WO2018121629A1 - 仿生韧带及仿生韧带系统 - Google Patents

仿生韧带及仿生韧带系统 Download PDF

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Publication number
WO2018121629A1
WO2018121629A1 PCT/CN2017/119127 CN2017119127W WO2018121629A1 WO 2018121629 A1 WO2018121629 A1 WO 2018121629A1 CN 2017119127 W CN2017119127 W CN 2017119127W WO 2018121629 A1 WO2018121629 A1 WO 2018121629A1
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Prior art keywords
ligament
body portion
fiber
bionic
main body
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PCT/CN2017/119127
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English (en)
French (fr)
Inventor
李广耀
邓坤学
袁玉宇
Original Assignee
广州迈普再生医学科技有限公司
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Publication of WO2018121629A1 publication Critical patent/WO2018121629A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/08—Muscles; Tendons; Ligaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/08—Muscles; Tendons; Ligaments
    • A61F2/0811—Fixation devices for tendons or ligaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/08—Muscles; Tendons; Ligaments
    • A61F2/0811—Fixation devices for tendons or ligaments
    • A61F2002/0817—Structure of the anchor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/10—Materials or treatment for tissue regeneration for reconstruction of tendons or ligaments

Definitions

  • the present disclosure relates to a biomimetic ligament and a biomimetic ligament system, and belongs to the field of biomedicine.
  • the ligament is a dense fibrous connective tissue bundle or connective tissue membrane that is connected between adjacent bones or between the cartilage of the joint, and is composed of elastic fibers and collagen fibers.
  • the ligament has strong tensile strength and a certain elasticity, which can maintain the stability of the joint and limit its activity beyond the physiological range. In daily life and physical activity, the risk of ligament injury is high, which directly leads to unstable joints, synovitis, joint water and other problems, and has become a health problem that cannot be ignored.
  • artificial ligaments have been used extensively in the clinic.
  • artificial ligaments prepared from carbon fiber, polytetrafluoroethylene, polypropylene, and PET fibers.
  • most of these artificial ligaments are woven structures, resulting in a structure that is too tight, the material is not degradable, and the biocompatibility is poor.
  • the artificial ligament is easy to strain and break.
  • the artificial ligament will eventually break.
  • the fibrous debris generated by the artificial ligament frictional strain will remain in the joint and cause obvious foreign body rejection, resulting in severe slip.
  • LC ligaments on the market can prevent foreign matter retention and reduce rejection, but biodegradable materials have different biomechanical properties from tendons, and their mechanical properties during degradation. The sharp decline is much faster than the formation speed of the new tendon, which is not conducive to the repair of the tendon and the maintenance of the function, and it is prone to breakage due to material fatigue two or three years after the operation.
  • the existing artificial ligament products have a single material, and it is difficult to simulate the complex anatomical structure of the human ligament, and the functional replacement cannot be achieved to the greatest extent. Since the joint point with the existing artificial ligament and the bone tunnel is small and the fusion is difficult, the ligament is easily detached from the bone tunnel. And the mechanical stability can not be controlled, resulting in difficulty in the fusion of bone tunnel and artificial ligament.
  • biomimetic ligament can promote the growth of new tissue, promote the three-dimensional fusion of the bone tunnel-bionic ligament, and maintain the mechanical attenuation of the bionic ligament and the incremental balance of the new ligament mechanics, thus providing stable mechanical support.
  • bionic ligament comprising:
  • main body portion including a porous film and a plurality of fiber lines, wherein the main body portion is a cylindrical shape having a cavity formed by winding a porous film, and the plurality of fiber wires are fixed on the porous film, At least one of the plurality of fiber strands extends substantially in the same direction as the length direction of the body portion;
  • a branching portion extending from both end portions of the main body portion in the longitudinal direction, and the branching portion is connected to the main body portion, and the free end portion of the branching portion remote from the main body portion can
  • the outer side is bent radially so that the free ends of the branch portions are separated from each other.
  • the body portion is integrally formed with the branch portion;
  • the branch portion includes the porous film and the plurality of fiber strands, and at least one of the plurality of fiber strands extends substantially in the same direction as the longitudinal direction of the branch portion.
  • the plurality of fiber strands are divided into a plurality of fiber strand sets, the fiber strand sets being substantially parallel to each other, and
  • a portion of the main body portion between the adjacent fiber bundle groups is provided with a through hole penetrating the main body portion.
  • the start end and the end end of at least one of the plurality of fiber strands are respectively located at both end portions of the porous film in the longitudinal direction of the body portion and respectively Connected at both ends.
  • the start end and the end end of at least one of the plurality of fiber strands are respectively located at free ends of the porous film in the longitudinal direction of the branch portion and respectively The free ends are connected.
  • the body portion and the branch portion each include a bone repair membrane, or only the body portion includes a bone repair membrane,
  • the bone repairing film is coated from the outer side to the porous film
  • the plurality of fiber strands secure the porous membrane to the bone repair membrane.
  • the main body portion includes at least a first bone repairing film and a second bone repairing film respectively covering both end portions of the porous film in the longitudinal direction of the main body portion,
  • the first bone repairing membrane and the second bone repairing membrane are spaced apart from each other in the longitudinal direction of the body portion.
  • the minimum distance between the first bone repairing membrane and the second bone repairing membrane in the longitudinal direction of the main body portion is 1 cm to 5 cm, preferably 2 cm to 4 cm.
  • the number of the branches is 2 to 4, and/or
  • the distance between the roots of the two adjacent branch portions in the circumferential direction of the main body portion is 0 cm to 4 cm, or the root portions of the adjacent two of the branch portions are in the circumferential portion of the main body portion Cascade.
  • the biomimetic ligament further includes a plurality of traction wires extending from the free end of the branch portion.
  • the porous membrane is an extracellular matrix porous membrane.
  • the extracellular matrix porous membrane comprises a nanofiber membrane.
  • the nanofiber membrane is made of a degradable material, and further preferably, the degradable material comprises polyurethane, polylactic acid, polycaprolactone, polyglycolic acid, polymethyl methacrylate, chitosan.
  • the degradable material comprises polyurethane, polylactic acid, polycaprolactone, polyglycolic acid, polymethyl methacrylate, chitosan.
  • the degradable material comprises polyurethane, polylactic acid, polycaprolactone, polyglycolic acid, polymethyl methacrylate, chitosan.
  • the degradable material comprises polyurethane, polylactic acid, polycaprolactone, polyglycolic acid, polymethyl methacrylate, chitosan.
  • the bone repairing film is obtained by compounding an inorganic compound and a polymer material; preferably, the inorganic compound includes a calcium phosphate compound, the polymer material including a degradable polymer material; more preferably The calcium phosphate compound includes one or a combination of two or more of hydroxyapatite, tricalcium phosphate, and calcium strontium sulfate, and the degradable polymer material includes polylactic acid, polycaprolactone, and poly One or a combination of two or more of glycolide, gelatin, collagen, chitosan and derivatives thereof, alginic acid and derivatives thereof, and silk proteins.
  • the fiber strand is made of a non-degradable fiber material, preferably, the non-degradable fiber material includes one of silk fiber, polyester fiber, ultra high molecular weight polyethylene fiber, and polypropylene fiber. Or a combination of two or more.
  • the present disclosure provides a biomimetic ligament system comprising the biomimetic ligament of the present disclosure and a fixation device that secures the biomimetic ligament within the bone tunnel.
  • the fixation device is capable of securing the biomimetic ligament within the bone tunnel at both ends of the body portion of the bionic ligament.
  • the fixing device includes a pressing cap and a pressing screw, the pressing cap is inserted into a cavity of the main body portion from both end portions in the longitudinal direction of the main body portion, and the pressing screw can be screwed and / or an interference fit is fastened in the extrusion cap.
  • the outer shape of the extrusion cap is a substantially truncated cone shape.
  • the material of the extrusion screw includes one or a combination of two or more of a titanium alloy, a polylactic acid, a polyaryletherketone compound, preferably, the polyaryletherketone compound
  • a titanium alloy a polylactic acid
  • a polyaryletherketone compound preferably, the polyaryletherketone compound
  • One or a combination of two or more of polyetheretherketone, polyetherketoneketone, polyetherketone, polyetherketoneetherketoneketone or polyetheretherketoneketone is included.
  • the material of the extrusion cap includes one or a combination of two or more of polyethylene, polypropylene, polylactic acid, silica gel, polyaryletherketone, and preferably, the poly
  • the aryl ether ketone compound includes one or a combination of two or more of polyether ether ketone, polyether ketone ketone, polyether ketone, polyether ketone ether ketone ketone or polyether ether ketone ketone.
  • the bionic ligament of the present disclosure has good mechanical properties, and at the same time has a soft texture and a porous structure, which is advantageous for tissue growth.
  • the biomimetic ligament system of the present disclosure can form a three-dimensional fixation, so that the bionic ligament is in full contact with the bone tunnel, thereby inducing the growth of the human ligament tissue, has a good fixation and repair effect, and can reduce the mechanical loss of the artificial ligament.
  • FIG. 1 is a schematic illustration of a bionic ligament in accordance with an embodiment of the present disclosure, in which only the half of the bionic ligament is shown.
  • FIG. 2 is a schematic illustration of a bionic ligament in accordance with another embodiment of the present disclosure, in which only the half of the bionic ligament is shown.
  • FIG. 3 is a schematic illustration of a bionic ligament in accordance with yet another embodiment of the present disclosure, in which only the half of the bionic ligament is shown.
  • FIG. 4 is a schematic illustration of a bionic ligament in accordance with yet another embodiment of the present disclosure, in which only the half of the bionic ligament is shown.
