 122 released by the artificial ligament 1 can promote the regeneration and repair of the damaged ligament.

In some examples, the composite artificial fiber element 10 shape is not particularly limited. For example, the shape of the composite artificial fiber element 10 may be a long strip.

In some examples, the composite artificial fiber element 10 may have a crimp ratio of no greater than 20%. Therefore, after the artificial fiber element is implanted into a human body, shrinkage displacement caused by shrinkage of the composite artificial fiber element 10 can be reduced, and further, complications such as pain and adhesion can be reduced. For example, the composite artificial fiber element 10 may have a crimp ratio of 20%, 18%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, etc.

In the present embodiment, the core wire 11 may be linear or bundle-shaped. In some examples, the core wire 11 may be 1 core. In other examples, the core wire 11 may be braided from a plurality of inner cores. Therefore, the mechanical strength and other properties of the core wire 11 can be effectively improved, and the requirement of the composite artificial fiber element 10 on the high strength of the material can be met.

In the present embodiment, the core wire 11 may be prepared from a polymer fiber. Preferably, the core wire 11 is made of polymer fibers, which may have a Young's modulus of 50GPa to 150GPa. In this case, the core wire 11 has high mechanical strength, and can provide effective strength support for the composite artificial fiber element 10, so that the composite artificial fiber element can have good mechanical support force in the pulling direction. For example, the core 11 is made of polymer fibers having a Young's modulus that may be 50GPa, 60GPa, 70GPa, 80GPa, 90GPa, 100GPa, 110GPa, 120GPa, 130GPa, 140GPa, or 150GPa.

In the present embodiment, as described above, the inner core may directly serve as the core wire 11, and in this case, the inner core may be made of the same material as the core wire 11. In addition, when the core wire 11 is woven from a plurality of inner cores, the inner cores may also be prepared from polymer fibers, and preferably, the young's modulus of the core wire 11 formed by weaving a plurality of inner cores also satisfies the range of 50GPa to 150GPa.

In some examples, the polymer fibers may have biodegradable properties. Additionally, in some examples, the polymer fiber may be at least one selected from polydioxanone, polyamide polymer, polyester polymer, polyethylene, and polypropylene. In this case, it is possible to impart biodegradability to the core wire 11 and also to contribute to improvement in mechanical strength of the core wire 11.

In other examples, the core wire 11 may be formed of a plurality of inner cores juxtaposed to form a bundle-like structure. For example, the core wire 11 may be formed in a bundle structure by arranging 2, 3, 4, and 5 cores in parallel.

In addition, in the present embodiment, the aspect ratio of the core wire 11 is not particularly limited. Therefore, the aspect ratio can be adjusted according to the requirements of practical application scenes.

In this embodiment, the support layer 12 may cover the outside of the core wire 11. In some examples, the support layer 12 may partially wrap the core wire 11. In addition, in some examples, as shown in fig. 2, the support layer 12 may partially wrap around the middle portion of the core wire 11, thereby exposing both ends of the core wire 11. In other examples, the support layer 12 may completely cover the exterior of the core wire 11. This can provide sufficient mechanical support and improve the hydrophilic performance and the like of the entire composite artificial fiber element 10 material.

In some examples, the support layer 12 may be prepared via electrospinning. Additionally, in some examples, support layer 12 may be electrospun from growth factor 122 and a polymeric material. For example, the growth factor 122 and the polymer material may be co-electrospun using an electrospinning machine, that is, a solution of the growth factor 122 and a solution of the polymer material may be blended and then electrospun. In this case, the growth factor 122 and the polymer material can be organically combined together, and not only the fusion problem of the growth factor 122 and the polymer material can be solved, but also the occurrence of problems such as shrinkage, imperfect biological activity of only the surface, and the like, which are generated when the material is impregnated with a biological agent, can be reduced. In addition, the support layer 12 can reach a micro-nano-scale superfine fiber porous structure through an electrostatic spinning process, the structure is very similar to a main component (collagen) of a natural extracellular matrix, and the structure can simulate an in vivo extracellular matrix (ECM) structure to the maximum extent. In addition, the support layer 12 prepared by electrospinning has a high porosity and a large specific surface area, and thus, after being implanted into human tissues, can be more advantageous to adhesion, differentiation, proliferation and secretion of ECM of cells. Wherein the polymer material may have biodegradability.

In other examples, the support layer 12 may be electrospun from a polymeric material. For example, the polymer material may be electrospun using an electrospinning machine.

In some examples, the parameters of the electrospinning machine may be set as: the electrospinning distance is 8-40cm, the electrospinning voltage is 20-80kV, and the solution flow rate of the electrospinning solution is 5-500ml/h. In this case, the fusion of the growth factor 122 and the polymer material can be facilitated.

In some examples, the solvent of the electrospinning solution used by the electrospinning machine may be one or more of hexafluoroisopropanol, trihalomethane, dimethylformamide, tetrahydrofuran, chloroform, or acetone.

In some examples, the core 11 may be used to collect the growth factors 122 and the polymeric material and form an artificial composite fiber element when electrospun. That is, in the electrospinning process, the electrospinning machine performs spinning using the electrospinning solution, and the growth factor 122 and the polymer material in the solution (described later) are collected by the core wire 11 to form the composite artificial fiber element 10.

In some examples, the equilibrium contact angle of support layer 12 may be 55 degrees or less. Thereby, the support layer 12 can have good hydrophilic performance, in this case, since the support layer 12 covers the outside of the core wire 11 to form the composite artificial fiber element 10, the composite artificial fiber element 10 can be made to have good hydrophilic performance, and thus, after being implanted into human tissue, it will be able to contribute to the creeping growth of cells. For example, the support layer 12 may have an equilibrium contact angle of 5 degrees, 10 degrees, 15 degrees, 20 degrees, 30 degrees, 40 degrees, or 50 degrees.