  • FIG. 5 is a schematic illustration of a biomimetic ligament system of yet another embodiment of a biomimetic ligament, in which only the half of the release ligament and a set of compression caps and compression screws are shown.
  • Figure 6 is an anatomical view of the animal's left knee joint after one year of implantation of the artificial ligament.
  • Figure 7 is a diagram showing the new tissue of the left knee joint of the experimental sheep dissected after one year of implantation of the artificial ligament.
  • Figure 8 is a comparison of the meniscus dissected from the left knee joint of the experimental sheep after one year of implantation of the artificial ligament and the right knee joint of the experimental sheep.
  • FIG. 1 is a schematic view of a bionic ligament according to an embodiment of the present disclosure, and in FIG. 1, only the half of the bionic ligament is shown.
  • 2 is a schematic illustration of a bionic ligament in accordance with another embodiment of the present disclosure, in which only half of a bionic ligament is shown.
  • 3 and 4 are schematic views of a bionic ligament according to yet another embodiment of the present disclosure, and in FIGS. 3 and 4, only the half of the bionic ligament is shown.
  • the other half of the bionic ligament of Figures 1 to 4 in this embodiment is symmetrical to the half shown. 2, 3, and 4 have the same functions as those of FIG. 1, and a detailed description of these components is omitted for the sake of brevity.
  • the bionic ligament has a substantially cylindrical body portion 1 and a branch portion 2 extending from both end portions of the body portion 1 in the longitudinal direction (in this embodiment)
  • the number of the branch portions 2 is two
  • the pull wire 3 extending from the free end portion of the branch portion 2.
  • the main body portion 1 has a cavity that penetrates the entire main body portion 1 in the longitudinal direction, and the cavity is used to fit a fixing device described below.
  • the branch portion 2 refers to a structure similar to a petal formed at both ends of the main body 1.
  • the main body portion 1 includes a porous film 11 and a plurality of fiber lines 13 .
  • the main body portion 1 is a cylindrical shape having a cavity formed by winding the porous film 11 , and a plurality of fiber lines 13 are fixed on the porous film 11 .
  • At least one of the fiber strands 13 extends substantially in the same direction as the longitudinal direction of the main body portion 1; the mechanical properties of the porous film 11 in the direction in which the fiber strands 13 extend can be remarkably enhanced.
  • at least one of the plurality of fiber strands 13 extends in the same direction as the longitudinal direction of the main body portion 1.
  • the body portion has a length of from 6 cm to 15 cm, preferably from 8 cm to 12 cm.
  • the branch portion 2 extends from both end portions in the longitudinal direction of the main body portion 1, and the branch portion 2 is connected to the main body portion 1, and the free end portion of the branch portion 2 away from the main body portion 1 can be bent radially outward so that the branch portion The free ends of 2 are separated from each other.
  • the function of the branching portion 2 is to form a hollow opening at both ends of the bionic ligament, so that the following fixing device can be inserted into the cavity of the bionic ligament for fixation, so that the bionic ligament can be fixed more firmly, and the bionic ligament and bone can be increased.
  • the contact area of the tunnel promotes the three-dimensional fusion of the bone tunnel-artificial ligament.
  • the number of the branch portions 2 is not limited, and may be set according to a specific case, and is preferably divided into two to four branch portions 2.
  • the fiber strand 13 is fixed to the porous film 11 by means of puncture up and down (for example, sewing).
  • the fiber line 13 includes a main line and an auxiliary line which are respectively distributed on both sides of the porous film 11 and are staggered in the porous film 11. Interlacing is a description of the relationship between lines and lines.
  • the A line and the B line are interlaced, it means that the A and B lines are entangled at the junction of the two lines.
  • Both the main line and the auxiliary line are composed of filaments.
  • the auxiliary line is subjected to twisting treatment; the auxiliary line has a twist of 10 to 100 ⁇ /m.
  • the fiber strand 13 By twisting the auxiliary wire, the fiber strand 13 can be preferably bonded to the electrospun fiber membrane main body to obtain good fit.
  • the main line can be twisted or not twisted, and the main line can be increased after being twisted.
  • the start end and the end end of at least one of the plurality of fiber strands 13 are respectively located at both end portions of the porous film 11 in the longitudinal direction of the main body portion 1. And connected to the two ends respectively.
  • a plurality of traction wires 3 extend from the free end of the branch portion 2 separated from the main body portion 1, the traction wire 3 for pulling the bionic ligament to the proper position of the bone tunnel and facilitating the fixation of the ligament.
  • the main body portion 1 is integrally formed with the branch portion 2; and, the branch portion 2 also includes the porous film 11 and the plurality of fiber lines 13, among the plurality of fiber lines 13. At least one of the fiber strands 13 extends substantially in the same direction as the longitudinal direction of the branch portion 2. The mechanical properties of the porous film 11 in the direction in which the fiber strands 13 extend can be remarkably enhanced. Preferably, at least one of the plurality of fiber strands 13 extends in the same direction as the longitudinal direction of the branch portion 2.
  • the fiber line 13 is a non-degradable fiber line 13.
  • the plurality of fiber strands 13 are divided into a plurality of fiber strands 13 groups.
  • the number of the fiber strands 13 is not limited in the present disclosure, and may be set according to specific conditions, preferably divided into 2 to 4 fiber strands 13 groups, and each The sets of fiber strands 13 extend substantially parallel; preferably, each set of fiber strands 13 extends in parallel.
  • a portion of the main body portion 1 between the adjacent groups of the fiber strands 13 is provided with a through hole penetrating the main body portion 1. The provision of the through hole can facilitate the nutrient exchange between the two sides of the porous membrane 11 and promote the growth of the new tissue.
  • the two branch portions 2 may be formed by cutting the main body portion 1 in the longitudinal direction at a gap between the groups of the respective fiber strands 13 at both end portions in the longitudinal direction of the main body portion 1, but it is ensured that the branch portion 2 is formed.
  • the structure of each part of the main body 1 is not affected thereafter.
  • the number of the branch portions 2 is two to four, and the distance between the root portions of the adjacent two branch portions 2 in the circumferential direction of the main body portion 1 is 0 cm to 4 cm, or two adjacent ones
  • the root of the branch portion 2 is partially laminated in the circumferential direction of the main body portion.
  • the distance between the root portions of the adjacent two branch portions 2 in the circumferential direction of the main body portion 1 is 0 cm.
  • the circumferential direction of the main body portion 1 means the circumference of the end portion of the main body portion 1.
  • the start end and the end end of at least one of the plurality of fiber strands 13 are respectively located at the free ends of the porous film 11 in the longitudinal direction of the branch portion 2 and respectively and the free ends Connected to the department.
  • the main body portion 1 includes a bone repairing membrane 12 in which the bone repairing membrane 12 is coated from the outer side to the porous membrane 11, and a plurality of The fiber line 13 holds the porous film 11 and the bone repair film 12 together.
  • the main body portion 1 is formed by crimping a laminate in which the porous film 11 and the bone repair film 12 are laminated into a cylindrical shape.
  • the porous film 11 constitutes a radially inner portion of the body portion 1
  • the bone repair film 12 constitutes a radially outer portion of the body portion 1 and is covered with a porous outer side from the radially outer side of the body portion 1.
  • Membrane 11 In the present embodiment, the bone repair film 12 is coated only on both end portions of the porous film 11 in the longitudinal direction of the main body portion 1.
  • a plurality of fiber lines 13 are pierced in the main body portion 1, and the porous film 11 and the bone repair film 12 are firmly joined by a plurality of fiber lines 13.
  • At least one of the plurality of fiber strands 13 extends substantially in the same direction as the longitudinal direction of the main body portion, and the plurality of fiber strands 13 can reinforce the bionics by recombining the porous film 11 and the bone repairing film 12 in the above manner.
  • the mechanical properties of the ligament for example, can enhance the mechanical properties of the length of the biomimetic ligament.
  • the porous film 11 and the bone repair film 12 have a moderate hardness after lamination, and are easily folded and rolled into a cylindrical shape.
  • the auxiliary line can be twisted to enable the fiber line 13 to be better adhered to the porous film 11 and the bone repair film 12, and the auxiliary line can have a twist of, for example, 10-100 ⁇ /m.
  • the auxiliary line has a twist between 10 and 100 ⁇ /m, it can have better fit, so that the prepared bionic ligament has higher comfort when implanted into the human body. If the twist of the auxiliary line is higher than 100 ⁇ / m, the fit will be lowered, which will cause difficulty in the processing. If the twist of the auxiliary line is less than 10 ⁇ / m, the fit performance is poor.
  • the diameter of the fiber constituting the main line and the auxiliary line is 0.01 mm or less, so that the fiber line 13 has a better fit with the porous film 11 and the bone repair film 12. If the diameter of the fiber filament is 0.01 mm or more, the strength of the fiber filament is high, so that the fit is lowered, and the foreign body sensation is increased.
  • the bone repair membrane 12 includes a first bone repair membrane 12 and a second bone repair membrane 12.
  • the first bone repairing membrane 12 and the second bone repairing membrane 12 are respectively coated on both ends of the porous membrane 11 in the longitudinal direction of the main body portion 1, and the first bone repairing membrane 12 and the second bone repairing membrane 12 are in the main body
  • the portions 1 are spaced apart from each other by a certain distance in the longitudinal direction.
  • the distance is from 1 cm to 5 cm, preferably from 2 cm to 4 cm. This distance, which is set according to the physiological structure of the human body, enables the bone repair membrane 12 to be in the bone tunnel, which can promote the repair and growth of the ligament.
  • the composition of the bone repair membrane 12 is similar to that of the autologous bone, the adhesion and growth of the autologous bone cells can be accelerated, which is beneficial to the repair and regeneration of the autologous ligament system.