In some examples, the support layer 12 may be a porous structure. In other words, the support layer 12 may have a porous structure having a plurality of micropores. Therefore, the specific surface area of the composite artificial fiber element 10 can be increased, and the adsorption of the composite artificial fiber element 10 on surrounding cell tissues and the like after being implanted into a human body is facilitated. Additionally, in some examples, the support layer 12 may have a plurality of pores that are uniformly distributed.

In addition, where the support layer 12 is a porous structure, there may be growth factors 122 within the plurality of pores. Thereby, the growth factor 122 can be uniformly distributed to the support layer 12 of the composite artificial fiber element 10, and thus, the regeneration of the damaged ligament can be facilitated.

In some examples, the porosity of the support layer 12 may be 30% to 85%. Thereby, tissue growth into the support layer 12 can be facilitated. For example, the porosity of the support layer 12 may be 30%, 32%, 35%, 40%, 45%, 50%, 53%, 55%, 58%, 60%, 62%, 65%, 70%, 75%, 80%, or 85%.

In some examples, the pore size of the micropores of support layer 12 may be 1 μm to 5 μm. In this case, the extracellular matrix structure can be simulated, thereby further contributing to tissue growth into the support layer 12. For example, the pores of the support layer 12 may have a pore diameter of 1 μm, 1.2 μm, 1.5 μm, 1.8 μm, 2 μm, 2.2 μm, 2.5 μm, 2.8 μm, 3 μm, 3.3 μm, 3.5 μm, 3.8 μm, 4 μm, 4.2 μm, 4.5 μm, 4.8 μm, or 5 μm.

In some examples, the support layer 12 may have a fiber mesh. Specifically, the support layer 12 may have a mesh woven from the fibers 121. In other words, the support layer 12 may be a fiber mesh woven from the fibers 121. Additionally, in some examples, the fibers 121 may be formed via electrospinning. In other examples, the fiber mesh may be woven by electrospinning.

In some examples, the fibers 121 may be randomly arranged, as shown in FIG. 3, and the fibers 121 are randomly distributed in various directions, exhibit a random arrangement, and form a plurality of meshes with different sizes. In other examples, fibers 121 may be arranged in a particular order along one of the directions, or may be arranged in a particular order along more than two of the directions. In this case, the fibers 121 are woven and combined to form a unified whole, and the mechanical strength and other properties of the support layer 12 can be effectively improved.

In some examples, the size of the fibers 121 is not particularly limited, i.e., the aspect ratio of the fibers 121 is not particularly limited. In general, since the aspect ratio of the fiber 121 is different and the properties such as mechanical strength are also different, the size (aspect ratio) of the fiber 121 can be adjusted to meet the requirements of the use environment according to the actual needs.

In this embodiment, the glass transition temperature of the fiber 121 may not be higher than the normal body temperature of the human body. In this case, when the composite artificial fiber element 10 is applied to a human tissue (for example, a knee joint cruciate ligament) for treatment, the fibers 121 can be maintained in a rubbery state (high elastic state) in a human body, and the rubbery fibers 121 can release stress concentration caused by an external force or the like, thereby improving the toughness of the composite artificial fiber element 10.

In some examples, the glass transition temperature of the fiber 121 may be from-40 ℃ to 36 ℃. For example, the glass transition temperature of the fiber 121 may be-40 ℃, -37 ℃, -30 ℃, -20 ℃, -10 ℃, -5 ℃, 0 ℃,10 ℃,20 ℃ or 36 ℃. In addition, in some instances, it may be preferable for the fibers 121 to have a glass transition temperature of-37 ℃ to 20 ℃ for the purpose of enabling the fibers 121 to remain rubbery in the human body.

In some examples, growth factors 122 may be added to the fibers 121. In other words, the growth factors 122 may be included in the fiber 121.

In this embodiment, the fibers 121 may be made of a degradable polymer material. In some examples, the polymeric material may include a degradable hydrophobic polymeric material and a hydrophilic polymeric material. In other words, the fibers 121 may include a degradable hydrophobic polymer material and a hydrophilic polymer material.

In the present embodiment, since the hydrophobic polymer material is easy to shrink when exposed to water (such as tissue fluid, biological agent, etc.), and the hydrophilic polymer material is easy to swell when exposed to water, the fiber 121 including both the hydrophobic polymer material and the hydrophilic polymer material can have good stability (i.e. no shrinkage and swelling) after being implanted into a human body, that is, the support layer 12 can have good stability after being implanted into a human body, that is, the composite artificial fiber element 10 can have good stability after being implanted into a human body, and further, the artificial ligament 1 can have good stability after being implanted into a human body.

In some examples, the degradable polymer material constituting the fiber 121 may be formed by mixing a hydrophobic polymer material and a hydrophilic polymer material.

In some examples, the hydrophobic polymer material may be uniformly mixed with the hydrophilic polymer material in the polymer material. In this case, since the support layer 12 formed by weaving the fibers 121 has degradability and hydrophilicity by improving the uniformity of the fibers 121 and making the entire fibers 121 have degradability and hydrophilicity, the composite artificial fiber element 10 coated with the support layer 12 can be made to have an extracellular matrix in its outer surface, and cells (for example, fibroblasts) can be facilitated to grow in an overgrowth manner on the composite artificial fiber element 10. In other words, the hydrophobic polymer material and the hydrophilic polymer material in the fiber 121 are uniformly mixed.

In some examples, the ratio of hydrophobic polymeric material to hydrophilic polymeric material in the fiber 121 can be from 1: 2 to 2: 1. Therefore, the support layers 12 with different degrees of hydrophilic performance can be obtained, and the requirements on the hydrophilic performance of the material under different application scenes can be met. For example, the ratio of the hydrophobic polymer material to the hydrophilic polymer material may be 1: 2, 2: 3, 1: 1, 5: 3, 4: 3, 3: 2, 2: 1, or the like.

In some examples, the fibers 121 may be prepared via electrospinning. In addition, in some examples, the fiber 121 may be made of the growth factor 122 and a polymer material mixed by a hydrophobic polymer material and a hydrophilic polymer material through electrospinning. In other examples, the fibers 121 may be made of a polymer material in which a hydrophobic polymer material and a hydrophilic polymer material are mixed through electrospinning.

In other examples, as shown in fig. 4, the fiber 121 may be a block fiber. Additionally, in some examples, as shown in fig. 4, the fiber 121 can include a hydrophobic block 1211 and a hydrophilic block 1212.

In some examples, the fibers 121 may be woven from hydrophilic fiber filaments and hydrophobic fiber filaments. Additionally, in some examples, the fibers 121 may be woven from hydrophilic fiber filaments and hydrophobic fiber filaments into a block fiber.

In some examples, the hydrophilic fiber filaments may be electrospun from the growth factor 122 and a hydrophilic polymer material. Additionally, in some examples, the hydrophobic fiber filaments may be electrospun from growth factor 122 and a hydrophobic polymer material. In other examples, the hydrophilic fiber filaments may be made of a hydrophilic polymer material through electrospinning. In addition, the hydrophobic fiber yarn can be made of hydrophobic polymer materials through electrostatic spinning.

In some examples, hydrophilic and hydrophobic filaments may be woven around the core 11 to form the composite artificial fiber element 10. Additionally, in some examples, hydrophilic and hydrophobic filaments may be woven around the core 11 to form the segmented composite artificial fiber element 10.

In some examples, the hydrophobic block 1211 can be composed of a degradable hydrophobic polymeric material. Additionally, in some examples, the hydrophilic block 1212 can be composed of a degradable hydrophilic polymeric material. In this case, the hydrophilic block 1212 can increase the hydrophilicity of the fiber 121, and thus can increase the hydrophilicity of the support layer 12, which can facilitate the creeping growth of cells.

In some examples, hydrophobic blocks 1211 and hydrophilic blocks 1212 can be arranged alternately. Thus, the support layer 12 (and the composite artificial fiber element 10) can be made biodegradable and have improved hydrophilicity, and thus can contribute to the growth of cells by creeping.

In the present embodiment, the number of the hydrophobic blocks 1211 and the hydrophilic blocks 1212 of the fiber 121 is not particularly limited. In some examples, the number of hydrophobic blocks 1211 and hydrophilic blocks 1212 may each be 3 segments or more. Therefore, a relatively perfect block structure (namely, a fully alternating structure of the hydrophobic blocks 1211 and the hydrophilic blocks 1212) can be formed, so that the application requirements of the material on hydrophilic performance and the like are met.

In some examples, the hydrophobic blocks 1211 and the hydrophilic blocks 1212 of the fiber 121 may be uniformly alternating, i.e., the length of each hydrophobic block 1211 may remain substantially uniform and the length of each hydrophilic block 1212 may remain substantially uniform, thereby forming a uniform and alternating arrangement of the hydrophobic blocks 1211 and the hydrophilic blocks 1212. In other examples, the hydrophobic blocks 1211 and the hydrophilic blocks 1212 of the fiber 121 may be unevenly alternating, i.e., each hydrophobic block 1211 may have a different length and each hydrophilic block 1212 may have a different length, thereby forming an uneven alternating arrangement. Therefore, the support layers 12 with different degrees of hydrophilic performance can be obtained, and the requirements on the hydrophilic performance of the material under different application scenes can be met.

In some examples, the hydrophobic polymeric material may be a polyester block. In addition, in some examples, the polyester block may be a polymer of at least one monomer selected from lactide, caprolactone, p-dioxanone, and glycolide. In some examples, the polyester block can be a blend of polymers of at least one monomer selected from lactide, caprolactone, p-dioxanone, and glycolide. Therefore, the composite artificial fiber element 10 can be degraded and maintain good biocompatibility, and is beneficial to the application of the composite artificial fiber element in implantable medical devices and the like.

In some examples, the polyester block may be a homopolymer of one monomer selected from lactide, caprolactone, p-dioxanone, and glycolide, or a binary or higher random or block copolymer selected from lactide, caprolactone, p-dioxanone, and glycolide.

In some examples, the hydrophilic polymer material may be one or more selected from starch, protein, cellulose-based natural polymer, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacrylamide, N- (2-hydroxypropyl) methacrylamide, divinyl ether maleic anhydride, poly (2-ethyl-2-oxazoline), polyphosphate, and polyphosphazene. Thus, the composite artificial fiber element 10 can be made to have good hydrophilicity, and can contribute to the creeping growth of cells.

In some examples, the hydrophobic polymer material may be made of polycaprolactone and the hydrophilic polymer material may be made of starch. In addition, in some examples, the hydrophobic polymer material may be a copolymer made of lactide and caprolactone, and the hydrophilic polymer material may be made of polyethylene glycol. In other examples, the hydrophobic polymer material may be a copolymer made of lactide and p-dioxanone, and the hydrophilic polymer material may be made of polyacrylic acid.

In this embodiment, the hydrophilic polymer material and the hydrophobic polymer material may have different degradation rates. In some examples, the degradation rate of the hydrophilic polymeric material may be greater than the degradation rate of the hydrophobic polymeric material. Under the condition, the degradation rate of the hydrophilic polymer material is high, so that space can be made for the new tissue, and the growth of the new tissue is facilitated; the degradation rate of the hydrophobic polymer material is low, and mechanical support can be provided at the initial stage of tissue repair.