  • the porous membrane 11 has a porous structure like an extracellular matrix, and by using the composite of the porous membrane 11 and the bone repair membrane 12, it is more advantageous for cell growth.
  • FIG. 5 is a schematic illustration of a biomimetic ligament system of yet another embodiment of a bionic ligament in which only the half of the bionic ligament and a set of extrusion caps and compression screws are shown.
  • the same components in Fig. 5 as those in Figs. 1 through 4 have the same functions, and a detailed description of these components will be omitted for the sake of brevity.
  • the fixing device can fix the bionic ligament in the bone tunnel at both end portions of the main body portion 1 of the bionic ligament, and the fixing device includes the pressing cap 4 and the pressing screw 5.
  • the outer shape of the pressing cap 4 is substantially a truncated cone shape for easy insertion into the bone tunnel, and the inside of the pressing cap 4 is provided with a threaded hole provided with an internal thread; preferably, the outer shape of the pressing cap 4 is Round table shape.
  • the portions of the two pressing caps 4 having a smaller diameter are inserted into the cavities of the main body portion 1 from both end portions in the longitudinal direction of the main body portion 1 of the bionic ligament.
  • the pressing screw 5 is provided with an external thread that cooperates with the internal thread of the pressing cap 4.
  • the pressing screw 5 can be fastened in the pressing cap 4 by screwing and interference fit, so that the pressing cap 4 is caused. It is firmly fixed in the bone tunnel and further securely fixes the bionic ligament in the bone tunnel.
  • the fixation device of the present disclosure and the biomimetic ligament are three-dimensionally fixed, which can increase the sufficient contact between the biomimetic ligament and the bone tunnel, induce the growth of the human ligament tissue, and have a good fixation effect. Moreover, by the use of the pressing cap 4 and the pressing screw 5, the shearing of the bionic ligament by the pressing screw 5 can be reduced, thereby reducing the mechanical loss of the bionic ligament.
  • the biomimetic ligament system can include the above-described biomimetic ligament and the above-described fixation device for securing the above-described biomimetic ligament in a bone tunnel.
  • the porous membrane 11 may be an extracellular matrix-like porous membrane.
  • Extracellular matrix is a macromolecule synthesized by animal cells and secreted extracellularly, distributed on the surface of cells or between cells, mainly polysaccharides and proteins, or proteoglycans. These substances constitute a complex network structure that supports and links tissue structures, regulates tissue development, and cellular physiological activities.
  • the extracellular matrix is part of animal tissue and does not belong to any cell. It determines the characteristics of connective tissue and plays an important role in the cells of some animal tissues.
  • the extracellular matrix porous membrane which has a structure similar to that of the extracellular matrix, makes the prepared biomimetic ligament closer to the complex anatomy of the human ligament and achieves functional replacement.
  • the use of extracellular matrix porous membrane is beneficial to cell ingrowth, further embedding non-degradable fiber of bearing capacity, reducing the wear of non-degradable fiber, and simultaneously realizing the repair and regeneration of autologous ligament system to meet the requirements of mechanics.
  • the extracellular matrix porous membrane comprises: a nanofiber membrane, preferably, the nanofiber membrane can be made of a degradable material, more preferably, the degradable material comprises polyurethane, polylactic acid, polycaprolactone, polyethanol Acid, polymethyl methacrylate, chitosan, lactic acid-glycolic acid copolymer, alginic acid, alginate, collagen, gelatin, chondroitin sulfate, hyaluronic acid, fibrin, one of modified cellulose or Combination of two or more.
  • the nanofiber membrane can be prepared by a method of electrospinning.
  • the bone repair film 12 may be obtained by compounding an inorganic compound and a polymer material; preferably, the inorganic compound includes a calcium phosphate compound, the polymer material includes a degradable polymer material; more preferably, the calcium phosphate compound includes hydroxyapatite , one or a combination of two or more of tricalcium phosphate and calcium sulphate, degradable polymer materials including polylactic acid, polycaprolactone, polyglycolide, gelatin, collagen, chitosan and derivatives thereof One or a combination of two or more of a substance, an alginic acid and a derivative thereof, and a silk protein.
  • the fiber strand 13 is made of a non-degradable fiber material, and preferably, the non-degradable fiber material includes one or a combination of two or more of silk fiber, polyester fiber, ultrahigh molecular weight polyethylene fiber, and polypropylene fiber. Among them, the degradation speed of silk fiber and polyester fiber is very slow, and in the present disclosure, it is attributed to the category of non-degradable fiber material.
  • the material of the extrusion screw 5 includes one or a combination of two or more of a titanium alloy, a polylactic acid, and a polyaryletherketone compound.
  • the polyaryletherketone compound includes polyetheretherketone, polyetherketoneketone, One or a combination of two or more of polyether ketone, polyether ketone ether ketone ketone or polyether ether ketone ketone.
  • the material of the extrusion cap 4 includes one or a combination of two or more of polyethylene, polypropylene, polylactic acid, silica gel, polyaryletherketone, and preferably, the polyaryletherketone compound includes polyetheretherketone, One or a combination of two or more of polyetherketoneketone, polyetherketone, polyetheretherketoneketone or polyetheretherketoneketone.
  • the present disclosure also provides an application of a biomimetic ligament system according to the present disclosure in ligament repair. Specifically, during the surgical operation, the pull wire 3 is pulled to expose the branch portion 2 of the bionic ligament, and the squeeze cap 4 is placed in the center of the root portion of the bionic ligament branch portion 2, and is squeezed along the cavity of the main body portion 1 of the bionic ligament Into the bone tunnel, the extrusion screw 5 is then screwed into the extrusion cap 4.
  • Dissolve polylactic acid with hexafluoroisopropanol dispose the electrospinning solution with a mass concentration of 10%, add the electrospinning solution to the syringe, and connect the micropump front tube and the spinning needle to set the spinning voltage to 25kV.
  • the advancement speed is 10 mL/h, and the receiving distance is 30 cm.
  • the obtained electrospun membrane was placed in a blast drying oven at 50 ° C for 5 h, then immersed in 75% alcohol for 1 h, and then placed in a dry box and dried at 50 ° C overnight to obtain a polylactic acid nanofiber membrane.
  • a fiber strand made of 45 (1 tuft) of PET fiber was used, and the fiber strand was fixed to the polylactic acid nanofiber membrane by sewing to obtain a composite film.
  • one fiber line is made of one tuft of PET fiber
  • four fiber lines are one fiber line group, the fiber lines in the same fiber line group extend in the same direction, and one fiber line group is co-sewn.
  • the composite film described above is crimped with the extending direction of the fiber strand as an axis, and the main body portion of the bionic ligament having the cavity is formed by winding and stitching, wherein the extending direction of the fiber line is the same as the length direction of the main body portion, Both ends of the main body portion of the bionic ligament are cut along the direction of the fiber bundle group, so that three branch portions are respectively extended from both end portions in the longitudinal direction of the main body portion of the bionic ligament, and traction is provided on each branch portion. Line, the biomimetic ligament was obtained, and the length of the main body of the bionic ligament was 6 cm.
  • Polyetheretherketone rods were selected and matched extrusion caps and extrusion screws were prepared using a five-axis machining facility.
  • the biomimetic ligament is then combined with a fixture consisting of a compression cap and a squeeze screw to provide a biomimetic ligament system.
  • the pressing cap can be inserted into the cavity of the main body portion of the bionic ligament from both end portions of the main body portion of the bionic ligament, and the pressing screw can be fastened in the pressing cap by both the screw fitting and the interference fit.
  • Dissolve polycaprolactone with hexafluoroisopropanol dispose the electrospinning solution with a mass concentration of 10%, add the electrospinning solution to the syringe, and connect the micropump front tube and the spinning needle to set the spinning voltage 28.5kV.
  • the solution advancement speed is 8 mL/h, and the receiving distance is 30 cm.
  • the obtained electrospun membrane was placed in a blast drying oven at 50 ° C for 5 h, then immersed in 75% alcohol for 1 h, and then placed in a dry box at 50 ° C overnight to obtain a polycaprolactone nanofiber membrane.
  • a fiber strand made of 25 (1 tuft) of PET fiber was used, and the fiber strand was fixed to the polycaprolactone nanofiber membrane by sewing to obtain a composite film.
  • one fiber line is made of one tuft of PET fiber
  • two fiber lines are one fiber line group
  • the fiber lines in the same fiber line group extend in the same direction
  • the distance between adjacent fiber line groups is 1 cm.
  • Four fiber strands were sewn and four fiber strands were parallel to each other.
  • the composite film is curled by the direction in which the fiber strand extends, and is wound and stitched to form a main body portion of the bionic ligament having a cavity in which the extending direction of the fiber line is the same as the length direction of the main body portion, in the bionic ligament
  • the two ends of the main body portion are cut along the direction of the fiber bundle group, so that the two ends of the main body portion of the bionic ligament have two branches, and a traction line is arranged on each branch portion to obtain a bionic ligament, bionic
  • the body of the ligament has a length of 12 cm.
  • Polyetheretherketone rods were selected and matched extrusion caps and extrusion screws were prepared using a five-axis machining facility.
  • the biomimetic ligament is then combined with a fixture consisting of a compression cap and a squeeze screw to provide a biomimetic ligament system.
  • the pressing cap can be inserted into the cavity of the main body portion of the bionic ligament from both end portions of the main body portion of the bionic ligament, and the pressing screw can be fastened in the pressing cap by both the screw fitting and the interference fit.
  • Dissolve L-polylactic acid with hexafluoroisopropanol dispose the electrospinning solution with a mass concentration of 20%, add the electrospinning solution to the syringe, and connect the micropump front tube and the spinneret to set the spinning voltage to 35kV.