In some examples, the degradation rate of the fibers 121 may be controlled by adjusting the ratio of the hydrophilic polymer material and the hydrophobic polymer material. Thereby, the degradation rate of the support layer 12 and thus the composite artificial fibre element 10 can be controlled.

In some examples, the degradation rate of the support layer 12 may be matched to the growth rate of the nascent tissue. This can contribute to the growth and creeping of the new tissue. For example, if the composite artificial fiber element 10 degrades too quickly, the newly formed tissue may not cover the formed defect, resulting in a failure of the tissue repair.

In this embodiment, the support layer 12 may have a growth factor 122 therein. Therefore, when the composite artificial fiber element 10 is implanted into a human body, the growth factors 122 in the support layer 12 can promote the growth and development of tissues around the implanted part (such as knee joint cruciate ligament), regulate the growth of cells and other cell functions, thereby improving the biological performance of the composite artificial fiber element 10.

In some examples, growth factors 122 may be added in the gap formed between the fibers 121 and 121 (see fig. 3). Additionally, in some examples, as shown in fig. 3, growth factors 122 may be added to the lattice woven from fibers 121.

In some examples, the fiber 121 may also include a growth factor 122. This can contribute to promoting the growth of cells. For example, in the case where the growth factor 122 is electrospun together with a polymer material, the growth factor 122 can be provided in the fiber 121, and the mesh woven from the fiber 121 can also be provided with the growth factor 122.

In some examples, the growth factors 122 may be added to the support layer 12 by coating, soaking, or the like. In addition, in some examples, the support layer 12 made of only a polymer material may be immersed in the growth factor 122 solution to obtain the support layer 12 having the growth factor 122. In other examples, a solution of growth factors 122 may be coated on the support layer 12 made of only a polymer material to obtain the support layer 12 having the growth factors 122.

In some examples, the coating of the growth factors 122 may be a block coating. This enables the growth factors 122 to be distributed in a block form. For example, a first growth factor block is applied to the surface of the fiber 121 or support layer 12 to form a first block, and a second growth factor block is applied to form a second block. Additionally, in some examples, the coating of the growth factors 122 may be intermittent. For example, the middle section of the fiber 121 or the surface of the support layer 12, which is coated with the growth factor 122 in the adjacent two sections, is not coated with the growth factor 122.

In the present embodiment, the kind of the growth factor 122 is not particularly limited. In some examples, growth factor 122 may be one or more selected from among vitamins, bases, purines, pyrimidines, biotin, and niacin. Therefore, the growth factor 122 in the composite artificial fiber element 10 can be combined with a specific and high-affinity cell membrane receptor to regulate the cell growth and other cell functions, thereby expanding the application scene of the composite artificial fiber element 10 in the aspect of human tissue substitution.

In one example, growth factor 122 may be nerve growth factor NGF and fibroblast growth factor FGF. In other examples, growth factor 122 may be a fibroblast growth factor FGF.

In some examples, growth factor 122 may be a growth factor that promotes healing of the tendon bone. Therefore, after the composite artificial fiber element 10 is implanted into a body, the rapid healing of the tendon and bone in the bone canal can be ensured, the early-stage mechanical basis of ligament automization is provided, and the safe climbing of the fiber cells in the follow-up joint cavity is ensured.

In some examples, growth factor 122 may also include an antimicrobial substance. In some examples, the antimicrobial substance may comprise one or more selected from the group consisting of penicillins, cephalosporins, carbapenems, aminoglycosides, tetracyclines, macrolides, glycosides, sulfonamides, quinolones, nitroimidazoles, lincosamides, fosfomycin, chloramphenicol, colistin B, bacitracin. Thus, the composite artificial fiber element 10 can resist harmful substances such as various bacteria, and the biological utility thereof can be enhanced.

In the present embodiment, the solvent of the growth factor 122 is not particularly limited. In some examples, the solvent for the growth factor 122 may be one or more selected from the group consisting of an aqueous solution, a salt solution, a buffer, and a cell culture medium. Thereby, different requirements on the structure, the performance and the like of the composite artificial fiber element 10 material under different application environments (such as acid, neutral or alkaline environments) can be met.

In the present embodiment, the size of the growth factor 122 is not particularly limited, and may be designed to be adjusted according to actual needs. In some examples, the growth factors 122 may be different in size, and thus can be formed in gaps or grids of different sizes, so that the distribution of the growth factors 122 is more uniform, and the practicability of the composite artificial fiber element 10 is improved.

In the present embodiment, the loading amount of the growth factor 122 is not particularly limited. Therefore, the design can be properly adjusted according to the needs of actual conditions, so that the requirements under different conditions are met.

Further, in the present embodiment, the release rate of the growth factor 122 is not particularly limited. In some examples, the growth factor 122 comprises an antimicrobial substance that is released in an amount no less than 25% of the total loading within 15 minutes after implantation in vivo. In this case, the antibacterial substance in the growth factor 122 can be released as soon as possible after being implanted into the body, so that the contamination of the composite artificial fiber element 10 by harmful substances such as bacteria can be reduced, and the composite artificial fiber element 10 can effectively exert the function of regulating the cell growth and the like.

The artificial ligament 1 including the composite artificial fiber element 10 is described in detail below with reference to fig. 5 and 6.

Fig. 5 is a schematic view showing a structure of an artificial ligament 1 according to an example of the present embodiment, and fig. 6 is a partial schematic view showing a structure of the artificial ligament 1 according to an example of the present embodiment.