  • the solution advancement speed is 2.5 mL/h, and the receiving distance is 30 cm.
  • the obtained electrospun membrane was placed in a blast drying oven at 50 ° C for 5 h, then immersed in 75% alcohol for 1 h, and then placed in a dry box at 50 ° C overnight to obtain an L-polylactic acid nanofiber membrane.
  • a fiber line made of 50 (1 tuft) of PET fiber is used, and the poly-L-polylactic acid nanofiber membrane is combined with the first bone repair membrane and the second bone repair membrane by the fiber thread by sewing.
  • a composite film was obtained.
  • one fiber thread is made of 1 tuft of PET fiber
  • 10 fiber strands are one fiber strand group
  • 10 fiber strands in the same fiber strand group extend in the same direction
  • the distance between adjacent fiber strand groups is 1 cm
  • 4 fiber strands were sewn
  • 4 fiber strands were parallel to each other
  • the distance between the first bone repair membrane and the second bone repair membrane was 5 cm.
  • the composite film is curled by the direction in which the fiber strand extends, and the body portion of the bionic ligament having the cavity is formed by winding and stitching, wherein the direction of the fiber line extends in the same direction as the length of the body portion.
  • Both ends of the main body portion of the bionic ligament are cut along the direction of the fiber bundle group so that four branch portions are extended from both end portions in the longitudinal direction of the main body portion of the bionic ligament (two branch portions are extended at each end portion)
  • a traction line is provided on each branch portion to obtain a bionic ligament, and the body portion of the bionic ligament has a length of 12 cm.
  • Polyetheretherketone rods were selected and matched extrusion caps and extrusion screws were prepared using a five-axis machining facility.
  • the biomimetic ligament is then combined with a fixture consisting of a compression cap and a squeeze screw to provide a biomimetic ligament system.
  • the pressing cap can be inserted into the cavity of the main body portion of the bionic ligament from both end portions of the main body portion of the bionic ligament, and the pressing screw can be fastened in the pressing cap by both the screw fitting and the interference fit.
  • Dissolve polycaprolactone with hexafluoroisopropanol dispose the electrospinning solution with a mass concentration of 15%, add the electrospinning solution to the syringe, and connect the micropump front tube and the spinneret to set the spinning voltage to 35kV.
  • the solution advancement speed is 10 mL/h, and the receiving distance is 30 cm.
  • the obtained electrospun membrane was placed in a blast drying oven at 50 ° C for 5 h, then immersed in 75% alcohol for 1 h, and then placed in a dry box at 50 ° C overnight to obtain a polycaprolactone nanofiber membrane.
  • Dissolve gelatin and L-polylactic acid with hexafluoroisopropanol dispose the L-polylactic acid-gelatin solution at a concentration of 12%, and then add hydroxyapatite powder to the L-polylactic acid-gelatin solution, and gelatin and L -
  • the mass ratio of the mixture of polylactic acid and hydroxyapatite was 5:1, and the mixture was stirred at a rotation speed of 1000 rpm for 40 minutes, introduced into a watch glass, and air-dried at normal temperature to obtain a bone repair film.
  • a fiber line made of 30 (1 cluster) PET fiber yarn is used, and the polycaprolactone nanofiber membrane is combined with the first bone repair membrane and the second bone repair membrane by a fiber thread to obtain a composite membrane.
  • one fiber line is made of 1 tuft of PET fiber, 10 fiber lines are one fiber line group, 10 fiber lines in the same fiber line group have the same extension direction, and the distance between adjacent fiber line groups is 1 cm.
  • Three fiber strands were sewn, three fiber strands were parallel to each other, and the distance between the first bone repair membrane and the second bone repair membrane was 4 cm.
  • the composite film is curled by the direction in which the fiber strand extends, and the body portion of the bionic ligament having the cavity is formed by winding and stitching, wherein the direction of the fiber line extends in the same direction as the length of the body portion.
  • Both ends of the main body portion of the bionic ligament are cut along the direction of the fiber bundle group so that four branch portions are extended from both end portions in the longitudinal direction of the main body portion of the bionic ligament (two branch portions are extended at each end portion)
  • a traction line is provided on each branch portion to obtain a bionic ligament, and the body portion of the bionic ligament has a length of 6 cm.
  • Polyetheretherketone rods were selected and matched extrusion caps and extrusion screws were prepared using a five-axis machining facility.
  • the biomimetic ligament is then combined with a fixture consisting of a compression cap and a squeeze screw to provide a biomimetic ligament system.
  • the pressing cap can be inserted into the cavity of the main body portion of the bionic ligament from both end portions of the main body portion of the bionic ligament, and the pressing screw can be fastened in the pressing cap by both the screw fitting and the interference fit.
  • the artificial ligament system of Example 1 was used for the animal experiment, and the artificial ligament and the fixation device in the artificial ligament system were sterilized before operation.
  • Three sheep were taken and anesthetized by intramuscular injection of 3.5% sodium pentobarbital solution.
  • the left knee joint of the hind leg was selected as the experimental group, and the knee was bent 90° to remove the anterior cruciate ligament.
  • An electric drill was drilled along the anterior cruciate ligament from the tibia to the femoral end.
  • the tibia and femur were drilled through, and the artificial ligament was implanted into the bone tunnel of the femur using an auxiliary implant device.
  • the traction device to pull the artificial ligament traction line to pull one end of the artificial ligament from the tibial bone tunnel, bend the knee 30°, fix the artificial ligament with the femoral bone tunnel and the tibial bone tunnel respectively, fix the two ends Excessive artificial ligaments are exposed, the knee joint is sutured, and free movement after surgery.
  • the right knee joint of the hind leg was not treated as a control group.
  • the sheep were painlessly sacrificed one year after surgery, and the left and right knee joints of the hind legs were dissected. Dissection of the left knee joint (experimental group) revealed that the nanofiber membrane was basically degraded, and the new tissue wrapped non-degradable fiber. The left knee joint (experimental group) and the right knee joint (control group) showed no difference in the meniscus between the two sides. The amount and color of the liquid are not visible to the naked eye. It is shown that the artificial ligament system of Embodiment 1 of the present disclosure has a good repairing effect.
  • Example 2-4 of the present disclosure was subjected to the above animal experiment, and the artificial ligament system prepared in Example 2-4 of the present disclosure had the same or superior technical effects as in Example 1. Therefore, the artificial ligament system of the present disclosure can be used for ligament repair and has a good repairing effect.

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Abstract

一种仿生韧带及仿生韧带系统，仿生韧带包括：主体部（1），主体部（1）包括多孔膜（11）和多条纤维线（13），主体部（1）为由多孔膜（11）卷绕形成的具有空腔的圆筒形状，多条纤维线（13）固定于多孔膜（11）上，多条纤维线（13）中的至少一条纤维线（13）大致沿着与主体部（1）的长度方向相同的方向延伸；以及分支部（2），分支部（2）从主体部（1）的长度方向上的两端部延伸出，且分支部（2）与主体部（1）相连，分支部（2）的远离主体部（1）的自由端部能够沿径向外侧弯曲，使得分支部（2）的自由端部彼此分开。仿生韧带既能够促进新生组织长入，促进骨隧道-仿生韧带的三维融合，还能够维持仿生韧带的力学衰减和新生韧带力学递增的平衡，从而提供稳定的力学支撑。

Description

仿生韧带及仿生韧带系统
交叉引用
本申请主张2016年12月28日提交的中国专利申请号为201611235653.3的优先权，其全部内容通过引用包含于此。
技术领域
本公开涉及一种仿生韧带及仿生韧带系统，属于生物医学领域。
背景技术
韧带是连接关节相邻两骨之间或软骨之间的致密纤维结缔组织束或结缔组织膜，由弹性纤维及胶原纤维交织而成。韧带抗拉力强，并具有一定的弹性，能够维持关节的稳定，并限制其超越生理范围的活动。在日常生活和体育活动中，韧带损伤的几率很高，直接导致关节连接不稳定、滑膜炎、关节积水等问题，已经成为不可忽视的健康问题。
由于韧带的自我修复能力很差，临床上常用的治疗方法包括自体移植、同种或异种肌腱移植和采用人工韧带等，其中自体肌腱移植应用最广，并取得了良好的临床效果，但也会造成供区病损的不良影响。同种或异种肌腱移植也存在疾病传播、免疫排斥等问题，而且生物移植物会经历组织坏死、血管重建、细胞增殖和塑形成熟“韧带化”的过程，导致移植物强度明显下降，影响术后效果。
随着合成材料的发展，临床上开始大量使用人工韧带。例如：采用碳纤维、聚四氟乙烯、聚丙烯、PET纤维制备得到的人工韧带。但该类人工韧带多为编织结构，导致结构过于严密，材料不可降解，生物相容性较差，新组织很难长入或难以实现包裹材料起到抗拉抗摩擦作用。且随长时间的摩擦、拉伸运动，人工韧带容易劳损断裂。并且，如果人工韧带上没有新的韧带组织生成以替代人工韧带，最终会导致人工韧带断裂，人工韧带摩擦劳损产生的纤维碎屑物会残留在关节内造成明显的异物排斥反应，导致严重的滑膜炎、关节炎等问题。
另外，可降解吸收的人工韧带越来越备受关注，如市场上的LC韧带，虽然能够避免异物存留和降低排斥反应，但可降解吸收材料与肌腱生物力学特性不同，其降解时力学性能的急剧下降远远快于新肌腱的形成速度，不利于肌腱的修复和功能的维持，并且 手术后两三年由于材料疲劳容易出现断裂。
还有，现有的人工韧带产品材料单一，很难模拟人体韧带复杂的解剖结构，无法最大程度实现功能替代。由于与现有的人工韧带与骨隧道的结合点少且融合难，容易会导致韧带从骨隧道中脱离。并且力学稳定性无法控制，导致骨隧道与人工韧带融合困难。
发明内容
发明要解决的问题
本公开的目的在于提供一种仿生韧带及仿生韧带系统。该仿生韧带既能够促进新生组织长入，促进骨隧道-仿生韧带的三维融合，还能够维持仿生韧带的力学衰减和新生韧带力学递增的平衡，从而提供稳定的力学支撑。
用于解决问题的方案
本公开提供一种仿生韧带，所述仿生韧带包括：