In the present embodiment, as shown in fig. 5 and 6, the artificial ligament 1 may include a plurality of composite artificial fiber elements 10, and the plurality of composite artificial fiber elements 10 may be woven into a predetermined shape.

The artificial ligament 1 according to the present embodiment uses the fiber 121 including the degradable hydrophobic polymer material and the hydrophilic polymer material as the support layer 12 of the composite artificial fiber element 10, so that the composite artificial fiber element 10 can improve hydrophilicity while maintaining the biodegradable characteristics of the material, and the artificial ligament 1 can have both degradability and hydrophilicity, and thus can be advantageous for the creeping growth of cells. In addition, the organic fusion of the growth factor 122 with the polymer material can reduce the occurrence of problems such as shrinkage, imperfect biological activity of only the surface, etc. generated when the material is impregnated with a biological agent, so that the biological activity of the artificial ligament 1 can be improved, and the regeneration of the ligament can be further promoted.

In some examples, the artificial ligament 1 may further include a housing 20 (see fig. 5 and 6). Therefore, the artificial ligament 1 can be better integrated, and the mechanical strength and other properties of the artificial ligament are improved. In some examples, the outer shell 20 may be wrapped around a plurality of composite artificial fiber elements 10.

In some examples, the outer shell 20 may partially encase a plurality of composite artificial fiber elements 10. For example, the outer shell 20 may be wrapped around the middle of the plurality of composite artificial fiber elements 10 and expose both ends of the plurality of composite artificial fiber elements 10. In other examples, the housing 20 may completely encase a plurality of composite artificial fiber elements 10.

In some examples, the housing 20 may include a housing 20a and a housing 20b, and the housing 20a and the housing 20b may be discontinuously formed, that is, there is a gap between the housing 20a and the housing 20b. In this case, the artificial ligament 1 may include a plurality of composite artificial fiber elements 10, and shells 20a and 20b respectively covering the plurality of composite artificial fiber elements 10.

In some examples, the central portion of the outer shell 20 may be the portion of the plurality of composite artificial fiber elements 10 that wraps the support layer 12. In addition, in some examples, as shown in fig. 5, the outer shell 20 may partially wrap the portion of the plurality of composite artificial fiber elements 10 that wraps the support layer 12.

In some examples, the artificial ligament 1 may further include a strapping 30 (see fig. 5 and 6). In this case, small diameter regions of a certain length can be formed at both ends of the artificial ligament 1, that is, the diameter of both ends of the artificial ligament 1 is smaller than the diameter of the middle portion of the artificial ligament 1, thereby contributing to smooth operation of the transplantation operation experiment as a traction wire structure. Additionally, in some examples, strapping bands 30 may be strapped across the plurality of composite artificial fiber elements 10.

In some examples, the strapping 30 may bundle a plurality of composite artificial fiber elements 10. In addition, in some examples, the strapping tape 30 may bundle a plurality of composite artificial fiber elements 10 by bundling the core wires 11 of the plurality of composite artificial fiber elements 10. That is, the core wires 11 are not covered with the support layer 12 at the binding portion, and in this case, the binding tape 30 directly binds the core wires 11 of the composite artificial fiber element 10 without contacting the support layer 12. In other examples, the strapping tape 30 may be strapped to the support layer 12 of a plurality of composite artificial fiber elements 10 to bundle the plurality of composite artificial fiber elements 10.

In some examples, strapping 30 may be strapped to the ends of the plurality of composite artificial fiber elements 10 (e.g., end 1a and end 1b of artificial ligament 1, as shown in fig. 5). For example, as shown in fig. 5, the binding tapes 30 may be bound to the core wires 11 at both ends of the plurality of composite artificial fiber elements 10.

In some examples, the artificial ligament 1 may be formed of a bundle structure of a plurality of composite artificial fiber elements 10 placed side by side. In some examples, the artificial ligament 1 may be in a single-strand or double-folded configuration (as shown in fig. 5). Therefore, different clinical requirements can be met.

In some examples, the artificial ligament 1 may be an elongated shape, but the present embodiment is not limited thereto, and in some examples, the artificial ligament 1 may be folded for use, for example, the artificial ligament 1 is folded in half to form a folded portion 1c (see fig. 5). Specifically, the artificial ligament 1 is folded in two, and the outer shell 20a covering the plurality of composite artificial fiber elements 10 in the artificial ligament 1 and the outer shell 20b covering the plurality of composite artificial fiber elements 10 are fixed (for example, bonded) together to form the folded portion 1c. In this case, the mechanical strength of the artificial ligament 1 can be further improved, and the folded portion 1c can be used as a traction structure in an operation by forming the folded portion 1c.

In some examples, the core wires 11 of the folded portion 1c may not be covered by the support layer 12. That is, the folded portion 1c may be composed of a plurality of core wires 11. This can facilitate folding of the artificial ligament 1 in half.

In addition, in some examples, the folded portion 1c may be composed of a plurality of composite artificial fiber elements 10. In addition, in some examples, the folded portion 1c may be formed by folding a plurality of composite artificial fiber elements 10 in half.

In the present embodiment, the predetermined shape into which the plurality of composite artificial fiber elements 10 are woven may be one or more selected from the group consisting of a film shape, a tubular shape, and a columnar shape. Therefore, the artificial ligaments 1 in different shapes can be prepared, and the special requirements on the shapes of the artificial ligaments 1 in different application scenes can be met.

In the present embodiment, the thickness of the film shape as described above is not particularly limited. In some examples, the film shape as described above may have a thickness of 10 to 1500 micrometers. In other examples, the film as described above may have a thickness of 50 to 500 micrometers. Thereby, the requirements for the size of the artificial ligament 1 in different application scenarios can be met.