主体部，所述主体部包括多孔膜和多条纤维线，所述主体部为由多孔膜卷绕形成的具有空腔的圆筒形状，所述多条纤维线固定于所述多孔膜上，所述多条纤维线中的至少一条纤维线大致沿着与所述主体部的长度方向相同的方向延伸；以及
分支部，所述分支部从所述主体部的长度方向上的两端部延伸出，且所述分支部与所述主体部相连，所述分支部的远离所述主体部的自由端部能够沿径向外侧弯曲，使得所述分支部的所述自由端部彼此分开。
根据本公开的仿生韧带，所述主体部与所述分支部一体成型；并且
所述分支部包括所述多孔膜和所述多条纤维线，所述多条纤维线中的至少一条纤维线大致沿着与所述分支部的长度方向相同的方向延伸。
根据本公开的仿生韧带，所述多条纤维线分成多个纤维线组，所述纤维线组大致彼此平行，并且
所述主体部的在相邻的所述纤维线组之间的部分设置有贯通所述主体部的通透孔。
根据本公开的仿生韧带，所述多条纤维线中的至少一条纤维线的起始端与终止端分别位于所述多孔膜的在所述主体部的长度方向上的两端部处且分别与该两端部相连。
根据本公开的仿生韧带，所述多条纤维线中的至少一条纤维线的起始端与终止端分别位于所述多孔膜的在所述分支部的长度方向上的自由端部处且分别与所述自由端部相连。
根据本公开的仿生韧带，所述主体部和所述分支部均包括骨修复膜，或者仅所述主体部包括骨修复膜，
在所述主体部和/或所述分支部中，所述骨修复膜从外侧包覆于所述多孔膜，并且
所述多条纤维线使所述多孔膜与所述骨修复膜固定在一起。
根据本公开的仿生韧带，所述主体部至少包括分别包覆于所述多孔膜的在所述主体部的长度方向上的两端部的第一骨修复膜和第二骨修复膜，所述第一骨修复膜与所述第二骨修复膜在所述主体部的长度方向上彼此分隔开。
根据本公开的仿生韧带，所述第一骨修复膜与所述第二骨修复膜之间的在所述主体部的长度方向上的最小间距为1cm至5cm，优选为2cm至4cm。
根据本公开的仿生韧带，所述分支部的数量为2个至4个，和/或
相邻的两个所述分支部的根部之间的在所述主体部的周向上的距离为0cm至4cm，或者相邻的两个所述分支部的根部在所述主体部的周向上部分层叠。
根据本公开的仿生韧带，所述仿生韧带还包括从所述分支部的所述自由端部延伸出的多条牵引线。
根据本公开的仿生韧带，所述多孔膜为类细胞外基质多孔膜。
优选地，所述类细胞外基质多孔膜包括纳米纤维膜。更优选地，所述纳米纤维膜由可降解材料制成，进一步优选地，所述可降解材料包括聚氨酯、聚乳酸、聚己内酯、聚乙醇酸、聚甲基丙烯酸甲酯、壳聚糖、乳酸-羟基乙酸共聚物、海藻酸、海藻酸盐、胶原、明胶、硫酸软骨素、透明质酸、纤维蛋白、改性纤维素的一种或两种以上的组合。
根据本公开的仿生韧带，所述骨修复膜由无机化合物和高分子材料复合得到；优选地，所述无机化合物包括磷酸钙类化合物，所述高分子材料包括可降解的高分子材料；更优选地，所述磷酸钙类化合物包括羟基磷灰石、磷酸三钙、含锶硫酸钙中一种或两种以上的组合，所述可降解的高分子材料包括聚乳酸、聚己内酯、聚乙交酯、明胶、胶原、壳聚糖类及其衍生物、海藻酸类及其衍生物、蚕丝蛋白中的一种或两种以上的组合。
根据本公开的仿生韧带，所述纤维线由不可降解纤维材料制成，优选地，所述不可降解纤维材料包括蚕丝纤维、聚酯纤维、超高分子量聚乙烯纤维、聚丙烯纤维中的一种或两种以上的组合。
本公开提供一种仿生韧带系统，所述仿生韧带系统包括本公开的仿生韧带以及将所述仿生韧带固定于骨隧道内的固定装置。
根据本公开的仿生韧带系统，所述固定装置能够在所述仿生韧带的主体部的两端部处将所述仿生韧带固定于所述骨隧道内。
所述固定装置包括挤压帽和挤压螺钉，所述挤压帽从所述主体部的长度方向上的两端部插入所述主体部的空腔，所述挤压螺钉能够通过螺纹配合和/或过盈配合紧固于所述挤压帽内。
优选地，所述挤压帽的外部形状为大致圆台形的形状。
根据本公开的仿生韧带系统，所述挤压螺钉的材料包括钛合金、聚乳酸、聚芳醚酮类化合物中的一种或两种以上的组合，优选地，所述聚芳醚酮类化合物包括聚醚醚酮、聚醚酮酮、聚醚酮、聚醚酮醚酮酮或聚醚醚酮酮中的一种或两种以上的组合。
根据本公开的仿生韧带系统，所述挤压帽的材料包括聚乙烯、聚丙烯、聚乳酸、硅胶、聚芳醚酮类化合物中的一种或两种以上的组合，优选地，所述聚芳醚酮类化合物包括聚醚醚酮、聚醚酮酮、聚醚酮、聚醚酮醚酮酮或聚醚醚酮酮中的一种或两种以上的组合。
发明的效果
本公开的仿生韧带具有良好的力学性能，同时质地柔软，具有多孔结构，有利于组织长入。
进一步地，本公开的仿生韧带系统能够形成三维固定，使得仿生韧带与骨隧道充分接触，从而诱导人体自身韧带组织的生长，具有良好的固定及修复效果，且能够减少人工韧带的力学损失。
附图说明
图1是根据本公开的一实施方式的仿生韧带的示意图，其中仅示出了仿生韧带的半部。
图2是根据本公开的另一实施方式的仿生韧带的示意图，其中仅示出了仿生韧带的半部。
图3是根据本公开的又一实施方式的仿生韧带的示意图，其中仅示出了仿生韧带的半部。
图4是根据本公开的又一实施方式的仿生韧带的示意图，其中仅示出了仿生韧带的半部。
图5是仿生韧带的再一实施方式的仿生韧带系统的示意图，其中仅示出了该放生韧带的半部以及一组挤压帽和挤压螺钉。
图6是实验羊的左膝关节在植入人工韧带一年后的动物解剖图。
图7是实验羊的左膝关节在植入人工韧带一年后解剖得到的新生组织图。
图8是实验羊的左膝关节在植入人工韧带一年后解剖得到的半月板与实验羊的右膝关节解剖得到的半月板的对比图。
附图标记说明
1主体部 11多孔膜 12骨修复膜 13纤维线 2分支部 3牵引线 4挤压帽 5挤压螺钉。
具体实施方式
以下将参考附图详细说明本公开的各种示例性实施例、特征和方面。在这里专用的词“示例性”意为“用作例子、实施例或说明性”。这里作为“示例性”所说明的任何实施例不必解释为优于或好于其它实施例。
另外，为了更好地说明本公开，在下文的具体实施方式中给出了众多的具体细节。本领域技术人员应当理解，没有某些具体细节，本公开同样可以实施。在另外一些实例中，对于本领域技术人员熟知的方法、手段、器材和步骤未作详细描述，以便于凸显本公开的主旨。
以下将结合说明书附图来说明根据本公开的一实施方式的仿生韧带系统的具体结构。
如图1至图4所示，图1为根据本公开的一实施方式的仿生韧带的示意图，在图1中，仅示出了仿生韧带的半部。图2是根据本公开的另一实施方式的仿生韧带的示意图，在图2中，仅示出了仿生韧带的半部。图3和图4是根据本公开的又一实施方式的仿生韧带的示意图，在图3和图4中，仅示出了仿生韧带的半部。本实施方式中图1至图4的仿生韧带的另一半部与所示出的半部对称。图2、图3、图4中标号与图1相同的组件具有相同的功能，为简明起见，省略对这些组件的详细说明。
(仿生韧带的具体结构)
以下结合图1至图4来说明仿生韧带的具体结构。
在一种具体的实施方式中，如图1所示，该仿生韧带具有大致圆筒状的主体部1、从主体部1的长度方向上的两端部延伸出的分支部2(在本实施例中，分支部2的个数为2个)以及从分支部2的自由端部延伸出的牵引线3。在本实施方式中，主体部1具有在长度方向上贯穿整个主体部1的空腔，该空腔用于配合下述的固定装置。所述分支部2是指在主体1的两端形成的类似花瓣的结构。
其中，主体部1包括多孔膜11和多条纤维线13，主体部1为由多孔膜11卷绕形成的具有空腔的圆筒形状，多条纤维线13固定于多孔膜11上，多条纤维线13中的至少一条纤维线13大致沿着与主体部1的长度方向相同的方向延伸；可以显著增强多孔膜11在纤维线13延伸方向上的力学性能。优选地，多条纤维线13中的至少一条纤维线13沿着与主体部1的长度方向相同的方向延伸。优选地，主体部的长度为6cm至15cm，优选为8cm至12cm。
分支部2从主体部1的长度方向上的两端部延伸出，且分支部2与主体部1相连，分支部2的远离主体部1的自由端部能够沿径向外侧弯曲，使得分支部2的自由端部彼此分开。设置分支部2的作用是使仿生韧带两端形成中空的开口，方便下述的固定装置插入仿生韧带的空腔进行固定，这样即可以使仿生韧带固定得更牢固，还可以增加仿生韧带与骨隧道的接触面积，促进骨隧道-人工韧带三维的融合。本公开中，对分支部2的数量不进行限定，可以根据具体情况进行设置，优选地，分成2个至4个分支部2。
纤维线13通过上下穿刺的方式(例如：缝纫的方式)固定于多孔膜11上。具体而言，纤维线13包括主线和辅助线，主线和辅助线分别分布于多孔膜11的两面，并在多孔膜11内发生交错。交错是描述线与线之间关系。当A线与B线发生交错，是指在两线相接处，A、B线发生缠绕。所述主线和辅助线均由纤维丝构成。优选地，所述辅助线经过加捻处理；所述辅助线的捻度为10～100捻/m。对辅助线进行加捻处理，能够使纤维线13较好地贴合到电纺纤维膜主体上，获得良好的贴合性。主线可以进行加捻处理，或者不进行加捻处理，主线进行加捻处理后，能提高主线的受力能力。另外，如图1所示，在本实施方式中，多条纤维线13中的至少一条纤维线13的起始端与终止端分别位于多孔膜11的在主体部1的长度方向上的两端部处且分别与该两端部相连。
在本实施方式中，多条牵引线3从分支部2的与主体部1分离的自由端部延伸出，该牵引线3用于将仿生韧带牵引到骨隧道的适当位置以及方便韧带的固定。
在另一种具体的实施方式中，如图2所示，主体部1与分支部2一体成型；并且， 分支部2也包括多孔膜11和多条纤维线13，多条纤维线13中的至少一条纤维线13大致沿着与分支部2的长度方向相同的方向延伸。可以显著增强多孔膜11在纤维线13延伸方向上的力学性能。优选地，多条纤维线13中的至少一条纤维线13沿着与分支部2的长度方向相同的方向延伸。
纤维线13为不可降解纤维线13。多条纤维线13被分成多个纤维线13组，本公开对纤维线13组的数量不进行限定，可以根据具体情况进行设置，优选地，分成2个至4个纤维线13组，且各纤维线13组大致平行地延伸；优选地，各纤维线13组平行地延伸。主体部1的在相邻的纤维线13组之间的部分设置有贯通主体部1的通透孔。设置通透孔能够有利于多孔膜11两面间的营养交换，促进新生组织长入。
可以通过在主体部1的长度方向上的两端部处，在各纤维线13组之间的间隙沿长度方向剪开主体部1来形成这两个分支部2，但是应当保证形成分支部2之后不会影响主体部1的各部分的结构。优选地，分支部2的数量为2个至4个，相邻的两个分支部2的根部之间的在主体部1的周向上的距离为0cm至4cm，或者相邻的两个所述分支部2的根部在所述主体部的周向上部分层叠。本实施方式中，相邻的两个分支部2的根部之间的在主体部1的周向上的距离为0cm。本公开中，“主体部1的周向上”意指所述主体部1的端部的圆周上。
另外，本实施方式中，多条纤维线13中的至少一条纤维线13的起始端与终止端分别位于多孔膜11的在分支部2的长度方向上的自由端部处且分别与该自由端部相连。