In some examples, the thickness and inner diameter of the tubular shape as described above are not particularly limited. For example, the tubular shape as described above may have a thickness of 1 to 1500 μm and an inner diameter of 2 to 200 mm. In other examples, the tubular shape described above may have a thickness of 50 to 500 microns and an internal diameter of 20 to 150 millimeters. Thereby, the requirements for the size of the artificial ligament 1 in different application scenarios can be met.

In some examples, the diameter of the pillar as described above is not particularly limited. For example, the diameter of the column as described above may be 2 to 20 mm. Thereby, the requirements for the size of the artificial ligament 1 in different application scenarios can be met.

In some examples, the plurality of composite artificial fiber elements 10 may be formed into the artificial ligament 1 by a weaving process. In this case, the composite artificial fiber elements 10 can be bonded together more effectively, so as to form the complete artificial ligament 1.

Further, in some examples, the number of composite artificial fiber elements 10 may be 4-50. In general, the mechanical strength of the artificial ligament 1 formed by the composite artificial fiber elements 10 will be different according to the number of the composite artificial fiber elements. Thereby, the requirements in terms of mechanical properties and the like required for the artificial ligament 1 in different situations can be met. For example, the number of composite artificial fiber elements 10 may be 4, 6, 8, 10, 15, 18, 20, 25, 30, 35, 40, 45, or 50.

In some examples, the porosity of the artificial ligament 1 may be 30% to 85%. Thereby, tissue growth into the artificial ligament 1 can be facilitated. For example, the porosity of the artificial ligament 1 may be 30%, 32%, 35%, 40%, 45%, 50%, 53%, 55%, 58%, 60%, 62%, 65%, 70%, 75%, 80%, or 85%.

In some examples, the pore size of the artificial ligament 1 may be 1 μm to 5 μm. In this case, the extracellular matrix structure can be simulated, thereby further contributing to the tissue growth into the artificial ligament 1. For example, the pore size of the artificial ligament 1 may be 1 μm, 1.2 μm, 1.5 μm, 1.8 μm, 2 μm, 2.2 μm, 2.5 μm, 2.8 μm, 3 μm, 3.3 μm, 3.5 μm, 3.8 μm, 4 μm, 4.2 μm, 4.5 μm, 4.8 μm, or 5 μm.

In order to further illustrate the present disclosure, the composite artificial fiber element 10 and the artificial ligament 1 provided by the present disclosure are described in detail with reference to the following examples, and the beneficial effects achieved by the present disclosure are fully illustrated with reference to the animal experiment results.

[ example 1]

Firstly, preparing an artificial ligament, specifically, weaving polypropylene fiber with Young modulus of 50GPa into a core wire, dissolving 2g of polycaprolactone by using 40ml of hexafluoroisopropanol, dissolving 1pg of nerve growth factor NGF by using 10ml of physiological saline, easily mixing the two to obtain a mixed solution A, dissolving 2g of starch by using 40ml of hexafluoroisopropanol, dissolving 1pg of fibroblast growth factor FGF by using 10ml of physiological saline, easily mixing the two to obtain a mixed solution B, respectively loading the mixed solution A and the mixed solution B into an injector, connecting the tail end of the mixed solution A with a No. 20 needle, and fixing the injector into a fixing frame; the electrostatic spinning parameters are set to be that the electrostatic spinning distance is 15cm, the electrostatic spinning voltage is 30kV, the solution flow rate is 5ml/h, long-strip-shaped hydrophobic cellosilk and hydrophilic cellosilk are obtained after the electrostatic spinning is finished, then the hydrophobic cellosilk and the hydrophilic cellosilk are woven into long-strip-shaped block fibers, the long-strip-shaped composite artificial fiber element 10 is woven by the block fibers around a core wire 11, finally, 18 woven composite artificial fiber elements 10 are woven into an artificial graft (artificial ligament 1), the diameter of the prepared artificial graft is 4mm, the length of the artificial graft is 5cm, and the length of a traction line at two ends is 5cm.

Subsequently, a tibialis posterior muscle graft was prepared, specifically, 6 adult male sex-checker (Beagle) dogs, which were kept in a cage of 120cm × 100cm × 75cm alone with an average body weight of about 15kg, were kept for 7 days, and only cage activities were restricted. Intravenous pentobarbital Nembutal (30 mg/kg) was anesthetized, the skin was preserved in the hind limbs after onset, the animals were fixed on the operating table in the supine position, and sterile drapes were laid for routine sterilization. The tibialis posterior muscle at the ankle joint of the hind limb on the same side (on the same side of the subsequent control group) was first excised as an ACL (anterior cruciate ligament) reconstruction graft. The length of the tibialis posterior muscle is cut to be 8.0cm, and the length of the double-folded tendon graft is more than 4.0 cm. The procedure was performed on an ACL reconstruction dedicated console, woven suture was made at both ends with a No. 2 non-absorbable suture, the folded ends were crossed with a flip line after double folding, and the diameter of the tendon graft of flexor digitorum longus after the procedure was modified was 4mm.

Then, an anterior-medial incision was made on the medial aspect of the knee joint of the left and right anterior knees of 6 beagle dogs, the incision was 5-7cm long, and the inferior-lateral patellar incision was made into the exposed joint, and the original normal ACL was excised. A4 mm matched drill is selected to establish a tibial tunnel, an outer opening of the tibial tunnel is positioned at a far position of an attachment point of a proximal medial accessory ligament of a tibia, an inner opening is positioned at an ACL (anterior border control List) stopping point of the tibial eminence, and an angle between the inner opening and a tibial axis is 45 degrees and an angle between the inner opening and a tibial sagittal plane is 15-30 degrees. After the tibia bone tunnel is positioned by a guide needle of a femur positioner, a femur tunnel is established by a 4.0-mm hollow drill bit, namely, the femur tunnel is formed by drilling from the middle of an intercondylar notch to the far upper part of a femoral attachment point of a lateral collateral ligament.