在另一种具体的实施方式中，如图3和图4所示，主体部1包括骨修复膜12，在主体部1中，骨修复膜12从外侧包覆于多孔膜11，并且多条纤维线13使多孔膜11与骨修复膜12固定在一起。通过将多孔膜11和骨修复膜12层叠而成的层叠体卷曲成圆筒形状来形成该主体部1。
在形成圆筒状的主体部1中，多孔膜11构成主体部1的径向内侧部分，骨修复膜12构成主体部1的径向外侧部分并且从主体部1的径向外侧包覆于多孔膜11。在本实施方式中，骨修复膜12仅包覆于多孔膜11的在主体部1的长度方向上的两端部。在主体部1中穿刺有多条纤维线13，通过多条纤维线13使多孔膜11与骨修复膜12牢固地连接在一起。
多条纤维线13中的至少一条纤维线13大致沿着与主体部的长度方向相同的方向延伸，多条纤维线13通过以上述方式将多孔膜11和骨修复膜12进行复合，能够增强仿生 韧带的力学性能，例如可以增强仿生韧带长度延伸方向上的力学性能。另外，多孔膜11和骨修复膜12复合后的硬度适中，并且容易折叠和卷制成圆筒形状。
一般而言，可以对辅助线进行加捻处理，能够使得纤维线13与多孔膜11和骨修复膜12能够更好的贴合在一起，辅助线的捻度例如可以是10-100捻/m。当辅助线的捻度在10-100捻/m之间时，能够具有更好的贴合性，使得制备得到的仿生韧带在植入人体时，具有更高的舒适度。如果辅助线的捻度高于100捻/m，则贴合性会下降，给加工过程造成困难，如果辅助线的捻度低于10捻/m，则贴合性能不佳。
另外，构成主线和辅助线的纤维丝的直径在0.01mm以下，从而使得纤维线13与多孔膜11和骨修复膜12具有更好的贴合性。如果纤维丝的直径在0.01mm以上时，纤维丝的强度较高，使得贴合性下降，并且会增加异物感。
进一步地，在本实施方式中，骨修复膜12包括第一骨修复膜12和第二骨修复膜12。第一骨修复膜12和第二骨修复膜12分别包覆于多孔膜11的在主体部1的长度方向上的两端部，并且第一骨修复膜12与第二骨修复膜12在主体部1的长度方向上彼此分隔开一定的距离。优选地，该距离为1cm至5cm、优选为2cm至4cm。根据人体生理结构设置的该距离能够使得骨修复膜12正好处于骨隧道中，能够促进自身韧带的修复与生长。
采用骨修复膜12，由于骨修复膜12的成分与自体骨的成分类似，能够加快自体骨细胞的粘附与生长，有利于自体韧带系统的修复与再生。并且，多孔膜11具有类细胞外基质的多孔结构，通过采用多孔膜11与骨修复膜12的复合，更有利于细胞的长入。
(固定装置的具体结构)
图5是仿生韧带的再一实施方式的仿生韧带系统的示意图，其中仅示出了该仿生韧带的半部以及一组挤压帽和挤压螺钉。图5中标号与图1至4相同的组件具有相同的功能，为简明起见，省略对这些组件的详细说明。
以下结合图5来说明固定装置的具体结构。
在本实施方式中，固定装置能够在仿生韧带的主体部1的两端部处将仿生韧带固定于骨隧道内，该固定装置包括挤压帽4和挤压螺钉5。
挤压帽4的外部形状为大致圆台形的形状以方便插入骨隧道中，挤压帽4的内部设置有螺纹孔，该螺纹孔设置有内螺纹；优选地，挤压帽4的外部形状为圆台形。当使用固定装置进行固定时，使两个挤压帽4的直径较小的部分从仿生韧带的主体部1的长度方向上的两端部插入主体部1的空腔内。
挤压螺钉5设置有与挤压帽4的内螺纹对应配合的外螺纹。当使用固定装置进行固定时，在挤压帽4插入上述空腔之后，能够通过螺纹配合和过盈配合两种方式将挤压螺钉5紧固于挤压帽4内，从而使得挤压帽4牢固地固定于骨隧道内并进一步将仿生韧带牢固地固定于骨隧道内。
本公开固定装置与仿生韧带之间是三维固定的，能够增加仿生韧带与骨隧道之间的充分接触，诱导人体自身韧带组织的生长，并且具有良好的固定效果。并且，通过挤压帽4和挤压螺钉5的配合使用，可以减少挤压螺钉5对仿生韧带的剪切，进而减少仿生韧带的力学损失。
(仿生韧带系统的具体结构)
仿生韧带系统可以包括上述的仿生韧带以及将上述仿生韧带固定于骨隧道内的上述固定装置。
以下将具体说明上述仿生韧带系统的各组成部分的化学组分以及制备方法。
(多孔膜的材料及制备方法)
多孔膜11可以为类细胞外基质多孔膜。细胞外基质(extracellular matrixc,ECM)，是由动物细胞合成并分泌到胞外、分布在细胞表面或细胞之间的大分子，主要是一些多糖和蛋白，或蛋白聚糖。这些物质构成复杂的网架结构，支持并连接组织结构、调节组织的发生和细胞的生理活动。细胞外基质是动物组织的一部分，不属于任何细胞。它决定结缔组织的特性，对于一些动物组织的细胞具有重要作用。
而类细胞外基质多孔膜，其具有与细胞外基质类似的结构，使得所制备得到的仿生韧带更加接近人体韧带复杂的解剖结构，实现功能替代。选用类细胞外基质多孔膜有利于细胞的长入，进一步包埋承力的不可降解纤维，减少不可降解纤维的磨损，同时实现自体韧带系统的修复与再生，满足力学的要求。
具体地，类细胞外基质多孔膜包括：纳米纤维膜，优选地，该纳米纤维膜可以由可降解材料制成，更优选地，可降解材料包括聚氨酯、聚乳酸、聚己内酯、聚乙醇酸、聚甲基丙烯酸甲酯、壳聚糖、乳酸-羟基乙酸共聚物、海藻酸、海藻酸盐、胶原、明胶、硫酸软骨素、透明质酸、纤维蛋白、改性纤维素的一种或两种以上的组合。优选地，纳米纤维膜可以通过静电纺丝的方法制备得到。
(骨修复膜的材料)
骨修复膜12可以由无机化合物和高分子材料复合得到；优选地，无机化合物包括 磷酸钙类化合物，高分子材料包括可降解的高分子材料；更优选地，磷酸钙类化合物包括羟基磷灰石、磷酸三钙、含锶硫酸钙中一种或两种以上的组合，可降解的高分子材料包括聚乳酸、聚己内酯、聚乙交酯、明胶、胶原、壳聚糖类及其衍生物、海藻酸类及其衍生物、蚕丝蛋白中的一种或两种以上的组合。
(纤维线的材料)
纤维线13由不可降解纤维材料制成，优选地，不可降解纤维材料包括蚕丝纤维、聚酯纤维、超高分子量聚乙烯纤维、聚丙烯纤维中的一种或两种以上的组合。其中，蚕丝纤维和聚酯纤维的降解速度很慢，在本公开中，将其归于不可降解纤维材料的范畴。
(固定装置的材料)
挤压螺钉5的材料包括钛合金、聚乳酸、聚芳醚酮类化合物中的一种或两种以上的组合，优选地，聚芳醚酮类化合物包括聚醚醚酮、聚醚酮酮、聚醚酮、聚醚酮醚酮酮或聚醚醚酮酮中的一种或两种以上的组合。
挤压帽4的材料包括聚乙烯、聚丙烯、聚乳酸、硅胶、聚芳醚酮类化合物中的一种或两种以上的组合，优选地，聚芳醚酮类化合物包括聚醚醚酮、聚醚酮酮、聚醚酮、聚醚酮醚酮酮或聚醚醚酮酮中的一种或两种以上的组合。
以下将具体说明上述仿生韧带系统的应用。
本公开还提供一种根据本公开的仿生韧带系统在韧带修复中的应用。具体在手术操作时，牵拉牵引线3，从而露出仿生韧带的分支部2，将挤压帽4放入仿生韧带分支部2的根部的中心，沿着仿生韧带的主体部1的空腔挤入骨隧道中，然后将挤压螺钉5拧入挤压帽4中。
实施例
下面将结合实施例对本公开的实施方案进行详细描述，但是本领域技术人员将会理解，下列实施例仅用于说明本公开，而不应视为限定本公开的范围。实施例中未注明具体条件者，按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者，均为可以通过市购获得的常规产品。
实施例1
<聚乳酸纳米纤维膜的制备>
采用六氟异丙醇溶解聚乳酸，配置质量浓度为10％的静电纺丝溶液，将静电纺丝溶液加入注射器中，并连接微量泵前管和喷丝针头，设定纺丝电压25kV，溶液推进速度 10mL/h，接收距离30cm。电纺结束后将获得的电纺膜片放置在鼓风干燥箱中50℃干燥5h，然后浸泡在75％酒精1h后置于干燥箱干燥50℃过夜得到聚乳酸纳米纤维膜。
<复合>
选用45根(1簇)的PET纤维丝制成的纤维线，通过缝纫的方式，将所述纤维线固定于聚乳酸纳米纤维膜上，得到复合膜。其中，一条纤维线由1簇的PET纤维丝制成，4条纤维线为一个纤维线组，同一纤维线组中的纤维线延伸方向相同，共缝上1个纤维线组。
<仿生韧带制备>
将上述的复合膜以纤维线的延伸方向为轴进行卷曲，并通过卷绕缝合来形成具有空腔的仿生韧带的主体部，其中纤维线的延伸方向与所述主体部的长度方向相同，在仿生韧带的主体部的两端沿着纤维线组的方向进行裁剪，使得从仿生韧带的主体部的长度方向上的两端部分别延伸出3个分支部，且在每个分支部上设置牵引线，得到仿生韧带，仿生韧带的主体部的长度为6cm。
<仿生韧带系统的制备>
选用聚醚醚酮棒材，利用五轴机加工设备制备出相匹配的挤压帽和挤压螺钉。然后把仿生韧带和由挤压帽和挤压螺钉组成的固定装置组合起来，得到仿生韧带系统。挤压帽能够从仿生韧带的主体部的长度方向上的两端部插入仿生韧带的主体部的空腔，挤压螺钉能够通过螺纹配合和过盈配合两种方式紧固于挤压帽内。
实施例2
<聚己内酯纳米纤维膜的制备>
采用六氟异丙醇溶解聚己内酯，配置质量浓度为10％静电纺丝溶液，将静电纺丝溶液加入注射器中，并连接微量泵前管和喷丝针头，设定纺丝电压28.5kV，溶液推进速度8mL/h，接收距离30cm。电纺结束后将获得的电纺膜片放置在鼓风干燥箱中50℃干燥5h，然后浸泡在75％酒精1h后置于干燥箱干燥50℃过夜得到聚己内酯纳米纤维膜。
<复合>
选用25根(1簇)的PET纤维丝制成的纤维线，通过缝纫的方式，将所述纤维线固定于聚己内酯纳米纤维膜上，得到复合膜。其中，一条纤维线由1簇的PET纤维丝制成，2条纤维线为一个纤维线组，同一纤维线组中的纤维线延伸方向相同，相邻纤维线组之间的距离为1cm，共缝上4个纤维线组，4个纤维线组彼此平行。
<仿生韧带的制备>
将上述的复合膜以纤维线的延伸方向为轴进行卷曲，并卷绕缝合形成具有空腔的仿生韧带的主体部，其中纤维线的延伸方向与所述主体部的长度方向相同，在仿生韧带的主体部的两端沿着纤维线组的方向进行裁剪，使得仿生韧带的主体部的两端各分叉有2个分支部，且在每个分支部上设置牵引线，得到仿生韧带，仿生韧带的主体部的长度为12cm。
<仿生韧带系统的制备>
选用聚醚醚酮棒材，利用五轴机加工设备制备出相匹配的挤压帽和挤压螺钉。然后把仿生韧带和由挤压帽和挤压螺钉组成的固定装置组合起来，得到仿生韧带系统。挤压帽能够从仿生韧带的主体部的长度方向上的两端部插入仿生韧带的主体部的空腔，挤压螺钉能够通过螺纹配合和过盈配合两种方式紧固于挤压帽内。
实施例3
<L-聚乳酸纳米纤维膜的制备>
采用六氟异丙醇溶解L-聚乳酸，配置质量浓度为20％的静电纺丝溶液，将静电纺丝溶液加入注射器中，并连接微量泵前管和喷丝针头，设定纺丝电压35kV，溶液推进速度2.5mL/h，接收距离30cm。电纺结束后将获得的电纺膜片放置在鼓风干燥箱中50℃干燥5h，然后浸泡在75％酒精1h后置于干燥箱干燥50℃过夜得到L-聚乳酸纳米纤维膜。
<骨修复膜的制备>