Finally, the woven artificial graft is implanted from the tibial tunnel of the left knee through the joint cavity to serve as an experimental group, the artificial graft is ensured to be 1.5cm in the femoral tunnel, 1.5cm in the tibia and 1.0cm in the joint, and then the suture at two ends is fixed on the screw outside the tunnel to complete suspension type fixation. Similarly, a tendon graft of flexor digitorum longus, which had been woven, was implanted from the tibial tunnel of the right knee through the joint cavity as a control group. After 12 weeks of surgery, complete healing of the anterior cruciate ligaments of the left and right knees of the beagle was observed.

[ example 2]

First, an artificial ligament was prepared by, specifically, weaving polypropylene fibers having a young's modulus of 50GPa into core wires, dissolving 2g of lactide-caprolactone copolymer with 40ml of hexafluoroisopropanol, dissolving 1pg of fibroblast growth factor FGF with 10ml of physiological saline, mixing the two easily to obtain a mixed solution a, dissolving 2g of polyethylene glycol with 40ml of hexafluoroisopropanol, dissolving 1pg of fibroblast growth factor FGF with 10ml of physiological saline, mixing the two easily to obtain a mixed solution B, preparing a composite artificial fiber in the same manner as in example 1, and finally weaving 18 composite artificial fiber into an artificial graft (artificial ligament), wherein the length of the prepared artificial graft was 2cm and the width was 1cm, and the prepared artificial graft was immersed in physiological saline for 1 min.

Next, a rabbit Achilles tendon defect model was prepared. Specifically, 6 adult male New Zealand white rabbits (3.0 kg or so) were anesthetized with 3% sodium pentobarbital (0.9-1 ml/1 kg) via the marginal vein. After satisfactory anesthesia, the animal takes the prone position and fixes the head, so as to ensure the smooth respiratory tract. The hair on the back of the rabbit was carefully shaved with a shaver on one side of the hind leg, exposing the skin at the achilles tendon. Iodophor sterilizes the surgical area, a sterile hole towel is laid, a sterile scalpel is used for making an incision of about 5cm longitudinally along the Achilles tendon, the subcutaneous tissue is separated bluntly, and the Achilles tendon is exposed. Fixing the separated skin at two sides with hemostatic forceps, completely cutting off the middle point of the Achilles tendon (about 2-3cm above the Achilles attachment point) with tissue scissors, cutting off the Achilles tendon again at the position 1cm near the cut end, removing the middle 2cm of Achilles tendon, completing the preparation of rabbit Achilles tendon defect model, and taking 4cm of fibula long tendon at the same incision.

Finally, the two severed ends of the Achilles tendon at both ends of the artificial graft were sutured using a modified "Giftbox" technique using a 4-0 absorbable suture (commercially available). Complete healing of the achilles tendon in new zealand white rabbits was observed 12 weeks after surgery.

[ example 3]

First, an artificial ligament is prepared. Specifically, a polypropylene fiber with Young modulus of 50GPa is woven into a core wire, then 80ml of hexafluoroisopropanol is used for dissolving 2g of p-dioxanone and 2g of cellulose natural polymer to form a solution A, 20ml of physiological saline is used for dissolving 2pg of fibroblast growth factor FGF to form a solution B, and the solution A and the solution B are uniformly mixed; then, the mixed solution is loaded into an injector, the tail end of the mixed solution is connected with a No. 20 needle, the prepared core wire 11 is used as a collecting device, the injector is fixed on a fixing frame, the electrostatic spinning parameters are set to be that the electrostatic spinning distance is 15cm, the electrostatic spinning voltage is 30kV, the solution flow rate is 5ml/h, after the electrostatic spinning is finished, a long strip-shaped electrostatic spinning bracket (composite artificial fiber element 10) is taken down, finally, the artificial graft (artificial ligament 1) is woven by utilizing 18 woven electrostatic spinning brackets, and the prepared artificial graft is 5cm in length and 5cm in width.

Then, 6 adult male New Zealand rabbits (about 3 kg) were randomly selected and were bred for 2 weeks without abnormality and with good activity. Then, the new zealand rabbit 6 is subjected to double-side supraspinatus tendon dissection of the shoulder joint and parallel supraspinatus tendon insertion reconstruction, and an animal model after rabbit rotator cuff acute rupture tendon-bone insertion reconstruction is constructed. And then pentobarbital sodium is used for ear vein anesthesia, after the anesthesia is successful, skin is prepared in an operation area, medical iodophor is used for disinfection, and a sterile hole towel is paved.

Then, experimental groups were prepared. Specifically, the skin of 6 new zealand rabbits was cut longitudinally along the long axis of the supraspinatus tendon greater humerus tuberosity attachment point on the left shoulder, and blunt separated layer by layer to find the supraspinatus tendon attachment point, the supraspinatus tendon was completely separated from the greater humerus tuberosity attachment point, a hole was made in the bony tissue below the original attachment point with a kirschner wire having a diameter of about 1mm in a direction almost perpendicular to the direction of the supraspinatus tendon detachment, and then an artificial graft of 2cm × 1cm was attached to the upper surface of the tendon attachment point, followed by tendon-bone suture to reconstruct the supraspinatus tendon attachment point. And after the tendon is determined to be broken and sutured without errors, the joint cavity and the subcutaneous part are flushed by gentamicin saline, drainage pieces are placed, and the incision is sutured discontinuously layer by layer.