采用六氟异丙醇溶解L-聚乳酸，配置质量浓度为8％的L-聚乳酸溶液，然后在L-聚乳酸溶液中加入羟基磷灰石粉末，且聚乳酸和羟基磷灰石的质量比为5:2，在转速为1500rpm下搅拌30分钟，导入表面皿中，常温下风干，得到骨修复膜。
<复合>
选用50根(1簇)的PET纤维丝制成的纤维线，通过缝纫的方式，利用所述纤维线将聚L-聚乳酸纳米纤维膜和第一骨修复膜、第二骨修复膜复合，得到复合膜。其中，一条纤维线由1簇的PET纤维丝制成，10条纤维线为一个纤维线组，同一纤维线组中的10条纤维线的延伸方向相同，相邻纤维线组之间的距离为1cm，缝上4个纤维线组，4个纤维线组彼此平行，并且第一骨修复膜与第二骨修复膜之间的间距为5cm。
<仿生韧带的制备>
将上述的复合膜以纤维线的延伸方向为轴进行卷曲，并通过卷绕缝合来形成具有空 腔的仿生韧带的主体部，其中纤维线的方向延伸与所述主体部的长度方向相同，在仿生韧带的主体部的两端沿着纤维线组的方向进行裁剪，使得从仿生韧带的主体部的长度方向上的两端部延伸出4个分支部(每端部延伸出2个分支部)，且在每个分支部上设置牵引线，得到仿生韧带，仿生韧带的主体部的长度为12cm。
<仿生韧带系统的制备>
选用聚醚醚酮棒材，利用五轴机加工设备制备出相匹配的挤压帽和挤压螺钉。然后把仿生韧带和由挤压帽和挤压螺钉组成的固定装置组合起来，得到仿生韧带系统。挤压帽能够从仿生韧带的主体部的长度方向上的两端部插入仿生韧带的主体部的空腔，挤压螺钉能够通过螺纹配合和过盈配合两种方式紧固于挤压帽内。
实施例4
<聚己内酯纳米纤维膜的制备>
采用六氟异丙醇溶解聚己内酯，配置质量浓度为15％的静电纺丝溶液，将静电纺丝溶液加入注射器中，并连接微量泵前管和喷丝针头，设定纺丝电压35kV，溶液推进速度10mL/h，接收距离30cm。电纺结束后将获得的电纺膜片放置在鼓风干燥箱中50℃干燥5h，然后浸泡在75％酒精1h后置于干燥箱干燥50℃过夜得到聚己内酯纳米纤维膜。
<骨修复膜的制备>
采用六氟异丙醇溶解明胶和L-聚乳酸，配置质量浓度为12％的L-聚乳酸-明胶溶液，然后在L-聚乳酸-明胶溶液中加入羟基磷灰石粉末，且明胶和L-聚乳酸的混合物与羟基磷灰石的质量比为5:1，在转速为1000rpm下搅拌40分钟，导入表面皿中，常温下风干，得到骨修复膜。
<复合>
选用30根(1簇)的PET纤维丝制成的纤维线，通过缝纫的方式，利用纤维线将聚己内酯纳米纤维膜和第一骨修复膜、第二骨修复膜复合，得到复合膜。其中，一条纤维线由1簇PET纤维丝制成，10条纤维线为一个纤维线组，同一纤维线组中的10条纤维线的延伸方向相同，相邻纤维线组之间的距离为1cm，缝上3个纤维线组，3个纤维线组彼此平行，并且第一骨修复膜与第二骨修复膜之间的间距为4cm。
<仿生韧带的制备>
将上述的复合膜以纤维线的延伸方向为轴进行卷曲，并通过卷绕缝合来形成具有空腔的仿生韧带的主体部，其中纤维线的方向延伸与所述主体部的长度方向相同，在仿生 韧带的主体部的两端沿着纤维线组的方向进行裁剪，使得从仿生韧带的主体部的长度方向上的两端部延伸出4个分支部(每端部延伸出2个分支部)，且在每个分支部上设置牵引线，得到仿生韧带，仿生韧带的主体部的长度为6cm。
<仿生韧带系统的制备>
选用聚醚醚酮棒材，利用五轴机加工设备制备出相匹配的挤压帽和挤压螺钉。然后把仿生韧带和由挤压帽和挤压螺钉组成的固定装置组合起来，从而得到仿生韧带系统。挤压帽能够从仿生韧带的主体部的长度方向上的两端部插入仿生韧带的主体部的空腔，挤压螺钉能够通过螺纹配合和过盈配合两种方式紧固于挤压帽内。
动物实验
采用实施例1的人工韧带系统进行动物实验，术前将人工韧带系统中的人工韧带及固定装置进行灭菌处理。
取3只羊，分别通过肌肉注射3.5％戊巴比妥钠溶液麻醉后，选择后腿的左膝关节作为实验组，屈膝90°，去除前交叉韧带。用电钻沿前交叉韧带从胫骨端向股骨端钻孔，胫骨和股骨均钻通，利用辅助植入装置将人工韧带植入股骨的骨隧道中。然后利用牵引器牵引人工韧带的牵引线将人工韧带的一端从胫骨骨隧道拉出，屈膝30°，将人工韧带与股骨骨隧道、胫骨骨隧道分别用固定装置进行固定，固定后剪掉两端外露的多余的人工韧带，缝合膝关节，术后自由活动。后腿的右膝关节不作处理，作为对照组。
术后一年将羊无痛处死，对后腿的左膝关节和右膝关节进行解剖。解剖左膝关节(实验组)发现纳米纤维膜基本降解完毕，并且新生组织包裹不可降解纤维，左膝关节(实验组)和右膝关节(对照组)两侧半月板对比无肉眼可见区别，关节液的量、颜色均与正常关节无肉眼可见的区别。表明本公开实施例1的人工韧带系统具有良好的修复效果。
同样地，对本公开实施例2-4制备得到的人工韧带系统进行上述动物实验，本公开实施例2-4制备得到的人工韧带系统具备与实施例1相同或更优的技术效果。因此，本公开的人工韧带系统能够用于韧带修复，并且具有很好的修复效果。
本公开的上述实施例仅仅是为清楚地说明本公开所作的举例，而并非是对本公开的实施方式的限定。对于所属领域的普通技术人员来说，在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。凡在本公开的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本公开权利要求的保护范围之内。

Claims (17)

  1. 一种仿生韧带，其特征在于，所述仿生韧带包括：
    主体部，所述主体部包括多孔膜和多条纤维线，所述主体部为由多孔膜卷绕形成的具有空腔的圆筒形状，所述多条纤维线固定于所述多孔膜上，所述多条纤维线中的至少一条纤维线大致沿着与所述主体部的长度方向相同的方向延伸；以及
    分支部，所述分支部从所述主体部的长度方向上的两端部延伸出，且所述分支部与所述主体部相连，所述分支部的远离所述主体部的自由端部能够沿径向外侧弯曲，使得所述分支部的所述自由端部彼此分开。
  2. 根据权利要求1所述的仿生韧带，其特征在于，所述主体部与所述分支部一体成型；并且
    所述分支部包括所述多孔膜和所述多条纤维线，所述多条纤维线中的至少一条纤维线大致沿着与所述分支部的长度方向相同的方向延伸。
  3. 根据权利要求1或2所述的仿生韧带，其特征在于，所述多条纤维线分成多个纤维线组，所述纤维线组大致彼此平行，并且
    所述主体部的在相邻的所述纤维线组之间的部分设置有贯通所述主体部的通透孔。
  4. 根据权利要求1所述的仿生韧带，其特征在于，所述多条纤维线中的至少一条纤维线的起始端与终止端分别位于所述多孔膜的在所述主体部的长度方向上的两端部处且分别与该两端部相连。
  5. 根据权利要求2所述的仿生韧带，其特征在于，所述多条纤维线中的至少一条纤维线的起始端与终止端分别位于所述多孔膜的在所述分支部的长度方向上的自由端部处且分别与所述自由端部相连。
  6. 根据权利要求1至5任一项所述的仿生韧带，其特征在于，所述主体部和所述分支部均包括骨修复膜，或者仅所述主体部包括骨修复膜，
    在所述主体部和/或所述分支部中，所述骨修复膜从外侧包覆于所述多孔膜，并且
    所述多条纤维线使所述多孔膜与所述骨修复膜固定在一起。
  7. 根据权利要求6所述的仿生韧带，其特征在于，所述主体部至少包括分别包覆于所述多孔膜的在所述主体部的长度方向上的两端部的第一骨修复膜和第二骨修复膜，所述第一骨修复膜与所述第二骨修复膜在所述主体部的长度方向上彼此分隔开。
  8. 根据权利要求7所述的仿生韧带，其特征在于，所述第一骨修复膜与所述第二骨修复膜之间的在所述主体部的长度方向上的最小间距为1cm至5cm，优选为2cm至4cm。
  9. 根据权利要求1至8任一项所述的仿生韧带，其特征在于，
    所述分支部的数量为2个至4个，和/或
    相邻的两个所述分支部的根部之间的在所述主体部的周向上的距离为0cm至4cm，或者相邻的两个所述分支部的根部在所述主体部的周向上部分层叠。
  10. 根据权利要求1至9任一项所述的仿生韧带，其特征在于，
    所述仿生韧带还包括从所述分支部的所述自由端部延伸出的多条牵引线。
  11. 根据权利要求1至10任一项所述的仿生韧带，其特征在于，所述多孔膜为类细胞外基质多孔膜，
    优选地，所述类细胞外基质多孔膜包括纳米纤维膜，更优选地，所述纳米纤维膜由可降解材料制成，进一步优选地，所述可降解材料包括聚氨酯、聚乳酸、聚己内酯、聚乙醇酸、壳聚糖、乳酸-羟基乙酸共聚物、海藻酸、海藻酸盐、胶原、明胶、硫酸软骨素、透明质酸、纤维蛋白、改性纤维素的一种或两种以上的组合。
  12. 根据权利要求6至11任一项所述的仿生韧带，其特征在于，所述骨修复膜由无机化合物和高分子材料复合得到；优选地，所述无机化合物包括磷酸钙类化合物，所述高分子材料包括可降解的高分子材料；更优选地，所述磷酸钙类化合物包括羟基磷灰石、磷酸三钙、含锶硫酸钙中一种或两种以上的组合，所述可降解的高分子材料包括聚乳酸、聚己内酯、聚乙交酯、明胶、胶原、壳聚糖类及其衍生物、海藻酸类及其衍生物、蚕丝蛋白中的一种或两种以上的组合。
  13. 根据权利要求1至12任一项所述的仿生韧带，其特征在于，所述纤维线由不可降解纤维材料制成，优选地，所述不可降解纤维材料包括蚕丝纤维、聚酯纤维、超高分子量聚乙烯纤维、聚丙烯纤维中的一种或两种以上的组合。
  14. 一种仿生韧带系统，其特征在于，所述仿生韧带系统包括权利要求1至13中任一项所述的仿生韧带以及将所述仿生韧带固定于骨隧道内的固定装置。
  15. 根据权利要求14所述的仿生韧带系统，其特征在于，所述固定装置能够在所述仿生韧带的主体部的两端部处将所述仿生韧带固定于所述骨隧道内，
    所述固定装置包括挤压帽和挤压螺钉，所述挤压帽从所述主体部的长度方向上的两端部插入所述主体部的空腔，所述挤压螺钉能够通过螺纹配合和/或过盈配合紧固于所述挤压帽内，
    优选地，所述挤压帽的外部形状为大致圆台形的形状。
  16. 根据权利要求15所述的仿生韧带系统，其特征在于，所述挤压螺钉的材料包括钛合金、聚乳酸、聚芳醚酮类化合物中的一种或两种以上的组合，优选地，所述聚芳醚酮类化合物包括聚醚醚酮、聚醚酮酮、聚醚酮、聚醚酮醚酮酮或聚醚醚酮酮中的一种或两种以上的组合。
  17. 根据权利要求15或16所述的仿生韧带系统，其特征在于，所述挤压帽的材料包括聚乙烯、聚丙烯、聚乳酸、硅胶、聚芳醚酮类化合物中的一种或两种以上的组合，优选地，所述聚芳醚酮类化合物包括聚醚醚酮、聚醚酮酮、聚醚酮、聚醚酮醚酮酮或聚醚醚酮酮中的一种或两种以上的组合。
PCT/CN2017/119127 2016-12-28 2017-12-27 仿生韧带及仿生韧带系统 WO2018121629A1 (zh)

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