Finally, 6 new zealand rabbits were sacrificed after 12 weeks of post-operation with excess anesthesia, the left rotator cuff repair area was exposed, then 2 specimen tissues were taken from each new zealand rabbit and fixed by immersion in 4% paraformaldehyde, and then one specimen tissue of each new zealand rabbit was HE-stained and another one of each new zealand rabbit was Masson-stained.

Fig. 7 is a graph showing the results of HE staining involved in example 3 of the present disclosure. Fig. 8 is a graph showing the results of Masson staining involved in example 3 of the present disclosure. As shown in fig. 6 and 7, HE staining and Masson staining of each new zealand rabbit at 12 weeks post-surgery showed more fibers Xia Beishi (sharey's fiber) at which the aponeurosis healed, and the left rotator cuff injury healed.

[ example 4]

First, an artificial ligament was prepared by, specifically, weaving polypropylene fibers having a young's modulus of 50GPa into core wires, dissolving 2g of lactide-p-dioxanone copolymer and 2g of polyacrylic acid with 80ml of hexafluoroisopropanol to form a solution a, dissolving 1pg of nerve growth factor NGF and 1pg of fibroblast growth factor FGF with 20ml of physiological saline to form a solution B, preparing an electrospun scaffold (composite artificial fiber element) in the same manner as in example 3, and weaving an artificial graft (artificial ligament) using 18 woven long-strip-shaped electrospun scaffolds, wherein the diameter of the prepared artificial graft was 1.7mm and the length was 7cm.

Then 10 adult New Zealand white rabbits with the body mass of 2.5-3.0kg are taken, the ear margin vein anesthesia is carried out by pentobarbital sodium, after the anesthesia is successful, the skin is prepared in the operation area, the medical iodophor is used for disinfection, and an aseptic hole towel is paved. And then, the skin is longitudinally cut along the long shaft of the supraspinatus tendon greater humerus nodule attachment point of the rabbit, the skin is subjected to blunt separation layer by layer to find the supraspinatus tendon attachment point, the supraspinatus tendon is completely separated from the greater humerus nodule attachment point of the rabbit, the supraspinatus tendon is cut off by 0.5cm in length towards the proximal end, the incision is sterilized, and the incision is sutured.

Then, after 4 weeks, bilateral giant rotator cuff injury repair experiments were performed, including the experimental group and the control group. The experimental groups were prepared as follows: taking a left shoulder as an experimental group, folding an artificial graft with the size of 1cm multiplied by 0.5mm, sewing an opening to a just superior tendon segment, punching a hole in a bone tissue below an original dead point along a direction almost perpendicular to the separation direction of the supraspinatus tendon by using a kirschner wire with the diameter of about 0.5mm, and then performing stent-bone suture; the control group was prepared as follows: the right shoulder was used as a control group, and was woven into a size of 1cm × 0.5mm by autologous fascia lata transplantation, and the repair was performed by the above method. The affected limb does not brake after the operation.

Finally, the healing of the giant rotator cuff prosthesis of the two shoulders of the white New Zealand rabbits can be observed at 12 weeks after the operation.

While the present disclosure has been described in detail in connection with the drawings and the embodiments, it should be understood that the above description is not intended to limit the present disclosure in any way. Variations and changes may be made as necessary by those skilled in the art without departing from the true spirit and scope of the disclosure, which fall within the scope of the disclosure.

Claims (8)

1. A composite artificial fiber element with a supporting layer is characterized in that:

the method comprises the following steps:

a core wire made of degradable polymer fibers; and

a support layer covering the core wire, the support layer having a mesh woven from fibers obtained by electrospinning and a growth factor added to gaps formed between the fibers, the core wire being used as a collecting device in the electrospinning,

wherein the fiber is made of degradable high polymer material, the degradable high polymer material is formed by mixing hydrophobic high polymer material and hydrophilic high polymer material,

the supporting layer is a porous structure, the porosity of the supporting layer is 30-85%,

the fibers of the grid are randomly distributed in a plurality of directions.

2. The composite artificial fiber element of claim 1, wherein:

the wrinkle rate of the composite artificial fiber element is not more than 20%.

3. The composite artificial fiber element of claim 1, wherein:

the growth factor comprises an antibacterial substance, and the antibacterial substance comprises one selected from penicillins, cephalosporins, carbapenems, aminoglycosides, tetracyclines, macrolides, sulfonamides, quinolones, nitroimidazoles, lincomamines, fosfomycin, chloramphenicol, colistin B and bacitracin.

4. The composite artificial fiber element of claim 1, wherein:

and performing electrostatic spinning on the hydrophobic polymer material and the hydrophilic polymer material through an electrostatic spinning machine, wherein the solvent of an electrostatic spinning solution used by the electrostatic spinning machine is one or more of hexafluoroisopropanol, trihalomethane, dimethylformamide, tetrahydrofuran, chloroform or acetone.

5. The composite artificial fiber element of claim 1, wherein:

the glass transition temperature of the fiber is-40 ℃ to 36 ℃.

6. The composite artificial fiber element of claim 1 or 4, wherein:

the hydrophobic high polymer material is a polyester block, and the polyester block is a homopolymer of one monomer selected from lactide, caprolactone, p-dioxanone and glycolide, or a binary or more random copolymer or block copolymer selected from lactide, caprolactone, p-dioxanone and glycolide.

7. The composite artificial fiber element of claim 1 or 4, wherein:

the hydrophilic polymer material is selected from more than one of starch, protein, cellulose natural polymer, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polyacrylamide, N- (2-hydroxypropyl) methacrylamide, divinyl ether maleic anhydride, poly (2-ethyl-2-oxazoline), polyphosphate and polyphosphazene.

8. An artificial ligament, comprising:

comprising a plurality of composite artificial fiber elements according to any one of claims 1 to 7, and weaving a plurality of said composite artificial fiber elements into a prescribed shape.

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